Reactivation of occult hepatitis B virus infection under treatment with abatacept: a case report.
Talotta Rossella,Atzeni Fabiola,Sarzi Puttini Piercarlo
BMC pharmacology & toxicology
BACKGROUND:Abatacept (ABA) is a fusion receptor protein containing the CTLA-4 domain that prevents the activation of naïve T cells by binding the CD80 and CD86 molecules expressed on the surface of dendritic cells, indicated for the treatment of moderate to severe rheumatoid arthritis (RA). There is still little evidence concerning the safety of ABA in RA patients with positive serology for hepatitis virus B (HBV) infection. CASE PRESENTATION:We report the case of a HBV infection reactivation in an ABA-treated male RA patient. The patient (caucasian race, 66-year-old) was diagnosed with RA in Novembre 2010 and in December 2010 he started a treatment with prednisone plus subcutaneous methotrexate. In October 2011, an anti-TNF agent (golimumab) was added but soon discontinued due to an adverse event. At baseline, screening for HBV markers showed a positivity for HBcAb and HBeAb IgG, being HBsAg, HBsAb, HBcAb IgM, HBeAg and HBV DNA negative. Serum amino-transferase (AST and ALT) levels were within the normal range. In January 2012 he was swapped to intravenous treatment with ABA 750 mg/month, that allowed the achievement of a good clinical response and the permanent discontinuation of corticosteroids. In November 2013, laboratory reports showed that he was positive for HBcAb but negative for the remaining HBV markers, and had a slightly increased AST level and, in December 2013, he became HBV DNA positive (326 IU/mL). In January 2014, his HBV DNA levels had further increased and ABA was stopped while maintaining MTX. He started lamivudine 100 mg/day in January 2014. After 1 month of lamivudine, his HBV DNA levels became undetectable (<10 IU/mL) and liver function was normal although RA had been reactivated (DAS28 5.53). Treatment with ABA was therefore resumed with the achievement of a good response after 6 months. The patient is currently being treated with lamivudine 100 mg/day, i.v. ABA 750 mg/month, and MTX 15 mg/week, with a good response (DAS28 2.27 in October 2015), and constantly monitored without any further evidence of HBV infection reactivation. CONCLUSIONS:Although there are still few reports in literature, we suggest caution in HBV- occult carriers RA patients undergoing a treatment with abatacept.
Presence of anti-cyclic citrullinated peptide antibodies is associated with better treatment response to abatacept but not to TNF inhibitors in patients with rheumatoid arthritis: a meta-analysis.
Alemao Evo,Postema Roelien,Elbez Yedid,Mamane Carole,Finckh Axel
Clinical and experimental rheumatology
OBJECTIVES:The objective of this study was to investigate whether anti-cyclic citrullinated peptide antibody (ACPA) status is associated with clinical responses to abatacept or TNF-α-inhibitors (TNF-α-i) in RA patients. METHODS:A systematic literature review (SLR) was performed in January 2018 to identify published studies and conference abstracts evaluating biologic DMARD response according to ACPA status. Mantel-Haenszel meta-analysis methods were used to pool risk ratios (RRs). In the base-case, treatment response was assessed using EULAR measure, while a scenario analysis assessed response by combining ACR20, DAS28 and EULAR measures. Subgroup analyses were performed for duration of study follow-up. RESULTS:Eighteen of the 30 SLR studies were included in the meta-analysis. The base-case showed a statistically significant positive association between ACPA positivity and EULAR response for patients treated with abatacept (RR: 1.13 [95% CI: 1.00, 1.26]), while ACPA positivity was associated with lower EULAR responses to TNF-α-i (RR: 0.91 [95% CI: 0.84, 0.98]). For the scenario analysis, results were consistent with the base-case for abatacept (RR 1.18 [95% CI 1.03, 1.35]), while for TNFα-i, no significant difference by ACPA status was observed (RR 0.97 [95% CI 0.86, 1.10]). Subgroups analyses showed results similar to the base-case for both abatacept and TNF-α-i. CONCLUSIONS:This meta-analysis confirms that ACPA-positive RA patients are marginally more likely to achieve EULAR and ACR20 response to abatacept compared to ACPA-negative patients. Additionally, the analysis demonstrates that there is no association between ACPA status and response to TNF-α-i, consistent with findings of previously published studies.
Anti-Ro/SSA antibodies are an independent factor associated with an insufficient response to tumor necrosis factor inhibitors in patients with rheumatoid arthritis.
Matsudaira Ran,Tamura Naoto,Sekiya Fumio,Ogasawara Michihiro,Yamanaka Kenjiro,Takasaki Yoshinari
The Journal of rheumatology
OBJECTIVE:To study the significance of anti-Ro/SSA antibodies (anti-Ro) in the clinical response to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA). METHODS:The clinical responses of a cohort of 190 patients with RA who were treated with infliximab, etanercept, or adalimumab (n = 112, 64, and 14, respectively) as the first biologics were examined using the Disease Activity Score in 28 joints (DAS28) at 24 weeks and the discontinuation rate at 56 weeks. The baseline characteristics of responders and the nonresponders were compared. The clinical response was compared between anti-Ro-negative and -positive patients. The factors associated with the inefficiency of TNF inhibitors were estimated with a multivariable logistic regression analysis. RESULTS:The positive rate of anti-Ro was significantly higher in patients with no European League Against Rheumatism (EULAR) response at 24 weeks (OR 3.64, 95% CI 1.45-9.01, p = 0.003). In anti-Ro-positive patients, a moderate or good EULAR response rate was significantly lower with a sustaining higher median DAS28 (p = 0.006), and this difference was greater among infliximab-treated patients. The discontinuation rate for TNF inhibitors due to inefficacy at 56 weeks was also higher in anti-Ro-positive patients (OR 4.68, 95% CI 1.82-11.99, p = 0.0005), and 75% of these patients received infliximab. The presence of anti-Ro was strongly associated with no EULAR response at 24 weeks and a higher discontinuation rate of TNF inhibitors by 56 weeks (OR 5.22, 95% CI 1.75-15.57, p = 0.003 and OR 10.18, 95% CI 2.18-49.56, p = 0.003). CONCLUSION:The presence of anti-Ro might be related to the lesser clinical response to infliximab compared to other TNF inhibitors, suggesting that the presence of anti-Ro should be considered when choosing the appropriate biologics for patients with RA.
Overlapping Sjogren's syndrome reduces the probability of reaching target in rheumatoid arthritis patients: a propensity score matched real-world cohort from 2009 to 2019.
Zhang Huijuan,Zhang Haoze,Gao Dai,Xie Wenhui,Geng Yan,Zhang Zhuoli
Arthritis research & therapy
BACKGROUND:Overlapping Sjogren's syndrome (SS) is not uncommon in rheumatoid arthritis (RA) and considered as a probable detrimental factor of RA. But data on the impact of overlapping SS on RA therapeutic response is limited. Our current study aimed to identify the effect in a real-world cohort from 2009 to 2019. METHODS:The medical records of RA patients who visited the rheumatology clinic of our medical center from 2009 to 2019 were reviewed. Their composite disease activity scores at each follow-up point were collected. The therapeutic response between RA patients with SS (RA-SS) and without (RA-noSS) was compared. To correct confounders which may affect the therapeutic response, both propensity score matched and unmatched cohorts were analyzed by using the Cox proportional hazards model. RESULTS:Among the 1099 RA patients, 129 (11.7%) overlapped with SS were validated by positive anti-SSA or a minor salivary gland biopsy with histological changes suggestive of SS. After propensity score matching based on their baseline characteristics, 126 of 129 RA-SS and 126 of 970 RA-noSS patients were statistically extracted. Overlapping SS was associated with a 29%, 26%, 18%, and 22% lower probability of reaching remission defined by DAS28-ESR, DAS28-CRP, SDAI, and CDAI in RA patients, respectively. Similar decreased probability of reaching low disease activity was also observed. Although ESR was most significantly affected (HR 0.69, 95% CI 0.61-0.79), other component of composite RA disease activity score was also affected by overlapping SS. Stratification by age, RF/ACPA status, or baseline DAS28-CRP was not associated with change of results. CONCLUSIONS:Overlapping SS is associated with lower probability of reaching remission or low disease activity in RA patients and should be regarded as one of the poor prognostic factors.
Association of anti-Ro/SSA antibody with response to biologics in patients with rheumatoid arthritis.
Hagiwara Shinya,Tsuboi Hiroto,Honda Fumika,Takahashi Hidenori,Kurata Izumi,Ohyama Ayako,Yagishita Mizuki,Abe Saori,Kurashima Yuko,Kaneko Syunta,Kawaguchi Hoshimi,Takahashi Hiroyuki,Ebe Hiroshi,Yokosawa Masahiro,Asashima Hiromitsu,Hirota Tomoya,Umeda Naoto,Kondo Yuya,Matsumoto Isao,Sumida Takayuki
OBJECTIVE:To compare the effectiveness of three different biologics in anti-Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA). METHODS:The study subjects were 110 biologics naïve patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody-negative patients. RESULTS:We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-β levels. CONCLUSIONS:Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-β levels, but not to TCZ and ABT.
Clinical characteristics and risk factors for overlapping rheumatoid arthritis and Sjögren's syndrome.
Yang Huaxia,Bian Sainan,Chen Hua,Wang Li,Zhao Lidan,Zhang Xuan,Zhao Yan,Zeng Xiaofeng,Zhang Fengchun
This study investigated the clinical characteristics and risk factors for overlapping rheumatoid arthritis and Sjögren's syndrome (RA/SS). Patients with RA/SS in Peking Union Medical College Hospital from January 2012 to January 2017 were retrospectively analysed and compared to those of sex- and age-matched RA or SS controls. Logistic regression analysis was used to identify risk factors. Altogether, 105 consecutive patients with RA/SS were enrolled. Ninety-seven (92.4%) of them were female, with a mean age of 51.5 ± 13.3 years or 45.2 ± 14.7years at the diagnosis of SS or RA, respectively. In addition to arthritis and Sicca symptom, patients with RA/SS had more visceral involvements including interstitial lung disease (ILD), and haematologic involvement, and received more glucocorticoid treatments than controls (p < 0.05). RA-onset, simultaneous-onset and SS-onset patients had significant differences in age at RA diagnosis, fever and thrombocytopenia (p < 0.05). Multivariate logistic analysis indicated that arthritis (OR = 44.804), rheumatoid factor (RF) (OR = 5.973), and anti-CCP (OR = 2.545) were independent risk factors for SS overlapping with RA. Xerostomia (OR = 3.960), ILD (OR = 6.210), and anti-SSA (OR = 24.640) were independent predictors of RA overlapping with SS. RA/SS patients have more visceral involvements. Our findings highlight the roles of arthritis/RF/anti-CCP and xerostomia/ILD/anti-SSA in the development of this overlapping disease.
Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report.
Hollstein Tim,Schulte Dominik M,Schulz Juliane,Glück Andreas,Ziegler Anette G,Bonifacio Ezio,Wendorff Mareike,Franke Andre,Schreiber Stefan,Bornstein Stefan R,Laudes Matthias
Here we report a case where the manifestations of insulin-dependent diabetes occurred following SARS-CoV-2 infection in a young individual in the absence of autoantibodies typical for type 1 diabetes mellitus. Specifically, a 19-year-old white male presented at our emergency department with diabetic ketoacidosis, C-peptide level of 0.62 µg l, blood glucose concentration of 30.6 mmol l (552 mg dl) and haemoglobin A1c of 16.8%. The patient´s case history revealed probable COVID-19 infection 5-7 weeks before admission, based on a positive test for antibodies against SARS-CoV-2 proteins as determined by enzyme-linked immunosorbent assay. Interestingly, the patient carried a human leukocyte antigen genotype (HLA DR1-DR3-DQ2) considered to provide only a slightly elevated risk of developing autoimmune type 1 diabetes mellitus. However, as noted, no serum autoantibodies were observed against islet cells, glutamic acid decarboxylase, tyrosine phosphatase, insulin and zinc-transporter 8. Although our report cannot fully establish causality between COVID-19 and the development of diabetes in this patient, considering that SARS-CoV-2 entry receptors, including angiotensin-converting enzyme 2, are expressed on pancreatic β-cells and, given the circumstances of this case, we suggest that SARS-CoV-2 infection, or COVID-19, might negatively affect pancreatic function, perhaps through direct cytolytic effects of the virus on β-cells.
Autoimmunity to ACE2 as a possible cause of tissue inflammation in Covid-19.
HYPOTHESIS:The delayed lung damage after SARS-CoV-2 infection may be caused by an autoimmune response to ACE2 induced by forced presentation of the ACE2 protein in a complex with CoV Spike in Fc Receptor positive Antigen Presenting Cells in the lung. The likelihood that this hypothesis is valid is low, but it is easily tested. TESTABLE PREDICTIONS:1) Autoantibodies and T cells to ACE2 may be found in patients with the lung damage but not in those without 2) There may be an HLA linkage with the delayed lung disease 3) Vaccines based on the spike protein might initiate the process by amplifying Fc mediated uptake of ACE2-Spike complexes into APCs. PRACTICAL IMPLICATIONS:The development of autoantibodies to ACE2 might predict the development of the inflammatory phase of Covid-19 disease. It might be wise to consider engineering versions of the spike that no longer bind to ACE2 for inclusion in vaccines.
New onset of ocular myasthenia gravis in a patient with COVID-19: a novel case report and literature review.
Sriwastava Shitiz,Tandon Medha,Kataria Saurabh,Daimee Maha,Sultan Shumaila
Journal of neurology
The novel coronavirus outbreak of SARS-CoV-2 first began in Wuhan, China, in December 2019. The most striking manifestation of SARS-CoV-2 is atypical pneumonia and respiratory complications; however, various neurological manifestations are now well recognized. Currently, there have been very few case reports regarding COVID-19 in patients with a known history of myasthenia gravis. Myasthenia gravis (MG) causes muscle weakness, especially respiratory muscles, in high-risk COVID-19 patients, which can lead to severe respiratory compromise. There are few reported cases of severe myasthenia crisis following COVID-19, likely due to the involvement of the respiratory apparatus and the use of immunosuppressive medication. We report the first case of ocular MG developing secondary to COVID-19 infection in a 65-year-old woman. Two weeks prior to hospitalization, the patient suffered from cough, fever, and diarrhea and was found to be positive for COVID-19 via a nasopharyngeal RT-PCR swab test. The electrodiagnostic test showed decremental response over more than 10% on repetitive nerve stimulation test of orbicularis oculi. She tested positive for antibodies against acetylcholine receptor. COVID-19 is known to cause the release of inflammatory cytokines, leading to immune-mediated damage. MG is an immune-mediated disorder caused by molecular mimicry and autoantibodies against the neuromuscular junction.
COVID-19 and Systemic Lupus Erythematosus: Focus on Immune Response and Therapeutics.
Spihlman Allison P,Gadi Nirupa,Wu Samantha C,Moulton Vaishali R
Frontiers in immunology
The SARS-CoV-2 novel coronavirus has caused the COVID-19 pandemic with over 35 million cases and over a million deaths worldwide as of early October 2020. The populations most affected are the elderly and especially those with underlying comorbidities. In terms of race and ethnicity, black and hispanic populations are affected at disproportionately higher rates. Individuals with underlying conditions that cause an immune-compromised state are considered vulnerable to this infection. The immune response is an important determinant in viral infections including coronaviruses, not only in the antiviral defense but also in the disease progression, severity, and clinical outcomes of COVID-19. Systemic lupus erythematosus is a chronic autoimmune disease which also disproportionately afflicts black and hispanic populations. In lupus patients, an aberrant immune response is characterized by the presence of circulating autoantibodies, lymphopenia, aberrant T cells, and proinflammatory cytokines along with defective regulatory mechanisms, leading to immune-mediated damage to tissues. Lupus patients are often treated with immune-suppressants and therefore are immune-compromised and more susceptible to infections and may be vulnerable to coronavirus infection. While the anti-viral immune response is important to protect from coronavirus infection, an uncontrolled proinflammatory cytokine response can lead to cytokine storm which causes damage to the lungs and other organs, causing significant morbidity and mortality. Better understanding of the underlying immune response and therapeutic strategies in lupus and COVID-19 is important to guide management of this deadly infectious disease in the context of lupus and vice-versa.
Prevalence of autoantibody responses in acute coronavirus disease 2019 (COVID-19).
Lerma L Angelica,Chaudhary Anu,Bryan Andrew,Morishima Chihiro,Wener Mark H,Fink Susan L
Journal of translational autoimmunity
Immunopathology may play a significant role in the pathogenesis of Coronavirus-Induced Disease-19 (COVID-19). Immune-mediated tissue damage could result from development of rapid autoimmune responses, characterized by production of self-reactive autoantibodies. In this study, we tested specimens from acutely ill patients hospitalized with COVID-19 for autoantibodies against nuclear, vasculitis-associated, and phospholipid antigens. Detectable autoantibodies were present in 30% of the patients in our cohort, with the majority of reactive specimens demonstrating antibodies to nuclear antigens. However, antinuclear antibodies were only weakly reactive and directed to single antigens, as is often seen during acute infection. We identified strongly reactive antibodies to nuclear antigens only in patients with a prior history of autoimmune disease. In our cohort, the prevalence of antiphospholipid antibodies was low, and we did not detect any vasculitis-associated autoantibodies. We found similar levels of inflammatory markers and total immunoglobulin levels in autoantibody positive versus negative patients, but anti-SARS-CoV-2 antibody levels were increased in autoantibody positive patients. Together, our results suggest that acute COVID-19 is not associated with a high prevalence of clinically significant autoantibody responses of the type usually associated with autoimmune rheumatic disease.
High levels of anti-SSA/Ro antibodies in COVID-19 patients with severe respiratory failure: a case-based review : High levels of anti-SSA/Ro antibodies in COVID-19.
Fujii Hiroyuki,Tsuji Taisuke,Yuba Tatsuya,Tanaka Shunya,Suga Yoshifumi,Matsuyama Aosa,Omura Ayaka,Shiotsu Shinsuke,Takumi Chieko,Ono Seiko,Horiguchi Masahito,Hiraoka Noriya
We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither of them had a history of autoimmune disease. Chest computed tomography scans before the antiviral therapy showed bilateral multiple patchy ground-glass opacities (GGO) consistent with COVID-19 pneumonia. The GGO regressed over the course of the antiviral treatment; however, new non-segmental patchy consolidations emerged, which resembled those of interstitial lung disease (ILD), specifically collagen vascular disease-associated ILD. We tested the patients' sera for autoantibodies and discovered that both patients had high anti-SSA/Ro antibody titers. In Case 1, the patient recovered with antiviral therapy alone. However, in Case 2, the patient did not improve with antiviral therapy alone but responded well to corticosteroid therapy (methylprednisolone) and made a full recovery. The relationship between some immunological responses and COVID-19 pneumonia exacerbation has been discussed previously; our discovery of the elevation of anti-SSA/Ro antibodies suggests a contribution from autoimmunity functions of the immune system. Although it is unclear whether the elevation of anti-SSA/Ro antibodies was a cause or an outcome of aggravated COVID-19 pneumonia, we hypothesize that both patients developed aggravated the COVID-19 pneumonia due to an autoimmune response. In COVID-19 lung injury, there may be a presence of autoimmunity factors in addition to the known effects of cytokine storms. In patients with COVID-19, a high level of anti-SSA/Ro52 antibodies may be a surrogate marker of pneumonia severity and poor prognosis.
Covid-19 and autoimmunity.
Ehrenfeld Michael,Tincani Angela,Andreoli Laura,Cattalini Marco,Greenbaum Assaf,Kanduc Darja,Alijotas-Reig Jaume,Zinserling Vsevolod,Semenova Natalia,Amital Howard,Shoenfeld Yehuda
Understanding immunopathological fallout of human coronavirus infections including COVID-19: Will they cross the path of rheumatologists?
Kabeerdoss Jayakanthan,Danda Debashish
International journal of rheumatic diseases
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) is the biggest pandemic of our lifetime to date. No effective treatment is yet in sight for this catastrophic illness. Several antiviral agents and vaccines are in clinical trials, and drug repurposings as immediate and alternative choices are also under consideration. Immunomodulatory agents like hydroxychloroquine (HCQ) as well as biological disease-modifying anti-rheumatic drugs (bDMARDs) such as tocilizumab and anakinra received worldwide attention for treatment of critical patients with COVID-19. This is of interest to rheumatologists, who are well versed with rational use of these agents. This brief review addresses the understandings of some of the common immunopathogenetic mechanisms in the context of autoimmune rheumatic diseases like systemic lupus erythematosus (SLE) and COVID-19. Apart from demographic comparisons, the role of type I interferons (IFN), presence of antiphospholipid antibodies and finally mechanism of action of HCQ in both the scenarios are discussed here. High risks for fatal disease in COVID-19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. HCQ acts by different mechanisms including prevention of cellular entry of SARS-CoV-2 and inhibition of type I IFN signaling. Recent controversies regarding efficacy of HCQ in management of COVID-19 warrant more studies in that direction. Autoantibodies were also reported in severe acute respiratory syndrome (SARS) as well as in COVID-19. Rheumatologists need to wait and see whether SARS-CoV-2 infection triggers development of autoimmunity in patients with COVID-19 infection in the long run.
Osteonecrosis in patients after severe acute respiratory syndrome (SARS): possible role of anticardiolipin antibodies.
Sun Wei,Wang Bai-Liang,Liu Bing-Li,Zhao Feng-Chao,Shi Zhen-Cai,Guo Wan-Shou,Liu Zhao-Hui,Li Zi-Rong
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases
OBJECTIVES:This study examined the anticardiolipin antibodies in post-SARS (severe acute respiratory syndrome) osteonecrosis patients to investigate the etiology of post-SARS osteonecrosis, and to eventually provide valuable information for the early diagnosis of nontraumatic osteonecrosis and for the susceptible population screening. METHODS:This study recruited 62 post-SARS osteonecrosis patients and 52 age- and gender-matched healthy controls. Fasting blood samples were collected from all the subjects through cubital veins. Immunoglobulins A, G and M (IgA, G and M) types of anticardiolipin antibodies were examined by enzyme-linked immunosorbent assay. The routine examinations of prothrombin time, thrombin time, prothrombin activity, and international normalized ratio were also performed. RESULTS:There were 21 of 62 post-SARS osteonecrosis patients (33.9%) who showed at least one type of anticardiolipin antibodies. The titers of specific IgA, IgG, and IgM were 11.33 +/- 11.209 APL, 5.127 +/- 5.927 GPL, and 17.821 +/- 10.606 MPL, respectively. There were only 4 of 52 subjects in the control group (7.7%) who showed positive anticardiolipin antibody with titers of IgA at 10.702 +/- 3.126 APL, IgG at 5.184 +/- 4.780 GPL, and IgM at 14.684 +/- 5.516 MPL. There were significant differences between the 2 groups confirmed by t-Test and chi(2) test (P < 0.05), while no significant differences were observed in prothrombin time, thrombin time, prothrombin activity, and international normalized ratio results between the 2 groups. CONCLUSIONS:The incidences of anticardiolipin antibodies were increased in the post-SARS osteonecrosis patients and anticardiolipin antibodies may play a role in the pathogenesis of post-SARS osteonecrosis.
[Analysis of false-positive associated with antibody tests for SARS-CoV in SLE patients].
Wang Yun Shan,Shen Hong,Sun Shan Hui,Jiang Li Hua,Liu Yang,Zhu Zhi Wei,Xiao Dong Jie,Huang Ping,Yang Bo,Du Xi Yan,Zhang Yuan Chao
Shi yan sheng wu xue bao
To discuss the false-positive of serological diagnostic testing for coronavirus antibody in patients with systemic lupus erythematosus(SLE), 66 normal individual and 31 SLE with non-SARS patients were detected for SARS-associated coronavirus (SARS-CoV) antibody and RNA by enzymelinked immunosorbent assays(ELISA) and reverse transcriptase-polymerase chain reaction(RT-PCR). The result showed 2/66 cases(3.0%) were positive of SARS-CoV-IgG antibody and 66 cases were negative of SARS-CoV-IgM antibody in the 66 cases healthy controls; in 31 cases with SLE, positive rates of SARS-CoV-IgG and IgM antibody were 58.1% (18/31) and 29% (9/31), respectively, in which 7 cases(22.6%) were positive of both SARS-CoV-IgG and IgM antibody. All samples of positive SARS-CoV-IgG and IgM antibody were negative by RT-PCR. The ELISA kit coated by non-purification antigen may induce the false-positive of SARS-CoV antibody in patients with SLE. This result suggested that the specificity of ELISA tests for SARS was excellent and has low false-positive rates when using SARS-CoV-IgG and IgM antibody tests. A possible cause of false-positive of SARS-CoV-IgG and IgM antibody in SLE patients is coated antigens with SARS-CoV and Vero-E6 cells in ELISA methods.
Broadly-targeted autoreactivity is common in severe SARS-CoV-2 Infection.
Woodruff Matthew C,Ramonell Richard P,Lee F Eun-Hyung,Sanz Ignacio
medRxiv : the preprint server for health sciences
Severe SARS-CoV-2 infection is linked to the presence of autoantibodies against multiple targets, including phospholipids and type-I interferons. We recently identified activation of an autoimmune-prone B cell response pathway as correlate of severe COVID-19, raising the possibility of autoreactive antibody production during the antiviral response. Here, we identify autoreactive antibodies as a common feature of severe COVID-19, identifying biomarkers of tolerance breaks that may indicate aggressive immunomodulation.
IgM autoantibodies recognizing ACE2 are associated with severe COVID-19.
Casciola-Rosen Livia,Thiemann David R,Andrade Felipe,Trejo Zambrano Maria Isabel,Hooper Jody E,Leonard Elissa,Spangler Jamie,Cox Andrea L,Machamer Carolyn,Sauer Lauren,Laeyendecker Oliver,Garibaldi Brian T,Ray Stuart C,Mecoli Christopher,Christopher-Stine Lisa,Gutierrez-Alamillo Laura,Yang Qingyuan,Hines David,Clarke William,Rothman Richard Eric,Pekosz Andrew,Fenstermacher Katherine,Wang Zitong,Zeger Scott L,Rosen Antony
medRxiv : the preprint server for health sciences
SARS-CoV-2 infection induces severe disease in a subpopulation of patients, but the underlying mechanisms remain unclear. We demonstrate robust IgM autoantibodies that recognize angiotensin converting enzyme-2 (ACE2) in 18/66 (27%) patients with severe COVID-19, which are rare (2/52; 3.8%) in hospitalized patients who are not ventilated. The antibodies do not undergo class-switching to IgG, suggesting a T-independent antibody response. Purified IgM from anti-ACE2 patients activates complement. Pathological analysis of lung obtained at autopsy shows endothelial cell staining for IgM in blood vessels in some patients. We propose that vascular endothelial ACE2 expression focuses the pathogenic effects of these autoantibodies on blood vessels, and contributes to the angiocentric pathology observed in some severe COVID-19 patients. These findings may have predictive and therapeutic implications.
Autoimmune and rheumatic musculoskeletal diseases as a consequence of SARS-CoV-2 infection and its treatment.
Shah Sanket,Danda Debashish,Kavadichanda Chengappa,Das Saibal,Adarsh M B,Negi Vir Singh
The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection.
Covid-19, induced activation of hemostasis, and immune reactions: Can an auto-immune reaction contribute to the delayed severe complications observed in some patients?
Amiral Jean,Vissac Anne Marie,Seghatchian Jerard
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis
Covid-19 is characterized by weak symptoms in most affected patients whilst severe clinical complications, with frequent fatal issues, occur in others. Disease severity is associated with age and comorbidities. Understanding of viral infectious mechanisms, and antibody immune response, can help to better control disease progression. SARS-CoV-2 has a major impact on the Renin Angiotensin Aldosterone System (RAAS), through its binding to the membrane cellular glycoprotein, Angiotensin Converting Enzyme-2 (ACE-2), then infecting cells for replication. This report hypothesizes the possible implication of an autoimmune response, induced by generation of allo- or autoantibodies to ACE-2, or to its complexes with viral spike protein. This could contribute to some delayed severe complications occurring in affected patients. We also propose a strategy for investigating this eventuality.
A case of postpartum thyroiditis following SARS-CoV-2 infection.
Mizuno Shinsuke,Inaba Hidefumi,Kobayashi Ken-Ichiro,Kubo Kenji,Ito Saya,Hirobata Tomonao,Inoue Gen,Akamizu Takashi,Komiya Nobuhiro
Postpartum thyroiditis (PPT) is characterized by mild thyrotoxicosis occurring within one year of parturition commonly followed by transient hypothyroidism. Having genetic background of autoimmune thyroid disorders is a risk factor for it because the immune reactivation during postpartum period is a trigger for PPT. Pandemic of COVID-19: caused by SARS-CoV-2 infection is a global health problem, and occurrence of Graves' disease and Hashimoto's thyroiditis after the viral infection have been reported but occurrence of PPT with COVID-19 has never been reported. A 29-year-old woman developed general fatigue four and a half months after parturition, and was diagnosed as having PPT: one month before, she had COVID-19. Hereafter, we define the date of delivery as Day 0 to make timeline clear. SARS-CoV-2 infection was diagnosed by PCR on Day 103, its disappearance from the upper airway confirmed on Day 124, and the thyroiditis diagnosed on Day 136. She had been euthyroid on Day 0 and 95, but thyrotoxic on Day 136. Serum thyroglobulin (Tg) concentration was normal in the presence of anti-Tg antibody, other thyroid-related autoantibodies were negative, and by ultrasonography, the thyroid gland was normal in size and no evidence of increased vascularity. Thyroid function returned to normal by Day 172 without any specific drug therapy. In conclusion, although a clear causal relationship could not be found, we documented the world's first case of PPT developed following COVID-19.
The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.
Consiglio Camila Rosat,Cotugno Nicola,Sardh Fabian,Pou Christian,Amodio Donato,Rodriguez Lucie,Tan Ziyang,Zicari Sonia,Ruggiero Alessandra,Pascucci Giuseppe Rubens,Santilli Veronica,Campbell Tessa,Bryceson Yenan,Eriksson Daniel,Wang Jun,Marchesi Alessandra,Lakshmikanth Tadepally,Campana Andrea,Villani Alberto,Rossi Paolo, ,Landegren Nils,Palma Paolo,Brodin Petter
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.
Immune-mediated neurological syndromes in SARS-CoV-2-infected patients.
Guilmot Antoine,Maldonado Slootjes Sofia,Sellimi Amina,Bronchain Maroussia,Hanseeuw Bernard,Belkhir Leila,Yombi Jean Cyr,De Greef Julien,Pothen Lucie,Yildiz Halil,Duprez Thierry,Fillée Catherine,Anantharajah Ahalieyah,Capes Antoine,Hantson Philippe,Jacquerye Philippe,Raymackers Jean-Marc,London Frederic,El Sankari Souraya,Ivanoiu Adrian,Maggi Pietro,van Pesch Vincent
Journal of neurology
BACKGROUND:Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations. METHODS:Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated. RESULTS:Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients. CONCLUSIONS:In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.
Anakinra for severe forms of COVID-19: a cohort study.
Huet Thomas,Beaussier Hélène,Voisin Olivier,Jouveshomme Stéphane,Dauriat Gaëlle,Lazareth Isabelle,Sacco Emmanuelle,Naccache Jean-Marc,Bézie Yvonnick,Laplanche Sophie,Le Berre Alice,Le Pavec Jérôme,Salmeron Sergio,Emmerich Joseph,Mourad Jean-Jacques,Chatellier Gilles,Hayem Gilles
The Lancet Rheumatology
Background:Coronaviruses can induce the production of interleukin (IL)-1β, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function. Methods:The Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death. The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra). Findings:From March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0·22 [95% CI 0·11-0·41; p<0·0001). The treatment effect of anakinra remained significant in the multivariate analysis (HR 0·22 [95% CI 0·10-0·49]; p=0·0002). An increase in liver aminotransferases occurred in seven (13%) patients in the anakinra group and four (9%) patients in the historical group. Interpretation:Anakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require controlled trials. Funding:Groupe Hospitalier Paris Saint-Joseph.
Evaluation of an Electrochemiluminescent SARS-CoV-2 Antibody Assay.
Lau C S,Hoo S P,Yew S F,Ong S K,Lum L T,Heng P Y,Tan J G,Wong M S,Aw T C
The journal of applied laboratory medicine
BACKGROUND:Little is known about the performance of the Roche novel severe acute respiratory syndrome coronavirus 2 antibody (anti-SARS-CoV-2) assay. We provide an extensive evaluation of this fully automated assay on Cobas e801/e602 immunoassay analyzers. METHODS:We assessed the linearity, precision, and throughput of the Roche anti-SARS-CoV-2 assay. Sensitivity was calculated from 349 SARS-CoV-2 polymerase chain reaction (PCR) positive samples; specificity was determined from 715 coronavirus disease 2019 (COVID-19)-naive samples. We examined cross-reactivity against other antibody positive samples [syphilis, rheumatoid factor (RF), antinuclear antibody (ANA), double-stranded DNA (ds-DNA), influenza, dengue, hepatitis B (HBV), hepatitis C (HCV)] and the anti-SARS-CoV-2 kinetics. RESULTS:The assay cut-off index (COI) was linear up to 90.8. The interassay precision was 2.9% for a negative control (COI = 0.1) and 5.1% for a positive control (COI = 3.0). Assay time is 18 min and results are available 1 min later; throughput for 300 samples was 76 min. Only 1 case positive for HBsAg tested falsely positive; specificity was 99.9%. The assay has a sensitivity of 97.1% 14 days after PCR positivity (POS) and 100% at ≥21 days POS; 48.2% of cases had anti-SARS-CoV-2 within 6 days POS. In 11 patients in whom serum was available prior to a positive antibody signal (COI ≥1.0) the interval between the last negative and first positive COI (time to "seroconversion") on average is 3 days (range 1-6 days) and 4 more days (range 1-7) for the anti-SARS-CoV-2 to plateau. CONCLUSION:The Roche anti-SARS-CoV-2 assay shows excellent performance with minimal cross-reactivity from other viral and confounding antibodies. Antibody development and seroconversion appears quite early.
Reactive Arthritis in a 37-Year-Old Female With SARS-CoV2 Infection.
Danssaert Zach,Raum George,Hemtasilpa Somkiat
We report the case of a 37-year-old female who presented for evaluation of acute 10/10 right hand pain, 12 days after testing positive for SARS-CoV2. The patient was admitted to the hospital due to the severity of her pain. As an inpatient, extensive workup by the medicine team and rheumatology revealed no structural, vascular, or neurogenic cause of her pain. The patient's blood work was unremarkable for elevations in lyme serology, antinuclear antibody (ANA), rheumatoid factor, and uric acid. It was determined that the cause of her pain was most likely reactive arthritis (ReA) secondary to her SARS-CoV2 infection. She was treated with voltaren gel, neurontin, and oral dilaudid as needed and discharged. Upon follow-up, her pain improved and she was prescribed a wrist splint, ultram, and occupational therapy for perceived wrist tendinitis. To our knowledge, this is the first description of a case of ReA caused by the SARS-CoV2 virus.
SARS-CoV-2 infection as a trigger of autoimmune response.
Sacchi Maria C,Tamiazzo Stefania,Stobbione Paolo,Agatea Lisa,De Gaspari Piera,Stecca Anna,Lauritano Ernesto C,Roveta Annalisa,Tozzoli Renato,Guaschino Roberto,Bonometti Ramona
Clinical and translational science
Currently, few evidences have shown the possible involvement of autoimmunity in patients affected by coronavirus disease 2019 (COVID-19). In this study, we elucidate whether severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) stimulates autoantibody production and contributes to autoimmunity activation. We enrolled 40 adult patients (66.8 years mean age) admitted to Alessandria Hospital between March and April 2020. All the patients had a confirmed COVID-19 diagnosis and no previously clinical record of autoimmune disease. Forty blood donors were analyzed for the same markers and considered as healthy controls. Our patients had high levels of common inflammatory markers, such as C reactive protein, lactate dehydrogenase, ferritin, and creatinine. Interleukin-6 concentrations were also increased, supporting the major role of this interleukin during COVID-19 infection. Lymphocyte numbers were generally lower compared with healthy individuals. All the patients were also screened for the most common autoantibodies. We found a significant prevalence of antinuclear antibodies, antineutrophil cytoplasmic antibodies, and ASCA immunoglobulin A antibodies. We observed that patients having a de novo autoimmune response had the worst acute viral disease prognosis and outcome. Our results sustain the hypothesis that COVID-19 infection correlates with the autoimmunity markers. Our study might help clinicians to: (a) better understand the heterogeneity of this pathology and (b) correctly evaluate COVID-19 clinical manifestations. Our data explained why drugs used to treat autoimmune diseases may also be useful for SARS-CoV-2 infection. In addition, we highly recommend checking patients with COVID-19 for autoimmunity markers, mainly when deciding on whether to treat them with plasma transfer therapy.
The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection.
Copaescu Ana,Smibert Olivia,Gibson Andrew,Phillips Elizabeth J,Trubiano Jason A
The Journal of allergy and clinical immunology
The coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 presents with a spectrum of clinical manifestations from asymptomatic or mild, self-limited constitutional symptoms to a hyperinflammatory state ("cytokine storm") followed by acute respiratory distress syndrome and death. The objective of this study was to provide an evidence-based review of the associated pathways and potential treatment of the hyperinflammatory state associated with severe acute respiratory syndrome coronavirus 2 infection. Dysregulated immune responses have been reported to occur in a smaller subset of those infected with severe acute respiratory syndrome coronavirus 2, leading to clinical deterioration 7 to 10 days after initial presentation. A hyperinflammatory state referred to as cytokine storm in its severest form has been marked by elevation of IL-6, IL-10, TNF-α, and other cytokines and severe CD4 and CD8 T-cell lymphopenia and coagulopathy. Recognition of at-risk patients could permit early institution of aggressive intensive care and antiviral and immune treatment to reduce the complications related to this proinflammatory state. Several reports and ongoing clinical trials provide hope that available immunomodulatory therapies could have therapeutic potential in these severe cases. This review highlights our current state of knowledge of immune mechanisms and targeted immunomodulatory treatment options for the current coronavirus disease 2019 pandemic.
[Detection of autoimmune parameter of SARS patients].
Li Bo-an,He Wei-ping,Liu Yan,Shu Cui-li,Li Jing,Gao Rong,Hou Jun,Li Jin,Cheng Yun
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology
OBJECTIVE:To explore whether autoimmune phenomena exist in SARS patients, and to seek for unusual autoimmune antibodies in SARS patients. METHODS:Autoantibodies against cell nuclei (ANA), autoantibodies against smooth muscles (SMA), autoantibodies against parietal cells (PCA), autoantibodies against heart cells (HRA) were detected by using immunofluorescence, and autoantibodies against live-kidney microsomes (LKM) and anti-M2 antibodies were detected by ELISA in sera taken from 27 SARS patients and 18 healthy controls. Immunofluorescence was used to localize the targets antigens in slides with biochips of lung (monkey) of SARS associated antibodies. RESULTS:ANA, AMA, LKM and SMA were found positive in 3, 1, 1, and 1 of the 27 SARS sera. In 18 healthy control sera, one ANA and one AMA were positive. Statistical analysis showed that there were no difference between two groups in every item detected. Twenty-six of 27 SARS patients and 5 of 18 healthy controls had strongly stained columnar epithelia of the bronchiole, especially the lumen border of the epithelia?the difference between two groups was significant. CONCLUSION:No antibodies against organs but lung were found in SARS patients. There are auto antibodies against lung tissues in sera of SARS patients.
Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD).
Gagiannis Daniel,Steinestel Julie,Hackenbroch Carsten,Schreiner Benno,Hannemann Michael,Bloch Wilhelm,Umathum Vincent G,Gebauer Niklas,Rother Conn,Stahl Marcel,Witte Hanno M,Steinestel Konrad
Frontiers in immunology
Background and Objectives:Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Methods:We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. Results:Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 10%; p = 0.002) and occurrence of severe complications (75 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. Conclusions:We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.