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J Clin Invest ; 131(24)2021 12 15.
Article in English | MEDLINE | ID: covidwho-1495792


Acute COVID-19, caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Diseases Association Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10% to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This Review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed.

Autoantibodies/chemistry , Autoimmunity/immunology , COVID-19/immunology , COVID-19/physiopathology , Signal Transduction , Animals , Autoimmune Diseases , B-Lymphocytes/cytology , Cytokines/metabolism , Disease Progression , Female , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Inflammation , Interleukin-1/metabolism , Interleukin-6/metabolism , Macrophage Activation , Male , Mice , Phospholipids/metabolism , SARS-CoV-2
Nat Commun ; 12(1): 5417, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1410404


COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.

Autoantibodies/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Aged , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoantibodies/blood , Autoantigens/immunology , Connective Tissue Diseases/immunology , Cytokines/immunology , Female , Hospitalization , Humans , Immunoglobulin G/blood , Male , Middle Aged , SARS-CoV-2/pathogenicity , Viral Proteins/immunology
Nat Rev Rheumatol ; 16(10): 581-589, 2020 10.
Article in English | MEDLINE | ID: covidwho-690837


Reports of widespread thromboses and disseminated intravascular coagulation (DIC) in patients with coronavirus disease 19 (COVID-19) have been rapidly increasing in number. Key features of this disorder include a lack of bleeding risk, only mildly low platelet counts, elevated plasma fibrinogen levels, and detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complement components in regions of thrombotic microangiopathy (TMA). This disorder is not typical DIC. Rather, it might be more similar to complement-mediated TMA syndromes, which are well known to rheumatologists who care for patients with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome. This perspective has critical implications for treatment. Anticoagulation and antiviral agents are standard treatments for DIC but are gravely insufficient for any of the TMA disorders that involve disorders of complement. Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy.

Betacoronavirus/immunology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Thrombosis/immunology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Complement System Proteins/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/immunology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/virology , Fibrinogen/analysis , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Pandemics , Plasma Exchange/methods , Platelet Count/methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Risk Factors , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/pathology , Thrombosis/virology , Thrombotic Microangiopathies/drug therapy , Thrombotic Microangiopathies/immunology , Thrombotic Microangiopathies/pathology , Thrombotic Microangiopathies/virology