The Association Between COVID-19 and Thyroxine Levels: A Meta-Analysis.
Chen Yiru,Li Xiuneng,Dai Yu,Zhang Jingjing
Frontiers in endocrinology
Objectives:Recently, a number of reports have described the potential relationship between COVID-19 and thyroid hormones, but the results were conflicting. We performed a meta-analysis to evaluate the effect of the severity of COVID-19 on thyroid-related hormones and the effect of thyroid-related hormones on the outcome of COVID-19 in order to try to confirm the association between the serum levels of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) and the severity or mortality of coronavirus-19 patients. Methods:The methodology was already registered in the International Prospective Register of Systematic Reviews (PROSPERO) database, and the protocol number is CRD42021269246. Systematic searches were carried out on the Cochrane Library, Embase, PubMed and Web of Science databases on November 15, 2021. We set up the literature search strategy based on the following keywords: [(T3 OR FT3 OR triiodothyronine) or (T4 OR FT4 OR thyroxine) or (TSH or thyrotropin)] and (COVID-19 OR SARS-CoV-2), without time restrictions. Results:Twenty studies satisfied the inclusion/exclusion criteria and were included in the meta-analysis. A total of 3609 patients were enrolled in the study. From the analysis of the included studies, the incidence of thyroid-related hormone abnormalities was higher in patients with severe COVID-19, and the serum levels of FT3 and TSH were lower than those of patients with nonsevere COVID-19. However, the difference in the FT4 levels was not significant. Similar characteristics were shown between survivors and nonsurvivors. In addition, the outcomes of the meta-analysis showed that patients with abnormal thyroid-related hormones had greater mortality. Conclusions:Low FT3 serum levels, low FT4 serum levels and low TSH serum levels may increase the mortality of COVID-19 patients during admission. On the other hand, the higher the severity level of COVID-19, the higher the probability of decreases in the FT3, FT4, TSH levels.
10.3389/fendo.2021.779692
Hypothyroidism does not lead to worse prognosis in COVID-19: findings from the Brazilian COVID-19 registry.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
BACKGROUND:It is not clear whether previous thyroid diseases influence the course and outcomes of COVID-19. METHODS:The study is a part of a multicentric cohort of patients with confirmed COVID-19 diagnosis from 37 hospitals. Matching for age, sex, number of comorbidities, and hospital was performed for the paired analysis. RESULTS:Of 7,762 patients with COVID-19, 526 had previously diagnosed hypothyroidism and 526 were matched controls. The median age was 70 years, and 68.3% were females. The prevalence of comorbidities was similar, except for coronary and chronic kidney diseases that were higher in the hypothyroidism group (p=0.015 and p=0.001). D-dimer levels were lower in patients with hypothyroid (p=0.037). In-hospital management was similar, but hospital length-of-stay (p=0.029) and mechanical ventilation requirement (p=0.006) were lower for patients with hypothyroidism. There was a trend of lower in-hospital mortality in patients with hypothyroidism (22.1% vs 27.0%; p=0.062). CONCLUSION:Patients with hypothyroidism had a lower requirement of mechanical ventilation and showed a trend of lower in-hospital mortality. Therefore, hypothyroidism does not seem to be associated with a worse prognosis.
10.1016/j.ijid.2022.01.016
Covid-19, the thyroid and the pituitary - The real state of play.
Annales d'endocrinologie
Thyroid and pituitary disorders linked to the coronavirus SARS-CoV-2, responsible for the COVID-19 epidemic, are mainly due to direct infection of the endocrine glands by the virus and to cell damage induced by the immune response. The two most frequent thyroid complications of COVID-19 are low T3 syndrome, or "non-thyroidal illness syndrome" (NTIS), and thyroiditis. Studies among in-patients with COVID-19 have shown that between one out of six and half of them have a low TSH level, related to NTIS and thyroiditis, respectively, sometimes found in the same patient. In NTIS, the decrease in free T3 concentration correlates with the severity of the infection and with a poor prognosis. Assessment of thyroid function in patients after a COVID-19 infection, shows normalization of thyroid function tests. Thyroiditis linked to COVID-19 can be divided into two groups, which probably differ in their pathophysiology. One is "destructive" thyroiditis occurring early in infection with SARS-CoV-2, with a severe form of COVID-19, usually observed in men. It is often asymptomatic and associated with lymphopenia. The other is subacute thyroiditis occurring, on average, one month after the COVID-19 episode, usually in clinically symptomatic women and associated with moderate hyperleukocytosis. Post-infection, one quarter to one third of patients remain hypothyroid. An Italian study demonstrated that low TSH in patients hospitalized for COVID-19 was associated with prolonged hospitalization and a higher mortality risk. Pituitary diseases associated with SARS-CoV-2 infection are much rarer and the causal relationship more difficult to ascertain. Several cases of pituitary apoplexy and diabetes insipidus during COVID-19 infection have been reported. Hyponatremia occurs in 20-50% of patients admitted to hospital for COVID-19. The prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) amongst these hyponatremic cases is difficult to determine. These endocrine complications may influence the prognosis of infection with SARS-CoV-2. Although they rarely require specific treatment, it is important that endocrinologists recognize them to ensure appropriate management, particularly in the acute phase.
10.1016/j.ando.2021.12.004
Impact of COVID-19 in immunosuppressive drug-naïve autoimmune disorders: Autoimmune gastritis, celiac disease, type 1 diabetes, and autoimmune thyroid disease.
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
Few conflicting data are currently available on the risk of SARS-CoV-2 infection in patients with autoimmune disorders. The studies performed so far are influenced, in most cases, by the treatment with immunosuppressive drugs, making it difficult to ascertain the burden of autoimmunity per se. For this reason, herein we assessed the susceptibility to COVID-19 in immunosuppressive drug-naïve patients with autoimmune diseases, such as autoimmune gastritis (AIG), celiac disease (CD), type 1 diabetes (T1D), and autoimmune thyroid disease (AITD). Telephone interviews were conducted on 400 patients-100 for each group-in May 2021 by looking at the positivity of molecular nasopharyngeal swabs and/or serology for SARS-CoV-2, the need for hospitalization, the outcome, and the vaccination status. Overall, a positive COVID-19 test was reported in 33 patients (8.2%), comparable with that of the Lombardy general population (8.2%). In particular, seven patients with AIG, 9 with CD, 8 with T1D, and 9 with AITD experienced COVID-19. Only three patients required hospitalization, none died, and 235 (58.7%) were vaccinated, 43 with AIG, 47 with CD, 91 with T1D, and 54 with AITD. These results seem to suggest that autoimmunity per se does not increase the susceptibility to COVID-19. Also, COVID-19 seems to be mild in these patients, as indicated by the low hospitalization rates and adverse outcomes, although further studies are needed to better clarify this issue.
10.1111/pai.13646
SARS-CoV-2 vaccine-associated subacute thyroiditis: insights from a systematic review.
Journal of endocrinological investigation
PURPOSE:To perform a systematic review on published cases of subacute thyroiditis (SAT) secondary to SARS-CoV-2 vaccination, to highlight main features and increase the awareness of this condition. METHODS:Original reports of SAT developed after SARS-CoV-2 vaccination (mRNA, viral vector, or inactivated virus vaccines) were retrieved from a search of electronic databases. Individual patient data on demographics, medical history, type of vaccine, workup and therapies were collected. Wilcoxon rank-sum, Kruskal-Wallis and chi-squared tests were employed for comparisons. RESULTS:30 articles including 48 reports were retrieved, 3 additional cases evaluated by the Authors were described and included for analysis. Of the 51 patients, 38 (74.5%) were women, median age was 39.5 years (IQR 34-47). Patients developed SAT after a median of 10 days (IQR 4-14) after the vaccine shot. Baseline thyroid exams revealed thyrotoxicosis in 88.2% of patients, decreasing at 31.6% at follow-up. Corticosteroids were used in 56.4% of treated patients. Patients undergoing non-mRNA vaccines were most frequently Asian (p = 0.019) and reported more frequently weight loss (p = 0.021). All patients with a previous diagnosis of thyroid disease belonged to the mRNA vaccine group. CONCLUSION:SARS-CoV-2 vaccine-associated SAT is a novel entity that should be acknowledged by physicians. Previous history of thyroid disease may predispose to develop SAT after mRNA vaccines, but further studies and larger cohorts are needed to verify this suggestion. SARS-CoV-2 vaccine-associated SAT is usually of mild/moderate severity and could be easily treated in most cases, thus it should not raise any concern regarding the need to be vaccinated.
10.1007/s40618-022-01747-0
The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients.
Frontiers in endocrinology
Background:Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated. Methods:We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission. Results:A total of 541 patients were included. Median LYM was 1.22 x 10/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001). Conclusion:TSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.
10.3389/fendo.2021.774346
The Prognostic Role of Metabolic and Endocrine Parameters for the Clinical Severity of COVID-19.
Disease markers
OBJECTIVE:An outbreak of coronavirus disease-19 (COVID-19) began in December 2019 and spread globally, overwhelming the entire world. COVID-19 is a public health emergency of international concern. Due to its high morbidity and mortality rate, recognition of its risk and prognostic factors is important. We aimed to understand the relationship between metabolic and endocrine parameters and the prognosis of COVID-19. METHODS AND MATERIALS:This was a cross-sectional clinical study. A total of 70 patients with severe COVID-19 were enrolled. Laboratory results at the first admission time (including complete blood count, C-reactive protein, lactate dehydrogenase, blood glucose, calcium, phosphate, albumin, creatinine, magnesium, lipid profiles, liver enzymes, thyroid hormones, cortisol, and vitamin D) and outcome data were recorded. We divided patients into (1) intensive care unit- (ICU-) admitted and non-ICU-admitted and (2) survivors and nonsurvivors for estimation of severity and prognosis. We determined the risk factors associated with critical illness and poor prognosis. RESULTS:Patients with higher white blood cell (WBC) count and phosphate levels had significantly higher ICU admission rates. According to univariate analysis, serum levels of T3, phosphate, and WBC as well as the duration of hospitalization were associated with mortality. Multivariate analysis revealed that only WBC and duration of hospitalization were independent predictors for mortality rate in COVID-19 patients. CONCLUSION:Our findings suggest that longer duration of hospitalization and higher WBC count are associated with poor outcomes in patients with COVID-19.
10.1155/2022/5106342
SARS-CoV-2 Vaccine-induced Thyroiditis: Safety of Revaccinations and Clinical Follow-up.
The Journal of clinical endocrinology and metabolism
CONTEXT:The number of reported cases with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) and Graves' disease (GD) is growing. However, active debate continues about managing such side effects and the safety of repeat or booster doses of the vaccines in such cases. OBJECTIVES:This study aims to present long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT or GD cases and provide data regarding the safety of revaccinations. METHODS:Patients diagnosed with SARS-CoV-2 vaccine-induced SAT or GD were included. Data regarding the long-term clinical follow-up of SARS-CoV-2 vaccine-induced SAT and GD cases and outcomes of repeat or booster SARS-CoV-2 vaccinations were documented. The literature, including cases of SARS-CoV-2 vaccine-induced SAT or GD, was reviewed. RESULTS:Fifteen patients with SARS-CoV-2 vaccine-induced SAT and 4 with GD were included. Pfizer/BioNTech COVID-19 vaccine (BNT162b2) was associated with symptoms in a majority of cases with SAT and all with GD. Median time from vaccination to symptom onset was 7 and 11.5 days, respectively, while 7 and 2 patients required medical treatment in SAT and GD groups, respectively. Remission was documented in 10 SAT patients, with a median time to remission of 11.5 weeks. No exacerbation/recurrence of SAT occurred in 7 of 9 patients who received a repeat vaccination dose, while symptoms of SAT worsened following the second vaccination in 2 cases. None of the patients experienced severe side effects that could be associated with revaccinations. CONCLUSIONS:Revaccinations appear to be safe in patients with SARS-CoV-2 vaccine-induced SAT cases, while more evidence is needed regarding SARS-CoV-2 vaccine-induced GD.
10.1210/clinem/dgac049
Post-COVID simultaneous onset of Graves' disease and ocular myasthenia gravis in a patient with a complex ocular motility impairment.
European journal of ophthalmology
A 74-years-old man experienced severe diplopia one month after recovery from an uncomplicated SARS-CoV-2 infection. Neurological examination was normal whereas ophthalmological examination showed bilateral exophthalmos with a complex ocular motility disorder characterized by a pseudo-internuclear ophthalmoplegia after fatigue associated to impairment of elevation and infraduction. Antibodies against TSH and acetylcholine receptors were positive; subsequent hormonal tests, ultrasonography of thyroid gland, single fiber electromyography and orbit MRI confirmed the diagnosis of concomitant Graves Disease (GD) and Myasthenia Gravis (MG). The coexistence between MG and GD is not rare but simultaneous onset after viral infection is very unsual. The complex ocular disorder simulated a deficit of the oculomotor nerve nuclei, and on clinical examination it posed some problems in the diagnosis. We suggest that recent SARS-COV-2 infection may have triggered a complex autoimmune response.
10.1177/11206721221077800
Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.
Clinical endocrinology
INTRODUCTION:Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS:In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS:Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS:In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.
10.1111/cen.14699
SARS-CoV-2 vaccine-associated subacute thyroiditis.
Journal of endocrinological investigation
PURPOSE:With coronavirus disease 2019 (COVID-19), subacute thyroiditis (SAT) cases are on the rise all over the world. COVID-19 vaccine-associated SAT cases have also been reported. In this article, we present our data on 11 vaccine-associated SAT cases. METHODS:Eleven patients were included in the study. Type of the vaccines patients received, time to the occurrence of SAT after vaccination, symptoms and laboratory findings, treatment given, and response to treatment were evaluated. RESULTS:The age of patients ranged from 26 to 73. Four of the patients were males, and seven were females. Symptoms of six patients were seen after BNT162b2 Pfizer/BioNTech COVID-19 mRNA vaccine®, and four of them after Coronavac inactivated SARS-CoV-2 vaccine®. In one patient, SAT developed after the first dose of BNT162b2, administered after two doses of Coronavac. The average time to the onset of symptoms was 22 days (15-37) after vaccination. CONCLUSIONS:The fact that both whole virus containing and genetic material containing vaccines cause SAT suggests that the trigger may be viral proteins rather than the whole viral particle. Although corticosteroids are commonly preferred in published vaccine-associated SAT cases, we preferred nonsteroidal anti-inflammatory therapy in our patients for sufficient vaccine antibody response. There is not enough information about whether patients who develop SAT can be revaccinated safely considering the ongoing pandemic. Further research is needed for a conclusion in the treatment and revaccination of these patients.
10.1007/s40618-022-01767-w
Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study.
Thyroid : official journal of the American Thyroid Association
Thyroiditis and Graves' disease have been reported after coronavirus disease 2019 (COVID-19) vaccination. We evaluated the risks of adverse events after COVID-19 vaccination among patients treated for hypothyroidism. In this retrospective population-based cohort study of Hong Kong Hospital Authority electronic health records with the Department of Health vaccination records linkage, levothyroxine (LT4) users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine), or CoronaVac (inactivated vaccine) between February 23, 2021, and September 9, 2021. Study outcomes were dosage reduction or escalation in LT4, emergency department (ED) visit, unscheduled hospitalization, adverse events of special interest (AESI) according to the World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Inverse probability of treatment weighting for propensity score was applied to balance baseline patient characteristics among the three groups. Hazard ratios (HR) were estimated using Cox regression models. Patients were observed from the index date until the occurrence of study outcome, death, or censored on September 30, 2021, whichever came first. In total, 47,086 LT4 users were identified (BNT162b2: = 12,310; CoronaVac: = 11,353; and unvaccinated: = 23,423). COVID-19 vaccination was not associated with increased risks of LT4 dosage reduction (BNT162b2: HR = 0.971 [confidence interval; CI 0.892-1.058]; CoronaVac: HR = 0.968 [CI 0.904-1.037]) or escalation (BNT162b2: HR = 0.779 [CI 0.519-1.169]; CoronaVac: HR = 0.715 [CI 0.481-1.062]). Besides, COVID-19 vaccination was not associated with a higher risk of ED visits (BNT162b2: HR = 0.944 [CI 0.700-1.273]; CoronaVac: HR = 0.851 [CI 0.647-1.120]) or unscheduled hospitalization (BNT162b2: HR = 0.905 [CI 0.539-1.520]; CoronaVac: HR = 0.735 [CI 0.448-1.207]). There were two (0.016%) deaths and six (0.062%) AESI recorded for BNT162b2 recipients, and one (0.009%) and three (0.035%) for CoronaVac recipients, respectively. BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism in general. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.
10.1089/thy.2021.0684
The potential impact of COVID-19 on thyroid gland volumes among COVID-19 survivors.
Endocrine
PURPOSE:Data about the effects of COVID-19 on the endocrine system are increasing over time. In the present study, we investigated the effects of COVID-19 on the thyroid gland among COVID-19 survivors by comparing them with healthy subjects. METHODS:Adult COVID-19 survivors who were managed and followed up in the Infectious Disease clinic were asked to participate in this study. COVID-19 survivors were recruited via a convenience sampling and those who agreed to participate in this study were seen by endocrinologists for assessments. The blood tests were obtained for thyroid antibodies and thyroid function tests. Thyroid ultrasonography (USG) was done by the same physician. The ellipsoid formula was used for the calculation of thyroid gland volume. RESULTS:64 adult COVID-19 survivors and 70 control subjects were enrolled in the study. The COVID-19 survivors were evaluated at median 5.7 months (IQR: 4-6.5) (range: 2-7 months) after acute infection. The mean thyroid gland volume was significantly lower in COVID-19 survivors (10.3 ± 3.4 mL) than in the controls (14 ± 5.3 mL) (p = 0.001). There was no significant difference in free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels between the groups. Among the twelve patients who had thyroid function evaluated in acute COVID-19, fT3 values were lower in acute COVID-19 than at the time of USG evaluation (3.04 ± 0.41 vs 3.47 ± 0.31 pg/mL), (p = 0.02). Among COVID-19 survivors, mild TSH elevation was detected in 4 (6.2%) patients and all of the other COVID-19 survivors (93.7%) were euthyroid. CONCLUSIONS:At 6 months after acute COVID, COVID-19 survivors had smaller thyroid gland volume than healthy controls, and only a few of the COVID-19 survivors had abnormal thyroid function.
10.1007/s12020-022-03019-6
Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study.
Paschou Stavroula A,Karalis Vangelis,Psaltopoulou Theodora,Vasileiou Vasiliki,Charitaki Ioanna,Bagratuni Tina,Ktena Vassiliki,Papandroulaki Fotini,Gumeni Sentiljana,Kassi Georgia N,Trougakos Ioannis P,Terpos Evangelos,Dimopoulos Meletios A
Frontiers in endocrinology
Background:This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods:The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results:Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions:This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.
10.3389/fendo.2022.840668
Coronavirus as a Trigger Of Graves' Disease.
Urbanovych A M,Laniush F,Borovets M,Kozlovska K
Acta endocrinologica (Bucharest, Romania : 2005)
Context:SARS-CoV-2 infection was declared a pandemic in 2020 and affected millions of people worldwide. Angiotensin-converting enzyme-2 receptors, through which coronavirus enters the cells of different organs, have been detected in the thyroid gland. The most common cause of thyrotoxicosis is Graves' disease in which thyroid-receptors antibodies (TRAb) stimulate the TSH receptor, increasing thyroid hormone production and release. Case presentation:A 22-year-old woman had symptoms of palpitation, tremor, muscle weakness, anxiety and sleep disturbance. 3 weeks before the onset of these symptoms, the patient suffered from COVID-19, which lasted 14 days and was characterized by a course of moderate severity with fever up to 38C, general weakness without shortness of breath. The patient had no pre-existing thyroid problems. Her TSH was <0.01 mU/L, FT4, FT3 and TRAb were increased. Antithyroid drugs, glucocorticosteroids and β-blockers were prescribed. During 3 months of treatment doses of methimazole, methylprednisolone and bisoprolol were gradually reduced due to the improvement of the patient's condition and thyroid tests normalization. Conclusions:COVID-19 infection can cause Graves' disease and thyrotoxicosis. The onset of this disease after SARS-CoV-2 does not depend on the presence of pre-existing thyroid pathology and requires the appointment of glucocortisteroids.
10.4183/aeb.2021.413
Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis.
Thyroid : official journal of the American Thyroid Association
Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. , and frequencies were analyzed by next-generation sequencing. The frequencies of alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (: 13 [93%] vs. 40 [40%], < 0.001; : 13 [93%] vs. 43 [43%], < 0.001, respectively). More severe thyrotoxicosis was seen in patients having and homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63], = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5], = 0.07). The frequencies of and alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for and was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.
10.1089/thy.2022.0010
Hypothyroidism and Subclinical Hypothyroidism as a Consequence of COVID-19 Infection.
Medical archives (Sarajevo, Bosnia and Herzegovina)
Background:Hypothyroidism occurs as a consequence of chronic autoimmune inflammation of the thyroid gland, which occurs due to the reduced function in the secretion of hormones FT3 and FT4 and requires replacement therapy for life. CoV-19 infection has shown many complications in all organic systems, during the acute phase of infection and in the post COVID period. Objectives:The aim of the study was a) to compare the frequency of patient visits for hypothyroidism and the average dose of levothyroxine in the SANASA polyclinic in the year before COVID pandemic, in the early 2019, with the frequency of patient visits during COVID infection in 2020 and 2021; b) to determine the incidence of hypothyroidism after the COVID 19 infection, the time of onset of hypothyroidism after acute phase of the disease, and the average dose of levothyroxine; and c) to monitor the incidence of subclinical hypothyroidism, which did not require substitution, before and after COVID 19 infection. Methods:In the SANASA polyclinic from the 2019 database we found 58 patients, at the age between 18-70 years, 53 women and 2 men with hypothyroidism and 2 female and 1 male patients with subclinical hypothyroidism. In 2020 there were a total of 89 patients, 73 women and 4 men with hypothyroidism, and 9 women and 3 men with subclinical hypothyroidism. In the 2021 there were 101 patients, 86 women and 7 men with hypothyroidism and 7 female and 1 male patients with subclinical hypothyroidism. Results:There was a significant difference in the number of patients with hypothyroidism and subclinical hypothyroidism during 2020 and 2021 in relation to 2019. The average dose of levothyroxine per patient did not differ statistically, comparing all three years, as well as comparing those who were ill, compared to patients who did not have COVID-19. There were diagnoses of post COVID subclinical hypothyroidism in 2020, as in 2021, with an average time of diagnosis of 2 months after infection for clinical hypothyroidism and 8 weeks for subclinical hypothyroidism. Conclusion:CoV-19 infection adversely affects thyroid tissue causing clinical hypothyroidism, requiring levothyroxine substitution as well as subclinical hypothyroidism which should be monitored.
10.5455/medarh.2022.76.12-16
Post-COVID-19 Condition: Where Are We Now?
Life (Basel, Switzerland)
COVID-19 is currently considered a systemic infection involving multiple systems and causing chronic complications. Compared to other post-viral fatigue syndromes, these complications are wider and more intense. The most frequent symptoms are profound fatigue, dyspnea, sleep difficulties, anxiety or depression, reduced lung capacity, memory/cognitive impairment, and hyposmia/anosmia. Risk factors for this condition are severity of illness, more than five symptoms in the first week of the disease, female sex, older age, the presence of comorbidities, and a weak anti-SARS-CoV-2 antibody response. Different lines of research have attempted to explain these protracted symptoms; chronic persistent inflammation, autonomic nervous system disruption, hypometabolism, and autoimmunity may play a role. Due to thyroid high ACE expression, the key molecular complex SARS-CoV-2 uses to infect the host cells, thyroid may be a target for the coronavirus infection. Thyroid dysfunction after SARS-CoV-2 infection may be a combination of numerous mechanisms, and its role in long-COVID manifestations is not yet established. The proposed mechanisms are a direct effect of SARS-CoV-2 on target cells, an indirect effect of systemic inflammatory immune response, and a dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis leading to decreased serum TSH. Only a few studies have reported the thyroid gland status in the post-COVID-19 condition. The presence of post-COVID symptoms deserves recognition of COVID-19 as a cause of post-viral fatigue syndrome. It is important to recognize the affected individuals at an early stage so we can offer them the most adequate treatments, helping them thrive through the uncertainty of their condition.
10.3390/life12040517
Differences in Clinical Aspects Between Subacute Thyroiditis Associated with COVID-19 Vaccines and Classical Subacute Thyroiditis.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
Subacute thyroiditis (SAT) developed after SARS-CoV-2 vaccines has been less studied. We aimed to compare classical SAT and SAT developed after SARS-CoV-2 vaccines in the context of clinical aspects. Adults with SAT detected in 90 days of COVID-19 vaccination (CoronaVac or Pfizer/BioNTech) were grouped as Vac-SAT. Those with a history of SARS-CoV-2 or upper respiratory tract infection in 6 months before the vaccination, or vaccination with another antiviral vaccine after COVID-19 vaccination were excluded. Those with SAT detected before COVID-19 pandemic were grouped as Classical-SAT. Of total (n=85), female/male (54/31) ratio and age [43 (23-65)] were similar in Vac-SAT (n=23) and Classical-SAT (n=62). Duration between vaccine and SAT was 45 (7-90) days, and similar in CoronaVac-SAT (n=5) and BioNTech-SAT (n=18). SAT-duration was 28 (10-150) days, and higher in Vac-SAT than in Classical-SAT (p=0.023). SAT was developed after the 1st dose vaccine in minority in CoronaVac-SAT (n=2) and BioNTech-SAT (n=3) (p=0.263). Previous LT4 use, and TSH elevation after resolution were more frequent in Vac-SAT than in Classical-SAT (p=0.027 and p=0.041). We included a considerable number of patients with SAT occurred after COVID-19 vaccines. We cannot provide clear evidence regarding the association of COVID-19 vaccines with SAT. SAT associated with CoronaVac or BioNTech seems unlikely to be occurred after the 1st dose, and to have a longer duration, more likely to be associated with previous LT4 use and lead TSH elevation after resolution than Classical-SAT. TSH should be followed-up after the resolution of SAT detected after COVID-19 vaccination.
10.1055/a-1840-4374
A Case of Graves' Disease Following Vaccination with the Oxford-AstraZeneca SARS-CoV-2 Vaccine: Case Report and Review of the Literature.
European journal of case reports in internal medicine
A 57-year-old man presented to the outpatient clinic with tremor, palpitations, weight loss and fatigue 1 week after receiving the first dose of the Oxford-AstraZeneca SARS-CoV-2 vaccine (ChAdOx1 nCoV-19). Laboratory studies showed a suppressed TSH with elevated total and free T4. Thyroid peroxidase and thyroglobulin antibodies were elevated but thyrotropin receptor autoantibodies were indeterminate. Thyroid scintigraphy with technetium Tc-99m pertechnetate revealed increased diffuse, symmetric uptake. The patient was treated with thiamazole 15 mg three times a day and propranolol with resolution of his symptoms and normalization of his thyroid function tests until discontinuation of the antithyroid drug 6 months after symptom onset. LEARNING POINTS:Thyroid autoimmunity triggered by SARS-CoV-2 vaccines is being increasingly recognized among patients with and without a history of autoimmune thyroid disease.Symptoms and signs of thyrotoxicosis, including fever and tachycardia, can be wrongly attributed to the systemic adverse events of these vaccines.Early recognition of this condition is mandatory to allow proper treatment with anti-thyroid medications and radioactive iodine when necessary.
10.12890/2022_003275
Acute Flaccid Tetraparesis after COVID-19 Infection: Think of the Thyroid.
Case reports in medicine
A previously well 32-year-old Chinese male presented with acute bilateral upper and lower limb paralysis upon waking, ten days after the onset of COVID-19 infection. Examination revealed areflexia over all four limbs, associated with reduced muscle strength, but no sensory or cranial nerve deficit. Initial concern was Guillain-Barre syndrome given the acute flaccid paralysis following COVID-19 infection. However, investigations revealed severe hypokalaemia (1.7 mmol/L) and primary hyperthyroidism. He was treated for thyrotoxic periodic paralysis (TPP) with -blockers, antithyroid medications, and intravenous potassium chloride (KCl). Despite frequent monitoring of potassium, rebound hyperkalaemia occurred with prompt resolution of paralysis.
10.1155/2022/5827664
Subacute thyroiditis associated with thyrotoxic periodic paralysis after COVID-19 vaccination: a case report.
Endocrinology, diabetes & metabolism case reports
Summary:We report a 26-year-old Japanese man who visited our outpatient clinic presenting fever immediately after i.m. injection of the second dose of a coronavirus disease 2019 (COVID-19) vaccine (Moderna®). At the first visit, the patient had a fever of 37.7°C and a swollen thyroid gland with mild tenderness. He was diagnosed with subacute thyroiditis (SAT) based on the presence of thyrotoxicosis (free tri-iodothyronine, 32.3 pg/mL; free thyroxine, >7.77 ng/dL; and thyroid-stimulating hormone (TSH) < 0.01 μIU/mL), high C-reactive protein level (7.40 mg/dL), negative TSH receptor antibody, and characteristic ultrasound findings. His HLA types were A*02:01/24:02, B*15:11/35:01, Cw*03:03, DRB1*09:01/12:01, DQB1*03:03, and DPB1*05: 01/41:01. He was initially administered prednisolone 15 mg/day, following which the fever subsided. After 10 days, he developed limb weakness and could not walk. The serum potassium level decreased to 1.8 mEq/L, which confirmed the diagnosis of thyrotoxic periodic paralysis (TPP). Potassium supplementation was initiated. The muscle weakness gradually decreased. Prednisolone therapy was terminated 6 weeks after the first visit. His thyroid function returned to normal 5 months after the first visit, through a hypothyroid state. To our knowledge, this is the first reported case of TPP-associated SAT following COVID-19 vaccination. Persistent fever following vaccination should be suspected of SAT. Additionally, TPP may be associated with SAT in Asian male patients. Learning points:Following coronavirus disease 2019 (COVID-19) vaccination, subacute thyroiditis may develop regardless of the vaccine type. If persistent fever, anterior neck pain, swelling and tenderness of thyroid gland, and symptoms of thyrotoxicosis are observed immediately after the COVID-19 vaccination, examination in consideration of the onset of subacute thyroiditis is recommended. HLA-B35 may be associated with the onset of subacute thyroiditis after the COVID-19 vaccination. Although rare, subacute thyroiditis can be associated with thyrotoxic periodic paralysis, especially in Asian men. Glucocorticoid therapy for subacute thyroiditis may induce thyrotoxic periodic paralysis through hypokalemia.
10.1530/EDM-22-0236
Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses.
Frontiers in endocrinology
Background and Objective:Nonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs. Methods:We performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results. Results:We observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality. Conclusions:NTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.
10.3389/fendo.2022.850328
ACE2 and TMPRSS2 Immunolocalization and COVID-19-Related Thyroid Disorder.
Biology
Thyroid dysfunction has been reported to be an extrapulmonary symptom of COVID-19. It is important to identify the tissue subset that expresses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are essential for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand the viral pathogenesis of COVID-19-related thyroid dysfunction. We investigated the expression and distribution of ACE2- and TMPRSS2-expressing cells in the thyroid gland. RT-PCR and Western blotting were performed on human thyroid follicular cells (Nthy-ori3-1) and rat thyroid tissues to detect the expression levels of ACE and TMPRSS2 mRNA and proteins. We also analyzed the expression patterns of ACE2 and TMPRSS2 in 9 Sprague-Dawley rats and 15 human thyroid tissues, including 5 normal, 5 with Hashimoto's thyroiditis, and 5 with Graves' disease, by immunohistochemistry (IHC) and immunofluorescence. Both ACE2 and TMPRSS2 mRNAs and proteins were detected in the thyroid tissue. However, ACE2 and TMPRSS2 proteins were not expressed in thyroid follicular cells. In IHC, ACE2 and TMPRSS2 were not stained in the follicular cells. No cells co-expressed ACE2 and TMPRSS2. ACE2 was expressed in pericytes between follicles, and TMPRSS2 was mainly stained in the colloid inside the follicle. There was no difference in expression between the normal thyroid, Hashimoto's thyroiditis, and Graves' disease. SARS-CoV-2 does not directly invade the thyroid follicular cells. Whether SARS-CoV-2 infection of pericytes can affect COVID-19-related thyroid dysfunction warrants further study.
10.3390/biology11050697
Safety and Immunogenicity of Inactivated and Recombinant Protein SARS-CoV-2 Vaccines in Patients With Thyroid Cancer.
Frontiers in immunology
Background:This study aimed at assessing the safety and immunogenicity of SARS-CoV-2 vaccines in patients with thyroid cancer. Methods:This observational study included thyroid cancer patients between April 1, 2021, and November 31, 2021, in the Second Affiliated Hospital of Chongqing Medical University. All participants received at least one dose of the SARS-CoV-2 vaccine. SARS-CoV-2 IgG was tested, and the interval time between the last dose and humoral response test ranged from <1 to 8 months. The complications after SARS-CoV-2 vaccines were recorded. Results:A total of 115 participants at least received one dose of SARS-CoV-2 vaccines with a 67.0% IgG-positive rate. Among them, 98 cases had completed vaccination, and the positivity of SARS-CoV-2 IgG antibodies was 96% (24/25) with three doses of ZF2001. SARS-CoV-2 IgG antibodies' positivity was 63.0% (46/73) of two doses of CoronaVac or BBIBP-CorV vaccine. Additionally, after 4 months of the last-dose vaccination, the IgG-positive rate (31.6%, 6/19) significantly decreased in thyroid cancer patients. The IgG-positive rate (81.0%, 64/79) was satisfactory within 3 months of the last-dose vaccination. Ten (10.2%) patients had side effects after SARS-CoV-2 vaccination. Among them, two (2.0%) patients had a fever, five (5.1%) patients had injection site pain, one (1.0%) patient felt dizzy, and one patient felt dizzy and had injection site pain at the same time. Conclusion:SARS-CoV-2 vaccines (CoronaVac, BBIBP-CorV, and ZF2001) are safe in thyroid cancer patients. The regression time of SARS-CoV-2 IgG is significantly shorter in thyroid cancer patients than in healthy adults. Therefore, a booster vaccination dose may be earlier than the systematic strategy for thyroid cancer patients.
10.3389/fimmu.2022.855311
The Effect of Inactivated SARS-CoV-2 Vaccines on TRAB in Graves' Disease.
Frontiers in endocrinology
Background:The ongoing coronavirus disease 2019 (COVID-19) pandemic has forced the development of vaccines. Reports have suggested that vaccines play a role in inducing autoimmune diseases (AIDs). Scattered cases have reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may promote thyroid disease, including Graves' disease (GD). However, the effect of inactivated SARS-CoV-2 vaccine on GD remains unclear. The aim of the present study was to investigate the response of thyrotropin receptor antibody (TRAB) to inactivated SARS-COV-2 vaccines. Methods:We conducted a retrospective study to observe the differences in thyroid function and TRAB trends between pre-vaccination (n=412) and post-vaccination (n=231) groups at an interval of 2 months. We then retrospectively observed the differences in serum thyroid function and TRAB levels at 3 months before (n=280), 1 month before (n=294), 1 month after (n=306), and 3 months after (n=250) vaccination. Subsequently, 173 GD patients who were not vaccinated with inactivated SARS-COV-2 vaccines were selected for a prospective study. Thyroid function and TRAB assessment were performed before 3 and 1 months and 1 and 3 months after the first dose of vaccination and were then compared by repeated measures ANOVA to explore their dynamic changes. Results:A retrospective study preliminarily observed that the trend of TRAB post-vaccination was opposite of that pre-vaccination (p=0.000), serum TRAB levels decreased before vaccination and increased after vaccination. In this prospective study, repeated measures ANOVA indicated significant differences in serum FT3 (p=0.000), FT4 (p=0.000), TSH (p=0.000), and TRAB (p=0.000) levels at different time points before and after vaccination. Serum TRAB levels showed dynamic changes that decreased significantly at 1 month before vaccination (p=0.000), no significant differences at 1 month after vaccination (p=0.583), and reflected an upward trend at 3 months after vaccination (p=0.034). Serum FT3 and FT4 levels showed similar trends to serum TRAB levels before and after vaccination. Instead, the serum TSH levels showed a continuous upward trend over time. Conclusion:Based on the results obtained in both retrospective and prospective studies, we concluded that serum TRAB levels decreased less after inactivated SARS-CoV-2 vaccination and showed an upward trend, which may be related to humoral immunity induced by vaccination.
10.3389/fendo.2022.835880
COVID-19 and Endocrine System: A Cross-Sectional Study on 60 Patients with Endocrine Abnormality.
Cell journal
Objective:COVID-19 is an infectious disease that has become pandemic with a high mortality rate. This study aims to provide new insight into the relations between SARS-CoV-2 and the Endocrine system. Materials and Methods:In this cross-sectional study, we have hospitalized 60 patients with a positive SARA-CoV-2 PCR test. The information of complete blood count and endocrine hormones was obtained when the patients were admitted to the hospital or for a maximum of 4 days onset the hospitalization. Results:Of 60 patients with COVID-19, forty-four (73.33%) had at least one abnormality mean item >×3. In total, 26 (43.33%), 21 (35%), 18 (30%), 13 (21.67%), 31 (51.67%), 12 (20%), 30 (50%), 25 (41.67%) patients having estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, testosterone, cortisol and thyroid stimulating hormone (TSH) abnormal test results, respectively. There was no change in creatinine levels. FSH has shown drastic changes in both sexes' intensity (F: 769, P<0.0001). Although TSH had many abnormalities in women, analysis has shown no significant P value (P=0.4558). Furthermore, prolactin and testosterone mean level in men and the estradiol mean level in women have shown no significant P value (P=0.2077, P=0.1446, P=0.1351, respectively). Conclusion:Results suggest that COVID-19 affects directly or non-directly glands and related hormones.
10.22074/cellj.2022.8079
Subacute thyroiditis and COVID-19 vaccines: a case/non-case study.
Endocrine
PURPOSE:Some case reports have suggested a possible association between COVID-19 vaccines and subacute thyroiditis (SAT), however, to our knowledge, no study has analyzed this possible relationship. This study aimed to analyze whether a disproportionate number of cases of SAT were reported in the EudraVigilance database for four COVID-19 vaccines (BNT162b2, mRNA-1273 ChAdOx1-S or Ad26.COV2.S). METHODS:A case/non-case study was conducted to assess the association between SAT and COVID-19 vaccines, calculating the reporting odds ratios (RORs) up to December 2, 2021. Cases were selected using the preferred term 'subacute thyroiditis'. First, cases involving COVID-19 vaccines were compared with those involving all other drugs. Secondly, the RORs for COVID-19 vaccines compared with other viral vaccines (overall and influenza vaccines only) were obtained. RESULTS:Until December 2, 2021, of 1,221,582 spontaneous cases of adverse reactions with the four vaccines, we found 162 SAT cases: BNT162b2 (n = 103), mRNA-1273 (n = 27), ChAdOx1-S (n = 31) and Ad26.COV2.S (n = 1). SAT cases were found to be reported more frequently in association with BNT162b2, mRNA-1273, and ChAdOx1-S vaccines than with other drugs. Moreover, we found a signal of disproportionate reporting for SAT with BNT162b2 and mRNA-1273 vaccines comparing with other viral vaccines (BNT162b2 ROR 3.58, 95% CI 1.92-6.66; mRNA-1273 ROR 3.44, 95% CI 1.71-6.94). However, this association was absent when these COVID-19 vaccines were compared with influenza vaccines. CONCLUSIONS:In EudraVigilance, SAT is relatively more frequently reported in association with mRNA COVID-19 vaccines than with other viral vaccines. Well designed observational studies are needed to confirm these results.
10.1007/s12020-022-03101-z
Effect of COVID-19 Vaccines on Thyroid Function and Autoimmunity and Effect of Thyroid Autoimmunity on Antibody Response.
The Journal of clinical endocrinology and metabolism
CONTEXT:There are concerns for COVID-19 vaccination in triggering thyroid autoimmunity and causing thyroid dysfunction. Also, data on the effect of preexisting thyroid autoimmunity on the efficacy of COVID-19 vaccination are limited. OBJECTIVES:We evaluated the effect of COVID-19 vaccination on thyroid function and antibodies, and the influence of preexisting thyroid autoimmunity on neutralizing antibody (NAb) responses. METHODS:Adults without a history of COVID-19/thyroid disorders who received the COVID-19 vaccination during June to August 2021 were recruited. All received 2 doses of vaccines. Thyrotropin (TSH), free thyroxine (fT4), free 3,5,3'-triiodothyronine (fT3), antithyroid peroxidase (anti-TPO), and antithyroglobulin (anti-Tg) antibodies were measured at baseline and 8 weeks post vaccination. NAb against SARS-CoV-2 receptor-binding domain was measured. RESULTS:A total of 215 individuals were included (129 [60%] BNT162b2; 86 [40%] CoronaVac recipients): mean age 49.6 years, 37.2% men, and 12.1% anti-TPO/Tg positive at baseline. After vaccination, TSH did not change (P = .225), but fT4 slightly increased (from 12.0 ± 1.1 to 12.2 ± 1.2 pmol/L [from 0.93 ± 0.09 to 0.95 ± 0.09 ng/dL], P < .001) and fT3 slightly decreased (from 4.1 ± 0.4 to 4.0 ± 0.4 pmol/L [from 2.67 ± 0.26 to 2.60 ± 0.26 pg/mL], P < .001). Only 3 patients (1.4%) had abnormal thyroid function post vaccination, none clinically overt. Anti-TPO and anti-Tg titers increased modestly after vaccination (P < .001), without statistically significant changes in anti-TPO/Tg positivity. Changes in thyroid function and antithyroid antibodies were consistent between BNT162b2 and CoronaVac recipients, except for greater anti-TPO titer increase post BNT162b2 (P < .001). NAb responses were similar between individuals with and without preexisting thyroid autoimmunity (P = .855). CONCLUSION:COVID-19 vaccination was associated with a modest increase in antithyroid antibody titers. Anti-TPO increase was greater among BNT162b2 recipients. However, there was no clinically significant thyroid dysfunction post vaccination. NAb responses were not influenced by preexisting thyroid autoimmunity. Our results provide important reassurance for people to receive the COVID-19 vaccination.
10.1210/clinem/dgac355
Orbital inflammatory disease following mRNA SARS-CoV-2 vaccine.
Clinical case reports
A 65-year-old woman reported orbital symptoms two days after her first dose and presented exacerbation of signs after the second dose of BNT162b2 mRNA vaccine. The temporal relationship between the COVID-19 vaccination and orbital symptoms suggests a probable link between SARS-CoV-2 mRNA vaccine and this orbital inflammatory disease.
10.1002/ccr3.5926
Thyroid Function Abnormalities in the Acute Phase of COVID-19: A Cross-Sectional Hospital-Based Study From North India.
Cureus
Introduction Viral illnesses like mumps, cytomegalovirus (CMV), and Cocksakievirus have been shown to affect the endocrine system, specifically the thyroid as a product of their systemic inflammatory process. The thyroid gland, having high levels of angiotensin-converting enzyme 2 (ACE2) is also predisposed to dysfunction due to coronavirus disease 2019 (COVID-19). Methodology A cross-sectional study was conducted using retrospective data of thyroid function tests in patients with COVID-19. Results The majority of patients with COVID-19 had normal thyroid function while low serum T3, seen in 47.3% of patients with severe disease, stood out as the most common thyroid abnormality in the acute phase of the disease. The disease severity was seen to correlate with the extent of thyroid function abnormalities, with severely diseased patients having lower T3 values and normal to low thyroid-stimulating hormone (TSH) values. Furthermore, a significant negative correlation was seen between TSH and the bio-inflammatory marker, C-reactive protein (CRP). Conclusion The acute phase of COVID-19 affects thyroid function in direct correlation with the severity of the disease.
10.7759/cureus.24942
Evaluation of the diagnostic features and clinical course of COVID-19 vaccine-associated subacute thyroiditis.
Hormones (Athens, Greece)
OBJECTIVE:This study aimed to identify cases of coronavirus disease 2019 (COVID-19) vaccine-associated subacute thyroiditis (SAT) during the active vaccination period of the pandemic, analyze the characteristics of these cases, and compare them with cases of non-vaccine associated SAT diagnosed in the same period. METHODS:A total of 55 patients diagnosed with SAT in our outpatient clinic between February and October, 2021, were included in this retrospective single-center study. RESULTS:Of the study population, 16 (29.1%) were diagnosed with COVID-19 vaccine-associated SAT (10 with CoronaVac® and six with Pfizer-BioNTech® vaccine), with a median time to onset of symptoms after vaccination of 6.5 (range, 2-20) days. There was no statistically significant difference between the vaccine-associated (VA) and non-vaccine associated (NVA) groups in terms of age, gender, time to diagnosis, thyroid volumes, thyroid function tests, and acute phase reactants. Seven (43.8%) and 25 (64.1%) patients were treated with methylprednisolone in the VA group and NVA group, respectively (p = 0.16). Follow-up data of 45 patients (16/16 for VA and 29/39 for NVA) were available. The mean follow-up of these patients was 47.4 ± 19.4 days, and the follow-up periods of the VA group and NVA group were comparable (p = 0.24). There was no difference between the two groups in terms of the frequency of euthyroidism at the follow-up visit (12/16 vs.14/29, p = 0.08). CONCLUSION:With the increase in COVID-19 vaccination rates during the current pandemic, VA SAT cases are seen more frequently. The present study demonstrated that these cases have similar diagnostic features and clinical course to that of classic forms of SAT. In addition, most patients with VA SAT had a mild clinical course that improved with non-steroidal anti-inflammatory drugs.
10.1007/s42000-022-00380-z
The Association Between FT3 With the Outcome and Inflammation/Coagulopathy/Fibrinolysis of COVID-19.
Frontiers in endocrinology
Background:The coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 5 million people worldwide. It is imperative to identify the disease severity and intervene with effective therapy as early as possible. Previous studies have shown that low free triiodothyronine (FT3) may possess the predictive value on COVID-19 prognosis. Methods:In this retrospective cohort study, 15-day clinical and laboratory data of 186 hospitalized patients of COVID-19 after admission were analyzed. Groups were based on the disease severity of COVID-19, survival or non-survival, and presence or absence of euthyroid sick syndrome (ESS). Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between FT3 with clinic parameters of multiple time points. Results:The non-survival patients had significant lower levels of FT3 (3.24 ± 0.42 vs. 4.19 ± 0.08 pmol/L, < 0.05) and thyroid-stimulating hormone (TSH) (0.69 ± 0.19 vs. 2.32 ± 0.2 uIU/ml, < 0.05), and the FT3 of severe patients was significantly lower than that of non-severe patients (3.67 ± 0.14 vs. 4.33 ± 0.09 pmol/L, < 0.05). Fifty-nine cases of COVID-19 patients were diagnosed with ESS. Compared with non-ESS patients, those with ESS were older and had higher proportions of fever, shortness of breath, hypertension, diabetes, severe disease, and mortality. In addition, the correlation analysis between FT3 and clinical parameters showed that FT3 were positively related to the lymphocyte count and albumin and negatively correlated with C-reactive protein, erythrocyte sedimentation rate, and D-dimer at all time points in the first 15 days after admission. Conclusion:Low FT3 had a significant predictive value on the prognosis of COVID-19 patients, and FT3 was significantly related with clinic parameters of inflammation/coagulopathy/fibrinolysis.
10.3389/fendo.2022.877010
COVID-19 and Thyroid Function: A Bi-Directional Two-Sample Mendelian Randomization Study.
Thyroid : official journal of the American Thyroid Association
Thyroid dysfunction has been observed among some patients with coronavirus disease (COVID-19). It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (or its severity) leads to the development of thyroid dysfunction, or vice versa. In this study, we examined the bi-directional causal relationship between host genetic liability to three COVID-19 phenotypes (including SARS-CoV-2 infection, hospitalized and severe COVID-19) and three thyroid dysfunction traits (including hyperthyroidism, hypothyroidism, and autoimmune thyroid disease [AITD]) and three continuous traits of thyroid hormones (including thyrotropin [TSH] and free thyroxine [fT4] within reference range, and TSH in full range). Summary statistics from the largest available meta-analyses of human genome-wide association studies were retrieved for the following variables: SARS-CoV-2 infection ( = 1,348,701), COVID-19 hospitalization ( = 1,557,411), severe COVID-19 ( = 1,059,456), hyperthyroidism ( = 51,823), hypothyroidism ( = 53,423), AITD ( = 755,406), TSH within reference range ( = 54,288), fT4 within reference range ( = 49,269), and TSH in full range ( = 119,715). Using a two-sample Mendelian randomization (MR) approach, the inverse-variance weighted (IVW) method was adopted as the main MR analysis. Weighted median, contamination mixture, MR-Egger, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods were applied as sensitivity analyses. Host genetic susceptibility to SARS-CoV-2 infection was causally associated with hypothyroidism in the main IVW analysis (per doubling in prevalence of SARS-CoV-2 infection, odds ratio [OR] = 1.335; 95% confidence interval [CI]: 1.167-1.526; = 2.4 × 10, surpassing the Bonferroni multiple-testing threshold). Similar causal estimates were observed in the sensitivity analyses (weighted median: OR = 1.296; CI: 1.066-1.575; = 9 × 10; contamination mixture: OR = 1.356; CI: 1.095-1.818; = 0.013; MR-Egger: OR = 1.712; CI: 1.202-2.439; = 2.92 × 10, and MR-PRESSO: OR = 1.335; CI: 1.156-1.542; = 5.73 × 10). Host genetic liability to hospitalized or severe COVID-19 was not associated with thyroid dysfunction or thyroid hormone levels. In the reverse direction, there was no evidence to suggest that genetic predisposition to thyroid dysfunction or genetically determined thyroid hormone levels altered the risk of the COVID-19 outcomes. This bi-directional MR study supports that host response to SARS-CoV-2 viral infection plays a role in the causal association with increased risk of hypothyroidism. Long-term follow-up studies are needed to confirm the expected increased hypothyroidism risk.
10.1089/thy.2022.0243
Ocular Complications after COVID-19 Vaccination, Vaccine Adverse Event Reporting System.
Vaccines
In December 2020, the U.S. Food and Drug Administration licensed COVID-19 vaccines for emergency use authorization. We investigated the ocular adverse event reports in patients reported to the Vaccine Adverse Event Reporting System (VAERS) following vaccination against COVID-19. We searched the VAERS database for U.S. reports among persons who received COVID-19 vaccines between December 2020 and December 2021. Our goal was to analyze and quantify the ocular adverse events submitted to VAERS to provide clinicians and researchers with a broader view of these ocular side effects. During the analysis period, VAERS received 55,313 adverse event reports and, after data cleaning, 6688 reports met the inclusion criteria. Note that 2229 (33.33%) adverse events were classified as cases of eyelid swelling, ocular hyperemia and conjunctivitis, 1785 (26.69%) as blurred vision and 1322 (19.77%) as visual impairment. Females accounted for 73.8% of adverse event reports and the age group between 40 and 59 years had the most frequent adverse events. A higher proportion of these adverse events reported to VAERS was linked with the Janssen and Moderna COVID-19 vaccines. At the time of vaccination, a high proportion of patients reported conditions like allergies, hypertension, diabetes, thyroid disease, vascular and other autoimmune diseases. A review of these data suggests a possible association between COVID-19 vaccines and ocular adverse events. Physicians are cautioned not only to be aware of this potential problem, but to check any underlying patient conditions, and to carefully document in VAERS within a few weeks of vaccination. Future COVID-19 vaccine safety studies in healthy subjects would help clarify the vaccine's safety profile.
10.3390/vaccines10060941
Thyroid Inconveniences With Vaccination Against SARS-CoV-2: The Size of the Matter. A Systematic Review.
Frontiers in endocrinology
After the beginning of COVID-19 vaccination campaigns, several reports of thyroid disease possibly related to the COVID-19 vaccination progressively appeared in the literature, raising the question of whether the thyroid disorder might be a SARS-CoV-2 vaccine complication. The aim of this study was to analyze the data about COVID-19 vaccination and thyroid disease, evaluate the size and quality of related literature, assess the type of these events, and investigate their timing of onset with respect the vaccination. Pubmed/MEDLINE and Cochrane were systematically reviewed until February 2022 to retrieve the largest number of original papers, case reports, and case series articles reporting thyroid disease after SARS-CoV-2 vaccination. Forty-six articles were included with a total of 99 patients aged from 26 to 73 years were described, of whom 74.75% female. Regarding the vaccination received, 49.49% of patients received Comirnaty (Pfizer/BioNTech), 14.14% CoronaVac (Sinovac), 12.12% Vaxzevria (Oxford/Astrazeneca), 11.11% Spikevax (Moderna), 3.03% Ad26.COV2.S (Janssen, Johnson & Johnson), one patient Covaxin (Bharat Biotech) and one patient Convidecia (Cansino). In 7 cases the thyroid disorder developed after the third dose with a combination of different vaccines. Regarding the type of thyroid disorder, 59 were subacute thyroiditis (SAT), 29 Graves' disease (GD), 2 co-occurrence of SAT and GD, 6 painless thyroiditis (PT), and single cases of thyroid eye disease and hypothyroidism associated with mixedema. The timeline between vaccination and thyroid disorder ranged between 0.5 to 60 days, with an average of 10.96 days. Considering the limited follow-up time, a complete remission was reported in most of SAT and PT cases while a persistence was observed in GD. In conclusion, both size and quality of published data about thyroid inconveniences after COVID-19 vaccination are limited; thyroid disorders may occur within 2 months after COVID-19 vaccination; among all thyroid diseases after COVID-19 vaccination, GD and SAT seem to be more frequent.
10.3389/fendo.2022.900964
Effect of Inactivated SARS-CoV-2 Vaccine on Thyroid Function and Autoimmunity Within 28 Days After the Second Dose.
Thyroid : official journal of the American Thyroid Association
The safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is widely appreciated. However, there is limited knowledge regarding the potential impact of SARS-CoV-2 vaccines on the thyroid. We performed two prospective clinical trials between April and June, 2021, enrolling recipients of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV and CoronaVac). Thyroid function, antithyroid antibody levels, and SARS-CoV-2 neutralizing antibody levels were detected for each participant before receiving the first vaccine dose and 28 days after receiving the second vaccine dose. A total of 657 recipients participated in the study. The overall median thyroid function and levels of antithyroid antibodies before and after SARS-CoV-2 vaccination were within the normal range. Among the 564 participants with normal thyroid function at baseline, 36 (6.38% [confidence interval; CI 4.51-8.73]) developed thyroid dysfunction. Of the 545 recipients with negative antithyroid antibodies at baseline, none developed abnormal antibodies after vaccination. Notably, 75.27% (70/93 [CI 65.24-83.63]) of the 93 recipients with thyroid dysfunction returned to normal function after vaccination. The levels of antithyroid peroxidase antibody (96.20% [CI 89.30-99.21]) and antithyroglobulin antibody (TgAb; 88.31% [CI 78.97-94.51]) remained positive after vaccination in most patients with abnormal values at baseline. However, the TgAb levels in more than half of the patients (48/77) decreased. All of 11 abnormal thyrotropin receptor antibody levels at baseline decreased postvaccination. Vaccination with an inactivated SARS-CoV-2 vaccine had no significant adverse impact on thyroid function or antithyroid antibodies within the first 28 days after the second dose. ChiCTR2100045109 and ChiCTR2100042222.
10.1089/thy.2022.0101
The Association of Clinical Symptoms and Coexistent Clinical Conditions with Ophthalmic Manifesting in COVID-19 Patients.
Caspian journal of internal medicine
Background:The ocular symptoms are common manifestations in coronavirus infectious disease 2019 (COVID-19), which faces secondary complications and therapeutic challenges. Underlying diseases actuate the body to infectious diseases and their related manifestations through the aberration of metabolism and suppressing the immune system. This study aimed to investigate the correlation of underlying diseases and ocular manifestations in COVID-19 patients. Methods:This cross-sectional study was held on 108 hospitalized COVID-19 patients (confirmed by molecular detection) admitted to Rouhani hospital, Babol, Iran. Upon hospitalization, all clinical symptoms and underlying diseases were registered. Detailed clinical examinations regarding ophthalmological protocols were used to investigate the ocular symptoms. All analyses were performed by SPSS, version 25. Results:Our results showed that 26.67% of patients with at least one ocular symptom had hyperlipidemia, while 10.42% of patients without any ocular symptoms had hyperlipidemia (P=0.049). In this study, 97.81% of COVID-19 patients without epiphora had no thyroid disorders (hyper-/hypo-thyroidism), while 82.35% of COVID-19 patients with epiphora had not any thyroid disorders (P=0.012). Also, 75.00% of patients with blurred vision had diabetes mellitus, while 35.00% of patients without blurred vision suffered from diabetes mellitus. This difference was borderline significant (P=0.051). Other results showed that 13.04% of COVID-19 patients with eye redness suffer from myalgia, while 35.29% of patients without eye redness had myalgia (P=0.044). Also, 35.11% of COVID-19 patients without photophobia had myalgia, while none of the patients with photophobia had myalgia (P=0.005). Finally, 70.00% of patients with respiratory distress had at least one ocular symptom, while 43.10% of patients without respiratory distress had at least one ocular symptom (P=0.007). Conclusion:Some underlying diseases, e.g., hyperlipidemia, diabetes mellitus, and thyroid disorders, and some clinical symptoms in hospitalized patients, e.g., myalgia and respiratory distress, are correlated with ocular manifestations in COVID-19 patients.
10.22088/cjim.13.0.180
Thyroid function changes and COVID-19 severity: egg or chicken?
Endocrine
The novel coronavirus disease 2019 (COVID-19) produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infectious disease. In addition to typical flu-like symptoms, COVID-19 can also cause extrapulmonary spread and systemic inflammation, potentially causing multiorgan dysfunction, including thyroid dysfunction. Thyroid function changes in patients with COVID-19 have been widely reported, but the results are inconsistent. Based on available data, SARS-CoV-2 infection can lead to changes in thyroid function, and the degree of thyroid function changes was positively correlated with the severity of COVID-19, which involved multiple potential mechanisms. In contrast, current evidence was insufficient to prove that thyroid function changes could induce the progression of COVID-19 clinical deterioration.
10.1007/s12020-022-03129-1
Detection of SARS-CoV-2 infection in thyroid follicular cells from a COVID-19 autopsy series.
European thyroid journal
Objective:To understand whether thyroid cells can be directly infected by the SARS-CoV-2 virus and to establish a putative correlation with the expression of the host entry machinery: ACE-2, TMPRSS2, and furin. Methods:We assessed the presence of SARS-CoV-2 virus at the gene level by RT-PCR, viral RNA transcripts localization by in situ hybridization, and by detecting viral proteins by immunohistochemistry for the nucleocapsid and the spike proteins. Furthermore, we also described the immunoexpression of key host factors for virus entry in the COVID-19 thyroid samples. Results:We performed RT-PCR for SARS-CoV-2 in all autopsy specimens and detected viral genome positivity in 13 of 15 thyroid tissues and in a lung specimen. In 9 of the 14 positive samples, we were also able to confirm SARS-CoV-2 signal by in situ hybridization. Immunohistochemistry for the viral nucleocapsid and spike protein was also positive for ten and nine of the RT-PCR-positive cases, respectively, but revealed a lower sensitivity. We also described, for the first time in a COVID-19 series, the immunohistochemical expression of ACE-2, TMPRSS2, and furin in the thyroid. Conclusions:Our results obtained in thyroid specimens from deceased COVID-19 patients indicate that thyrocytes can be directly infected by SARS-CoV-2 since we detected the presence of SARS-CoV-2 genome in follicular cells. Nevertheless, we did not find a clear correlation between the presence of viral genome and the expression of the host factors for virus entry, namely ACE-2, TMPRSS2, and furin.
10.1530/ETJ-22-0074
Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population.
Research (Washington, D.C.)
The SARS-CoV-2 variants have been emerging and have made great challenges to current vaccine and pandemic control strategies. It is urgent to understand the current immune status of various Chinese populations given that the preexisting immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases which suffered a breakthrough infection after being fully vaccinated, and 49 healthy vaccinees), we showed significantly enhanced neutralizing activities against SRAS-CoV-2 variants in convalescent sera, especially those who had been fully vaccinated. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy vaccinees ( = 0.006), with a GMT of 289.5, 180.9-463.3, and 42.6, 31.3-59, respectively. However, the neutralizing activities were weaker in young convalescents (aged < 18 y), with a detectable rate of 50% and a GMT of 46.4 against Omicron. We also examined and found no pan-sarbecovirus neutralizing activities in vaccinated SARS-CoV-1 survivors. A booster dose could further increase the breadth and magnitude of neutralization against WT and variants of concern (VOCs) to different degrees. In addition, we showed that COVID-19-inactivated vaccines can elicit Omicron-specific T-cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively, although without statistically significant difference. The neutralizing antibody titers declined while T-cell responses remain consistent over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants. . Breakthrough infection significantly boosted neutralizing activities against SARS-CoV-2 variants as compared to booster immunization with inactivated vaccine. Vaccine-induced virus-specific T-cell immunity, on the other hand, may compensate for the shortfall. Furthermore, the public health system should target the most vulnerable group due to a poorer protective serological response in both infected and vaccinated adolescents.
10.34133/2022/9873831
Thyroid Function, Inflammatory Response, and Glucocorticoids in COVID-19.
Frontiers in endocrinology
The ongoing COVID-19 pandemic calls for extensive research on various medical topics. Since the beginning of the pandemic, multiple studies investigated the impact of SARS CoV-2 on thyroid function. However, crucial data, such as trend progression over time or influence of commonly used drugs, might still be missing. We checked the thyroid function in 174 patients with PCR-confirmed COVID-19. Our research covered three separate time points of hospitalization (days 1, 4, and 10). We did not exclude patients treated with glucocorticoids but, instead, compared them with patients not treated with steroids. We correlated the results of thyroid function tests with markers of systemic inflammation. We checked if abnormal thyroid function can predict unfavorable outcomes defined as combined primary endpoint and/or secondary endpoints; the combined primary endpoint was the occurrence of death, mechanical ventilation, non-invasive ventilation, vasopressor infusion, or prolonged hospital stay, and the secondary endpoint was any of the listed events. In general, 80.46% of evaluated patients displayed abnormalities in thyroid function tests over at least one time point throughout the observation. We noticed a high prevalence of features typical for thyroid dysfunction in non-thyroidal illness (NTI). Free triiodothyronine (fT3) concentration was significantly lower in the group requiring glucocorticoids. Patients displaying abnormal thyroid function were statistically more likely to meet the predefined combined primary endpoint. We found that fT3 measured at admission could be perceived as an independent predictor of endpoint completion for all analyzed groups. Thyroid involvement is common in COVID-19. Our study supports the idea of thyroid function abnormalities being important clinical tools and allowing early recognition of possible detrimental outcomes of the disease.
10.3389/fendo.2022.939842
Bimodal distribution of thyroid dysfunction triggered by COVID-19 Infection: An experience from a single endocrine center-a case series and literature review.
Qatar medical journal
BACKGROUND:COVID-19 infection has been spreading across the globe since the end of 2019, and it continues to cause chronic multi-system sequelae, of which thyroid dysfunction appears to be the major one. We have discussed here 10 cases of thyroid dysfunction after COVID-19 infection. METHODS:Case series report. From October 2020 to July 2021, a series of 10 cases of thyroid dysfunction after COVID-19 infection were recorded and managed in a single outpatient endocrine center in Doha, Qatar. CASES PRESENTATION:We have reported 5 cases of Graves's hyperthyroidism, 2 of chronic primary hypothyroidism (including one with Grave's disease [GD]) who was treated through radioactive iodine (RAI) therapy, one case of subacute thyroiditis, one case with "Sick euthyroid disease," and one case of central hypothyroidism. Presently, patients with GD are being treated with carbimazole and those with hypothyroidism are being treated with levothyroxine. The remaining patients had recovered with euthyroid. CONCLUSION:This is the largest case series reported from a single center to date. The findings of this series indicate a bimodal distribution of thyroid dysfunction in patients with COVID-19 infection. A review of the literature and discussion of potential pathophysiological mechanisms has been presented. We have emphasized the importance of screening for thyroid dysfunction in "post-COVID-19" cases, considering that the prevalence may be underestimated.
10.5339/qmj.2022.39
Four cases of Graves' disease following viral vector severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) vaccine.
Endocrine journal
Mass immunization has led to a decrease in the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) worldwide. At the same time, awareness regarding possible adverse effects of newly developed vaccines is critical. The present study was undertaken to report the cases of Graves' disease occurring after administration of viral vector vaccine (ChAdox1nCoV-19) and describe the clinical profile, response to treatment, and effect of administration of a second dose in patients developing Graves' disease. Four cases of Graves' disease after administration of the vaccine were noted. Two of these had a mild thyroid eye disease. Three cases were female and had a family/self-history of autoimmune disease. All cases responded well to treatment and became euthyroid within two to four months. Two patients exhibited worsening thyrotoxicosis after receiving a second dose of the vaccine. We propose that the temporal relationship between administration of the vaccine and the onset of symptoms establishes Graves' disease as an adverse event after the SARS-CoV-2 viral vector vaccine. Close follow-up is advisable in individuals developing Graves' disease after SARS-CoV-2 vaccination.
10.1507/endocrj.EJ22-0208
Case report: subacute thyroiditis after receiving SARS-CoV-2 vaccine, maybe not only adjuvants.
Frontiers in medicine
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced the new coronavirus disease 2019 (COVID-19) pandemic worldwide. SARS-CoV-2 vaccines are designed to control the transmission of the disease. However, post-vaccination subacute thyroiditis (SAT) also appears with increase vaccination rate. Three cases of SAT after SARS-CoV-2 vaccines are described in this study. We have reported the patients' clinical symptoms, laboratory tests, and thyroid imaging. Tests for COVID-19 were all negative, and the patients did not report thyroid-related diseases, autoimmune diseases, or preceding upper respiratory system infections in their medical history. Three female patients showed neck pain on physical examination. The laboratory test results and imaging findings were consistent with the diagnostic criteria of SAT. The patients were carried out a standardized treatment according to their symptoms, and we closely followed up their response to the treatment. Clinicians must be aware of the possibility of SAT after receiving the vaccines and make timely therapy.
10.3389/fmed.2022.856572
Thyroid Function and COVID-19 Susceptibility and Its Severity: A Two-Sample Mendelian Randomization Study.
Endocrinology
Several observational studies have confirmed the relationship between thyroid hormones and coronavirus disease 2019 (COVID-19), but this correlation remains controversial. We performed a two-sample Mendelian randomization (MR) analysis based on the largest publicly available summary datasets. Summary statistics with 49 269 individuals for free thyroxine (FT4) and 54 288 for thyroid stimulating hormone (TSH) were used as exposure instruments. Genome-wide association studies of susceptibility (cases = 38 984; controls = 1 644 784), hospitalization (cases: 9986 = controls = 1 877 672), and very severe disease (cases = 5101; controls = 1 383 241) of COVID-19 were used as the outcome. We used the inverse-variance weighted (IVW) method as the primary analysis, and utilized MR-Egger regression, weighted median, and robust adjusted profile score (RAPS) for sensitivity analysis. Genetic predisposition to higher serum levels of FT4 within the normal range was negatively associated with the risk of COVID-19 hospitalization (odds ratio [OR] = 0.818; 95% CI, 0.718-0.932; P = 2.6 × 10-3) and very severe disease (OR = 0.758; 95% CI, 0.626-0.923; P = 5.8 × 10-3), but not susceptibility. There is no evidence that genetically predicted circulating TSH levels are associated with COVID-19 susceptibility and severity risk. Neither apparent pleiotropy nor heterogeneity were detected in the sensitivity analysis. In summary, we found that higher FT4 levels may reduce the risk of COVID-19 severity, suggesting that thyroid function testing may be required for patients with COVID-19.
10.1210/endocr/bqac139
Graves' Disease Caused by SARS-CoV-2 Infection.
European journal of case reports in internal medicine
Graves' disease is an autoimmune disorder that results in hyperthyroidism, caused by autoantibodies to the thyrotropin receptor (TRAbs) stimulating thyroid hormone synthesis, giving rise to a variety of systemic manifestations such as goitre, dermatopathy and orbitopathy. The authors present the case of a 28-year-old man admitted to hospital for a 3-week history of fatigue, shortness of breath, palpitations and diffuse goitre, after recent mild SARS-CoV-2 infection. Laboratory investigation revealed hyperthyroidism with TRAbs elevation. Thyroid ultrasound confirmed a diffusely heterogeneous and irregular thyroid gland and a nodular image below the sternal notch. Thyroid scintigraphy excluded the nodule and confirmed a Graves' disease pattern. Following the initiation of methimazole, the patient had complete resolution of symptoms and normalization of thyroid values. The results suggest a possible association between Graves' disease and SARS-CoV-2 infection acting as a trigger. Graves' disease is an important differential diagnosis to keep in mind when patients present with hyperthyroidism after COVID-19 disease. LEARNING POINTS:Graves' disease may be induced after SARS-CoV-2 infection by a possible autoimmune pathway.Graves' disease induced by SARS-CoV-2 infection responds well to antithyroid medication.
10.12890/2022_003470
Subacute thyroiditis post viral vector vaccine for COVID-19.
Endocrinology, diabetes & metabolism case reports
Summary:Subacute thyroiditis is an inflammatory disorder of the thyroid gland that has previously been described following viral illnesses and occasionally post vaccination such as influenza vaccine. 2021 was a revolutionary year for the development of SARS-CoV-2 vaccinations with multiple different vaccines now available. There are increasing numbers of case reports of thyroiditis following these vaccinations. We report a case of a 50-year-old female who developed subacute thyroiditis 6 days post ChAdOx1 nCoV-19 vaccine (AZD1222 produced by AstraZeneca Vaxzevria). The initial thyrotoxic phase was followed by overt hypothyroidism. This resolved spontaneously within 5 months without levothyroxine replacement. We hope that our case will add to the growing literature of cases of thyroiditis occurring after multiple different types of SARS-CoV-2 vaccination and create awareness of this rare but treatable adverse effect. We also review the literature on the proposed mechanisms behind this adverse effect. Learning points:Subacute thyroiditis is an inflammatory disorder of the thyroid gland that can occur after a viral illness or vaccination against certain infections. Subacute thyroiditis is a rare adverse effect that has been reported to occur after different types of SARS-CoV-2 vaccinations. Subacute thyroiditis post vaccination is relatively straightforward to manage, with some patients requiring non-steroidal anti-inflammatory drugs and beta-blockers, while more severe cases may require corticosteroid therapy. This adverse effect should not dissuade vaccination use at a population level. There are many postulated mechanisms for the development of subacute thyroiditis following vaccination including the presence of the ACE-2 receptor for SARS-CoV-2 on the thyroid gland, an inflammatory/immune response as is seen in COVID-19 infection itself and molecular mimicry between SARS-CoV-2 spike protein and healthy thyroid antigen.
10.1530/EDM-21-0193
COVID-19 Infection-Related Thyrotoxic Hypokalemic Periodic Paralysis.
Case reports in endocrinology
SARS-CoV-2 infection induces the dysfunction of many organs including the thyroid gland through the role of ACE2 receptors as well as the consequences of the cytokine storm. Thyroid diseases such as subacute thyroidism, Graves' disease, thyrotoxicosis, and Hashimoto's thyroiditis have been documented in patients with SARS-CoV-2 infection. However, there are limited reports about the consequences of SARS-CoV-2 infection-related thyroid complications. We describe a case of man who was admitted to the emergency department due to repeated lower limb weakness since diagnosed with COVID-19. He had refractory hypokalemia and was treated with potassium replacement therapy for 2 months. However, the complaints continued. The patient has no history of thyroid disease, yet the laboratory result showed hyperthyroidism. Accordingly, he received oral thiamazole. As the laboratory parameters of the thyroid hormones improved, potassium levels returned to normal and the limb weakness stopped. This unusual thyroid complication should be considered in SARS-CoV-2 infection. The prompt diagnosis and appropriate therapy can reduce the burden of the disease.
10.1155/2022/1382270
Thyroid hormones and platelet activation in COVID-19 patients.
Journal of endocrinological investigation
PURPOSE:To retrospectively describe the association between thyroid hormones (TH) and platelet activation, as represented by mean platelet volume (MPV), in a cohort of patients hospitalized for COVID-19 with no known thyroid disease, and to correlate these data with the severity of COVID-19 and the occurrence of death/ARDS (Acute Respiratory Distress Syndrome). METHODS:103 patients with real-time polymerase chain reaction (RT-PCR) testing-confirmed COVID-19 and hospitalized were enrolled. Serum samples were collected from patients upon admission before starting any treatment. Chi-squared test was used to determine the association between euthyroid sick syndrome (ESS) and COVID-19 severity. Multivariate logistic regression was performed to evaluate the best independent predictors of COVID-19 deaths/ARDS. RESULTS:39/103 (37.9%) of patients were found to have ESS, and this condition was an independent predictor for the severity of COVID-19 (p = 0.003). Lower TSH and lower FT3/FT4 ratio correlated with higher MPV (p = 0,001 and p = 0.010), with an opposite trend with respect to what has been documented in non-COVID patients. Increasing MPV and lower FT3 significantly increased the risk, in COVID-19 patients, of an adverse outcome of death/ARDS. CONCLUSION:Increased platelet activation, as represented by increased MPV, has already been reported to correlate with COVID-19 severity, possibly as a consequence of cytokine release. We demonstrated, in a cohort of 103 patients with COVID-19, that MPV is inversely correlated to TH levels, in particular in the case of ESS, where downregulation of TH axis may occur in case of systemic cytokine inflammation and more severe outcomes (death/ARDS). That ESS itself may directly cause platelet activation, as demonstrated by higher MPV in these patients, is an interesting hypothesis which deserves further investigation.
10.1007/s40618-022-01896-2
Thyroid diseases are associated with coronavirus disease 2019 infection.
Frontiers in endocrinology
Background:In 2019, there was a global outbreak of new coronary pneumonia. Studies have found that the severity of patients with new coronary pneumonia may be related to their comorbidities. This article discusses the impact of thyroid disease on the severity of new coronary pneumonia through a meta-analysis and provides new treatment ideas for the later treatment and recovery of new coronary pneumonia. Methods:Databases including PubMed, Embase, Cochrane Library, SINOMED, China national knowledge infrastructure (CNKI), and Wanfang for coronavirus disease 2019 (COVID-19) infection and thyroid diseases were searched. Reference lists of all eligible articles and related previous review articles were handsearched. Fifty-three articles were included to conduct the meta-analysis. Results:Fifty-three articles with 12,022 COVID-19 infection patients were included in this meta-analysis. The proportion of patients with thyroid diseases in all COVID-19 infection patients fluctuates between 0% and 88.46%. Of the 53 included studies, 22 studies reported the severity of COVID-19 infection and grouped. The fixed-effects model was used to merge odds ratio (OR) values, and the pooled effect size in favor of non-severe patients is 2.62 (95% CI = 1.96-3.49, < 0.0001), which means that patients with severe COVID-19 infection are more likely to have thyroid diseases. The analysis subgrouped into Asia and Europe shows that patients with COVID-19 severe infection in Asia are 3.77 times more likely to have thyroid diseases than non-severe patients (fixed-effects model: OR = 3.77, 95% CI = 2.66-5.35, < 0.00001). No significant statistical heterogeneity was found by the heterogeneity analysis (chi-square = 19.85, = 0.34, = 9%). Severe COVID-19 infection patients are more likely to be complicated by hypothyroidism and low T3 syndrome. The pooled ORs with fixed-effects model are 3.72 (95% CI = 1.62-8.58, = 0.002) and 5.86 (95% CI = 2.79-12.33, < 0.00001), respectively. Conclusion:COVID-19 infection patients with thyroid diseases are very common, and severe patients are more likely to have thyroid diseases. Asian COVID-19 infection, hypothyroidism patients, and patients with low T3 syndrome are more likely to progress to severe condition. Systematic Review Registration:https://inplasy.com, identifier INPLASY202190079.
10.3389/fendo.2022.952049
Impact of the COVID-19 pandemic on the incidence, seasonal distribution, and characteristics of subacute thyroiditis.
Endocrine
PURPOSE:An increasing number of cases of subacute thyroiditis (SAT) related to the coronavirus disease 2019 (COVID-19) and its vaccines continue to be published. The aim of this study was to investigate any change in the incidence and characteristics of SAT by comparing the pre-pandemic and pandemic periods. METHODS:This retrospective, single-center study included 432 newly-diagnosed SAT patients between January 2018 and December 2021. The annual frequency of SAT was calculated as the number of newly-diagnosed SAT cases divided by the total number of outpatients that year. RESULTS:The frequencies of newly-diagnosed SAT were 0.136% in 2018, 0.127% in 2019, 0.157% in 2020, and 0.114% in 2021 (p = 0.19). While SAT patients were clustered in the autumn (35.1%) in 2018 and 2019, it was found that this cluster shifted to the winter (33.0%) in 2020 and 2021, in parallel with COVID-19 case peaks (p = 0.017). The patients were separated into two groups as pre-COVID-19 pandemic SAT (n = 272) and COVID-19 pandemic SAT (n = 160). The mean ages of the groups were similar. There were more male patients in the COVID-19 pandemic SAT group than in the pre-pandemic group (30.6% vs. 18.7%, p = 0.005). Frequencies of overt hyperthyroidism and median free-thyroxine levels were significantly higher in the COVID-19 pandemic SAT group (p = 0.029, p = 0.001). Treatment modalities, recurrence rates, and permanent hypothyroidism were similar in both groups. CONCLUSION:With the COVID-19 pandemic, although there was a change in seasonal variation of SAT and an increase in the number of male patients, there was no change in the incidence and clinical course of SAT.
10.1007/s12020-022-03197-3
Distinct Clinical Features of Post-COVID-19 Vaccination Early-onset Graves' Disease.
The Journal of clinical endocrinology and metabolism
CONTEXT:Several case reports of Graves' disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently. OBJECTIVE:The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021. METHODS:Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included. RESULTS:Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation. CONCLUSION:This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD.
10.1210/clinem/dgac550
Causal associations between thyroid dysfunction and COVID-19 susceptibility and severity: A bidirectional Mendelian randomization study.
Frontiers in endocrinology
Background:Observational studies have reported an association between coronavirus disease 2019 (COVID-19) risk and thyroid dysfunction, but without a clear causal relationship. We attempted to evaluate the association between thyroid function and COVID-19 risk using a bidirectional two-sample Mendelian randomization (MR) analysis. Methods:Summary statistics on the characteristics of thyroid dysfunction (hypothyroidism and hyperthyroidism) were obtained from the ThyroidOmics Consortium. Genome-wide association study statistics for COVID-19 susceptibility and its severity were obtained from the COVID-19 Host Genetics Initiative, and severity phenotypes included hospitalization and very severe disease in COVID-19 participants. The inverse variance-weighted (IVW) method was used as the primary analysis method, supplemented by the weighted-median (WM), MR-Egger, and MR-PRESSO methods. Results were adjusted for Bonferroni correction thresholds. Results:The forward MR estimates show no effect of thyroid dysfunction on COVID-19 susceptibility and severity. The reverse MR found that COVID-19 susceptibility was the suggestive risk factor for hypothyroidism (IVW: OR = 1.577, 95% CI = 1.065-2.333, = 0.022; WM: OR = 1.527, 95% CI = 1.042-2.240, = 0.029), and there was lightly association between COVID-19 hospitalized and hypothyroidism (IVW: OR = 1.151, 95% CI = 1.004-1.319, = 0.042; WM: OR = 1.197, 95% CI = 1.023-1.401, = 0.023). There was no evidence supporting the association between any phenotype of COVID-19 and hyperthyroidism. Conclusion:Our results identified that COVID-19 might be the potential risk factor for hypothyroidism. Therefore, patients infected with SARS-CoV-2 should strengthen the monitoring of thyroid function.
10.3389/fendo.2022.961717
Tissue-specific pathway activities: A retrospective analysis in COVID-19 patients.
Frontiers in immunology
The ACE2 receptors essential for SARS-CoV-2 infections are expressed not only in the lung but also in many other tissues in the human body. To better understand the disease mechanisms and progression, it is essential to understand how the virus affects and alters molecular pathways in the different affected tissues. In this study, we mapped the proteomics data obtained from Nie X. (2021) to the pathway models of the COVID-19 Disease Map project and WikiPathways. The differences in pathway activities between COVID-19 and non-COVID-19 patients were calculated using the Wilcoxon test. As a result, 46% (5,235) of the detected proteins were found to be present in at least one pathway. Only a few pathways were altered in multiple tissues. As an example, the Kinin-Kallikrein pathway, an important inflammation regulatory pathway, was found to be less active in the lung, spleen, testis, and thyroid. We can confirm previously reported changes in COVID-19 patients such as the change in cholesterol, linolenic acid, and arachidonic acid metabolism, complement, and coagulation pathways in most tissues. Of all the tissues, we found the thyroid to be the organ with the most changed pathways. In this tissue, lipid pathways, energy pathways, and many COVID-19 specific pathways such as RAS and bradykinin pathways, thrombosis, and anticoagulation have altered activities in COVID-19 patients. Concluding, our results highlight the systemic nature of COVID-19 and the effect on other tissues besides the lung.
10.3389/fimmu.2022.963357
Risk of thyroid dysfunction associated with mRNA and inactivated COVID-19 vaccines: a population-based study of 2.3 million vaccine recipients.
BMC medicine
BACKGROUND:In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset. METHODS:We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves' disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression. RESULTS:A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670-1.114; CoronaVac: IRR 0.707, 95% CI 0.549-0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716-1.159; CoronaVac: IRR 0.778, 95% CI 0.618-0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744-1.023; CoronaVac: IRR 0.830, 95% CI 0.713-0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838-1.199; CoronaVac: IRR 0.963, 95% CI 0.807-1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770-1.227; CoronaVac: IRR 0.879, 95%CI 0.693-1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833-1.246; CoronaVac: IRR 0.768, 95% CI 0.613-0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899-1.201; CoronaVac: IRR 0.911, 95% CI 0.786-1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794-1.102; CoronaVac: IRR 0.945, 95% CI 0.799-1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines. CONCLUSIONS:Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac.
10.1186/s12916-022-02548-1
Graves' disease following vaccination against SARS-CoV-2: A systematic review of the reported cases.
Frontiers in endocrinology
The newly developed COVID-19 vaccines have established a safe profile, yet some individuals experience a wide range of adverse events. Recently, thyroid dysfunction, including Graves' disease, has been observed after administration of different COVID-19 vaccines, although causality remains a matter of debate. The aim of this systematic review was to examine the available literature and provide an overview of reported cases of Graves' disease following COVID-19 vaccination. We identified 21 eligible articles which included 57 patients with Graves' disease following COVID-19 vaccination. Fourteen participants were males (25%, 14/57) and 43 (75%, 44/57) were females with a mean age of 44.3 years. The most common presenting symptom was palpitations (63%, 27/43) followed by weight loss (35%, 15/43). The majority of patients received thionamides (47%, 25/53). The clinical status after treatment was provided for 37 patients and it was improved in the majority of them (84%, 31/37). Graves' disease is possibly a condition clinicians may expect to encounter in patients receiving COVID-19 vaccines. While the above adverse event is rare, considering the scarcity of available data in scientific literature, and causality is not yet confirmed, the increased awareness of clinicians and the early recognition of the disorder are important for the optimal management of these patients.
10.3389/fendo.2022.938001
Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome.
Frontiers in neurology
Objective:Regarding pathogenesis, clinical manifestations, at-risk individuals, and diagnostic methods for stratifying patients for therapeutic approaches, our understanding of post-COVID syndrome is limited. Here, we set out to assess sociodemographic and clinical aspects in patients with the long-COVID and post-COVID syndrome. Methods:We performed a cross-sectional analysis of patients presenting at our specialized university hospital outpatient clinic. We assessed patients' clinical presentation, fatigue, symptoms of depression and anxiety, and impairment of smell. Results:A total of 101 patients were included (73.3% female), of whom 78.2% had a mild course of COVID-19. At presentation, 93.1% suffered from fatigue, 82.2% from impaired concentration, and 79.2% from impaired memory, 53.5% had impaired sleep. The most common secondary diagnosis found in our cohort was thyroid disease. Fatigue analysis showed that 81.3% of female and 58.8% of male patients had severe combined fatigue. Female gender was an independent risk factor for severe fatigue (severe cognitive fatigue OR = 8.045, = 0.010; severe motor fatigue OR = 7.698, = 0.013). Males suffered from more depressive symptoms, which correlated positively with the duration of symptom onset. 70.3% of patients with anamnestic smell impairment had hyposmia, and 18.9% were anosmic. Interpretation:Most long-COVID patients suffered from severe fatigue, with the female sex as an independent risk factor. Fatigue was not associated with symptoms of depression or anxiety. Patients with long-COVID symptoms should receive an interdisciplinary diagnostic and therapeutic approach depending on the clinical presentation.
10.3389/fneur.2022.979152
Retrospective observation of subacute thyroiditis before and during the COVID-19 vaccination campaign in a single secondary endocrine centre in the Savona district, Liguria, Italy.
Thyroid research
BACKGROUND:Clinicians should be aware that subacute thyroiditis (SAT) might be an under-reported adverse effect of COVID-19 vaccines. AIM:In records from endocrinological examinations, we reviewed the incidence of diagnoses of SAT from 2000 to 2020 and during the 2021 COVID-19 vaccination campaign. METHODS:Review of electronic records from June to December in each year from 2000 to 2021. RESULTS:From 2000 to 2020, 51 patients in our centre had SAT (0.6%). From June to December 2021, 7 females were diagnosed with SAT after vaccination. The percentage of SAT in 2021 medical files was 1.5%. SAT diagnoses significantly (P = 0.03) increased in 2021 in comparison with the 2000-2020 period. The median age of SAT patients in 2021 (51 years; IQR 35-66 years) was higher than in the 2000-2020 period (45 years, IQR 38-52 years; P = 0.05). CONCLUSION:To date, few cases of SAT after COVID-19 vaccinations have been described in the literature, with sub-clinical, normal or increased thyroid function during 1-3-month follow-up. Our findings indicate that SAT after COVID-19 vaccination occurs more frequently than in other virus-related cases and at a greater age. Our observation of a local increase in SAT during the 2021 COVID-19 vaccination campaign indicates that physicians should be aware of this infrequent side effect, which must be considered and monitored after COVID-19 vaccination.
10.1186/s13044-022-00139-z
The Clinical Characteristics and Outcomes of COVID-19 Patients with Pre-Existing Thyroid Dysfunction: A Nationwide Study.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
To which extent the pre-existing hypothyroidism or hyperthyroidism has an impact on coronavirus infection 2019 (COVID-19) outcomes remains unclear. The objective of this study was to evaluate COVID-19 morbidity and mortality in patients with pre-existing thyroid dysfunction. A retrospective cohort of patients with a polymerase chain reaction (PCR)-confirmed COVID-19 infection (n=14 966) from March 11 to May 30, 2020, was established using the database of the Turkish Ministry of Health. We compared the morbidity and mortality rates of COVID-19 patients with pre-existing hypothyroidism (n=8813) and hyperthyroidism (n=1822) to those patients with normal thyroid function (n=4331). Univariate and multivariate regression analyses were performed to identify the factors associated with mortality. Mortality rates were higher in patients with hyperthyroidism (7.7%) and hypothyroidism (4.4%) than those with normal thyroid function (3.4%) (p<0.001 and p=0.008, respectively). Pre-existing hyperthyroidism was significantly associated with an increased risk of mortality (OR 1.54; 95% CI, 1.02-2.33; p=0.042) along with advanced age, male gender, lymphopenia and chronic kidney disease (p<0.001 for all). Although a potential trend was noted, the association between pre-existing hypothyroidism and mortality was not significant (OR 1.36; 95% CI, 0.99-1.86; p=0.055). In conclusion, this study showed an association between pre-existing hyperthyroidism with higher COVID-19 mortality. A potential trend towards increased mortality was also observed for hypothyroidism. The risk was more pronounced in patients with hyperthyroidism.
10.1055/a-1971-8781
The Expression Levels of SARS-CoV-2 Infection-Mediating Molecules Promoted by Interferon-γ and Tumor Necrosis Factor-α Are Downregulated by Hydrogen Sulfide.
International journal of molecular sciences
Autoimmune thyroid diseases (AITDs), which include Hashimoto's thyroiditis (HT) and Graves' disease (GD), have a higher prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the literature. The effects of AITD-associated cytokines on SARS-CoV-2 infection-mediating molecule levels might be involved in the pathogenesis of susceptibility. We speculated that hydrogen sulfide (HS) might attenuate this process since HS has antiviral effects. Using immunohistochemistry, we found that angiotensin-converting enzyme-II (ACE2) expression was higher in the HT group and neuropilin 1 (NRP1) expression was higher in HT and GD groups than in the normal group, while transmembrane protease serine type 2 (TMPRSS2) expression was lower in HT and GD groups. When culturing primary thyrocytes with cytokines or sodium hydrosulfide (NaHS) plus cytokines, we found that and mRNA levels were upregulated while levels were downregulated by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). After pretreatment with NaHS in thyrocytes, ACE2 and NRP1 expression were downregulated compared to IFN-γ or TNF-α treatment, and NaHS had no effect on TMPRSS2 expression. Our findings suggested that IFN-γ and TNF-α, which are elevated in AITDs, promoted ACE2 and NRP1 expression and inhibited TMPRSS2 expression. HS might protect against SARS-CoV-2 infection by downregulating ACE2 and NRP1 levels.
10.3390/ijms232113624
Graves' orbitopathy post-SARS-CoV-2 vaccines: report on six patients.
Journal of endocrinological investigation
CONTEXT:Autoimmune and inflammatory thyroid diseases (Graves' disease, subacute thyroiditis, chronic autoimmune thyroiditis) have been reported following SARS-CoV-2 vaccines but Graves' orbitopathy (GO) post-COVID-19 vaccination is uncommon. METHODS:We describe six new patients seen in Endocrinology Departments with Outpatient Clinics for GO following SARS-CoV-2 vaccines in France. RESULTS:After COVID-19 vaccination, GO was observed in six patients (three men, three women, mean age 53 ± 6 years) with a personal past history of Graves' disease (5/6) or orbitopathy (4/6). New-onset (n = 2) or recurrence (n = 4) of GO was observed following mRNA vaccines after the first (3/6) or second (3/6) dose, with the mean time from vaccination to GO at 23.8 ± 10.4 days. In one patient, thyrotoxicosis was confirmed by increased free T4 and low TSH concentrations while others had normal TSH levels, during chronic levothyroxine treatment in three patients. Four patients had significant anti-TSH receptor antibodies levels. According to the severity and activity of GO, the patients were treated using selenium (n = 2), intravenous glucocorticoids (n = 2), teprotumumab (n = 1), tocilizumab (n = 2) and orbital decompression (n = 1) with a significant improvement in GO signs and symptoms observed by most patients. CONCLUSION:In this study, we report the main data from six new patients with GO following SARS-CoV-2 vaccines. Clinicians need to be aware of the risk of new-onset or recurrent GO in predisposed patients with autoimmune thyroid diseases after COVID-19 vaccination. This study should not raise any concerns regarding SARS-CoV-2 vaccination since the risk of COVID-19 undoubtedly outweighs the incidence of uncommon GO after SARS-CoV-2 vaccination.
10.1007/s40618-022-01955-8
Effects of covid-19 infection on thyroid functions.
Journal of medical biochemistry
Background:COVID-19 may affect many endocrine tissues as well as thyroid gland and hypothalamus-pituitary-thyroid axis. It has been shown that COV D-19 infection suppresses thyroid hormones in some studies and causes subacute thyroiditis in the others so that its effects are still not fully known. The aim of our study is to retrospectively evaluate thyroid functions, clinical findings, biochemical and inflammatory markers in PCR positive patients infected with COVID-19; and to evaluate the relationship between abnormal thyroid function tests (TFT) and clinical and laboratory findings and whether it has potential prognostic significance. Methods:The data of patients aged 18 years and older, 201 patients who applied to Mersin City Training and Research Hospital due to COVID-19 infection between 1st of March and 1st of April in 2021 and received inpatient treatment were evaluated retrospectively. Results:Large TFT (TSH, T3, T4, anti-TPO) and laboratory data of 201 patients with mild, moderate or severe pneumonia on CT were scanned retrospectively. 121 (60.2%) of the patients were male, mean age was 51.9 ± 14.6 years, and the most common comorbid disease was hypertension in 65 (32.3%) patients. Conclusions:It has been determined that the deterioration in TFTs is associated with LDH and D-dimer which are indicators of cell and endothelial damage, duration of hospitalization, clinical severity, and having mutant strains and it has been concluded that low TSH can be used as a prognostic indicator in COVID-19 patients. Further studies with healthy control groups, quantitative RT-PCR tests, histological and pathological correlations, and long-term follow-up are needed.
10.5937/jomb0-34934
Ocular motility disorders following coronavirus disease-19 vaccination.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
PURPOSE:To describe clinical manifestations and short-term prognosis of ocular motility disorders following coronavirus disease-2019 (COVID-19) vaccination. METHODS:Ocular motility disorders were diagnosed by clinical assessment, high-resolution magnetic resonance imaging, and laboratory testing. Clinical manifestations, short-term prognosis, and rate of complete recovery were analyzed. RESULTS:Sixty-three patients (37 males, 26 females) with a mean age of 61.6 ± 13.3 years (range, 22-81 years) were included in this study. Among 61 applicable patients with sufficient information regarding medical histories, 38 (62.3%) had one or more significant underlying past medical histories including vasculopathic risk factors. The interval between initial symptoms and vaccination was 8.6 ± 8.2 (range, 0-28) days. Forty-two (66.7%), 14 (22.2%), and 7 (11.1%) patients developed symptoms after the first, second, and third vaccinations, respectively. One case of internuclear ophthalmoplegia, 52 cases of cranial nerve palsy, two cases of myasthenia gravis, six cases of orbital diseases (such as myositis, thyroid eye disease, and IgG-related orbital myopathy), and two cases of comitant vertical strabismus with acute onset diplopia were found. Among 42 patients with follow-up data (duration: 62.1 ± 40.3 days), complete improvement, partial improvement, no improvement, and exacerbation were shown in 20, 15, 3, and 4 patients, respectively. CONCLUSION:This study provided various clinical features of ocular motility disorders following COVID-19 vaccination. The majority of cases had a mild clinical course while some cases showed a progressive nature. Close follow-up and further studies are needed to elucidate the underlying mechanisms and long-term prognosis.
10.1007/s00417-022-05888-z
Effect of Inactivated and mRNA COVID-19 Vaccination on Thyroid Function Among Patients Treated for Hyperthyroidism.
The Journal of clinical endocrinology and metabolism
CONTEXT:Reports of thyroid dysfunction following COVID-19 vaccination included cases of relapse of Graves' disease and worsening of pre-existing Graves' disease. Little is known about the thyroid-specific outcomes among patients treated for hyperthyroidism who have received COVID-19 vaccination. OBJECTIVE:Among patients treated for hyperthyroidism, we evaluated factors associated with not receiving the COVID-19 vaccination and whether COVID-19 vaccination was associated with thyroid function instability. METHODS:We included consecutive patients treated for hyperthyroidism attending the thyroid clinic at a teaching hospital between January and September 2021. They were categorized into vaccinated and unvaccinated groups. The index date was the date of first-dose vaccination for the vaccinated group, and the first date of attendance in the inclusion period for the unvaccinated group. They were followed up until March 2022 or occurrence of thyroid function instability (worsening of thyroid function/increase in antithyroid drug dosage), whichever was earlier. RESULTS:A total of 910 patients were included (mean age 51.6 years; 82.1% female). Of these, 86.2% had Graves disease and 67.3% were vaccinated (67.3% BNT162b2; 30.6% CoronaVac; 2.1% heterologous). Abnormal thyroid function and cardiovascular comorbidities were independently associated with unvaccinated status. Upon median follow-up of 5.3 months, thyroid function instability occurred in 15.9% of patients. COVID-19 vaccination did not increase risks of thyroid function instability (hazard ratio 0.78, 95% CI 0.56-1.09, P = .151); this was consistent in Graves disease, both types of vaccines, and regardless of whether baseline thyroid function was normal. Twenty-seven patients overtly thyrotoxic at the time of vaccination received COVID-19 vaccines without triggering a thyroid storm or difficulty in subsequent thyroid function control. CONCLUSION:Among patients treated for hyperthyroidism, abnormal thyroid function was a factor predicting unvaccinated status. Our results should encourage patients treated for hyperthyroidism to receive COVID-19 vaccination to protect themselves from adverse outcomes and potential long-term sequelae of COVID-19.
10.1210/clinem/dgac684
Thyroidal Angiotensin-Converting Enzyme 2 Protein Expression and Thyroid Function Tests in Patients with COVID-19: Results from a Retrospective Case Series and a Prospective Cohort Study.
Thyroid : official journal of the American Thyroid Association
Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is owing to fatal inflammatory responses apart from lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to nonthyroidal illness syndrome have been described. Furthermore, angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland. To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients who died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFTs with the severity of the disease in a prospective cohort study. Thyroid tissue of deceased COVID-19 patients ( = 23) was analyzed for histopathology and ACE2 expression by immunohistochemical staining. A total of 153 patients with confirmed SARS-CoV-2 were evaluated regarding TFTs and divided into a severe (intubation, intensive care treatment) and an intermediate group. Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and thyrotropin (TSH) was associated significantly with deadly disease. The high percentage of positive ACE2 immunostaining in deceased patients compared with normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L were associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFTs is crucial in the treatment of severely ill COVID-19 patients. COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.
10.1089/thy.2022.0229
A case report of subacute thyroiditis after inactivated SARS-CoV-2 vaccine.
SAGE open medical case reports
Subacute thyroiditis is an inflammatory thyroid disorder. It is often triggered following viral infections. Amid the current COVID-19 pandemic, several cases of subacute thyroiditis were reported worldwide related to SARS-CoV-2 infection and vaccines. We report a rare case of subacute thyroiditis possibly related to immunization with inactivated SARS-CoV-2 vaccine Sinopharm BIBP. A 29-year-old previously healthy Sri Lankan woman presented with anterior neck pain, low-grade fever and fatigue appearing 7 days after immunization with the second dose of inactivated SARS-CoV-2 vaccine Sinopharm BIBP. She apparently reported similar symptoms which subsided spontaneously within a few days, following immunization with first dose of vaccine. On examination, she had tenderness over the anterior neck. She was afebrile, not tachycardic and clinically euthyroid. Her inflammatory markers were elevated. An ultrasound scan of the neck demonstrated two low echogenic micronodules of 6 x 3 mm and 5 x 3 mm and low background thyroid vascularity. Technetium 99 m pertechnetate (Tc - 99 m) thyroidal uptake scan shows reduced thyroidal uptake suggestive of subacute thyroiditis. Thyroid function tests were normal at the time of the assessment. The patient was treated symptomatically with non-steroidal anti-inflammatory drugs. Her neck pain and tenderness resolved gradually. Serial measurements of thyroid functions during follow-up were within normal limits. Inflammatory markers normalized over the course of follow-up. Subacute thyroiditis following COVID-19 vaccination is a rare occurrence. However, due to its mild clinical course, it could very well be underreported. It is a mild and self-limiting illness with transient thyroid dysfunction; thus, it should be emphasized that the benefits of COVID-19 vaccination outweigh any rare and mild side effects reported.
10.1177/2050313X221140243
Study of thyroid function among COVID-19-affected and non-affected people during pre and post-vaccination.
BMC endocrine disorders
The novel coronavirus COVID-19 has caused a global pandemic with many long-ranging effects on the physiological balance of the human body. The impact of COVID-19 on the thyroid axis remains uncertain. Our aim was to assess the long-term consequences of COVID-19 infection and its vaccination with thyroid hormones. Thirty laboratory-confirmed COVID-19-positive patients with no vaccination record, thirty COVID-19-negative patients with vaccination records, and ten healthy subjects were retrospectively, and cross-sectionally enrolled in this study. An ELISA assay was performed to evaluate thyroid function tests, including the total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH). We found decreased levels of TT3, average or low plasma T4 levels, and standard or slightly decreased TSH levels in unvaccinated COVID-19-positive patients than in the healthy group, while the vaccinated COVID-19-negative group had normal thyroid hormone levels compared to controls. The correlation between TT3 and TSH levels gradually shifted from no association to a negative pattern in the unvaccinated COVID-19-positive group. Again, a highly significant negative correlation between TSH and TT3 was observed on days above 150, although a slight fluctuation was noted on day 90. This pilot study from Bangladesh shows that abnormalities in thyroid function can be observed during COVID-19 infection and after vaccination, which gradually recovers over time.
10.1186/s12902-022-01187-0
Increased incidence of Graves' disease during the SARS-CoV2 pandemic.
Clinical endocrinology
INTRODUCTION:COVID-19 has a wide spectrum of clinical severity and there is evidence that SARS-Cov2 affects several organs and systems. Among the organs affected since the beginning of the pandemic, the relationship between SARS-CoV-2 infection and thyroid involvement has been demonstrated. Novel and highly effective messenger RNA and DNA-based vaccines have been rapidly developed to decrease SARS-CoV-2 morbidity and mortality. Early after mass vaccinations, cases of thyroid dysfunction mainly including episodes of subacute thyroiditis, began to be reported like adverse effects. The objective of this study is to determine the impact of the pandemic, both due to SARS-CoV2 infections and vaccinations, on the incidence of Graves' disease (GD). METHODS:Cross-sectional, observational study comparing incidence of GD in adult population (over 18 years) before (2017-2019) and after (2020-2021) Covid-19 pandemic. Only patients with new cases of GD, no relapsed diseases, were included. SARS-CoV-2 diagnosis was based on nucleic acid amplification tests on nasopharyngeal swabs or measurement of class M and class G antibodies to SARS-CoV-2 by highly specific assays. Data on incidence and vaccination related to SARS-CoV-2 infection were obtained from the public records from Castilla y León autonomous regional government. RESULTS:A total of 180 subjects were diagnosed and treated for GD during the study period. We observed a notable increase in expected GD cases in 2021 compared to 2017-19. The number of GD cases was higher in the second (Q2) quarter. Among 2021 GD cases, 42/66 patients (63.6%) had been vaccinated in the 90 days before symptom onset, but none of them in the first quarter of the year. A total of 97.7% were women with a mean age of 48.9 (SD 15.6) years. On average they were diagnosed 19.9 (SD 17.6) days after receiving the vaccine. A total of 7/42 (16.67%) had another previously diagnosed autoimmune disease and 11/42 (26.19%) were smokers. DISCUSSION:Our results show a notable increase in the incidence of GD during the year 2021, specially in women with a history of smoking. Hyper activation of the immune system induced by SARS-CoV2 and by the recently released SARS-COV-2 vaccines has been highlighted in recent months. To assess whether this observed increase in the incidence of GD is sustained in the coming years or has simply been a precipitous trigger for individuals who were already predisposed to develop the disease, future studies will be needed.
10.1111/cen.14860
Thyrotropin Levels in Patients with Coronavirus Disease 2019: Assessment during Hospitalization and in the Medium Term after Discharge.
Life (Basel, Switzerland)
BACKGROUND:The objectives of this study were (1) to compare TSH levels between inpatients with critical versus non-critical coronavirus disease 19 (COVID-19), and (2) to describe the status of TSH levels three months after hospitalization. METHODS:We collected data on adult patients hospitalized with COVID-19 at Amiens University Hospital. We compared TSH levels between inpatients with critical (intensive care unit admission and/or death) versus non-critical COVID-19. Thereafter, survivors were invited to return for a three-month post-discharge visit where thyroid function tests were performed, regardless of the availability of TSH measurement during hospitalization. RESULTS:Among 448 inpatients with COVID-19, TSH assay data during hospitalization were available for 139 patients without prior thyroid disease. Patients with critical and non-critical forms of COVID-19 did not differ significantly with regard to the median (interquartile range) TSH level (0.96 (0.68-1.71) vs. 1.27 mIU/L (0.75-1.79), = 0.40). Abnormal TSH level was encountered in 17 patients (12.2%); most of them had subclinical thyroid disease. TSH assay data at the three-month post-discharge visit were available for 151 patients without prior thyroid disease. Only seven of them (4.6%) had abnormal TSH levels. Median TSH level at the post-discharge visit was significantly higher than median TSH level during hospitalization. CONCLUSIONS:Our findings suggest that COVID-19 is associated with a transient suppression of TSH in a minority of patients regardless of the clinical form. The higher TSH levels three months after COVID-19 might suggest recovery from non-thyroidal illness syndrome.
10.3390/life12122014
A Novel Finding of an HLA Allele's and a Haplotype's Relationship with SARS-CoV-2 Vaccine-Associated Subacute Thyroiditis.
Vaccines
Subacute thyroiditis (SAT) is a thyroid disease associated with viral infections. Its relationship with major histocompatibility complex (MHC) antigens was shown before. SAT cases triggered by different types of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been reported. In this study, human leukocyte antigen (HLA) genotypes of 27 SAT patients (13 vaccine-associated (V-SAT) and 14 non-SARS-CoV-2-infection non-vaccine-associated (non-V-SAT)) were compared with those of 362 healthy donors. HLA analyses were performed with low-resolution DNA-based sequence-specific oligonucleotide or sequence-specific primer methods. Statistical analyses were performed using IBM SPSS Statistics 25 and Stata/MP 14.1 with the hapipf function. Allele and haplotype frequencies were estimated by PyPop and gene[RATE] tool programs. The allele frequencies of HLA-A*11, HLA-B*35, and HLA-C*04 were higher in the patient groups. Both the allele frequency of HLA-A*11 and the haplotype frequency of A*11-B*35-C*04 were higher in the V-SAT group. The A*11-B*35-C*04 haplotype, including all three loci of MHC class I genes, is shown to be associated with the disease for the first time, especially in the V-SAT group. This finding will contribute to a better understanding of the etiopathogenesis of vaccine-associated SAT and the role of HLA genotypes in the functioning mechanisms of the SARS-CoV-2 vaccines.
10.3390/vaccines10121986
A prospective follow-up on thyroid function, thyroid autoimmunity and long COVID among 250 COVID-19 survivors.
Endocrine
PURPOSE:We evaluated the evolution of thyroid function and autoimmunity among COVID-19 survivors over 6 months in relation to interferon beta-1b treatment and long COVID. METHODS:We included COVID-19 survivors managed in a major COVID-19 centre between July 2020 and May 2021 who were reassessed three and/or six months after acute COVID-19. Thyroid function tests (TFTs) and anti-thyroid antibody titres were measured at acute COVID-19, 3-month and 6-month. RESULTS:250 COVID-19 survivors were included (mean age 52.7 years, 50.4% men). Persistent thyroid function abnormalities were more likely in those with abnormal TFTs in acute COVID-19 (P < 0.001). Among 51 patients with abnormal TFTs in acute COVID-19, 82.4% resolved upon follow-up. Of 199 patients with normal TFTs in acute COVID-19, only 4.5% had incident abnormal TFTs, more likely in interferon-treated patients (P = 0.044) and none clinically overt. Among 129 patients with complete 6-month follow-up for anti-thyroid antibody titres, there was no significant change overall, except for modest increase in anti-thyroid antibody titres among the 84 interferon-treated patients (P < 0.05 at both 3 months and 6 months). Long COVID occurred in 19.5% and 10.4% at 3 and 6 months respectively, where TFTs and anti-thyroid antibody titres were not predictive of its occurrence. CONCLUSION:Over 6 months, most abnormal TFTs in acute COVID-19 resolved, with no significant incident thyroid dysfunction. SARS-CoV-2 infection did not lead to change in thyroid autoimmunity, while interferon treatment was associated with modest increase in anti-thyroid antibody titres. Thyroid function and anti-thyroid antibodies did not play a significant role in long COVID.
10.1007/s12020-022-03281-8
Correlation between Thyroid Responses and Inflammatory Cytokines in Critically Ill COVID-19 Patients.
Biomedicines
Mechanisms involved in thyroid dysfunction in critically ill coronavirus disease 2019 (COVID-19) patients are not clear. Our objective was to correlate the thyroid response with the pro- and anti-inflammatory cytokines profile in critically ill COVID-19 patients. This was a prospective single-center study. We studied the relationship between continuous variables by using Pearson correlation and simple linear regression. Multiple logistic regression analysis was performed to analyze the factors independently associated with mortality. Seventy-eight patients were included in the study at intensive care unit (ICU) admission and 72 had a measurement of the thyroid and inflammatory profile at day 5. No significant correlations were found between thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) and inflammatory cytokines at ICU admission. At day 5, fT4, was inversely correlated with IL-10 (p = 0.035). IL-10 was associated with maximum lactate (p < 0.001) and SOFA score values (p = 0.012). The multiple logistic regression analysis showed that there was a significant relationship between IL-10 (day 5) and in-hospital mortality after adjusting by age and severity of illness. In conclusion, we found that the thyroid hormone profile and inflammatory cytokines had a weak correlation at ICU admission. Associations of interest between fT4 and IL-10 were found at day 5. IL-10 at day 5 was found to be correlated with low fT4 and markers of organ failure and death.
10.3390/biomedicines11010026
Long-term outcome of thyroid abnormalities in patients with severe Covid-19.
European thyroid journal
Objective:We have previously observed thyroid dysfunction, i.e. atypical thyroiditis (painless thyrotoxicosis associated with non-thyroidal illness syndrome), in patients with severe acute respiratory syndrome coronavirus 2 disease (Covid-19). This study aimed to analyse the evolution of thyroid dysfunction over time. Methods:One hundred eighty-three consecutive patients hospitalised for severe Covid-19 without known thyroid history were studied at hospital admission (baseline). Survivors were offered 12-month longitudinal follow-up including assessment of thyroid function, autoantibodies and ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive of thyroiditis (focal hypoechogenicity) also underwent thyroid 99mTc or 123I uptake scan. Results:At baseline, after excluding from TSH analysis, 63 out of 183 (34%) Covid-19 patients commenced on steroids before hospitalisation, and 12 (10%) showed atypical thyroiditis. Follow-up of 75 patients showed normalisation of thyroid function and inflammatory markers and no increased prevalence of detectable thyroid autoantibodies. Baseline US (available in 65 patients) showed focal hypoechogenicity in 28% of patients, of whom 82% had reduced thyroid 99mTc/123I uptake. The presence of focal hypoechogenicity was associated with baseline low TSH (P = 0.034), high free-thyroxine (FT4) (P = 0.018) and high interleukin-6 (IL6) (P = 0.016). Focal hypoechogenicity persisted after 6 and 12 months in 87% and 50% patients, respectively, but reduced in size. After 9 months, thyroid 99mTc/123I uptake partially recovered from baseline (+28%) but was still reduced in 67% patients. Conclusions:Severe Covid-19 induces mild transient thyroid dysfunction correlating with disease severity. Focal hypoechogenicity, associated with baseline high FT4, IL6 and low TSH, does not seem to be related to thyroid autoimmunity and may persist after 1 year although decreasing in size. Long-term consequences seem unlikely.
10.1530/ETJ-22-0200
Effect of SARS-CoV-2 BNT162b2 mRNA vaccine on thyroid autoimmunity: A twelve-month follow-up study.
Frontiers in endocrinology
Objectives:Graves' disease (GD) has been highlighted as a possible adverse effect of the respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. However, it is unknown if the SARS-CoV-2 vaccine disrupts thyroid autoimmunity. We aimed to present long-term follow-up of thyroid autoimmunity after the SARS-CoV-2 BNT162b2 mRNA vaccine. Methods:Serum samples collected from seventy Japanese healthcare workers at baseline, 32 weeks after the second dose (pre-third dose), and 4 weeks after the third dose of the vaccine were analyzed. The time courses of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibody, thyroid-stimulating hormone receptor antibody (TRAb), and thyroid function were evaluated. Anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were additionally evaluated in thirty-three participants. Results:The median age was 50 (IQR, 38-54) years and 69% were female. The median anti-spike IgG antibody titer was 17627 (IQR, 10898-24175) U/mL 4 weeks after the third dose. The mean TRAb was significantly increased from 0.81 (SD, 0.05) IU/L at baseline to 0.97 (SD, 0.30) IU/L 4 weeks after the third dose without functional changes. An increase in TRAb was positively associated with female sex (β = 0.32, = 0.008) and low basal FT4 (β = -0.29, = 0.02) and FT3 (β = -0.33, = 0.004). TgAb was increased by the third dose. Increase in TgAb was associated with history of the thyroid diseases (β = 0.55, 0.001). Conclusions:SARS-CoV-2 BNT162b2 mRNA vaccine can disrupt thyroid autoimmunity. Clinicians should consider the possibility that the SARS-CoV-2 vaccine may disrupt thyroid autoimmunity.
10.3389/fendo.2023.1058007
Subacute Thyroiditis Developing Within 2 Days of Vaccination Against COVID-19 with BNT162b2 mRNA.
European journal of case reports in internal medicine
A 32-year-old woman presented to the outpatient clinic with persistent fever, anterior neck pain, and palpitations over the past week which developed 2 days after she had received the first dose of the Pfizer/BioNTech SARS-CoV-2 mRNA vaccine. On examination, the patient's heart rate was 140 beats per minute and the thyroid gland was tender on palpation. Laboratory studies showed a low serum TSH level with elevated free thyroxine. Thyroid ultrasound revealed low-echoic lesions compatible with the site of tenderness. The patient was diagnosed with subacute thyroiditis and treatment was initiated with acetaminophen and propranolol, which resulted in symptom resolution within 2 weeks. Clinicians should be aware that subacute thyroiditis may occur within a few days following COVID-19 vaccination, especially in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations, because differentiating them from early non-specific adverse reactions can be challenging. LEARNING POINTS:Cases of subacute thyroiditis after vaccination, including against COVID-19, have been increasingly reported.Subacute thyroiditis should be considered in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations after COVID-19 vaccination because these can be diagnostic clues.It is important to note that this condition can occur as early as a few days after vaccination, in order to avoid diagnostic pitfalls.
10.12890/2023_003735
Thyroid Function Abnormalities and Outcomes in Hospitalized Patients with COVID-19 Infection: A Cross-Sectional Study.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
Thyroid gland can be affected by the COVID-19 infection. The pattern of thyroid function abnormality reported in COVID-19 is variable; in addition, some drugs used in COVID-19 patients like glucocorticoids and heparin can affect the thyroid function tests (TFT). We conducted an observational, cross-sectional study of thyroid function abnormalities with thyroid autoimmune profile in COVID-19 patients with varying severity from November 2020 to June 2021. Serum FT4, FT3, TSH, anti-TPO, and anti-Tg antibodies were measured before the initiation of treatment with steroids and anti-coagulants. A total of 271 COVID-19 patients were included in the study, of which 27 were asymptomatic and remaining 158, 39, and 47 were classified to mild, moderate and severe categories, respectively, according to MoHFW, India criteria. Their mean age was 49±17 years and 64.9% were males. Abnormal TFT was present in 37.2% (101/271) patients. Low FT3, low FT4, and low TSH were present in 21.03%, 15.9% and 4.5% of patients, respectively. Pattern corresponding to sick euthyroid syndrome was the most common. Both mean FT3 and FT3/FT4 ratio decreased with increasing severity of COVID-19 illness (p=0.001). In multivariate analysis, low FT3 was associated with increased risk of mortality (OR 12.36, 95% CI: 1.23-124.19; p=0.033). Thyroid autoantibodies were positive in 58 (27.14%) patients; but it was not associated with any thyroid dysfunction. Thyroid function abnormality is common among COVID-19 patients. Both low FT3 and FT3/FT4 ratio are indicators of disease severity while low FT3 is a prognostic marker of COVID-19 associated mortality.
10.1055/a-2014-4634
Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis.
Frontiers in endocrinology
Objective:COVID-19 infection may affect thyroid function. However, changes in thyroid function in COVID-19 patients have not been well described. This systematic review and meta-analysis assess thyroxine levels in COVID-19 patients, compared with non-COVID-19 pneumonia and healthy cohorts during the COVID-19 epidemic. Methods:A search was performed in English and Chinese databases from inception to August 1, 2022. The primary analysis assessed thyroid function in COVID-19 patients, comparing non-COVID-19 pneumonia and healthy cohorts. Secondary outcomes included different severity and prognoses of COVID-19 patients. Results:A total of 5873 patients were enrolled in the study. The pooled estimates of TSH and FT3 were significantly lower in patients with COVID-19 and non-COVID-19 pneumonia than in the healthy cohort (P < 0.001), whereas FT4 were significantly higher (P < 0.001). Patients with the non-severe COVID-19 showed significant higher in TSH levels than the severe (I = 89.9%, = 0.002) and FT3 (I = 91.9%, < 0.001). Standard mean differences (SMD) of TSH, FT3, and FT4 levels of survivors and non-survivors were 0.29 (= 0.006), 1.11 ( < 0.001), and 0.22 ( < 0.001). For ICU patients, the survivors had significantly higher FT4 (SMD=0.47, =0.003) and FT3 (SMD=0.51, P=0.001) than non-survivors. Conclusions:Compared with the healthy cohort, COVID-19 patients showed decreased TSH and FT3 and increased FT4, similar to non-COVID-19 pneumonia. Thyroid function changes were related to the severity of COVID-19. Thyroxine levels have clinical significance for prognosis evaluation, especially FT3.
10.3389/fendo.2023.1089190
The Spectrum of Thyroid Function Tests and Autoantibodies During Hospitalization and After Six Months of Discharge in COVID-19 Patients: Does COVID-19 Trigger Autoimmunity?
Endocrine research
OBJECTIVE:The aim of the study was to investigate thyroid function test (TFT) results and anti-thyroid antibody titers in acutely infected COVID-19 patients, as well as the changes in TFT and autoantibody results during the 6-months recovery period among survivors. PATIENTS AND DESIGN:A total of 163 adult COVID-19 patients and 124 COVID-19 survivors were evaluated in terms of TFT (thyroid stimulating hormone [TSH], free triiodothyronine [fT3], and free thyroxine [fT4]) and anti-thyroid antibodies (anti-thyroglobulin [anti-Tg] and anti-thyroid peroxidase [anti-TPO]). RESULTS:Thyroid dysfunction was noted in 56.4% of patients on admission, including the non-thyroidal illness syndrome (NTIS) in most cases. Presence vs. absence of thyroid dysfunction on admission was associated with significantly higher rate of severe disease ( < 0.001), while severe vs. mild-to-moderate disease was associated with significantly lower serum fT3 levels ( = 0.001). Overall, 94.4% of survivors were euthyroid at the time of 6 months post-discharge, while in some patients, the post-COVID-19 recovery period was also associated with significantly increased anti-TPO titers and the presence of new-onset or persistent subclinical hypothyroidism. CONCLUSION:This is one of the few studies to evaluate TFT and autoantibodies over a 6-month period after recovery from COVID-19. The presence of emergent or persistent subclinical hypothyroidism and the significantly increased anti-TPO titers in some patients during the convalescence period suggest the need for follow-up for development of thyroid dysfunction and autoimmunity among COVID-19 survivors.
10.1080/07435800.2023.2188086
Clinical presentation and prognosis of COVID-19 in older adults with hypothyroidism: data from the GeroCovid observational study.
Journal of endocrinological investigation
BACKGROUND:The prevalence of hypothyroidism among older patients hospitalized for COVID-19 and its association with mortality is unclear. This study aims to investigate the prevalence of hypothyroidism in older COVID-19 inpatients and verify if this comorbidity is associated with a specific pattern of onset symptoms and a worse prognosis. METHODS:COVID-19 inpatients aged ≥ 60 years, participating in the GeroCovid acute wards cohort, were included. The history of hypothyroidism was derived from medical records and the use of thyroid hormones. Sociodemographic data, comorbidities, symptoms/signs at the disease onset and inflammatory markers at ward admission were compared between people with vs without history of hypothyroidism. The association between hypothyroidism and in-hospital mortality was tested through Cox regression. RESULTS:Of the 1245 patients included, 8.5% had a history of hypothyroidism. These patients were more likely to present arterial hypertension and obesity compared with those without an history of hypothyroidism. Concerning COVID-19 clinical presentation, patients with hypothyroidism had less frequently low oxygen saturation and anorexia but reported muscle pain and loss of smell more commonly than those without hypothyroidism. Among the inflammatory markers, patients with hypothyroidism had higher lymphocytes values. At Cox regression, hypothyroidism was associated with reduced in-hospital mortality only in the univariable model (HR = 0.66, 95% CI 0.45-0.96, p = 0.03); conversely, no significant result were observed after adjusting for potential confounders (HR = 0.69, 95% CI 0.47-1.03, p = 0.07). CONCLUSIONS:Hypothyroidism does not seem to substantially influence the prognosis of COVID-19 in older people, although it may be associated with peculiar clinical and biochemical features at the disease onset.
10.1007/s40618-023-02048-w
Increased prevalence of autoimmune thyroid disease after COVID-19: A single-center, prospective study.
Frontiers in endocrinology
Introduction:Thyroid dysfunctions associated with SARS-CoV-2 acute infection have been extensively described since the beginning of COVID-19 pandemics. Conversely, few data are available on the occurrence of thyroid autoimmunity after COVID-19 resolution. We assessed the prevalence of autoimmune thyroid disease (ATD) and thyroid dysfunctions in COVID-19 survivors three months after hospital admission. Design and methods:Single-center, prospective, observational, cohort study performed at ASST Papa Giovanni XXIII Hospital, Bergamo, Italy. 599 COVID-19 survivors were prospectively evaluated for thyroid function and autoimmunity thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb). When a positive antibody concentration was detected, thyroid ultrasound was performed. Multiple logistic regression model was used to estimate the association between autoimmunity and demographic characteristics, respiratory support, and comorbidities. Autoimmunity results were compared to a cohort of 498 controls referred to our Institution for non-thyroid diseases before the pandemic onset. A sensitivity analysis comparing 330 COVID-19 patients with 330 age and sex-matched controls was performed. Results:Univariate and multivariate analysis found that female sex was positively associated (OR 2.01, SE 0.48, p = 0.003), and type 2 diabetes (T2DM) was negatively associated (OR 0.36, SE 0.16, p = 0.025) with thyroid autoimmunity; hospitalization, ICU admission, respiratory support, or COVID-19 treatment were not associated with thyroid autoimmunity (p > 0.05). TPOAb prevalence was greater in COVID-19 survivors than in controls: 15.7% vs 7.7%, p = 0.002. Ultrasonographic features of thyroiditis were present in 94.9% of the evaluated patients with positive antibodies. TSH was within the normal range in 95% of patients. Conclusions:Autoimmune thyroid disease prevalence in COVID-19 survivors was doubled as compared to age and sex-matched controls, suggesting a role of SARS-CoV-2 in eliciting thyroid autoimmunity.
10.3389/fendo.2023.1126683
Thyroglobulin levels in COVID-19-positive patients: Correlations with thyroid function tests, inflammatory markers, and glucocorticoid use.
Frontiers in endocrinology
COVID-19 often results in generalized inflammation and affects various organs and systems. Endocrine research focused on the possible sequelae of COVID-19, with special interest given to the thyroid gland. Clinical problems such as thyroid function in non-thyroidal illness (NTI), autoimmune thyroiditis, and COVID-19-related subacute thyroiditis (SAT) quickly gained wide coverage. Thyrotoxicosis of various origins leads to the release of peripheral thyroid hormones and thyroglobulin (TG), the main glycoprotein contained within the thyroid follicular lumen. In our study, we evaluated TG levels in COVID-19-positive patients and investigated the possible relationships between TG, thyroid function tests (TFTs), and inflammatory markers. Our approach included separate subanalyses of patients who received and those who did not receive glucocorticoids (GCs). In the entire population studied, the concentration of TG tended to decrease with time (p<0.001; p1,2 = 0.025, p1,3 = 0.001, p2,3 = 0.003), and this pattern was especially clear among patients treated with GCs (p<0.001; p1,2=<0.001; p1,3=<0.001; p 2,3=<0.001). The concentration of TG differed significantly between patients treated and those not treated with GC at the second and third time points of observation (p=0.033 and p=0.001, consecutively). TG concentration did not differ between the patients with normal and abnormal TFTs. The correlations between TG, TFTs, and inflammatory markers were very limited. 19 patients had elevated TG levels, but a TFT pattern suggestive of thyrotoxicosis was not common in this group. There were no statistically significant differences between patients who met and those who did not meet the predefined combined primary endpoint.
10.3389/fendo.2022.1031188
Thyrotoxic hypokalemic periodic paralysis and COVID-19 infection.
Journal of family medicine and primary care
Various conditions causing weakness associated with coronavirus disease 2019 (COVID-19) infection have been described, including cerebrovascular diseases, acute myelitis, Guillain-Barré syndrome, myasthenia gravis, critical illness myopathy and neuropathy, myositis, and rhabdomyolysis. We report an adult man presenting with an unusual etiology of weakness after a COVID-19 infection. Thyrotoxic hypokalemic periodic paralysis (THPP) was diagnosed from the presence of Graves' disease and hypokalemia because of intra-cellular potassium shifting. His weakness and hypokalemia responded well to potassium supplements and a non-selective b-blocker, whereas his thyrotoxicosis was initially controlled by an anti-thyroid medication and subsequently with radioactive iodine therapy. He was also treated as having mild COVID-19 based on his normal chest X-ray and oxygenation level. This is the first report showing an association between COVID-19 infection and a paralysis attack of THPP. Physicians should be alerted about this unusual cause of weakness, particularly in Asian patients.
10.4103/jfmpc.jfmpc_475_22
A Comprehensive Review of COVID-19-Associated Endocrine Manifestations.
Southern medical journal
Coronavirus disease 2019 COVID-19) has played a significant part in systematic damage, affecting lives and leading to significant mortality. The endocrine system is one of the systems affected by this pandemic outbreak. The relationship between them has been identified in previous and ongoing research. The mechanism through which severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can achieve this is similar to that for organs that express angiotensin-converting enzyme 2 receptors, which is the primary binding site of the virus. Endocrine cells widely express angiotensin-converting enzyme 2 receptors and transmembrane serine protease 2, the primary mediators initiating the acute phase of the disease. This review aimed to identify and discuss the endocrine complications of COVID-19. This primary focus is on presenting thyroid disorders or newly diagnosed diabetes mellitus (DM). Thyroid dysfunction with subacute thyroiditis, Graves' disease, and hypothyroidism caused by primary autoimmune thyroiditis has been reported. Pancreatic damage leads to type 1 DM because of the autoimmune nature of the disease and type 2 DM because of postinflammatory insulin resistance. Because follow-up data on COVID-19 on the endocrine glands are limited, long-term investigations are needed to assess specific effects.
10.14423/SMJ.0000000000001542
A Review of Thyroid Dysfunction Due to COVID-19.
Mini reviews in medicinal chemistry
Coronavirus disease 2019 (COVID-19) affects thyroid function. These changes are due to the direct impact of the virus on thyroid cells via angiotensin-converting-enzyme 2 (ACE2) receptors, inflammatory reaction, apoptosis in thyroid follicular cells, suppression of hypothalamus-pituitarythyroid axis, an increase in activity of adrenocortical axis, and excess cortisol release due to cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Euthyroid sick syndrome (ESS), thyroiditis, clinical and subclinical hypothyroidism, central hypothyroidism, exacerbation of underlying autoimmune thyroid disease, and clinical and subclinical hyperthyroidism can be associated with coronavirus. Adjuvants in coronavirus vaccines induce autoimmune/inflammatory syndrome known as vaccine adjuvants (ASIA) syndrome. Thyroiditis and Graves' disease have been reported to be associated with ASIA syndrome after some coronavirus vaccinations. Some coronavirus medications, such as hydroxychloroquine, monoclonal antibodies, lopinavir/ritonavir, remdesivir, naproxen, anticoagulants, and glucocorticoids can also affect thyroid tests, and correct diagnosis of thyroid disorders will be more difficult. Changes in thyroid tests may be one of the most important manifestations of COVID-19. These changes can be confusing for clinicians and can lead to inappropriate diagnoses and decisions. Prospective studies should be conducted in the future to increase epidemiological and clinical data and optimize the management of thyroid dysfunctions in patients with COVID-19.
10.2174/1389557523666230413090332
Thyrotoxicosis after COVID-19 Infection with a Delay in Graves' Disease Antibody Positivity.
Case reports in endocrinology
. Mounting evidence implicates COVID-19 as a cause of thyroid dysfunction, including thyrotoxicosis due to both thyroiditis and Graves' disease (GD). In this report, we present a case of thyrotoxicosis following COVID-19 infection that was ultimately found to represent GD with significantly delayed diagnostic serum antibody positivity. . A 65-year-old woman with a history of uncomplicated COVID-19 infection one month prior, presented to the Emergency Department with exertional dyspnea and palpitations, and was found to be in atrial fibrillation with rapid ventricular response (AF with RVR). Labs showed subclinical hyperthyroidism and the patient was started on a beta-blocker and methimazole. One month later, thyroid-stimulating immunoglobulin (TSI) resulted negative and thyroid function tests had normalized. The clinical picture suggested thyroiditis, and methimazole was stopped. One month later, the patient again presented in AF with RVR, with labs showing overt biochemical thyrotoxicosis. Antibodies were re-tested, and the thyrotropin receptor antibody (TRAb) and TSI resulted positive, confirming GD. . Most notable in this case is the feature of delayed GD antibody positivity: the diagnostic immunoassay for GD resulted negative one and two months after infection, but was ultimately positive three months after infection. To the authors' knowledge, this represents the longest delayed antibody positivity reported to date, amongst cases of new-onset GD following COVID. . The clinical course of GD following COVID-19 infection is highly variable. This case underscores the need for vigilance in monitoring for delayed GD antibody positivity due to the important therapeutic implications of distinguishing thyroiditis from GD.
10.1155/2023/8402725
Thyroid function and associated mood changes after COVID-19 vaccines in patients with Hashimoto thyroiditis.
Frontiers in immunology
Context:Severe acute respiratory syndrome-coronavirus 2 (COVID-19) vaccines may incur changes in thyroid functions followed by mood changes, and patients with Hashimoto thyroiditis (HT) were suggested to bear a higher risk. Objectives:We primarily aim to find whether COVID-19 vaccination could induce potential subsequent thyroid function and mood changes. The secondary aim was to find inflammatory biomarkers associated with risk. Methods:The retrospective, multi-center study recruited patients with HT receiving COVID-19-inactivated vaccines. C-reactive proteins (CRPs), thyroid-stimulating hormones (TSHs), and mood changes were studied before and after vaccination during a follow-up of a 6-month period. Independent association was investigated between incidence of mood state, thyroid functions, and inflammatory markers. Propensity score-matched comparisons between the vaccine and control groups were carried out to investigate the difference. Results:Final analysis included 2,765 patients with HT in the vaccine group and 1,288 patients in the control group. In the matched analysis, TSH increase and mood change incidence were both significantly higher in the vaccine group (11.9% versus 6.1% for TSH increase and 12.7% versus 8.4% for mood change incidence). An increase in CRP was associated with mood change (p< 0.01 by the Kaplan-Meier method) and severity (r = 0.75) after vaccination. Baseline CRP, TSH, and antibodies of thyroid peroxidase (anti-TPO) were found to predict incidence of mood changes. Conclusion:COVID-19 vaccination seemed to induce increased levels and incidence of TSH surge followed by mood changes in patients with HT. Higher levels of pre-vaccine serum TSH, CRP, and anti-TPO values were associated with higher incidence in the early post-vaccine phase.
10.3389/fimmu.2023.1129746
Subacute thyroiditis following COVID-19: A systematic review.
Frontiers in endocrinology
Background:Subacute thyroiditis (SAT) is a self-limiting thyroid inflammatory disease occurring specifically after upper respiratory tract infections. Since COVID-19 is a respiratory disease leading to multi-organ involvements, we aimed to systematically review the literature regarding SAT secondary to COVID-19. Methods:We searched Scopus, PubMed/MEDLINE, Cochrane, Web of Science, ProQuest, and LitCovid databases using the terms "subacute thyroiditis" and "COVID-19" and their synonyms from inception to November 3, 2022. We included the original articles of the patients with SAT secondary to COVID-19. Studies reporting SAT secondary to COVID-19 vaccination or SAT symptoms' manifestation before the COVID-19 infection were not included. Results:Totally, 820 articles were retained. Having removed the duplicates, 250 articles remained, out of which 43 articles (40 case reports and three case series) with a total of 100 patients, were eventually selected. The patients aged 18-85 years (Mean: 42.70, SD: 11.85) and 68 (68%) were women. The time from the onset of COVID-19 to the onset of SAT symptoms varied from zero to 168 days (Mean: 28.31, SD: 36.92). The most common symptoms of SAT were neck pain in 69 patients (69%), fever in 54 (54%), fatigue and weakness in 34 (34%), and persistent palpitations in 31 (31%). The most common ultrasonographic findings were hypoechoic regions in 73 (79%), enlarged thyroid in 46 (50%), and changes in thyroid vascularity in 14 (15%). Thirty-one patients (31%) were hospitalized, and 68 (68%) were treated as outpatients. Corticosteroids were the preferred treatment in both the inpatient and outpatient settings (25 inpatients (81%) and 44 outpatients (65%)). Other preferred treatments were nonsteroidal anti-inflammatory drugs (nine inpatients (29%) and 17 outpatients (25%)) and beta-blockers (four inpatients (13%) and seven outpatients (10%)). After a mean duration of 61.59 days (SD: 67.07), 21 patients (23%) developed hypothyroidism and thus, levothyroxine-based treatment was used in six of these patients and the rest of these patients did not receive levothyroxine. Conclusion:SAT secondary to COVID-19 seems to manifest almost similarly to the conventional SAT. However, except for the case reports and case series, lack of studies has limited the quality of the data at hand.
10.3389/fendo.2023.1126637
Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.
The lancet. Diabetes & endocrinology
BACKGROUND:Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS:In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS:Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION:Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING:None.
10.1016/S2213-8587(23)00094-3
Subacute THYROiditis Related to SARS-CoV-2 VAccine and Covid-19 (THYROVAC Study): A Multicenter Nationwide Study.
The Journal of clinical endocrinology and metabolism
CONTEXT:The aims of the study are to compare characteristics of subacute thyroiditis (SAT) related to different etiologies, and to identify predictors of recurrence of SAT and incident hypothyroidism. METHODS:This nationwide, multicenter, retrospective cohort study included 53 endocrinology centers in Turkey. The study participants were divided into either COVID-19-related SAT (Cov-SAT), SARS-CoV-2 vaccine-related SAT (Vac-SAT), or control SAT (Cont-SAT) groups. RESULTS:Of the 811 patients, 258 (31.8%) were included in the Vac-SAT group, 98 (12.1%) in the Cov-SAT group, and 455 (56.1%) in the Cont-SAT group. No difference was found between the groups with regard to laboratory and imaging findings. SAT etiology was not an independent predictor of recurrence or hypothyroidism. In the entire cohort, steroid therapy requirement and younger age were statistically significant predictors for SAT recurrence. C-reactive protein measured during SAT onset, female sex, absence of antithyroid peroxidase (TPO) positivity, and absence of steroid therapy were statistically significant predictors of incident (early) hypothyroidism, irrespective of SAT etiology. On the other hand, probable predictors of established hypothyroidism differed from that of incident hypothyroidism. CONCLUSION:Since there is no difference in terms of follow-up parameters and outcomes, COVID-19- and SARS-CoV-2 vaccine-related SAT can be treated and followed up like classic SATs. Recurrence was determined by younger age and steroid therapy requirement. Steroid therapy independently predicts incident hypothyroidism that may sometimes be transient in overall SAT and is also associated with a lower risk of established hypothyroidism.
10.1210/clinem/dgad235
Short- and long-term outcomes of patients with hyper or hypothyroidism following COVID vaccine.
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
Since the beginning of the wide-scale anti-Coronavirus disease 2019 (COVID-19) vaccination program, sporadic cases of thyroid disease following vaccination have been reported. We describe 19 consecutive cases of COVID vaccine-related thyroid disease. Medical records were reviewed for 9 patients with Graves' disease (GD) and 10 with Thyroiditis, all of whom were diagnosed following COVID-19 vaccination. In the , the median age was 45.5 years, female/male(F/M) ratio 5:4, thyroid-stimulating immunoglobulins were elevated in seven patients. The median time from vaccination to diagnosis was 3 months. Methimazole treatment was given to all but one patient. At a median follow-up of 8.5 months from vaccination, three patients were still on methimazole, five went into remission (data were missing for one). In the , the median age was 47 years, the F/M ratio 7:3. Thyroiditis was diagnosed after the first, second, and third doses in one, two, and seven patients, respectively. The median time from vaccination to diagnosis was 2 months. TPO antibodies were positive in three patients. All patients were euthyroid off medication at the last visit. Six patients were diagnosed in the hypothyroid phase at 2.5 months from vaccination. Four resolved spontaneously at 3, 6, 4, and 8 months; the other two were treated with thyroxine at 1.5 and 2 months from vaccination and remained on treatment at their last visit, at 11.5 and 8.5 months, respectively. Thyroid disease should be included among possible complications of COVID-19 vaccine and either a late onset or delayed diagnosis should be considered.
10.1177/10815589231173876
Graves' Disease after mRNA COVID-19 Vaccination, with the Presence of Autoimmune Antibodies Even One Year Later.
Vaccines
A 45-year-old man who had received his second mRNA COVID-19 vaccination one week earlier was presented to the emergency department with chest discomfort. Therefore, we suspected post-vaccination myocarditis; however, the patient showed no signs of myocarditis. After 2 weeks, he revisited the hospital complaining of palpitations, hand tremors, and weight loss. The patient exhibited high free thyroxine (FT4) (6.42 ng/dL), low thyroid-stimulating hormone (TSH) (<0.01 μIU/mL), and high TSH receptor antibody (17.5 IU/L) levels, and was diagnosed with Graves' disease. Thiamazole was administered, and the patient's FT4 levels normalized after 30 days. One year later, the patient's FT4 is stable; however, their TSH receptor antibodies have not become negative and thiamazole has continued. This is the first case report to follow the course of Graves' disease one year after mRNA COVID-19 vaccination.
10.3390/vaccines11050934
Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19.
Journal of molecular medicine (Berlin, Germany)
Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. KEY MESSAGES: • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.
10.1007/s00109-023-02334-3
Autoimmune/inflammatory syndrome induced by adjuvants in a woman with Hashimoto thyroiditis and familial autoimmunity-a case report and literature review.
Frontiers in immunology
Introduction:Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) consists of a wide spectrum of symptoms and immunological features that are believed to develop in predisposed individuals after exposure to an adjuvant, including a silicone breast implant (SBI). Different autoimmune diseases (AIDs) have been associated with ASIA, but ASIA development after SBI in women with Hashimoto thyroiditis (HT) and familial autoimmunity has rarely been described. Case report:A 37-year-old woman presented in 2019 with arthralgia, sicca symptoms, fatigue, + antinuclear antibody (ANA), + anti SSA, and + anticardiolipin Immunoglobulin G (IgG) antibodies. She was diagnosed with HT and vitamin D deficiency in 2012. The familial autoimmunity was present: the patient's mother had been diagnosed with systemic lupus erythematosus and secondary Sjogren's syndrome and her grandmother with cutaneous lupus and pernicious anemia. In 2017, the patient had a cosmetic SBI procedure that was complicated by repeated right breast capsulitis. After 2 years of irregular visits due to COVID-19, she presented with + ANA, + anticentromere antibodies both in sera and seroma, sicca syndrome, arthralgias, twinkling in extremities, abnormal capillaroscopic findings, and reduced diffusing capacity of the lungs for carbon monoxide. She was diagnosed with ASIA, and antimalarial and corticosteroid therapy were introduced. Conclusion:In patients with HT and familial autoimmunity, SBI should be carefully considered due to the possibility of ASIA development. Hashimoto thyroiditis, familial autoimmunity, and ASIA seem to be interconnected in the complex mosaic of autoimmunity in predisposed individuals.
10.3389/fimmu.2023.1139603
Overview of autoantibodies in COVID-19 convalescents.
Journal of medical virology
Accumulating evidence shows that SARS-CoV-2 can potentially trigger autoimmune processes, which can be responsible for the long-term consequences of COVID-19. Therefore, this paper aims to review the autoantibodies reported in COVID-19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G-protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS-CoV-2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically-relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS-CoV-2 infection or the accidental post-COVID-19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post-COVID-19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age- and sex-related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS-CoV-2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS-CoV-2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID-19 convalescents.
10.1002/jmv.28864
An unusual occurrence of autoimmune pancreatitis after gam-Covid-Vac (Sputnik V): A case report and literature review.
British journal of clinical pharmacology
The safety profile of the Sputnik V vaccine is generally reassuring. Nevertheless, an enhanced risk of new-onset of immune-mediated diseases has been increasingly reported following the adenoviral-based Covid-19 vaccine, including inflammatory arthritis, Guillain-Barré syndrome, optical neuromyelitis, acute disseminated encephalomyelitis, subacute thyroiditis and acute liver injury as well as glomerulopathy. However, no case of autoimmune pancreatitis has been reported yet. Herein, we describe a case of type I autoimmune pancreatitis that may be due to the Sputnik V Covid-19 vaccine.
10.1111/bcp.15817
Graves' disease after exposure to the SARS-CoV-2 vaccine: a case report and review of the literature.
BMC endocrine disorders
BACKGROUND:Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is characterized by immune system dysregulation after exposure to adjuvants, such as aluminum. Although cases of autoimmune thyroid diseases caused by ASIA have been reported, Graves' disease is one of the rarer diseases. There are some reports that vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause ASIA. Here, we describe a case of Graves' disease following SARS-CoV-2 vaccination and a review of the literature. CASE PRESENTATION:A 41-year-old woman was admitted to our hospital because of palpitations and fatigue. Two weeks after receiving the second SARS-CoV-2 vaccine (BNT162b2, Coronavirus Modified Uridine messenger RNA (mRNA) Vaccine, Pfizer), she developed fatigue and gradually worsened. On admission, she exhibited thyrotoxicosis (thyroid-stimulating hormone (TSH) < 0.01 mIU/L (0.08-0.54), free triiodothyronine (FT3) 33.2 pmol/L (3.8-6.3), and free thyroxine (FT4) 72.1 pmol/L (11.6-19.3)) and palpitations associated with atrial fibrillation. TSH receptor antibody (TRAb) was positive (TRAb 5.0 IU/L (< 2.0)), and Tc scintigraphy showed diffuse uptake in the thyroid gland, suggesting that the thyrotoxicosis in this case was caused by Graves' disease. Thiamazole was prescribed to correct her condition, and soon after this treatment was initiated, her symptoms and thyroid hormone levels were significantly reduced. CONCLUSIONS:This case report reinforces the potential correlation between ASIA affecting the thyroid and SARS-CoV-2 mRNA vaccines. The clinical course suggests that it is essential to consider the possibility of developing ASIA, such as Graves' disease, after exposure to the SARS-CoV-2 vaccine.
10.1186/s12902-023-01387-2
Subacute thyroiditis following recovery from COVID-19 infection: novel clinical findings from an Eastern Indian cohort.
Postgraduate medical journal
OBJECTIVE:Recent reports have suggested a link between COVID-19 infection and subacute thyroiditis (SAT). We aimed to describe variations in clinical and biochemical parameters in patients developing post-COVID SAT. DESIGN:Ours was a combined retrospective-prospective study on patients presenting with SAT within 3 months of recovery from COVID-19 infection, who were subsequently followed up for a further 6 months since diagnosis of SAT. RESULTS:Out of 670 patients with COVID-19, 11 patients presented with post-COVID-19 SAT (6.8%). Those with painless SAT (PLSAT, n = 5) presented earlier, had more severe thyrotoxic manifestations and exhibited higher C-reactive protein, interleukin 6 (IL-6), neutrophil-lymphocyte ratio and lower absolute lymphocyte count than those with painful SAT (PFSAT, n = 6). There were significant correlations of total and free T4 and total and free T3 levels with serum IL-6 levels (pall <0.04). No differences were observed between patients with post-COVID SAT presenting during the first and second waves. Oral glucocorticoids were needed for symptomatic relief in 66.67% of patients with PFSAT. At 6 months of follow-up, majority (n = 9, 82%) achieved euthyroidism, while subclinical and overt hypothyroidism were found in one patient each. CONCLUSIONS:Ours is the largest single-centre cohort of post-COVID-19 SAT reported until, demonstrating two distinct clinical presentations-without and with neck pain-depending on time elapsed since COVID-19 diagnosis. Persistent lymphopaenia during the immediate post-COVID recovery period could be a key driver of early,painless SAT. Close monitoring of thyroid functions for at least 6 months is warranted in all cases.
10.1136/postgradmedj-2021-141429
Incident autoimmune diseases in association with SARS-CoV-2 infection: a matched cohort study.
Clinical rheumatology
OBJECTIVES:To investigate whether the risk of developing an incident autoimmune disease is increased in patients with prior COVID-19 disease compared to those without COVID-19, a large cohort study was conducted. METHOD:A cohort was selected from German routine health care data. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. RESULTS:In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune diseases of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune disease. CONCLUSIONS:SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. Key Points • In the 3 to 15 months after acute infection, patients who had suffered from COVID-19 had a 43% (95% CI: 37-48%) higher likelihood of developing a first-onset autoimmune disease, meaning an absolute increase in incidence of 4.50 per 1000 person-years over the control group. • COVID-19 showed the strongest association with vascular autoimmune diseases.
10.1007/s10067-023-06670-0
Insights into SARS-CoV-2-associated subacute thyroiditis: from infection to vaccine.
Virology journal
Since the COVID-19 emergence as a global pandemic in March 2020, more than 5 million SARS-CoV-2-related deaths have been globally documented. As the pandemic progressed, it became clear that, although the infection is mainly characterized as a respiratory disease, it also affects other organs and systems, including the thyroid gland. Indeed, emerging evidence suggests that SARS-CoV-2 can act as a trigger for various thyroid disorders, for example, subacute thyroiditis (SAT), Grave's disease, and non-thyroidal illness syndrome. The entry of SARS-CoV-2 into the host cells is mainly mediated by the ACE2-receptor, making organs and systems with high expression of this receptor, such as the thyroid gland, highly vulnerable to COVID-19. Accumulating data propose that SAT may be an underestimated manifestation of COVID-19 infection. Importantly, if SAT remains unrecognized, it may trigger or aggravate potential other complications of the disease, for example, respiratory insufficiency and cardiovascular complications, and thus negatively influence prognosis. Moreover, recent case reports, case series, and systematic reviews highlight SAT as a potential side effect of the vaccination against SARS-CoV-2. The present review aims to raise awareness of SARS-CoV-2-associated- and post-vaccination subacute thyroiditis, to discuss recent evidence regarding its pathophysiology, and to present useful information for this special form of SAT related to daily clinical practice.
10.1186/s12985-023-02103-1
Subacute Thyroiditis Complicating COVID-19 Infection.
Clinical medicine insights. Case reports
Subacute thyroiditis (SAT) is a self-limited inflammatory disease and a rare cause of thyrotoxicosis. Although the exact etiology of SAT is not sufficiently understood, it is generally associated to viral infections. Current evidence highlights that SAT may be a potentially uncommon manifestation of ongoing Coronavirus disease 2019 (COVID-19) infection or a post-viral complication of the disease. Despite that SAT is a rare manifestation associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease both in ongoing and resolved COVID-19 infection, the ever-increasing numbers of COVID-19 patients strengthens the possibility that this particular disease entity will be of more immediate concern in the future. The current work aims to summarize the approach of SARS-CoV-2-associated SAT, present its pathophysiology, outline current research evidence found in the literature, and discuss potential differential diagnoses and diagnostic dilemmas through an illustrative case.
10.1177/11795476231181560
Thyroid disease post-COVID-19 infection: Report of a case with new-onset autoimmune thyroid disease.
Asia Pacific allergy
We present hyperthyroidism with autoimmune thyroid disease, which developed a few weeks after the COVID-19 infection in a patient with no prior thyroid disease. Our case was described with clinical presentations, diagnostic tests, and subsequent patient management and compared to other similar reported cases. A 28-year-old female patient with no prior history of thyroid dysfunction developed hyperthyroidism 8 weeks after COVID-19 infection, confirmed by low thyroid stimulating hormone, high free thyroxine 4, and thyroid receptor antibody. She was treated and responded well to methimazole 20 mg in a few weeks. We searched the literature and found three other similar reported cases and compared those. The effects of COVID-19 infection on the immune system and the thyroid gland might explain the pathology of hyperthyroidism post-COVID-19 infection in this patient. This new-onset hyperthyroidism was found in a woman with mild symptoms and responded well to thiamazole and β-blockers.
10.5415/apallergy.0000000000000023
The Incidence of Graves' Hyperthyroidism Before and After COVID-19 Messenger RNA Vaccination.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE:Case reports of postvaccine early-onset Graves' hyperthyroidism (PVGD) after the administration of COVID-19 vaccination have emerged. Our aim was to investigate whether the incidence of Graves' hyperthyroidism (GD) has increased after the introduction of COVID-19 vaccination. METHODS:We compared the incidence of new-onset GD at a single academic center during 2 periods: December 2017 to October 2019 and December 2020 to October 2022, ie, before and after the implementation of COVID-19 vaccinations. We defined PVGD as laboratory-confirmed hyperthyroidism and GD within 4 weeks after the vaccination or clear onset of symptoms of thyrotoxicosis within 4 weeks of vaccination with evidence of hyperthyroidism and GD within 3 months. RESULTS:During the prevaccination period, 803 patients carried diagnoses of GD, and of these, 131 were new. During the postvaccination period, 901 patients carried diagnoses of GD, and of these, 138 were new. There was no statistically significant difference in the incidence of GD (P = .52), age at onset, gender, or race between the 2 groups. Twenty-four of 138 newly diagnosed patients in the post-COVID-19 group met the criteria for PVGD. The median free T4 was higher, but this was not statistically significant (3.9 vs 2.5 ng/dL, P = .05). There were no differences in age, gender, race, antibody titers, or type of vaccination between PVGD and controls. CONCLUSION:There was no increase in new-onset GD after COVID-19 vaccination. Median free T4 was higher in patients with PVGD, but this was not statistically significant.
10.1016/j.eprac.2023.05.005
Immune-related adverse events and disease outcomes after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients receiving immune checkpoint inhibitors.
Cancer immunology, immunotherapy : CII
BACKGROUND:The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. METHODS:Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible. RESULTS:The current analysis included 56 patients with metastatic disease (median age: 66 years; male: 71%), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 486 BAU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 486 BAU/mL) or high-responders (High-R, ≥ 486 BAU/mL). After a median follow-up time of 226 days, 21.4% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but an increase in the cumulative incidence of immuno-related thyroiditis was observed within the High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. CONCLUSIONS:Our findings would strengthen the recommendation not to change anti-PD-1/PD-L1 treatment plans based on current or future immunization schedules, implying that all these patients should be closely monitored.
10.1007/s00262-023-03489-1
New-onset and relapsed Graves' disease following COVID-19 vaccination: a comprehensive review of reported cases.
European journal of medical research
Global Coronavir us disease 2019 (COVID-19) vaccination efforts are being intensified to combat the pandemic. As the frequency of immunization against COVID-19 has increased, some adverse effects related to vaccination have emerged. Within this context, this article reviewed 62 Graves' disease (GD) cases following COVID-19 vaccination, to probe the potential association between the vaccination and the onset of GD. A comprehensive search of the PubMed, Web of Science, and Scopus databases was conducted to collect GD cases following COVID-19 vaccination up to June 7, 2023. Among the 62 GD cases included in this review, there were 33 (53.2%) new-onset GD and 10 (16.1%) relapsed GD patients following mRNA vaccination, 14 (22.6%) new-onset GD and 4 (6.5%) relapsed GD patients following viral vector vaccination, and 1 (1.6%) relapsed GD patients following inactivated vaccination. Median durations to symptoms onset for new-onset and relapsed GD were 12 (range: 1-60) and 21 (range: 5-30) days following mRNA vaccination, while 7 (range: 1-28) and 14 (range: 10-14) days following viral vector vaccination, respectively. While the definitive pathogenesis of GD following COVID-19 vaccination remains unclear, it might be associated with cross-immune responses triggered by molecular mimicry, and an adjuvant-induced autoimmune/inflammatory syndrome. However, due to the limited number of observed GD cases following COVID-19 vaccination and the lack of systematic experimental studies, a causal relationship between COVID-19 vaccination and the onset of GD has not been definitively confirmed. It should be highlighted that most of GD patients following COVID-19 vaccination experienced positive outcomes after treatment. In the broader context of ending the COVID-19 pandemic and reducing mortality rates, the benefits of COVID-19 vaccination significantly outweigh mild risks such as treatable GD. Adherence to the COVID-19 vaccination schedule is therefore imperative in effectively managing the pandemic.
10.1186/s40001-023-01210-7
SARS-COV-2 specific t-cells in patients with thyroid disorders related to COVID-19 are enriched in the thyroid and acquire a tissue-resident memory phenotype.
Clinical immunology (Orlando, Fla.)
BACKGROUND:SARS-CoV-2 infections have been associated with the onset of thyroid disorders like classic subacute thyroiditis (SAT) or atypical SAT upon severe COVID disease (COV-A-SAT). Little is known about thyroid anti-viral immune responses. OBJECTIVES:To define the role of T-cells in COV-A-SAT. METHODS:T-cells from COV-A-SAT patients were analyzed by multi-dimensional flow cytometry, UMAP and DiffusionMap dimensionality reduction and FlowSOM clustering. T-cells from COVID-naïve healthy donors, patients with autoimmune thyroiditis (ATD) and with SAT following COVID vaccination were analyzed as controls. T-cells were analyzed four and eight months post-infection in peripheral blood and in thyroid specimen obtained by ultrasound-guided fine needle aspiration. SARS-COV2-specific T-cells were identified by cytokine production induced by SARS-COV2-derived peptides and with COVID peptide-loaded HLA multimers after HLA haplotyping. RESULTS:COV-A-SAT was associated with HLA-DRB1*13 and HLA-B*57. COV-A-SAT patients contained activated Th1- and cytotoxic CD4+ and CD8+ effector cells four months post-infection, which acquired a quiescent memory phenotype after eight months. Anti-SARS-CoV-2-specific T-cell responses were readily detectable in peripheral blood four months post-infection, but were reduced after eight months. CD4+ and CD8+ tissue-resident memory cells (TRM) were present in the thyroid, and circulating CXCR3+T-cells identified as their putative precursors. SARS-CoV-2-specific T-cells were enriched in the thyroid, and acquired a TRM phenotype eight months post-infection. CONCLUSIONS:The association of COV-A-SAT with specific HLA haplotypes suggests a genetic predisposition and a key role for T-cells. COV-A-SAT is characterized by a prolonged systemic anti-viral effector T-cell response and the late generation of COVID-specific TRM in the thyroid target tissue.
10.1016/j.clim.2023.109684
Subclinical Hypothyroidism among Patients with COVID-19 Infection in a Tertiary Care Centre: A Descriptive Cross-sectional Study.
JNMA; journal of the Nepal Medical Association
Introduction:Hypothyroidism occurs as a consequence of chronic autoimmune inflammation of the thyroid gland, which occurs due to the reduced function in the secretion of thyroid hormones. The coronavirus disease infection has shown many complications in all organic systems, during the acute phase of infection and in the post-COVID-19 period. SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. The aim of this study was to find out the prevalence of subclinical hypothyroidism among patients with COVID-19 infection in a tertiary care centre. Methods:A descriptive cross-sectional study was conducted in the Department of Internal Medicine of a tertiary care centre from 1 September 2022 to 28 February 2023 after obtaining ethical approval from the Research and Institutional Review Committee (Reference number: 15-079/080). Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results:Among 38 patients with COVID-19, subclinical hypothyroidism was seen among 23 (60.53%) (44.99-76.07, 95% Confidence Interval). Conclusions:The prevalence of subclinical hypothyroidism among COVID-19 patients was found to be similar to other studies done in similar settings. Keywords:COVID-19; hypothyroidism; thyroid gland.
10.31729/jnma.8187
Evaluation of Thyroid Function Tests in Patients With COVID-19.
Cureus
Background SARS-CoV-2 infects cells via angiotensin-converting enzyme 2 (ACE2). ACE2 levels are high in the thyroid gland. Although the thyroid gland can be directly infected in COVID-19 patients, the hypothalamic-pituitary-thyroid axis is also affected. Therefore, changes in thyroid function occur in COVID-19 patients. This study aimed to examine the effect of thyroid function tests on the prognosis of COVID-19. Methodology A total of 146 patients who were diagnosed with COVID-19 and treated in the intensive care unit between August and November 2021 and who had no previous history of thyroid disease were included in the study. Demographic information, laboratory tests, and thyroid hormone levels during hospitalization and discharge patterns were evaluated. The patients were divided into two groups: group I included those who were discharged after recovery, and group II included those who did not respond to treatment and died. Results When the fT3 and fT4 levels of the patients were compared, the hormone levels decreased as the clinical severity of the disease increased. The amount of decrease in hormone levels was mostly seen in group II. In the recovered patient group, the amount of hormone decreased was less. The difference between fT3 and ft4 values between the groups was found to be statistically significant (= 0.015 and = 0.004). In addition, the difference between the groups' C-reactive protein (CRP), D-dimer, and ferritin values was statistically significant (= 0.036, = 0.022, and < 0.000, respectively). There was no statistically significant difference between the groups in terms of demographic characteristics (> 0.05). Conclusions Thyroid hormone changes were found to be an important prognostic parameter affecting disease severity and mortality in COVID-19 patients and can be used to predict mortality.
10.7759/cureus.40628
Behçet's patients' response to COVID-19 vaccination.
Clinical immunology (Orlando, Fla.)
Immune hyperstimulation by SARS-CoV2 results in multi-system involvement with consequent organ damage not dissimilar to Behçet's Disease (BD). Management of BD includes immunosuppressive medication, which led to concerns that; firstly, SARS-CoV-2 would stimulate BD activity, thrombin, clotting times, TPO antibodies, and the effectiveness and duration of the COVID-19 vaccines' response in this potentially vulnerable group. The main objectives of this study were: to assess BD patients' immune response to the COVID-19 vaccines based on age, gender, disease activity, BD phenotype, and immunomodulatory medication compared to healthy control participants by measuring anti-spike IgG levels. Further to evaluate the effect of the COVID-19 vaccines on T and B cells, immunoglobulins, thrombophilia, thyroid function and COVID-19 antibody production. Patients on immunosuppressive medication had a reduced immune response to COVID-19 vaccines. -Also, patients over 40 years and with the neurologic BD phenotype had lower responses. mRNA COVID-19 vaccines were more effective and had fewer side effects compared to conventional COVID-19 vaccines.
10.1016/j.clim.2023.109700
COVID-Induced Hyperthyroidism in a 30-Year-Old Female: A Case Study.
Cureus
Thyroiditis should be in the differential for hyperthyroidism when thyroid-stimulating hormone (TSH) is suppressed and T3/T4 levels are elevated. Suspicion of hyperthyroidism is further increased when the patient can exhibit symptoms such as weight loss, anxiety, feeling feverish, tremors, shaking, and sweating. Hyperthyroidism is generally classified as being overt or subclinical. In the following case, the patient had overt hyperthyroidism which is considered more severe than subclinical hyperthyroidism. Coronavirus disease is not typically associated with thyroiditis; however, in this case, the patient's disorder was accidentally found on her blood results which were originally taken due to her coronavirus disease 2019 (COVID-19) diagnosis. In this case study, we present a 30-year-old female patient, with suspicions of COVID-19-induced hyperthyroidism found incidentally on her blood panel. An original diagnosis of thyroiditis was made prior to the visualization of increased release of thyroid hormone. A sonogram was done, and a follow-up blood panel was ordered, confirming the patient's diagnosis of hyperthyroidism post COVID-19 recovery.
10.7759/cureus.40851
COVID-19-induced autoimmune thyroiditis: Exploring molecular mechanisms.
Journal of medical virology
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1β, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.
10.1002/jmv.29001
Patients with Hashimoto's thyroiditis present higher immune response to COVID-19 mRNA vaccine compared to normal individuals.
Hormones (Athens, Greece)
AIM:To evaluate the response (titers of anti-COVID-19 antibodies) to COVID-19 mRNA vaccine of patients with Hashimoto's thyroiditis and normal individuals. PATIENTS AND METHODS:Twenty-four patients with Hashimoto's thyroiditis and 51 normal individuals were studied after the third dose of the vaccine. RESULTS:Patients with Hashimoto's thyroiditis showed significantly higher immune response after the third dose of the COVID-19 mRNA vaccine compared with normal individuals (p = 0.020). After elimination of the four smokers with Hashimoto's thyroiditis, the immune response between the remaining 20 non-smoking patients compared with the response of the 23 non-smoking normal individuals was not different (p = 0.564). There was a significant positive correlation of the anti-COVID-19 antibodies with BMI (p = 0.029) but not with waist circumference in the patients with Hashimoto's thyroiditis (p = 0.054). Similar correlations were not found in normal individuals. Waist circumference could be considered as representative of visceral adipose tissue. In obese normal individuals (BMI ≥ 30), anti-COVID-19 antibodies were not different from those in lean normal individuals (BMI < 25). In obese patients with Hashimoto's thyroiditis, anti-COVID-19 antibodies were significantly higher compared to those in lean patients (p = 0.013). Median anti-COVID-19 antibody titer in obese patients with Hashimoto's thyroiditis was also significantly higher compared to that in obese normal individuals (p = 0.009). CONCLUSIONS:Patients with Hashimoto's thyroiditis show significantly higher immune response after the third dose of the COVID-19 mRNA vaccine compared with normal individuals. Obese patients with Hashimoto's thyroiditis show additionally a significantly higher immune response compared with lean patients.
10.1007/s42000-023-00470-6
Thyroid hormones modifications among COVID-19 patients undergoing pulmonary rehabilitation.
Frontiers in endocrinology
Introduction:Patients with severe COVID-19 often experience long-lasting disabilities that can improve after pulmonary rehabilitation. Moreover patients with severe COVID-19 display thyroid function alterations due to a non-thyroidal illness syndrome (NTIS). The aim of our study was to evaluate thyroid function parameters among patients hospitalized for COVID-19 who were eligible or not to respiratory rehabilitation and their modifications during follow-up. Materials and methods:Post-COVID-19 patients referred to a Respiratory Rehabilitation Unit were evaluated. Outpatients, not candidate for rehabilitation, were enrolled as Control group. Patients who had completed a 4-week-rehabilitation program were enrolled as Rehabilitation Group. All patients were evaluated at T0 (4 weeks after the discharge home in Control Group and after completion of rehabilitation in Rehabilitation Group) and at T1 (3 months after T0). Results:The final study group included 39 patients (20 in the Rehabilitation group and 19 in the Control group). Patients in the Rehabilitation Group had more frequently received invasive or non-invasive ventilation, had a longer length-of-stay in referring hospitals, had a higher number of comorbidities and displayed a worse performance at 6-minute-walking-test (6MWT) and Short-Physical-Performance-Battery-test (SPPB). FT3 values were lower at T0 in the Rehabilitation Group, while TSH and FT4 values were similar in the two groups. While no significant modifications in thyroid-function-parameters were observed in the Control Group, a significant increase in FT3 value was observed in the Rehabilitation Group at T1. Participants of both groups had improved the results of 6MWT at T1, while SPPB values improved only in the Rehabilitation Group. Conclusions:COVID-19 patients after pulmonary rehabilitation experience an increase in FT3 values during follow-up, paralleled with an amelioration of functional capabilities.
10.3389/fendo.2023.1192561
Overt Hypothyroidism Status Post Pfizer-BioNTech Vaccination: A Case Study.
Cureus
Coronavirus disease (COVID-19) is among the most contagious viral illnesses, affecting millions worldwide. Although precautions such as social distancing, hand sanitizing, and the use of masks decreased the transmission of the virus, the situation went uncontrolled until vaccination came to light. Vaccination was vital in limiting the incidence, prevalence, and severity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on the mechanism, several types of vaccines, such as Pfizer-BioNTech, Moderna, AstraZeneca, Johnson & Johnson, and Covaxin, were approved by the US Food and Drug Administration (FDA). A booster dose was implemented as the vaccine's effectiveness decreased with time. Several side effects, such as fever, soreness around the injection site, fatigue, chills, muscle weakness, and headache, have been reported after vaccination with Pfizer-BioNTech, but thyroid dysfunction is relatively rare. Several case reports and even case series describing links between COVID-19 vaccination and various types of thyroid dysfunction have appeared in the literature. However, the exact reasons have yet to be explained. This report presents the case of a healthy 50-year-old woman diagnosed with overt hypothyroidism three weeks after the administration of the Pfizer-BioNTech vaccine.
10.7759/cureus.41180
Inactivated SARS-CoV-2 vaccination does not disturb the clinical course of Graves' disease: An observational cohort study.
Vaccine
SARS-CoV-2 vaccination has been reported to be associated with the induction of thyroid disorders. To investigate the influence of SARS-CoV-2 vaccination on the disease course of patients who were undergoing treatment for Graves' disease (GD), a total of 651 consecutive GD patients who attended follow-up visits in Jiangyuan Hospital were enrolled in this retrospective study, including 443 inactivated SARS-CoV-2 vaccine recipients and 208 unvaccinated participants. The changes in serum levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and TSH receptor antibody (TRAb) were analyzed. Crude and adjusted hazard ratios (HRs) were estimated using Cox regression models to investigate the risks in incident TRAb positivity and hyperthyroidism recurrence following vaccination. The median levels of TRAb and fT3 significantly decreased in both vaccinated and unvaccinated groups during the GD hyperthyroidism treatment. The fT4 levels of both groups were well within normal limits and presented downward trends simultaneously. Although the present study observed an increasing trend of TSH level during follow-up, significant difference was not seen in both vaccinated and unvaccinated groups. Except for newly diagnosed GD patients, vaccinated participants had significantly lower risks of incident TRAb positivity (adjusted HR = 0.22; 95%CI: 0.10-0.48, P < 0.001) after adjusted for sex, age, disease duration and MMI dose at baseline. Besides, vaccination was unlikely to serve as a risk factor for hyperthyroidism recurrence (adjusted HR = 1.20; 95%CI: 0.51-2.83, P = 0.678). Notably, newly diagnosed patients who received vaccination were just as likely to achieve remission of thyrotoxicosis as those not receiving the vaccination at any time. Our results concluded that inactivated SARS-CoV-2 vaccination would not disturb the treatment course among GD hyperthyroidism patients.
10.1016/j.vaccine.2023.07.053
Beyond Acute COVID-19: Investigating the Incidence of Subacute Thyroiditis in Long COVID-19 in Korea.
Endocrinology and metabolism (Seoul, Korea)
BACKGRUOUND:The correlation between acute coronavirus disease 2019 (COVID-19) and subacute thyroiditis (SAT) has not been clearly investigated in "long COVID" patients. We aimed to investigate the incidence of SAT during convalescence and after the acute phase of COVID-19, comparing with that of the general population. METHODS:Data from a total of 422,779 COVID-19 patients and a control group of 2,113,895 individuals were analyzed. The index date was defined as the date 3 months after confirmation of COVID-19. The incidence rate (IR) of SAT and hazard ratios (HRs) were calculated per 100,000 persons. Subgroup analysis included analysis of HRs 90-179 and 180 days post-COVID-19 diagnosis; and additional analysis was conducted according to hospitalization status, sex, and age group. RESULTS:The IR of SAT was 17.28 per 100,000 persons (95% confidence interval [CI], 12.56 to 23.20) in the COVID-19 group and 8.63 (95% CI, 6.37 to 11.45) in the control group. The HR of COVID-19 patients was 1.76 (95% CI, 1.01 to 3.06; P=0.045). The HR of SAT was 1.39 (95% CI, 0.82 to 2.34; P=0.220) up to 6 months after the index date and 2.30 (95% CI, 1.60 to 3.30; P<0.001) beyond 6 months. The HR for SAT among COVID-19 patients was 2.00 (95% CI, 1.41 to 2.83) in hospitalized patients and 1.76 (95% CI, 1.01 to 3.06) in non-hospitalized patients compared to the control group. The IR of SAT was 27.09 (95% CI, 20.04 to 35.82) for females and 6.47 (95% CI, 3.34 to 11.30) for males. In the 19 to 64 age group, the IR of SAT was 18.19 (95% CI, 13.70 to 23.67), while the IR was 9.18 (95% CI, 7.72 to 10.84) in the 65 to 69 age group. CONCLUSION:SAT could be a potential long-term complication of COVID-19. Long-term surveillance for thyroid dysfunction is needed especially in hospitalized, female and young-aged subjects.
10.3803/EnM.2023.1711
IMPACT OF COVID-19 ON THYROID FUNCTION: EVIDENCE FROM IRAN.
Acta endocrinologica (Bucharest, Romania : 2005)
Context:We assessed the association between the severity of COVID-19 and the thyroid function, and the relationship of thyroid hormones with inflammatory markers in COVID-19 patients. Subjects and methods:This observational study contained 95 COVID-19 patients. The covariates of interest included the thyroid-stimulating hormone (TSH) and the total form of thyroid hormones thyroxine and triiodothyronine. Furthermore, the inflammatory markers including C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase (LDH), and lymphocyte were measured. To analyze the data, the t-test, the nonparametric test for comparing the medians, and the Spearman correlation were used. Results:The median (interquartile range) of ages was equal to 53 (41-66) years old, including 54 men (56.8%). As the severity of COVID-19 progressed from moderate to severe, increasing, though non-significant, trends of thyroid dysfunction were observed, the most remarkable for TSH. The only significant association between thyroid hormones and inflammatory markers was a Spearman correlation of -0.28 between TSH and LDH. Moreover, a direct association was found between the severity of COVID-19 and the LDH levels (p-value<0.001). Conclusions:A direct relation between the severity of COVID-19 and the LDH level and a reverse association between the LDH level and the thyroid hormone, TSH was obtained.
10.4183/aeb.2023.68
Graves' disease after COVID mRNA vaccination for the first time diagnosed in adolescence-case report. Cause and effect relationship or simple coincidence?
Journal of pediatric endocrinology & metabolism : JPEM
OBJECTIVES:Over the past 3 years, coronavirus disease 2019 with its worldwide spread has profoundly marked public health, therefore anti-COVID-19 vaccinations have been developed to prevent the dissemination of the disease. To date, 71 cases of Graves' disease (GD) after vaccination against SARS-Cov-2 were described in the adult population. Our goal is to present the first case in the paediatric population. CASE PRESENTATION:We present the first case of a 16-year-old adolescent girl who developed GD 6-7 weeks after the second dose anti-COVID-19 mRNA vaccine. Therapy with methimazole and propranolol was started, achieving normal thyroid function and negativity of thyroid autoantibodies at the time of therapy discontinuation after 8 months. CONCLUSIONS:This case shows that the development of GD after COVID-19 mRNA vaccination can occur also in the adolescent population. Nevertheless, the small number of cases of GD described so far, after many millions of vaccinations, makes it impossible to determine whether this is simple a coincidence or a cause. Further epidemiological data on the incidence of GD in the vaccination period compared to the previous period will be able to clearly define this question.
10.1515/jpem-2023-0181
Increased Risk of Thyroid Eye Disease Following Covid-19 Vaccination.
The Journal of clinical endocrinology and metabolism
CONTEXT:SARS-CoV-2 infection and Covid-19 vaccines have been associated with thyroid disorders. OBJECTIVE:We analyzed the risk of thyroid eye disease (TED) following Covid-19 vaccination. This was a self-controlled case series study at a tertiary referral center for TED. A total of 98 consecutive patients with newly developed (n = 92) or reactivated (n = 6) TED occurring between January 1, 2021, and August 31, 2022, were included. TED was assessed in patients undergoing Covid-19 vaccination. Person-days were defined as exposed if TED occurred 1 to 28 days after vaccination, and unexposed if occurring outside this time window. Conditional Poisson regression models were fitted to calculate incidence rate ratio (IRR) and 95% CI of exposed vs unexposed. Sensitivity analyses were conducted considering different exposed periods, and effect modification by potential TED risk factors. RESULTS:Covid-19 vaccines were administered in 81 people, 25 (31%) of whom developed TED in exposed and 56 (69%) in unexposed periods. The IRR for TED was 3.24 (95% CI 2.01-5.20) and 4.70 (95% CI 2.39-9.23) in patients below 50 years of age. Sex, smoking, and radioiodine treatment did not modify the association between TED and vaccination. TED risk was unrelated to the number of vaccine doses, and progressively decreased over time following vaccination (P trend = .03). CONCLUSION:The risk of TED was significantly increased after Covid-19 vaccination, especially in people below 50 years of age. Possible mechanisms include spike protein interaction with the angiotensin-converting enzyme II receptor, cross-reactivity with thyroid self-proteins, and immune reactions induced by adjuvants. We suggest monitoring of individuals undergoing Covid-19 vaccination, especially if young and at risk for autoimmunity.
10.1210/clinem/dgad501
SARS-CoV-2 spread to endocrine organs is associated with obesity: an autopsy study of COVID-19 cases.
Endocrine
PURPOSE:SARS-CoV-2 infection may be limited to the respiratory tract or may spread to multiple organs. Besides disease severity, factors associated with virus spread within the host are elusive. Here, we tried to identify features associated with SARS-CoV-2 spread to endocrine organs. METHODS:In a retrospective autoptic cohort of 51 subjects who died because of COVID-19, we analyzed the severity and type of lung pathology, patients' features and the detection of virus in thyroid, testis, adrenal gland, pancreas, anterior pituitary, and the white adipose tissue (WAT). RESULTS:The SARS-CoV-2 genome was detected in endocrine organs of 30/51 cases. The anterior pituitary and WAT were most frequently positive for virus. While pathological features of lung were not associated with the presence of virus in endocrine organs, obesity (BMI > 30) was significantly associated to virus detection in pancreas (p = 0.01) and thyroid (p = 0.04). WAT infection was detected more frequently in males (p = 0.03). CONCLUSION:In subject with obesity dying of COVID-19, the virus frequently spreads to endocrine organs. The findings emphasize the need for optimal treatment of patients with obesity at the very onset of COVID-19. Since post-COVID conditions remain a major issue worldwide, a rigorous follow-up of endocrine function-especially of thyroid and pancreas-is advocated in subjects with obesity.
10.1007/s12020-023-03518-0
Clinical and thyroid profile in patients with COVID-19 hospitalized in an intensive care unit.
European review for medical and pharmacological sciences
OBJECTIVE:This study aimed to summarize the epidemiological and clinical features of thyroid function in COVID-19 patients in the intensive care unit (ICU) of Civil Fray Antonio Alcalde Hospital in Mexico. PATIENTS AND METHODS:This is a cross-sectional study that included 63 ICU patients with COVID-19 from August 2021 to December 2021. Thyroid function was evaluated through the TSH, T4, T3, and FT3 measures. Comorbidities such as diabetes mellitus type 2 (T2DM), arterial hypertension (HT), body mass index (BMI), and biochemical biomarkers, including procalcitonin (PCT) and C reactive protein (CRP), were also analyzed. RESULTS:A total of 63 patients with COVID-19 were hospitalized in the ICU; 42 (67%) were male, and 21 (33%) were female, with a mean age of 47 (range of 26-76 years). A total of 49 (78%) patients were non-vaccinated, 5 (8%) had an incomplete vaccination schedule, and 4 (6%) had completed the vaccination schedule. Regarding BMI, 10 (16%) were overweight, and 26 (40%) reported obesity. When assessing thyroid function, 8 (13%) patients were euthyroid, and 55 (87%) showed alterations on the thyroid hormonal axis, mainly a low concentration of TSH (0.56±0.79; p=0.0001) and FT3 (2.34±0.52; p=0.0006). In addition, increased PCT concentrations were associated with a higher risk to decease (1.22 vs. 8.21; p=0.0001) in this group of patients. CONCLUSIONS:Based on our findings, it appears that COVID-19 patients with low TSH and FT3 levels, who have not been vaccinated against SARS-CoV-2, are overweight or obese, and exhibit high levels of PCT are more likely to experience a poor prognosis and even mortality.
10.26355/eurrev_202309_33591
Long-term effects of COVID-19 on the endocrine system - a pilot case-control study.
Frontiers in endocrinology
Background:Coronavirus disease 2019 (COVID-19) has permanently changed the world. Despite having been a pandemic for nearly 3 years, the mid- and long-term complications of this disease, including endocrine disorders, remain unclear. Our study aimed to evaluate the lasting effects of COVID-19 on the endocrine system 6 months after initial infection. Methods:We compared patients who underwent COVID-19 to age- and sex-matched subjects from a population-based study conducted before the pandemic. We evaluated differences in multiple parameters related to metabolism and the endocrine system including fasting glucose, insulin, lipids, body composition, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroglobulin (aTG) and anti-thyroid peroxidase (aTPO) antibodies, prolactin, cortisol, testosterone, and estradiol. Results:We found significantly lower levels of fT3 and fT4, accompanied by higher levels of TSH and aTPO antibodies, in COVID-19 survivors. Moreover, we found that patients who underwent SARS-CoV2 infection had higher levels of prolactin and lower levels of testosterone than controls. Interestingly, differences in testosterone levels were observed only in male subjects. We did not detect significant differences in body composition or metabolic and glycemic parameters between cases and controls, except for significantly higher values of the HOMA2-B index in COVID-19 survivors. Conclusion:Our study indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might have long-term consequences on the endocrine system, including the suppressed function of the thyroid gland, prolactin, and male sex hormone secretion. Moreover, we showed that in a 6-month follow-up, COVID-19 had no consequences on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels.
10.3389/fendo.2023.1192174
Graves' Disease Following COVID-19 Vaccination: A Population-based, Matched Case-control Study.
The Journal of clinical endocrinology and metabolism
OBJECTIVE:Multiple cases and case series reported Graves' disease (GD) following coronavirus disease 2019 (COVID-19) vaccination. We aimed to determine whether COVID-19 vaccination was associated with the incidence of GD. METHODS:We analyzed data from Clalit Health Services, the largest healthcare organization in Israel, which insures 4.7 million patients. A population-based, matched, case-control study was performed. Cases were defined as adult patients diagnosed with GD between December 2020 and November 2022. Each case was matched with controls in a 1:2 ratio. Each control was assigned an index date, which was identical to that of their matched case, defined as the date of GD diagnosis. Time between vaccination date and the diagnosis of GD or index date was assessed. RESULTS:A total of 726 patients with GD were matched with 1452 controls. The study patients and controls have received similar proportions of the COVID-19 vaccine [at least 1 dose: 80% (581/726) vs 77.8% (1129/1452), P = .22, respectively]. In a univariate analysis, at least 1 dose of the COVID-19 vaccine was not associated with the incidence of GD [odds ratio 95% confidence interval: 1.15 (.92-1.43)]. The mean time between first COVID-19 vaccination and the diagnosis of GD for cases or index date for controls was not significantly different [275.69 days (SD 144.37) for cases compared to 275.45 days (SD 145.76) for controls]. CONCLUSION:Our study found no association between COVID-19 vaccination and the incidence of GD.
10.1210/clinem/dgad582
The association of subacute thyroiditis with viral diseases: a comprehensive review of literature
Przeglad epidemiologiczny
Introduction:Subacute thyroiditis (SAT), also known as de Quatrain's thyroiditis or granulomatous thyroiditis, is an inflammatory disease of the thyroid. Most of the time, it manifests in the thirties to fifties and is more common in women. SAT can have either viral or post-viral origin. Some viruses, like influenza, COVID-19, Epstein-Barr virus, cytomegalovirus, hepatitis, coxsackievirus 16, and mumps virus, have been linked to SAT development. The COVID-19 pandemic has affected people's lives all around the world and has changed our attitude toward the treatment of many diseases. It has also made us look deeper into the subject in a way that we would be able to treat this sort of disease with a newer insight. Objective:Regarding the importance of this issue, we decided to summarize our extensive searches from online databases, including PubMed, Google Scholar, Medline, Web of Science, and Scopus until February 2023, which we found effective in elucidating the association of subacute thyroiditis and viral diseases. Method:Different online databases were searched for narrative review articles, systemic review articles, and original articles, which were published until February 2023. Result:According to the included studies, we found that there is a correlation between SAT and several viruses such as Epstein-Barr virus, influenza virus, human immunodeficiency virus, cytomegalovirus, oral and cervical virus, hepatitis, dengue virus, and SARS-COV-2. The effect of each of the viral diseases mentioned in the SAT is given in the text. Conclusions:According to the results mentioned in the text, because SAT may be challenging for early diagnosis, due to the potential of classic symptoms as well as the interference of similar clinical symptoms between thyrotoxicosis and viral reactions, the correlation between SAT and viral diseases should be considered so that we can avoid misdiagnosis and lateness.
10.32394/pe.77.13
Thyroid Autoimmunity and SARS-CoV-2 Infection.
Journal of clinical medicine
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological culprit of COronaVIrus Disease 19 (COVID-19), can enter the cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which has been found in several tissues including in endocrine organs, such as the ovaries, testes, pancreas, and thyroid. Several thyroid disorders have been associated with SARS-CoV-2 infection [subacute thyroiditis (SAT), thyrotoxicosis, and non-thyroidal illness syndrome (NTIS)] and, in part, they are believed to be secondary to the local virus replication within the gland cells. However, as documented for other viruses, SARS-CoV-2 seems to interfere with several aspects of the immune system, inducing the synthesis of autoantibodies and triggering latent or new onset autoimmune disease (AID), including autoimmune thyroid disease (AITD), such as Hashimoto Thyroiditis (HT) and Graves' disease (GD). Several mechanisms have been hypothesized to explain this induction of autoimmunity by SARS-CoV-2 infection: the immune system hyper-stimulation, the molecular mimicry between the self-antigens of the host and the virus, neutrophils extracellular traps, and finally, the virus induced transcriptional changes in the immune genes; nonetheless, more evidence is needed especially from large, long-term cohort studies involving COVID-19 patients, to establish or reject this pathogenetic relationship.
10.3390/jcm12196365
Hashimoto's thyroiditis-related myopathy in a patient with SARS-CoV-2 infection: A case report and systematic literature review.
Medicine
RATIONALE:Hashimoto's thyroiditis (HT) is a common autoimmune disease. However, its presentation and management in the context of COVID-19 are unclear, and COVID-19-triggered HT, along with myopathy and persistent creatine kinase (CK) levels, have not been previously reported. Moreover, no literature review is currently available on HT in the context of COVID-19. This study is a case report and systematic review of the literature. PATIENT CONCERNS:A 33-year-old man was admitted with acute-onset myalgia, anosmia, loss of taste, fever, and upper respiratory tract symptoms. DIAGNOSES:He was diagnosed with coronavirus disease (COVID-19) during hospitalization and had abnormal CK levels. The elevated CK level persisted even after the resolution of COVID-19. After excluding myopathies and cardiac factors, HT was diagnosed. INTERVENTIONS:CK levels did not decrease appreciably until 14 d after levothyroxine administration. OUTCOMES:The patient was discharged from the hospital in good health. In the systematic literature review, 7 case reports on COVID-19-associated HT were observed, although no incidence of associated myopathy or persistent elevation of CK was noted. LESSONS:This case report highlights the potential link between COVID-19 and autoimmune thyroid diseases. In particular, this study underscores the significance of recognizing new-onset autoimmune thyroid disease in COVID-19-positive patients with elevated CK levels that cannot be attributed to other factors. This systematic review offers additional perspectives for diagnosing and managing HT in COVID-19 settings. Overall, the findings of this study could have important clinical implications for the care of COVID-19 patients, as early identification and treatment of autoimmune thyroid disease could help prevent long-term complications. Additional research is essential to elucidate the fundamental correlations between COVID-19 and HT and assess the effectiveness of therapeutic approaches for autoimmune thyroid conditions related to COVID-19.
10.1097/MD.0000000000035720
Subacute thyroiditis following COVID-19 vaccination: Case presentation.
Antiviral therapy
Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19 vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2 direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroid damage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the form of permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated with COVID-19. The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limited documentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19 vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of Pfizer BioNTech's COVID-19 mRNA vaccine. Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccine against SARS-CoV-2 viral infection. The patient denied ever having an autoimmune disease or any other disease. Painful neck palpation and a firm, slightly enlarged thyroid gland with no surrounding lymphadenopathy were identified during the exam. The heart rate was 104 beats per minute. All of the remaining physical findings were normal. Data collected during the disease are integral to the medical record. Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocytic anaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient's thyroid function and morphology had recovered entirely from post-vaccine SAT.: Results from this study emphasise the need for healthcare professionals to promptly report any case of SAT related to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition.
10.1177/13596535231208831
Thyroid Storm Unmasked: A Rare Case of Acute COVID-19-Induced Thyroid Storm.
Cureus
Thyroid storm is a severe form of thyrotoxicosis with a mortality rate of 8%-25% despite modern advancements in both early identification and treatment. It is more common in patients with a history of Graves' disease; however, its incidence remains as low as 0.57-0.76 cases per 100,000 per year. In the setting of newly diagnosed COVID-19 with subsequent development of thyroid storm, the presentation is increasingly rare with only two reported cases in the current literature.
10.7759/cureus.45906
Thyroid Eye Disease as Initial Manifestation of Graves' Disease Following Viral Vector SARS-CoV-2 Vaccine: Report of a Case and Review of the Literature.
Vaccines
COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves' disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD, is rarely observed post-COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post-viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED 10 days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids, and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery.
10.3390/vaccines11101574
Two Cases of Thyroiditis in Adolescents Following COVID-19 Vaccinations.
JCEM case reports
With the onset of the COVID-19 pandemic and the development of widespread vaccination strategies, there have been case reports in the adult literature suggesting an increase in thyroiditis after COVID-19 vaccination. We herein describe 2 children who presented with thyroiditis after COVID-19 vaccination. Two children who received Pfizer-BioNTech COVID-19 messenger RNA vaccines later developed symptoms of thyroid hyperactivity, had positive thyroid-stimulating immunoglobulin (TSI) levels and received treatment directed toward Graves disease. Our case series is the first to demonstrate Graves disease after COVID-19 vaccination in the pediatric population. Given this possibility, it is important for pediatricians to be watchful for symptoms of thyroiditis post vaccination to prevent treatment delays.
10.1210/jcemcr/luad017
SARS-CoV-2 and thyroid diseases.
Journal of translational autoimmunity
SARS-CoV-2 virus responsible for acute respiratory disease affected other organs leading to co-existence symptoms or complications. Thyroid gland was one of them due to expression of angiotensin-converting enzyme 2 (ACE2), the protein facilitating viral binding to the host cells. Moreover, thyroid gland, important for regulation of hormonal network, is extremely sensitive to any changes in homeostasis and metabolism. It was shown, that COVID-19 was associated with induction of thyroid disease or increasing existing functional disturbances or autoimmune process. Thyroid diseases are mainly based on immunological pathomechanism although the relation between immune system and thyroid function is bidirectional e.g. thyroid hormones modulate specific immune responses, including cell-mediated immunity, NK cell activity, the production of antiviral interferon (IFN) and proliferation of T- and B-lymphocytes. The effects of COVID-19 and mRNA vaccine on thyroid function and diseases are discussed.
10.1016/j.jtauto.2023.100214
A case of subacute thyroiditis after influenza vaccination.
Endocrinology, diabetes & metabolism case reports
Summary:A 40-year-old Japanese woman presented to the outpatient clinic with fever and palpitations 2 days after receiving the influenza vaccine (Influenza HA Vaccine 'KMB'®) following the second dose of coronavirus disease 2019 (COVID-19) vaccine (COVID-19 vaccine Moderna intramuscular injection®). At the first visit, the patient presented with a swollen thyroid gland with mild tenderness, and she was diagnosed with subacute thyroiditis (SAT) based on the presence of thyrotoxicosis (free T3: 5.42 pg/mL; free T4: 2.34 ng/dL; and thyroid-stimulating hormone (TSH): <0.01 μIU/mL), a high C-reactive protein level (5.77 mg/dL), a negative TSH receptor antibody, and characteristic ultrasound findings. The patient's human leukocyte antigen types were A2, A11, B35, B51, DR4, and DR1403. Prednisolone (15 mg/day) was given as an initial dose, after which the fever subsided, and the dose was tapered and discontinued after 6 weeks. The patient was thought to have developed SAT due to influenza vaccination. SAT after influenza vaccination may be overlooked. For patients with SAT, it is necessary to obtain information regarding their vaccination history. Learning points:After influenza vaccination, subacute thyroiditis (SAT) may develop. If persistent fever, anterior neck pain, swelling, tenderness of the thyroid gland, and symptoms of thyrotoxicosis are observed immediately after vaccination for several viruses, including influenza, an examination to rule out the onset of SAT is recommended. Human leukocyte antigen type A2 (HLA-A2) and HLA-B35 may be linked to the development of SAT following influenza vaccination. The two doses of the coronavirus disease 2019 (COVID-19) vaccine given before the influenza vaccine may affect the onset of SAT.
10.1530/EDM-22-0364
Effects of COVID-19 vaccination on cervical lymph nodes in patients with thyroid cancer.
Translational cancer research
Background:Cervical lymph node enlargement caused by coronavirus disease 2019 (COVID-19) vaccination has been reported, but little is known on whether the vaccination would influence preoperative cervical lymph node evaluation and its risk of lymph node metastasis in thyroid cancer. Methods:We retrospectively analyzed data of patients who underwent thyroid cancer surgery in Tangdu Hospital, China, from 1 March 2021 to 30 June 2021. A total of 182 patients were included in the cohort study. All patients with suspected malignant tumors underwent ultrasound (US)-guided fine needle aspiration (FNA) of thyroid lesions before surgery to confirm the diagnosis. Cervical lymph nodes were evaluated by preoperative physical examination and imaging. Wilcoxon rank-sum test and Fisher's exact test were used to evaluate the effect of vaccination on cervical lymph nodes in patients with thyroid cancer. Statistical significance was defined at P<0.05. Results:The patients were divided into two groups according to whether they had been vaccinated or not. Our results showed that there were no significant differences between the two groups in the brand of the vaccine, operation method, and the extent of surgery. Moreover, there was no significant difference in the evaluation of US characteristics of cervical lymph nodes between the two groups regardless of having the vaccination or not. Interestingly, US evaluation found that the experimental group's proportion of cervical lymph node enlargement increased significantly within 14 days after vaccination, which was statistically significant. Conclusions:This study found that vaccination against COVID-19 did not increase the number of cervical lymph node metastases, but inaccurate assessment of cervical lymph nodes in thyroid cancer patients within 14 days of vaccination (due to temporary lymph node enlargement) may lead to more extensive surgery.
10.21037/tcr-23-374
Patterns and outcomes of late onset thyroid disturbances after COVID-19 vaccination: A report of 75 cases.
Tropical medicine & international health : TM & IH
Isolated cases of subacute thyroiditis exist in the early period of COVID-19 vaccination, largely after mRNA vaccines. Here we report late onset thyroid disturbances and persistent health issues in patients of thyroid disorders after COVID-19 vaccination. Seventy-five patients with post COVID-19 vaccination thyroid disturbances were identified. Among these, 41 had flare of underlying thyroid illness, majority occurring at a median time lag of 28.4 weeks since 2nd dose. Thirty-one cases of new onset hypothyroidism and three of new onset hyperthyroidism were reported, with a median time lag respectively of 17.2 and 22.6 weeks since 2nd dose. Most cases occurred after ChAdOx1-nCoV-19, which was the commonest vaccine employed in mass roll out in India. Significant improvement was observed in majority, after a median follow up of 22-26 weeks. New onset health issues persisting for ≥4 weeks were reported in 37.3% and were common in individuals with history of COVID-19 before vaccine. New onset metabolic, musculoskeletal, and reproductive disorders were the common health complaints. Active monitoring is warranted for late onset adverse events after COVID-19 vaccines of all types. Larger studies with involvement of unvaccinated individuals are required to understand the incidence and causality of late onset thyroid disturbances after COVID-19 vaccines.
10.1111/tmi.13947
Endocrine diseases associated with COVID-19 vaccination: case report.
Revista peruana de medicina experimental y salud publica
SARS-CoV-2 vaccination is not free of adverse effects. We present two cases of endocrine involvement associated with COVID-19 vaccination. A 46-year-old woman who, after receiving the first COVID-19 vaccination dose, presented persistent fever and signs of thyrotoxicosis after being diagnosed with subacute thyroiditis associated with COVID-19 vaccination; the condition remitted with the use of corticoids. A 71-year-old male, who after COVID-19 vaccination, presented hyperinsulinemic hypoglycemia, testing positive for anti-insulin antibodies; he was diagnosed with autoimmune hypoglycemia associated with COVID-19 vaccination and received treatment with prednisone, controlling the episodes of hypoglycemia. In conclusion, endocrine diseases associated with COVID-19 vaccination are extremely rare and their timely detection allows adequate treatment.
10.17843/rpmesp.2023.403.12572
A prospective study on endocrine function in patients with long-COVID symptoms.
Hormones (Athens, Greece)
OBJECTIVE:To investigate hormonal status in patients with long-COVID and explore the interrelationship between hormone levels and long-COVID symptoms. DESIGN:Prospective observational study. PARTICIPANTS:Patients who visited our long-COVID outpatients' clinic due to long-COVID symptoms from February 2021 to December 2022. MEASUREMENTS:Total triiodothyronine, free thyroxine, thyrotropin, thyroglobulin, anti-thyroperoxidase, and antithyroglobulin autoantibodies were measured for thyroid assessment. Other hormones measured were growth hormone, insulin-like growth factor 1 (IGF-1), adrenocorticotropic hormone (ACTH), serum cortisol, dehydroepiandrosterone sulfate (DHEA-S), total testosterone, plasma insulin, and C-peptide. Blood glucose and glycosylated hemoglobin were also measured. To assess adrenal reserve, an ACTH stimulation test was performed. The fatigue assessment scale (FAS) was used to evaluate fatigue severity. RESULTS:Eighty-four adult patients were included. Overall, 40.5% of the patients had at least one endocrine disorder. These included prediabetes (21.4%), low DHEA-S (21.4%), subclinical hypothyroidism (3.6%), non-specific thyroid function abnormality (7.1%), thyroid autoimmunity (7.1%), low testosterone in males (6.6%), and low IGF-1 (3.6%). All patients had normal adrenal reserve. Long-COVID-19 symptoms were present in all patients and the most commonly reported symptom was fatigue (89.3%). The FAS score was higher than normal (≥ 22) in 42.8% of patients. There were no associations between patients' symptoms and hormone levels. Diabetic patients reported confusion (p = 0.020) and hair loss (p = 0.040) more often than non-diabetics. CONCLUSIONS:The evaluation of endocrine function 3 months after a positive SARS-CoV2 test revealed only subclinical syndromes. The vast majority of patients reported mainly fatigue, among other symptoms, which were unrelated, however, to endocrine function.
10.1007/s42000-023-00511-0
SARS-CoV-2 Affects Thyroid and Adrenal Glands: An F-FDG PET/CT Study.
Biomedicines
BACKGROUND:Since most endocrine glands express ACE-2 receptors and can be infected by SARS-CoV-2 virus, this retrospective multicentre observational study aims to assess the metabolic activity of thyroid and adrenal glands of COVID-19 patients by F-FDG PET/CT. METHODS:We retrospectively evaluated the F-FDG PET/CT scans of COVID-19 patients admitted by three different centres, either in a low-intensity department or in the intensive care unit (ICU). A visual assessment and a semi-quantitative evaluation of areas of interest in thyroid and adrenal glands were performed by recording SUVmax and SUVmean. The F-FDG PET/CT uptake in COVID-19 patients was compared with those observed in normal age-matched controls. RESULTS:Between March 2020 and March 2022, 33 patients from three different centres (twenty-eight patients in a low-intensity department and five patients in ICU), were studied by F-FDG PET/CT during active illness. Seven of them were also studied after clinical remission (3-6 months after disease onset). Thirty-six normal subjects were used as age-matched controls. In the thyroid gland, no statistically significant differences were observed between control subjects and COVID-19 patients at diagnosis. However, at the follow-up PET/CT study, we found a statistically higher SUVmax and SUVmean ( = 0.009 and = 0.004, respectively) in the thyroid of COVID-19 patients. In adrenal glands, we observed lower SUVmax and SUVmean in COVID-19 patients at baseline compared to control subjects ( < 0.0001) and this finding did not normalize after clinical recovery ( = 0.0018 for SUVmax and = 0.002 for SUV mean). CONCLUSIONS:In our series, we observed persistent low F-FDG uptake in adrenal glands of patients at diagnosis of COVID-19 and after recovery, suggesting a chronic hypofunction. By contrast, thyroid uptake was comparable to normal subjects at disease onset, but after recovery, a subgroup of patients showed an increased metabolism, thus possibly suggesting the onset of an inflammatory thyroiditis. Our results should alert clinicians to investigate the pituitary-adrenal axis and thyroid functionality at the time of infection and to monitor them after recovery.
10.3390/biomedicines11112899
Clinical Aspects in Subacute Thyroiditis: A Real-Life Study on 226 Cases in Greece Amid the COVID-19 Pandemic.
Journal of clinical medicine
PURPOSE:This study aimed to evaluate various therapeutic approaches, identify potential predictive factors for the recurrence and development of hypothyroidism, and examine specific clinical and laboratory characteristics of patients with subacute thyroiditis (SAT) due to SARS-CoV-2 infection. METHODS:We retrospectively analyzed the medical records of 226 patients with confirmed SAT diagnosed from January 2020 to November 2022. RESULTS:The mean age was 48.01 ± 0.75 years, and the F/M ratio was 2.3/1. At the end of the follow-up period, 69 patients (32.1%) had developed hypothyroidism. Treatment duration was significantly shorter with nonsteroidal anti-inflammatory drugs (NSAIDs) (17.40 ± 2.56 days), while time-to-symptom relief was shorter with glucocorticoids (CGs). Recurrence was observed only in those treated with corticosteroid preparations (14.1%). C-reactive protein levels at treatment discontinuation were higher in patients who experienced SAT recurrence, while the coexistence of Hashimoto's thyroiditis was a significant predictive factor for the development of hypothyroidism. The TSH value at the time of treatment withdrawal >4.12 μIU/mL showed optimal sensitivity and specificity for the prediction of permanent hypothyroidism. Regarding COVID-19, 34 patients (15%) experienced related SAT, with similar clinical manifestations of the disease but a higher BMI and shorter time-to-symptom relief. CONCLUSION:In conclusion, GCs administration alleviated acute symptoms earlier during the onset of SAT, whereas NSAIDs had a shorter treatment duration, and both regimens could not prevent the development of delayed hypothyroidism. The clinical characteristics of SAT due to COVID-19 infections were similar to those of typical SAT disease.
10.3390/jcm12227171
Impact of COVID-19 on thyroid gland functions with reference to Graves' disease: A systematic review.
Journal of family medicine and primary care
Coronavirus disease 2019 (COVID-19) is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both immediate and long-term adverse effects arise out of this disease's aftermath. It involves various organs, which include endocrine glands, nervous system, musculoskeletal system, and other organs. The long-term outcomes of the SARS-CoV-2 infection are influenced by preexisting comorbidities. Genetic, environmental, and immunological factors contribute to the development of various autoimmune diseases, which include Graves' disease (GD). The growing mystery surrounding this virus is exacerbated by auto-inflammatory diseases, such as pediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), which raises concerns about the nature of the virus' connection to the autoimmune and auto-inflammatory sequelae. There is a need to understand the underlying mechanisms of developing GD in post-COVID-19 patients. There are limited data regarding the pathogenesis involved in post-COVID-19 GD. Our goal was to understand the various mechanisms involved in post-COVID-19 GD among patients with confirmed COVID-19 infection. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for 2020, a literature search of medical databases (PubMed, Cochrane Central Register of Controlled Trials, and Scopus) from February 2021 to February 2022 was performed by five authors. The keywords used were "Post COVID-19," "Grave's disease," "Cytokine storm," "Autoimmunity," and "Molecular mimicry." This review revealed three underlying mechanisms that resulted in post-COVID GD, which included cytokine storm, molecular mimicry, ACE2 receptor concentration, and cell-mediated immunity. The full spectrum of the effects of COVID-19 needs to be researched.
10.4103/jfmpc.jfmpc_2246_22
New-Onset Graves' Disease With Thyroid Storm After COVID-19 Infection.
Cureus
COVID-19 has been a known cause of triggering autoimmune conditions. Previous literature demonstrates an increase in the incidence of Graves' disease during the COVID-19 pandemic. The virus is thought to affect genetics, leading to a cascade of events that cause hyperthyroidism. In our case, an 81-year-old male presented with symptoms of palpitations, tremors, dizziness, diarrhea, and fatigue. He was found to be in atrial fibrillation with rapid ventricular response, and his workup was consistent with hyperthyroidism. Based on his Burch-Wartofsky score, the diagnosis of thyroid storm was made. There are a limited number of case reports with new-onset Graves' disease after COVID-19 infection. Interestingly, our patient was also in a thyroid storm. He was treated with hydrocortisone cholestyramine, potassium, and propylthiouracil. After treatment, his symptoms resolved, and his thyroid studies improved. We chose to present this case because it demonstrates one of the many autoimmune effects that COVID-19 has been linked to.
10.7759/cureus.47995
Autoimmune Thyroid Diseases.
Seminars in nuclear medicine
Autoimmune thyroid diseases (AITDs) include a wide spectrum of thyroid diseases affecting more commonly women than men. The most frequent forms are Graves' Disease (GD) and Hashimoto's thyroiditis / Autoimmune Thyroiditis (AIT), but there are also other immunogenic destructive forms of thyroiditis, that is, silent and postpartum thyroiditis. In the last decade, AITDs and other inflammatory thyroid diseases related to anti-tumor molecular drugs are more frequently seen due to the widespread use of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs). Autoimmune thyroiditis related to SARS-CoV-2 infection has been a novel entity in recent years. Graves' Disease and AIT may shift from hyperthyroidism to hypothyroidism, which may complicate the differential diagnosis and further treatment strategy. Moreover, all AITDs may manifest with thyrotoxicosis (a clinical condition marked with high serum levels of thyroid hormones) which has to be distinguished from hyperthyroidism (increased thyroid hormone production and secretion as a result of hyperfunctioning thyroid gland) due to different therapeutic approaches. Nuclear medicine techniques, such as radioiodine uptake (RAIU) and thyroid scintigraphy, using Tc- pertechnetate (Na[Tc]TcO) or 123-Iodine (Na[I]I), have a crucial role in the differential diagnosis. Measurement of thyroid antibodies, e.g. thyroid peroxidase antibodies (TPO) and thyrotropin receptor antibodies (TRAb), as well as thyroid ultrasound, are complementary methods in the evaluation of thyroid disorders.
10.1053/j.semnuclmed.2023.11.002
Thyroid Inflammation and Immunity During the COVID-19 Pandemic: A Comprehensive Review and Case Study.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the development of various vaccines. Reports have emerged suggesting a possible association between SARS-CoV-2 vaccination and the onset of thyroid diseases. This review explores the clinical aspects of thyroid disorders following SARS-CoV-2 vaccination, including a case report of a patient with concomitant subacute thyroiditis (SAT) and Graves' disease (GD) with blocking thyrotropin receptor autoantibodies (TSH-R-Ab) following SARS-CoV-2 vaccination. SAT, characterized by transient inflammation of the thyroid gland, has been reported after SARS-CoV-2 vaccination. GD, an autoimmune hyperthyroidism, has also been observed post-vaccination, often with stimulating TSH-R-Ab. Graves' orbitopathy (GO) has been associated with SARS-CoV-2 vaccination in patients with a history of immune thyroid disease. The unique case underscores a very rare thyroid condition of functional hypothyroidism in possible relation to SARS-CoV-2 vaccination and the usefulness of functional analysis of TSH-R-Ab that can provide valuable insights into disease pathogenesis and help to guide treatment. This review highlights the need for continued monitoring and awareness of potential thyroid-related complications following SARS-CoV-2 vaccination.
10.1055/a-2222-6300
COVISHIELD vaccine-induced thyroiditis: a case report.
Journal of medical case reports
BACKGROUND:The rapid development of coronavirus disease 2019 vaccines during the pandemic has left their long-term effects largely unknown. Instances of autoimmune and subacute thyroiditis showing features of autoimmune/inflammatory syndrome induced by adjuvants have been reported post-vaccination. This case report aims to highlight the autoimmune/inflammatory syndrome induced by adjuvants syndrome after coronavirus disease 2019 vaccination, drawing attention to a possible connection with thyroid dysfunction and urging for further thorough research. CASE PRESENTATION:We present a case of thyroiditis induced by the COVISHIELD vaccine in a 37-year-old Indian woman. An apparently normal and healthy adult woman developed neck pain and easy fatigability 2 weeks after the second dose of COVISHIELD, which gradually increased and was associated with irritability, decreased sleep, excessive sweating, tremor, palpitation, and weight loss. She presented to the outpatient department after 1 week of symptoms and was evaluated with laboratory tests and imaging. She was diagnosed with thyroiditis due to the coronavirus disease 2019 vaccine and was treated with propranolol. CONCLUSION:This case report adds to the growing evidence of coronavirus disease 2019 vaccine-related thyroid issues. The development of thyroiditis is rare and underreported post-coronavirus disease 2019 vaccination; hence, research to evaluate the association of coronavirus disease 2019 vaccines with thyroid dysfunction needs to be done in the future.
10.1186/s13256-023-04279-0
Effects of SARS-CoV-2 infection on hypothyroidism and subclinical hypothyroidism: a meta-analysis.
Frontiers in endocrinology
Background:In recent years, the outbreak of COVID-19 caused by SARS-CoV-2 has been witnessed globally. However, the impact of SARS-CoV-2 infection on thyroid dysfunction and subclinical thyroid dysfunction remains unclear. Therefore, this meta-analysis aimed to assess the effects of SARS-CoV-2 infection on thyroid dysfunction and its relationship with the severity of COVID-19. Methods:We systematically searched databases including PubMed, Willey Library, Embase, Web of Science, CNKI, Wanfang, and VIP. We focused on randomized controlled trials, case-control studies, and cohort studies published between December 2019 and August 2023, examining the association between SARS-CoV-2 infection and hypothyroidism, with a specific emphasis on the severity of the infection. The quality of the research was assessed using the Newcastle-Ottawa Scale (NOS), while statistical analysis was conducted using the meta and metafor packages in R 4.2.1 software. Results:For the meta-analysis, a total of eight articles were identified based on strict inclusion and exclusion criteria. For the association between SARS-CoV-2 infection and hypothyroidism, three studies (266 samples) comparing TSH levels of COVID-19 and control groups showed no difference in TSH levels [SMD=-0.04,95%CI(-1.22,1.15),]. Additionally, two studies examining TT3 (a sample of 176 cases) and two studies examining TT4 (a sample of 176 cases) also showed no difference in TT3 and TT4 between the COVID-19 group and the control group, respectively. However, when evaluating the severity of COVID-19, six studies (565 samples) showed that TSH in the severe group was significantly lower than in the mild group [SMD = -0.55, 95% CI (-0.96, -0.14)], while FT3 was also lower in the severe group [SMD = -0.96, 95% CI (-1.24, -0.67)]. No noticeable differences were observed between the severe and mild groups in their TT3, FT4, and TT4 levels. Conclusion:SARS-CoV-2 infection may have detrimental effects on thyroid function in individuals with severe symptoms. More research is needed to confirm and explore this relationship. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023486042.
10.3389/fendo.2023.1291774
Exploring the Potential Association between COVID-19 and Thyroid Cancer: A Mendelian Randomization Study.
ACS omega
In order to address the ongoing debate surrounding the potential link between COVID-19 and thyroid cancer, our study was specifically designed to investigate the association between these two factors. We acquired summary data from a genome-wide association study (GWAS) concerning COVID-19 susceptibility and severity of COVID-19 in the European population, with a focus on their relationship with thyroid cancer. We applied three distinct methodologies to evaluate the causality between COVID-19 and thyroid cancer, employing Mendelian randomization (MR)-Egger, weighted median (WM), and inverse variance-weighted (IVW) approaches. Furthermore, we utilized a variety of techniques to assess pleiotropy and heterogeneity, including the MR-Egger intercept, MR-pleiotropy residual sum and outlier method (PRESSO), and Cochran's test. The MR analysis revealed associations between the susceptibility of COVID-19 and thyroid cancer (IVW odds ratio [OR]: 2.826, 95% confidence interval [CI]: [0.842, 9.483], = 0.093) as well as between the risk of COVID-19 hospitalization and thyroid cancer (IVW OR: 1.630, 95% CI: [1.050, 2.529], = 0.029). However, the relationship between COVID-19 and the occurrence of severe thyroid cancer cases was less evident (IVW OR: 1.061, 95% CI: [0.575, 1.956], = 0.850). Our sensitivity analyses did not reveal any signs of horizontal pleiotropy or heterogeneity. Our MR study provided compelling evidence supporting a causal connection between the risk of COVID-19 hospitalization and thyroid cancer. Nevertheless, the MR results derived from genetic data do not support a causal link between susceptibility to COVID-19 and the risk of thyroid cancer or between very severe cases of COVID-19 and the risk of thyroid cancer. These findings have significant implications for further investigations into the impact of COVID-19 on health and the etiology of thyroid cancer.
10.1021/acsomega.3c07287
The prevalence of thyroid disorders in COVID-19 patients: a systematic review and meta-analysis.
BMC endocrine disorders
OBJECTIVES:To conduct a systematic review and meta-analysis to evaluate the prevalence of thyroid disorders in COVID-19 patients. DATA SOURCES:Scopus, PubMed, ISI Web of Science, and Google Scholar databases were used in this review. We also consider the results of grey literature. STUDY SELECTIONS:Cohort, cross-sectional, and case-control studies were included. DATA EXTRACTION AND SYNTHESIS:The required data were extracted by the first author of the article and reviewed by the second author. The Pooled prevalence of outcomes of interest was applied using the meta-prop method with a pooled estimate after Freeman-Tukey Double Arcsine Transformation to stabilize the variances. OUTCOMES AND MEASURED:The different thyroid disorders were the main outcomes of this study. The diseases include non-thyroidal illness syndrome, thyrotoxicosis, hypothyroidism, isolated elevated free T4, and isolated low free T4. RESULTS:Eight articles were included in our meta-analysis(Total participants: 1654). The pooled prevalence of events hypothyroidism, isolated elevated FT4, isolated low FT4, NTIS, and thyrotoxicosis were estimated (Pooled P = 3%, 95% CI:2-5%, I2: 78%), (Pooled P = 2%, 95% CI: 0-4%, I2: 66%), (Pooled P = 1%, 95% CI: 0-1%, I2: 0%), (Pooled P = 26%, 95% CI: 10-42%, I2: 98%), and (Pooled P = 10%, 95% CI: 4-16%, I2: 89%), respectively. CONCLUSION:Thyroid dysfunction is common in COVID-19 patients, with a high prevalence of non-thyroidal illness syndrome (NTIS) and thyrotoxicosis. Our meta-analysis found a 26% prevalence of NTIS and a 10% prevalence of thyrotoxicosis. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42022312601.
10.1186/s12902-023-01534-9
Graves' Disease Exacerbation with Impending Thyroid Storm After SARS-CoV-2 Infection: A Case Report.
The American journal of case reports
BACKGROUND Since the COVID-19 pandemic, several cases of COVID-19 have been linked to the development of autoimmune disorders, including of the thyroid. Graves' disease (GD) is a rare complication that can occur following SARS-CoV-2 infection. Reports have linked COVID-19 to new onset and exacerbation of GD. We present a case of a 42-year-old woman with a history of GD presenting with impending thyroid storm 3 weeks following a diagnosis of COVID-19. CASE REPORT A 42-year-old woman with a history of GD presented to the Emergency Department (ED) for an acute exacerbation of hyperthyroidism 3 weeks after SARS-CoV-2 infection was diagnosed on a home test. Symptoms included daily headaches, increased bilateral eye pressure, fatigue, muscle weakness, episodes of confusion and agitation, persistent heart palpitations, and goiter. Elevated free T4 of 5.57, free T3 of 15.68, total T3 of 4.43, and near-absent thyroid stimulating hormone were noted. The Burch-Wartofsky scale was 40, which was concerning for an impending thyroid storm; however, at the time of admission, she was not in a thyroid storm. Treatment included propylthiouracil, potassium iodide oral solution, and propranolol, with symptom improvement. Due to prior history of intolerance to antithyroid medications and recent exacerbation, a thyroidectomy was performed once she was in a euthyroid state. CONCLUSIONS Our case demonstrates the importance of recognizing COVID-19 as an etiology or a trigger for new onset or exacerbation of GD. Our case highlights that being vigilant to recognize the association between COVID-19 and thyroid abnormalities for early diagnosis and treatment is imperative.
10.12659/AJCR.941311
Autoimmune disorders reported following COVID-19 vaccination: A disproportionality analysis using the WHO database.
European journal of clinical pharmacology
PURPOSE:Owing to adverse event following immunization (AEFI) related to autoimmune disorders and coronavirus disease 2019 (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AEFIs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AEFIs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase. METHODS:We assessed the occurrence of 16 AEFIs following COVID-19 vaccination through the Standardized MedDRA Queries group "Immune-mediated/Autoimmune Disorders" from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs). RESULTS:We identified 25,219 events associated with COVID-19 vaccines in VigiBase. Although rare, we detected four potential safety signals related to autoimmune disorders following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53-2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60-1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30-1.55), and thyroiditis (ROR 1.40; 95% CI 1.30-1.50), with positive IC values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs. CONCLUSION:In addressing the imperative to comprehend AEFI related to autoimmune disorders following COVID-19 vaccination, our study identified four potential safety signals. Thus, our research underscores the importance of proactive safety monitoring for the identification of the four AEFIs following COVID-19 vaccination, considering the associated advantages.
10.1007/s00228-023-03618-w
Thyroid dysfunction in COVID-19.
Nature reviews. Endocrinology
The COVID-19 pandemic has affected over 772 million people globally. While lung damage is the major contributor to the morbidity and mortality of this disease, the involvement of multiple organs, including the endocrine glands, has been reported. This Review aims to provide an updated summary of evidence regarding COVID-19 and thyroid dysfunction, incorporating highlights of recent advances in the field, particularly in relation to long COVID and COVID-19 vaccination. Since subacute thyroiditis following COVID-19 was first reported in May 2020, thyroid dysfunction associated with COVID-19 has been increasingly recognized, secondary to direct and indirect effects on the hypothalamic-pituitary-thyroid axis. Here, we summarize the epidemiological evidence, pattern and clinical course of thyroid dysfunction following COVID-19 and examine radiological, molecular and histological evidence of thyroid involvement in SARS-CoV-2 infection. Beyond acute SARS-CoV-2 infection, it is also timely to examine the course and implication of thyroid dysfunction in the context of long COVID owing to the large population of survivors of COVID-19 worldwide. This Review also analyses the latest evidence on the relationship between the therapeutics and vaccination for COVID-19 and thyroid dysfunction. To conclude, evidence-based practice recommendations for thyroid function testing during and following COVID-19 and concerning COVID-19 vaccination are proposed.
10.1038/s41574-023-00946-w
SUBACUTE THYROIDITIS FOLLOWING SARS-COV-2 VACCINATION: AN AUTOIMMUNE/INFLAMMATORY SYNDROME INDUCED BY ADJUVANTS (ASIA SYNDROME).
Acta endocrinologica (Bucharest, Romania : 2005)
Context:Subacute thyroiditis, a manifestation of Autoimmune/inflammatory syndrome induced by adjuvants that may develop after vaccination. Objective:The aim of this study is to determine the importance of vaccination against COVID-19 in the etiology of subacute thyroiditis. Design:This case reports/series is an observational, descriptive research design. Subjects and Methods:Five of the thirty patients who applied to our clinic with subacute thyroiditis in the last 6 months had a history of inactivated and mRNA vaccines in the last four weeks, after exclusion of infection and comorbidities. We present three cases of mRNA-based vaccination and two cases of inactive SARS-CoV-2 vaccination that met ASIA criteria. Results:Our findings suggest that subacute thyroiditis may be a complication of vaccination against COVID-19. Conclusion:Vaccine administration may led to autoimmune manifestation induction as well as autoantibody production. Adjuvant-induced autoimmune/inflammatory syndrome, an abnormal autoimmune response as a result of exposure to an adjuvant such as vaccine, appears likely in our cases.
10.4183/aeb.2023.390
Subacute Thyroiditis in Active COVID-19 Infection: A Report of Two Cases With a Systematic Review of the Literature.
Cureus
Subacute thyroiditis (SAT) is a self-limiting inflammatory condition of the thyroid gland with distinct symptoms and a predictable outcome. During the current COVID-19 pandemic, there have been multiple isolated reports of SAT either during the active viral illness or following recovery. Here, we report two such cases of COVID-19 infection presenting with SAT. A 65-year-old male presented with a two-week history of anterior neck pain, odynophagia, high-grade fever (38.9°C), sweating, palpitations, and tremulousness. At physical examination, the patient presented with a slightly increased heart rate and a tender and enlarged thyroid on palpation. Laboratory examination showed high C-reactive protein levels, with elevated erythrocyte sedimentation rate, and thyroid function tests were suggestive of thyrotoxicosis. Ultrasonography showed a heterogeneous thyroid gland with ill-defined hypoechoic areas, and thyroid scintigraphy showed reduced uptake, confirming the diagnosis of SAT. In another case, a 52-year-old male presented with fever, cough, and myalgias, and was diagnosed with mild COVID-19 pneumonia, and managed conservatively. After two weeks, the patient had a recurrence of high-grade fever, odynophagia, palpitations, and tremors. Examination revealed tachycardia, hyperhidrosis, and a tender and enlarged thyroid on palpation. Thyroid function tests revealed low thyroid-stimulating hormone, with normal total T4 and total T3. Ultrasonography examination showed a heterogeneous thyroid gland with bilateral ill-defined hypoechoic areas. In our systematic review, including 103 SAT cases, it has been suggested that SAT should be recognized as an uncommon extra-pulmonary clinical manifestation of COVID-19 infection and clinicians need to be aware of the association. Pending larger multicentric studies, management of the condition has to be on a case-by-case basis.
10.7759/cureus.52611
Development of autoimmune thyroid disease after COVID-19 infection: case report.
Frontiers in medicine
Background:SARS-CoV-2 could trigger multiple immune responses, leading to several autoimmune diseases, including thyroid diseases. Many cases of thyroid diseases caused by COVID-19 infection have been reported. Here, we describe the disease development of patients with autoimmune thyroid disease after COVID-19 infection. Methods:The clinical characteristics, diagnosis and treatment of five different patients with autoimmune thyroid disease after COVID-19 infection were reported. Results:Female patients with primary autoimmune thyroid disease which have been stable for many years were reported. One month after COVID-19 infection, the disease has undergone different evolution. Case 1, a patient with history of long-term stable Hashimoto's thyroiditis, suddenly suffered from Graves disease after COVID-19 infection. Case 2, a patient with history of long-term stable Hashimoto's thyroiditis with thyroid nodules, suddenly suffered from Graves disease after infection. Case 3, a patient with history of long-term stable Graves disease, suddenly suffered from worsening after infection. The above three cases showed thyroid-stimulating antibodies were enhanced. Case 4, a patient with history of previous hypothyroidism had an increase in thyroid-related antibody (TPOAb and TRAb) activity after infection, followed by a marked worsening of hypothyroidism. Case 5, a patient with no history of thyroid disease suddenly developed controllable "thyrotoxicosis" after infection, suggesting the diagnosis of painless thyroiditis. Conclusion:The five case reports show a different development of the primary autoimmune thyroid disease after COVID-19 infection. The change in the trend of thyroid disease is closely related to the immune response induced by SARS-CoV-2 infection.
10.3389/fmed.2024.1303855
The Influence of Autoimmune Thyroid Diseases on Viral Pneumonia Development, Including COVID-19: A Two-Sample Mendelian Randomization Study.
Pathogens (Basel, Switzerland)
The association between thyroid function and viral pneumonia has undergone extensive examination, yet the presence of a causal link remains uncertain. The objective of this paper was to employ Two-Sample Mendelian Randomization (MR) analysis to investigate the connections between three thyroid diseases and thyroid hormone indicators with viral pneumonia and COVID-19. We obtained summary statistics datasets from seven genome-wide association studies (GWASs). The primary method used for estimating relationships was inverse-variance weighting (IVW). In addition, we employed weighted median, weighted mode, MR-Egger, and MR-PRESSO as supplementary analytical tools. Sensitivity analyses encompassed Cochran's Q test, MR-Egger intercept test, and MR-PRESSO. Our study revealed significant causal relationships between having a genetic predisposition to autoimmune thyroid disease (AITD) and an increased susceptibility to viral pneumonia (odds ratio [OR]: 1.096; 95% confidence interval [CI]: 1.022-1.176). Moreover, it demonstrated a heightened susceptibility and severity of COVID-19 (OR for COVID-19 susceptibility, COVID-19 hospitalization, and COVID-19 critical illness, with 95% CIs of 1.016, 1.001-1.032; 1.058, 1.003-1.116; 1.045, 1.010-1.081). However, no statistically significant associations were found between TSH, FT4, subclinical hypo- or hyperthyroidism, and the risk of viral pneumonia incidence, or the susceptibility and severity of COVID-19 (all > 0.05). This study establishes a cause-and-effect relationship between AITD and the development of viral pneumonia, as well as the susceptibility and severity of COVID-19.
10.3390/pathogens13020101
Thyroid Stimulating Hormone as a Possible Additional COVID-19 Outcome Marker.
Medicina (Kaunas, Lithuania)
: The interaction between thyroid and SARS-CoV-2 is complex and not yet fully understood. This study aimed to identify a predictive value of serum TSH levels on the short-term and middle-term outcomes of patients hospitalized for COVID-19. : We retrospectively analyzed electronic records (ERs) data for hospitalized COVID-19 patients between March 2020 and June 2021 and their ERs during outpatient visits, 6-8 weeks post-discharge, in cases of known serum TSH levels and no previous thyroid disorder. The short-term (length of hospital stay, MSCT findings of lung involvement, required level of oxygen supplementation, admission to the ICU, and death) and middle-term outcomes after 6 to 8 weeks post-discharge (MSCT findings of lung involvement) were analyzed. : There were 580 patients included: 302 males and 278 females, average age of 66.39 ± 13.31 years, with no known thyroid disease (TSH mean 1.16 ± 1.8; median 0.80; no value higher than 6.0 mIU/L were included). Higher TSH was observed in patients with less severe outcomes and was associated with significantly higher SpO during hospitalization. Patients who required overall more oxygen supplementation or HFOT, mechanical ventilation, and patients who were more frequently admitted to the ICU or were more often treated with corticosteroids had lower TSH than those who did not show these indicators of disease severity. Lower TSH was also present in non-survivors when compared to survivors (all < 0.01). Patients with low TSH during hospitalization more often had persistent lung involvement during the post-COVID-19 period ( = 0.028). In the post-COVID-19 period, there was an overall, statistically significant increase in the TSH levels when compared to TSH during hospitalization ( < 0.001). : Low/suppressed serum TSH levels during acute COVID-19 may be an additional laboratory test that should be included in the prediction of unfavorable short- and middle-term outcomes.
10.3390/medicina60020314
Association of COVID-19 Infection with Subsequent Thyroid Dysfunction: An International Population-Based Propensity Score Matched Analysis.
Thyroid : official journal of the American Thyroid Association
The COVID-19 pandemic's impact on thyroid function is a growing concern. Previous studies have produced inconclusive results, and there is a lack of comprehensive research into the long-term risks of thyroid dysfunction following COVID-19 infection. In this retrospective cohort study, we used data from the TriNetX international database, which includes electronic health records from a broad, diverse patient population. We compared patients with COVID-19 (cases) to those without (controls), matching for age, sex, race, and comorbidities using propensity score matching. The primary outcome was the diagnosis of thyroid dysfunction (thyrotoxicosis or hypothyroidism) within a 12-month period, analyzed using hazard ratios (HRs) and Kaplan-Meier curves, and stratified by age and sex. Initially, the study included 1,379,311 COVID-19 patients and 6,896,814 non-COVID-19 patients from the TriNetX database. After matching, the cohorts were comparable in demographics and baseline characteristics. This study consistently demonstrated a significant increase in the risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, among COVID-19 patients compared to non-COVID-19 patients. In the short term (3 months postexposure), the COVID-19 group exhibited a HR of 2.07 (95% confidence interval [CI] 2.01-2.12) for thyroid dysfunction, which included both thyrotoxicosis (HR 2.10, CI 1.92-2.29) and hypothyroidism (HR 2.08, CI 2.01-2.13). This heightened risk persisted over the long term (up to 12 months), with HRs indicating an ∼2.01-fold increased risk for overall thyroid dysfunction, a 1.8-fold increased risk for thyrotoxicosis, and a 2.04-fold increased risk for hypothyroidism. Subgroup analysis, stratified by age and sex, revealed a notably higher risk of thyroid dysfunction in patients aged 65 and above (HR 2.18, CI 2.11-2.25), compared to those in the under-65 age group (HR 1.97, CI 1.91-2.03). Both male and female patients were associated with an elevated risk, with females showing a slightly higher association with thyroid dysfunction (HR 2.12, CI 2.06-2.16) compared to males (HR 1.76, CI 1.69-1.82). COVID-19 infection was associated with an increased risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, regardless of age or sex, during a 12-month follow-up period. Further research is required to validate these findings.
10.1089/thy.2023.0626
Subacute Thyroiditis Due to COVID-19 Vaccine.
Journal of community hospital internal medicine perspectives
In this report, we present a case of a 90-year-old female who exhibited a sudden onset of confusion and severe generalized weakness after receiving her second dose of mRNA SARS-CoV-19 vaccination 19 days prior to her admission in 2021. Her thyroid-stimulating hormone (TSH) levels were low, while her thyroxine (T4), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were elevated. Triiodothyronine (T3) level was not measured. Ultrasonography of the thyroid revealed multiple nodules with heterogeneous tissue, and a nuclear medicine thyroid uptake scan showed very low uptake. These findings indicated limited thyroid destruction in the form of subacute thyroiditis, likely triggered by the mRNA SARS-CoV-2 vaccine. This case illustrates an acute complication due to a novel vaccine. There are three key takeaways for physicians. First, there should be a discussion of the benefits and risks of Covid-19 vaccine. Second, patients who present with encephalopathy should have their thyroid function checked. Third, clinicians must be aware of the signs and symptoms of potentially life-threatening hyperthyroidism. Additional studies are needed to identify those patients at highest risk for Covid-19 vaccine complications.
10.55729/2000-9666.1301
Apathetic Graves' disease with severe hepatic and renal dysfunction induced by COVID-19 infection: Case report and literature review.
Medicine
RATIONALE:A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk of missing diagnosis and delayed treatment during the COVID-19 pandemic. PATIENT CONCERN:A 60-year-old female patient developed anorexia, exhaustion, jaundice, nausea, and vomiting 10 days after COVID-19 infection. She was admitted to the Infectious Diseases Department because of recurring symptoms for more than a month. DIAGNOSIS:Based on the patient's epidemiological history, clinical symptoms, and prior history, she was preliminarily diagnosed with GD induced by COVID-19 with severe hyperthyroid-related liver injury and chronic kidney disease stage 4. Drug-induced and radiation-induced liver injuries occurred sequentially throughout the therapy. INTERVENTION:Methimazole (MMI) (10 mg/d) was administered for 1 week, and the patient's symptoms, thyroid function, and liver and kidney function improved. Nevertheless, the aforementioned symptoms and liver and kidney function deteriorated 20 days after increasing the MMI dose (20 mg/d). Therefore, in the presence of an artificial liver, hemodialysis, and other medical conditions, the treatment schedule was adjusted to individualized 131I anti-hyperthyroidism therapy. OUTCOME:After 131I treatment, the patient's liver function returned to almost normal levels after a month, but worsened when the hepatoprotective drugs were stopped. Renal function did not deteriorate significantly and returned to baseline after 3 months. Thyroid function was restored to normal approximately 4 months later. CONCLUSION:COVID-19 may induce GD. Multidisciplinary collaboration can be initiated as early as possible. Individualized 131I therapy or long-term low-dose MMI (10 mg/d) can be considered to manage hyperthyroidism in GD patients with liver and kidney dysfunction and to prolong liver protection therapy appropriately.
10.1097/MD.0000000000037456
Case report: Neglected subacute thyroiditis: a case following COVID-19 vaccination.
Frontiers in medicine
We report a case of overlooked Subacute Thyroiditis (SAT) potentially induced by the administration of a COVID-19 vaccine. This case prompted a thorough review of the existing literature to elucidate possible mechanisms by which immune responses to the COVID-19 vaccine might precipitate thyroid damage. The primary objective is to enhance the clinical understanding and awareness of SAT among healthcare professionals. Subacute thyroiditis is a prevalent form of self-limiting thyroid disorder characterized by fever, neck pain or tenderness, and palpitations subsequent to viral infection. The development of numerous SARS-CoV-2 vaccines during the COVID-19 pandemic was intended to mitigate the spread of the virus. Nevertheless, there have been documented instances of adverse reactions arising from SARS-CoV-2 vaccines, such as the infrequent occurrence of subacute thyroiditis. While the majority of medical practitioners can discern classic subacute thyroiditis, not all cases exhibit typical characteristics, and not all systematic treatments yield positive responses. In this study, we present a rare case of subacute thyroiditis linked to the administration of the SARS-CoV-2 vaccine. A previously healthy middle-aged female developed fever and sore throat 72 h post-inoculation with the inactivated SARS-CoV-2 vaccine. Initially attributing these symptoms to a common cold, she self-administered ibuprofen, which normalized her body temperature but failed to alleviate persistent sore throat. Suspecting a laryngopharyngeal disorder, she sought treatment from an otolaryngologist. However, the pain persisted, accompanied by intermittent fever over several days. After an endocrinology consultation, despite the absence of typical neck pain, her examination revealed abnormal thyroid function, normal thyroid antibodies, heterogeneous echogenicity on thyroid ultrasonography, and elevated levels of Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP). These findings led to a consideration of the diagnosis of SAT. Initially, she was treated with non-steroidal anti-inflammatory drugs (NSAIDs) for her fever, which proved effective, but her neck pain remained uncontrolled. This suggested a poor response to NSAIDs. Consequently, steroid therapy was initiated, after which her symptoms of fever and neck pain rapidly resolved.
10.3389/fmed.2024.1349615
Subacute thyroiditis after SARS-CoV-2 vaccination: A case report.
Clinical case reports
Key Clinical Message:Subacute thyroiditis which is typically characterized by cervical pain and fever is caused by viral infection and is seen after SARS-CoV-2 vaccination. Here we report a post-vaccination subacute thyroiditis after SARS-CoV-2 vaccination. Abstract:Subacute thyroiditis (SAT) is possibly caused by a viral infection and is typically characterized by cervical pain and fever. SAT associated with SARS-CoV-2 infection or SARS-CoV-2 vaccination has been reported, albeit in limited numbers. A 34-year-old woman was referred to our clinic with typical SAT symptoms. The diagnosis was confirmed through thyroid scintigraphy after receiving the SARS-CoV-2 vaccination, despite testing negative for COVID-19 via RT-PCR. There is a theoretical correlation between SARS-CoV-2 vaccination and SAT. Vaccination may have a direct or indirect impact on the thyroid, but further studies are required to confirm this relationship. A systematic review of the literature of similar cases was performed for comparison. Ultimately, the overall benefits of SARS-CoV-2 vaccination outweigh the potential adverse effects. Therefore, these types of reports should not divert attention from the actual reality.
10.1002/ccr3.8678
Risk of Incident Thyroid Dysfunction in the Post-Acute Phase of COVID-19: A Population-Based Cohort Study in Hong Kong.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE:The evidence of thyroid dysfunction in the post-acute phase of SARS-CoV-2 infection is limited. This study aimed to evaluate the risk of incident thyroid dysfunction in the post-acute phase of COVID-19. METHODS:This retrospective, propensity-score matched, population-based study included COVID-19 patients and non-COVID-19 individuals between January 2020 and March 2022, identified from the electronic medical records of the Hong Kong Hospital Authority. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Patients with COVID-19 were 1:1 matched to controls based on various variables. The primary outcome was a composite of thyroid dysfunction (hyperthyroidism, hypothyroidism, initiation of antithyroid drug or levothyroxine, and thyroiditis). Cox regression was employed to evaluate the risk of incident thyroid dysfunction during the post-acute phase. RESULTS:A total of 84 034 COVID-19 survivors and 84 034 matched controls were identified. Upon a median follow-up of 303 days, there was no significant increase in the risk of diagnosed thyroid dysfunction in the post-acute phase of COVID-19 (hazard ratio [HR] 1.058, 95% confidence interval 0.979-1.144, P = .154). Regarding the secondary outcomes, patients with COVID-19 did not have increased risk of hyperthyroidism (HR 1.061, P = .345), hypothyroidism (HR 1.062, P = .255), initiation of antithyroid drug (HR 1.302, P = .070), initiation of levothyroxine (HR 1.086, P = .426), or thyroiditis (P = .252). Subgroup and sensitivity analyses were largely consistent with the main analyses. CONCLUSION:Our population-based cohort study provided important reassuring data that COVID-19 was unlikely to be associated with persistent effects on thyroid function.
10.1016/j.eprac.2024.03.389
Thyroid tuberculosis and cold abscess after infection with COVID-19: A case report.
Heliyon
There is mounting evidence that coronavirus disease 2019 (COVID-19) can cause immune dysregulation. The consequence of this immune dysregulation may contribute to susceptibility to tuberculosis (TB). Thyroid gland involvement by TB is extremely uncommon and typically the result of disseminated infection. It can be hard to diagnose because there are no identifiable symptoms. We present the case of a Chinese patient who had a fever again after COVID-19 infection that was finally diagnosed as thyroid tuberculosis with a cold abscess. Clinicians should maintain a high index of suspicion for high-risk patients from endemic regions with medical comorbidities, such as immunocompromised disease and malnutrition.
10.1016/j.heliyon.2024.e28469
The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China.
The Lancet. Infectious diseases
BACKGROUND:Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms. METHODS:This single-centre, cross-sectional cohort study was done at China-Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18-33 days), 2 months (55-84 days), or 4 months (115-134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms. FINDINGS:Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64-10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms. INTERPRETATION:Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms. FUNDING:National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.
10.1016/S1473-3099(24)00171-3
The Aftermath of COVID-19: Exploring the Long-Term Effects on Organ Systems.
Biomedicines
BACKGROUND:Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalised. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected by PASC and its complications. The severity and the later development of PASC symptoms are positively associated with the early intensity of the infection. RESULTS:The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. The cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as conditions that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with the respiratory system in long-COVID causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. The renal system also was impacted, which resulted in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite, and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints linked to PASC. CONCLUSIONS:Long-COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy, and more study to address its underlying causes and long-term effects is needed.
10.3390/biomedicines12040913