
Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study.
BMC neurology
BACKGROUND:The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. METHODS:Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia. RESULTS:Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. CONCLUSIONS:The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.
10.1186/1471-2377-11-37
Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health.
Trends in molecular medicine
Decreased smell function is related to brain health, future mortality, and quality of life. Most people inflicted with the SARS-CoV-2 virus evidence some measurable smell dysfunction during its acute phase, although many are unaware of the loss. Long-term deficits occur in up to 30% of COVID-19 cases, although total anosmia is relatively rare. This review explores what is presently known about the nature and pathophysiology of olfactory dysfunction due to the SARS-CoV-2 virus, including reversible inflammation within the olfactory cleft, downregulation of olfactory receptor proteins, and long-lasting peripheral and central damage to olfactory structures. It also addresses the question as to whether long-term smell loss might increase the likelihood of future development of cognitive and neurological deficits.
10.1016/j.molmed.2022.06.005
Pulmonary Aspects of COVID-19.
Doerschug Kevin C,Schmidt Gregory A
Annual review of medicine
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that gains entry via angiotensin-converting enzyme 2 (ACE2) within airway epithelium. Patients exhibit a spectrum of respiratory symptoms from asymptomatic to respiratory failure. Patient factors including obesity, tobacco use, and black race are all associated with increased ACE2 expression and may contribute to increased complications. Consolidation and ground-glass opacities on chest imaging are typical but not specific for coronavirus disease 2019 (COVID-19). Venous thromboembolism occurs infrequently when prophylactic anticoagulation is provided. However, capillary microthrombosis is nearly ubiquitous, suggesting that it contributes to hypoxemia. Remdesivir and glucocorticoids may benefit some hospitalized patients. Many of those afflicted remain symptomatic two weeks following diagnosis and continue to require health care. Total lung capacity, diffusion capacity, and maximal oxygen consumption may be reduced for months in some survivors. Lung transplant offers chronically critically ill patients new hope, and this option may have increasing potential for outpatients with COVID-19-associated fibrosis.
10.1146/annurev-med-042220-014817
Neurologic Manifestations and Complications of COVID-19.
Hensley Matthew K,Markantone Desiree,Prescott Hallie C
Annual review of medicine
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global pandemic. Beyond the well-described respiratory manifestations, SARS-CoV-2 may cause a variety of neurologic complications, including headaches, alteration in taste and smell, encephalopathy, cerebrovascular disease, myopathy, psychiatric diseases, and ocular disorders. Herein we describe SARS-CoV-2's mechanism of neuroinvasion and the epidemiology, outcomes, and treatments for neurologic manifestations of COVID-19.
10.1146/annurev-med-042320-010427
Open resource of clinical data from patients with pneumonia for the prediction of COVID-19 outcomes via deep learning.
Nature biomedical engineering
Data from patients with coronavirus disease 2019 (COVID-19) are essential for guiding clinical decision making, for furthering the understanding of this viral disease, and for diagnostic modelling. Here, we describe an open resource containing data from 1,521 patients with pneumonia (including COVID-19 pneumonia) consisting of chest computed tomography (CT) images, 130 clinical features (from a range of biochemical and cellular analyses of blood and urine samples) and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical status. We show the utility of the database for prediction of COVID-19 morbidity and mortality outcomes using a deep learning algorithm trained with data from 1,170 patients and 19,685 manually labelled CT slices. In an independent validation cohort of 351 patients, the algorithm discriminated between negative, mild and severe cases with areas under the receiver operating characteristic curve of 0.944, 0.860 and 0.884, respectively. The open database may have further uses in the diagnosis and management of patients with COVID-19.
10.1038/s41551-020-00633-5
Gastrointestinal sequelae 90 days after discharge for COVID-19.
Weng Jingrong,Li Yichen,Li Jie,Shen Lihan,Zhu Lixin,Liang Yufan,Lin Xutao,Jiao Na,Cheng Sijing,Huang Yibo,Zou Yifeng,Yan Guangjun,Zhu Ruixin,Lan Ping
The lancet. Gastroenterology & hepatology
10.1016/S2468-1253(21)00076-5
Policy stringency and mental health during the COVID-19 pandemic: a longitudinal analysis of data from 15 countries.
The Lancet. Public health
BACKGROUND:To date, public health policies implemented during the COVID-19 pandemic have been evaluated on the basis of their ability to reduce transmission and minimise economic harm. We aimed to assess the association between COVID-19 policy restrictions and mental health during the COVID-19 pandemic. METHODS:In this longitudinal analysis, we combined daily policy stringency data from the Oxford COVID-19 Government Response Tracker with psychological distress scores and life evaluations captured in the Imperial College London-YouGov COVID-19 Behaviour Tracker Global Survey in fortnightly cross-sections from samples of 15 countries between April 27, 2020, and June 28, 2021. The mental health questions provided a sample size of 432 642 valid responses, with an average of 14 918 responses every 2 weeks. To investigate how policy stringency was associated with mental health, we considered two potential mediators: observed physical distancing and perceptions of the government's handling of the pandemic. Countries were grouped on the basis of their response to the COVID-19 pandemic as those pursuing an elimination strategy (countries that aimed to eliminate community transmission of SARS-CoV-2 within their borders) or those pursuing a mitigation strategy (countries that aimed to control SARS-CoV-2 transmission). Using a combined dataset of country-level and individual-level data, we estimated linear regression models with country-fixed effects (ie, dummy variables representing the countries in our sample) and with individual and contextual covariates. Additionally, we analysed data from a sample of Nordic countries, to compare Sweden (that pursued a mitigation strategy) to other Nordic countries (that adopted a near-elimination strategy). FINDINGS:Controlling for individual and contextual variables, higher policy stringency was associated with higher mean psychological distress scores and lower life evaluations (standardised coefficients β=0·014 [95% CI 0·005 to 0·023] for psychological distress; β=-0·010 [-0·015 to -0·004] for life evaluation). Pandemic intensity (number of deaths per 100 000 inhabitants) was also associated with higher mean psychological distress scores and lower life evaluations (standardised coefficients β=0·016 [0·008 to 0·025] for psychological distress; β=-0·010 [-0·017 to -0·004] for life evaluation). The negative association between policy stringency and mental health was mediated by observed physical distancing and perceptions of the government's handling of the pandemic. We observed that countries pursuing an elimination strategy used different policy timings and intensities compared with countries pursuing a mitigation strategy. The containment policies of countries pursuing elimination strategies were on average less stringent, and fewer deaths were observed. INTERPRETATION:Changes in mental health measures during the first 15 months of the COVID-19 pandemic were small. More stringent COVID-19 policies were associated with poorer mental health. Elimination strategies minimised transmission and deaths, while restricting mental health effects. FUNDING:None.
10.1016/S2468-2667(22)00060-3
COVID-19 mortality and excess mortality among working-age residents in California, USA, by occupational sector: a longitudinal cohort analysis of mortality surveillance data.
The Lancet. Public health
BACKGROUND:During the first year of the COVID-19 pandemic, workers in essential sectors had higher rates of SARS-CoV-2 infection and COVID-19 mortality than those in non-essential sectors. It is unknown whether disparities in pandemic-related mortality across occupational sectors have continued to occur during the periods of SARS-CoV-2 variants and vaccine availability. METHODS:In this longitudinal cohort study, we obtained data from the California Department of Public Health on all deaths occurring in the state of California, USA, from Jan 1, 2016, to Dec 31, 2021. We restricted our analysis to residents of California who were aged 18-65 years at time of death and died of natural causes. We classified the occupational sector into nine essential sectors; non-essential; or unemployed or without an occupation provided on the death certificate. We calculated the number of COVID-19 deaths in total and per capita that occurred in each occupational sector. Separately, using autoregressive integrated moving average models, we estimated total, per-capita, and relative excess natural-cause mortality by week between March 1, 2020, and Nov 30, 2021, stratifying by occupational sector. We additionally stratified analyses of occupational risk into counties with high versus low vaccine uptake, categorising high-uptake regions as counties where at least 50% of the population were fully vaccinated according to US guidelines by Aug 1, 2021. FINDINGS:From March 1, 2020, to Nov 30, 2021, 24 799 COVID-19 deaths were reported in residents of California aged 18-65 years and an estimated 28 751 (95% prediction interval 27 853-29 653) excess deaths. People working in essential sectors were associated with higher COVID-19 deaths and excess deaths than were those working in non-essential sectors, with the highest per-capita COVID-19 mortality in the agriculture (131·8 per 100 000 people), transportation or logistics (107·1 per 100 000), manufacturing (103·3 per 100 000), facilities (101·1 per 100 000), and emergency (87·8 per 100 000) sectors. Disparities were wider during periods of increased infections, including during the Nov 29, 2020, to Feb 27, 2021, surge in infections, which was driven by the delta variant (B.1.617.2) and occurred during vaccine uptake. During the June 27 to Nov 27, 2021 surge, emergency workers had higher COVID-19 mortality (113·7 per 100 000) than workers from any other sector. Workers in essential sectors had the highest COVID-19 mortality in counties with low vaccination uptake, a difference that was more pronounced during the period of the delta infection surge during Nov 29, 2020, to Feb 27, 2021. INTERPRETATION:Workers in essential sectors have continued to bear the brunt of high COVID-19 and excess mortality throughout the pandemic, particularly in the agriculture, emergency, manufacturing, facilities, and transportation or logistics sectors. This high death toll has continued during periods of vaccine availability and the delta surge. In an ongoing pandemic without widespread vaccine coverage and with anticipated threats of new variants, the USA must actively adopt policies to more adequately protect workers in essential sectors. FUNDING:US National Institute on Aging, Swiss National Science Foundation, and US National Institute on Drug Abuse.
10.1016/S2468-2667(22)00191-8
Early prediction of COVID-19 severity using extracellular vesicle COPB2.
Fujita Yu,Hoshina Tokio,Matsuzaki Juntaro,Yoshioka Yusuke,Kadota Tsukasa,Hosaka Yusuke,Fujimoto Shota,Kawamoto Hironori,Watanabe Naoaki,Sawaki Kenji,Sakamoto Yohei,Miyajima Makiko,Lee Kwangyole,Nakaharai Kazuhiko,Horino Tetsuya,Nakagawa Ryo,Araya Jun,Miyato Mitsuru,Yoshida Masaki,Kuwano Kazuyoshi,Ochiya Takahiro
Journal of extracellular vesicles
The clinical manifestations of COVID-19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID-19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID-19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID-19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID-19 severity. Strikingly, we identified three distinct groups of markers (antiviral response-related EV proteins, coagulation-related markers, and liver damage-related exRNAs) with the potential to serve as early predictive biomarkers for COVID-19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID-19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00-1.00)). The validation set included 40 COVID-19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73-0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID-19 therapy.
10.1002/jev2.12092
Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19.
Genome medicine
Since the start of the coronavirus disease 2019 (COVID-19) pandemic, important insights have been gained into virus biology and the host factors that modulate the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 displays a highly variable clinical picture that ranges from asymptomatic disease to lethal pneumonia. Apart from well-established general risk factors such as advanced age, male sex and chronic comorbidities, differences in host genetics have been shown to influence the individual predisposition to develop severe manifestations of COVID-19. These differences range from common susceptibility loci to rare genetic variants with strongly predisposing effects, or proven pathogenic variants that lead to known or novel inborn errors of immunity (IEI), which constitute a growing group of heterogeneous Mendelian disorders with increased susceptibility to infectious disease, auto-inflammation, auto-immunity, allergy or malignancies. The current genetic findings point towards a convergence of common and rare genetic variants that impact the interferon signalling pathways in patients with severe or critical COVID-19. Monogenic risk factors that impact IFN-I signalling have an expected prevalence between 1 and 5% in young, previously healthy individuals (<60 years of age) with critical COVID-19. The identification of these IEI such as X-linked TLR7 deficiency indicates a possibility for targeted genetic screening and personalized clinical management. This review aims to provide an overview of our current understanding of the host genetic factors that predispose to severe manifestations of COVID-19 and focuses on rare variants in IFN-I signalling genes and their potential clinical implications.
10.1186/s13073-022-01100-3
Non-pharmaceutical interventions during the COVID-19 pandemic: A review.
Physics reports
Infectious diseases and human behavior are intertwined. On one side, our movements and interactions are the engines of transmission. On the other, the unfolding of viruses might induce changes to our daily activities. While intuitive, our understanding of such feedback loop is still limited. Before COVID-19 the literature on the subject was mainly theoretical and largely missed validation. The main issue was the lack of empirical data capturing behavioral change induced by diseases. Things have dramatically changed in 2020. Non-pharmaceutical interventions (NPIs) have been the key weapon against the SARS-CoV-2 virus and affected virtually any societal process. Travel bans, events cancellation, social distancing, curfews, and lockdowns have become unfortunately very familiar. The scale of the emergency, the ease of survey as well as crowdsourcing deployment guaranteed by the latest technology, several Data for Good programs developed by tech giants, major mobile phone providers, and other companies have allowed unprecedented access to data describing behavioral changes induced by the pandemic. Here, I review some of the vast literature written on the subject of NPIs during the COVID-19 pandemic. In doing so, I analyze 348 articles written by more than 2518 authors in the first 12 months of the emergency. While the large majority of the sample was obtained by querying PubMed, it includes also a hand-curated list. Considering the focus, and methodology I have classified the sample into seven main categories: epidemic models, surveys, comments/perspectives, papers aiming to quantify the effects of NPIs, reviews, articles using data proxies to measure NPIs, and publicly available datasets describing NPIs. I summarize the methodology, data used, findings of the articles in each category and provide an outlook highlighting future challenges as well as opportunities.
10.1016/j.physrep.2021.02.001
Transmission of Respiratory Viral Diseases to Health Care Workers: COVID-19 as an Example.
Annual review of public health
Health care workers (HCWs) can acquire infectious diseases, including coronavirus disease 2019 (COVID-19), from patients. Herein, COVID-19 is used with the source-pathway-receptor framework as an example to assess evidence for the roles of aerosol transmission and indirect contact transmission in viral respiratory infectious diseases. Evidence for both routes is strong for COVID-19 and other respiratory viruses, but aerosol transmission is likely dominant for COVID-19. Key knowledge gaps about transmission processes and control strategies include the distribution of viable virus among respiratory aerosols of different sizes, the mechanisms and efficiency by which virus deposited on the facial mucous membrane moves to infection sites inside the body, and the performance of source controls such as face coverings and aerosol containment devices. To ensure that HCWs are adequately protected from infection, guidelines and regulations must be updated to reflect the evidence that respiratory viruses are transmitted via aerosols.
10.1146/annurev-publhealth-052120-110009
Therapeutic Potential of Metformin in COVID-19: Reasoning for Its Protective Role.
Trends in microbiology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections present with increased disease severity and poor clinical outcomes in diabetic patients compared with their nondiabetic counterparts. Diabetes/hyperglycemia-triggered endothelial dysfunction and hyperactive inflammatory and immune responses are correlated to twofold to threefold higher intensive care hospitalizations and more than twice the mortality among diabetic coronavirus disease 2019 (COVID-19) patients. While comorbidities such as obesity, cardiovascular disease, and hypertension worsen the prognosis of diabetic COVID-19 patients, COVID-19 infections are also associated with new-onset diabetes, severe metabolic complications, and increased thrombotic events in the backdrop of aberrant endothelial function. While several antidiabetic medications are used to manage blood glucose levels, we discuss the multifaceted ability of metformin to control blood glucose levels and possibly attenuate endothelial dysfunction, inhibit viral entry and infection, and modify inflammatory and immune responses during SARS-CoV-2 infections. These actions make metformin a viable candidate drug to be considered for repurposing and gaining ground against the SARS-CoV-2-induced tsunami in diabetic COVID-19 patients.
10.1016/j.tim.2021.03.004
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a review.
Molecular cancer
In recent years, the prevalence and spread of coronavirus has had a huge impact on global public health. Due to the incomplete understanding of the pathogenic mechanism of the virus, it is difficult for humans to fight against the virus quickly and effectively once the outbreak occurs. In early 2020, a novel coronavirus was discovered in Wuhan, China. Soon after, similar cases were found in other countries around the world, and the number of infected people increased rapidly. So far, the global cumulative number of infected people has exceeded 3 million, and more than 200,000 people have died, which has had a huge impact on global human health and economic development. Every outbreak of disease makes a deep impression on mankind. Herein, we summarize the virology, epidemiology, clinical manifestations, diagnosis, treatment and prevention of SARS-CoV-2, and hope that countries can control the outbreak as soon as possible to minimize the loss.
10.1186/s12943-020-01218-1
Planetary healthy publics after COVID-19.
The Lancet. Planetary health
COVID-19 is a sign of a global malaise. The pandemic is an outcome of what we term a planetary dysbiosis, for which underlining drivers include inequality and the exploitation and extraction of human and non-human labours. The implication is that the usual fixes to outbreaks of infectious diseases (ie, surveillance, pharmaceutical measures, and non-pharmaceutical measures) will be insufficient without a thorough reappraisal of and investment in planetary health. Given the heterogeneity and diversity of environments and populations, we envisage these actions as a matter for the generation of new kinds of public, requiring widespread and multiple forms of engagement to generate lasting solutions. We use and extend the concept of healthy publics to suggest a movement that can start to reclaim planetary health as a collective and ongoing issue.
10.1016/S2542-5196(21)00050-4
COVID-19 Critical Illness: A Data-Driven Review.
Annual review of medicine
The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges in critical care medicine, including extreme demand for intensive care unit (ICU) resources and rapidly evolving understanding of a novel disease. Up to one-third of hospitalized patients with COVID-19 experience critical illness. The most common form of organ failure in COVID-19 critical illness is acute hypoxemic respiratory failure, which clinically presents as acute respiratory distress syndrome (ARDS) in three-quarters of ICU patients. Noninvasive respiratory support modalities are being used with increasing frequency given their potential to reduce the need for intubation. Determining optimal patient selection for and timing of intubation remains a challenge. Management of mechanically ventilated patients with COVID-19 largely mirrors that of non-COVID-19 ARDS. Organ failure is common and portends a poor prognosis. Mortality rates have improved over the course of the pandemic, likely owing to increasing disease familiarity, data-driven pharmacologics, and improved adherence to evidence-based critical care.
10.1146/annurev-med-042420-110629
Maintaining face mask use before and after achieving different COVID-19 vaccination coverage levels: a modelling study.
The Lancet. Public health
BACKGROUND:Face mask wearing has been an important part of the response to the COVID-19 pandemic. As vaccination coverage progresses in countries, relaxation of such practices is increasing. Subsequent COVID-19 surges have raised the questions of whether face masks should be encouraged or required and for how long. Here, we aim to assess the value of maintaining face masks use indoors according to different COVID-19 vaccination coverage levels in the USA. METHODS:In this computational simulation-model study, we developed and used a Monte Carlo simulation model representing the US population and SARS-CoV-2 spread. Simulation experiments compared what would happen if face masks were used versus not used until given final vaccination coverages were achieved. Different scenarios varied the target vaccination coverage (70-90%), the date these coverages were achieved (Jan 1, 2022, to July 1, 2022), and the date the population discontinued wearing face masks. FINDINGS:Simulation experiments revealed that maintaining face mask use (at the coverage seen in the USA from March, 2020, to July, 2020) until target vaccination coverages were achieved was cost-effective and in many cases cost saving from both the societal and third-party payer perspectives across nearly all scenarios explored. Face mask use was estimated to be cost-effective and usually cost saving when the cost of face masks per person per day was ≤US$1·25. In all scenarios, it was estimated to be cost-effective to maintain face mask use for about 2-10 weeks beyond the date that target vaccination coverage (70-90%) was achieved, with this added duration being longer when the target coverage was achieved during winter versus summer. Factors that might increase the transmissibility of the virus (eg, emergence of the delta [B.1.617.2] and omicron [B.1.1.529] variants), or decrease vaccine effectiveness (eg, waning immunity or escape variants), or increase social interactions among certain segments of the population, only increased the cost savings or cost-effectiveness provided by maintaining face mask use. INTERPRETATION:Our study provides strong support for maintaining face mask use until and a short time after achieving various final vaccination coverage levels, given that maintaining face mask use can be not just cost-effective, but even cost saving. The emergence of the omicron variant and the prospect of future variants that might be more transmissible and reduce vaccine effectiveness only increases the value of face masks. FUNDING:The Agency for Healthcare Research and Quality, the National Institute of General Medical Sciences, the National Science Foundation, the National Center for Advancing Translational Sciences, and the City University of New York.
10.1016/S2468-2667(22)00040-8
The Psychology of Pandemics.
Annual review of clinical psychology
This article reviews the current state of knowledge and promising new directions concerning the psychology of pandemics. Pandemics are disease outbreaks that spread globally. Historically, psychological factors have been neglected by researchers and health authorities despite evidence that pandemics are, to a large extent, psychological phenomena whereby beliefs and behaviors influence the spreading versus containment of infection. Psychological factors are important in determining () adherence to pandemic mitigation methods (e.g., adherence to social distancing), () pandemic-related social disruption (e.g., panic buying, racism, antilockdown protests), and () pandemic-related distress and related problems (e.g., anxiety, depression, posttraumatic stress disorder, prolonged grief disorder). The psychology of pandemics has emerged as an important field of research and practice during the coronavirus 2019 (COVID-19) pandemic. As a scholarly discipline, the psychology of pandemics is fragmented and diverse, encompassing various psychological subspecialties and allied disciplines, but is vital for shaping clinical practice and public health guidelines for COVID-19 and future pandemics.
10.1146/annurev-clinpsy-072720-020131
Tissue-resident CD8 T cells drive age-associated chronic lung sequelae after viral pneumonia.
Science immunology
Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8 tissue-resident memory T cells (T) in the respiratory tract of aged hosts. T cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that T cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, T cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8 T cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated T cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.
10.1126/sciimmunol.abc4557
Environmental Factors Influencing COVID-19 Incidence and Severity.
Annual review of public health
Emerging evidence supports a link between environmental factors-including air pollution and chemical exposures, climate, and the built environment-and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and coronavirus disease 2019 (COVID-19) susceptibility and severity. Climate, air pollution, and the built environment have long been recognized to influence viral respiratory infections, and studies have established similar associations with COVID-19 outcomes. More limited evidence links chemical exposures to COVID-19. Environmental factors were found to influence COVID-19 through four major interlinking mechanisms: increased risk of preexisting conditions associated with disease severity; immune system impairment; viral survival and transport; and behaviors that increase viral exposure. Both data and methodologic issues complicate the investigation of these relationships, including reliance on coarse COVID-19 surveillance data; gaps in mechanistic studies; and the predominance of ecological designs. We evaluate the strength of evidence for environment-COVID-19 relationships and discuss environmental actions that might simultaneously address the COVID-19 pandemic, environmental determinants of health, and health disparities.
10.1146/annurev-publhealth-052120-101420
Immune signatures underlying post-acute COVID-19 lung sequelae.
Science immunology
Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific memory T and B cells were enriched at the site of infection compared with those of blood. Detailed evaluation of the lung immune compartment revealed that dysregulated respiratory CD8 T cell responses were associated with the impaired lung function after acute COVID-19. Single-cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8 T cells contributing to persistent tissue conditions after COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae after SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.
10.1126/sciimmunol.abk1741
COVID-19-associated coagulopathy and antithrombotic agents-lessons after 1 year.
The Lancet. Haematology
COVID-19 is associated with a high incidence of thrombotic complications, which can be explained by the complex and unique interplay between coronaviruses and endothelial cells, the local and systemic inflammatory response, and the coagulation system. Empirically, an intensified dose of thrombosis prophylaxis is being used in patients admitted to hospital with COVID-19 and several guidelines on this topic have been published, although the insufficiency of high quality and direct evidence has led to weak recommendations. In this Viewpoint we summarise the pathophysiology of COVID-19 coagulopathy in the context of patients who are ambulant, admitted to hospital, and critically ill or non-critically ill, and those post-discharge from hospital. We also review data from randomised controlled trials in the past year of antithrombotic therapy in patients who are critically ill. These data provide the first high-quality evidence on optimal use of antithrombotic therapy in patients with COVID-19. Pharmacological thromboprophylaxis is not routinely recommended for patients who are ambulant and post-discharge. A first ever trial in non-critically ill patients who were admitted to hospital has shown that a therapeutic dose of low-molecular-weight heparin might improve clinical outcomes in this population. In critically ill patients, this same treatment does not improve outcomes and prophylactic dose anticoagulant thromboprophylaxis is recommended. In the upcoming months we expect numerous data from the ongoing antithrombotic COVID-19 studies to guide clinicians at different stages of the disease.
10.1016/S2352-3026(21)00105-8
Sex Differences in Immunity.
Annual review of immunology
Strong epidemiological evidence now exists that sex is an important biologic variable in immunity. Recent studies, for example, have revealed that sex differences are associated with the severity of symptoms and mortality due to coronavirus disease 2019 (COVID-19). Despite this evidence, much remains to be learned about the mechanisms underlying associations between sex differences and immune-mediated conditions. A growing body of experimental data has made significant inroads into understanding sex-influenced immune responses. As physicians seek to provide more targeted patient care, it is critical to understand how sex-defining factors (e.g., chromosomes, gonadal hormones) alter immune responses in health and disease. In this review, we highlight recent insights into sex differences in autoimmunity; virus infection, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; and cancer immunotherapy. A deeper understanding of underlying mechanisms will allow the development of a sex-based approach to disease screening and treatment.
10.1146/annurev-immunol-101320-125133
Neutralizing monoclonal antibodies for treatment of COVID-19.
Nature reviews. Immunology
Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.
10.1038/s41577-021-00542-x
Global pandemics interconnected - obesity, impaired metabolic health and COVID-19.
Nature reviews. Endocrinology
Obesity and impaired metabolic health are established risk factors for the non-communicable diseases (NCDs) type 2 diabetes mellitus, cardiovascular disease, neurodegenerative diseases, cancer and nonalcoholic fatty liver disease, otherwise known as metabolic associated fatty liver disease (MAFLD). With the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), obesity and impaired metabolic health also emerged as important determinants of severe coronavirus disease 2019 (COVID-19). Furthermore, novel findings indicate that specifically visceral obesity and characteristics of impaired metabolic health such as hyperglycaemia, hypertension and subclinical inflammation are associated with a high risk of severe COVID-19. In this Review, we highlight how obesity and impaired metabolic health increase complications and mortality in COVID-19. We also summarize the consequences of SARS-CoV-2 infection for organ function and risk of NCDs. In addition, we discuss data indicating that the COVID-19 pandemic could have serious consequences for the obesity epidemic. As obesity and impaired metabolic health are both accelerators and consequences of severe COVID-19, and might adversely influence the efficacy of COVID-19 vaccines, we propose strategies for the prevention and treatment of obesity and impaired metabolic health on a clinical and population level, particularly while the COVID-19 pandemic is present.
10.1038/s41574-020-00462-1