Severe Coronavirus Disease 2019 (COVID-19) is Associated With Elevated Serum Immunoglobulin (Ig) A and Antiphospholipid IgA Antibodies

Clinical Infectious Diseases - Tập 73 Số 9 - Trang e2869-e2874 - 2021
Omar Hasan Ali1,2,3, David Bomze3,4, Lorenz Risch5,6, Silvio D. Brugger7, Matthias Paprotny8, Myriam Weber8, Sarah Thiel8, Lukas Kern9, Werner C. Albrich10, Philipp Köhler10, Christian R. Kahlert11,10, Pietro Vernazza10, Philipp K. Buehler12, Reto A. Schuepbach12, Alejandro Gómez-Mejía7, Alexandra Popa13, Andreas Bergthaler13, Josef Penninger2,14, Lukas Flatz15,1,16,3
1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
2Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada
3Institute of Immunobiology, Kantonsspital St Gallen, St Gallen, Switzerland
4Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
5Center of Laboratory Medicine, University Institute of Clinical Chemistry, University of Bern, Bern, Switzerland
6Labormedizinisches zentrum Dr. Risch, Vaduz, Liechtenstein
7Department of Infectious Diseases and Hospital Hygiene, University Hospital Zurich, Zurich, Switzerland
8Department of General Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein
9Department of Pulmonology, Kantonsspital St. Gallen, St. Gallen, Switzerland
10Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
11Department of Infectious Diseases and Hospital Epidemiology, Children’s Hospital of Eastern Switzerland, St. Gallen, Switzerland
12Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland
13Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
14Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
15Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland
16Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland

Tóm tắt

AbstractBackgroundSevere coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there are little data on possible immunoglobulin (Ig) A–mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and whether IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome, our approach focused on antiphospholipid antibodies (aPL).MethodsIn this retrospective cohort study, clinical data and aPL from 64 patients with COVID-19 were compared from 3 independent tertiary hospitals (1 in Liechtenstein, 2 in Switzerland). Samples were collected from 9 April to 1 May 2020.ResultsClinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID; 41%), a discovery cohort with severe illness (sdCOVID; 22%) and a confirmation cohort with severe illness (scCOVID; 38%). Total IgA, IgG, and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P = .01; scCOVID, P < .001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anticardiolipin IgA (sdCOVID and scCOVID, P < .001), anticardiolipin IgM (sdCOVID, P = .003; scCOVID, P< .001), and anti–beta 2 glycoprotein-1 IgA (sdCOVID and scCOVID, P< .001). Systemic lupus erythematosus was excluded from all patients as a potential confounder.ConclusionsHigher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.

Từ khóa


Tài liệu tham khảo

Gorbalenya, 2020, The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2, Nat Microbiol, 5, 536, 10.1038/s41564-020-0695-z

Drosten, 2003, Identification of a novel coronavirus in patients with severe acute respiratory syndrome, N Engl J Med, 348, 1967, 10.1056/NEJMoa030747

Banerjee, 2019, Molecular pathogenesis of Middle East respiratory syndrome (MERS) coronavirus, Curr Clin Microbiol Rep, 6, 139, 10.1007/s40588-019-00122-7

Monteil, 2020, Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2, Cell, 181, 905, 10.1016/j.cell.2020.04.004

Brandtzaeg, 1996, Immune functions and immunopathology of the mucosa of the upper respiratory pathways, Acta Otolaryngol, 116, 149, 10.3109/00016489609137812

Yu, 2020, Distinct features of SARS-CoV-2–specific IgA response in COVID-19 patients, Eur Respir J, 56, 2001526, 10.1183/13993003.01526-2020

Chen, 2020, Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study, BMJ, 368, m1091, 10.1136/bmj.m1091

Carsana, 2020, Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study, Lancet Infect Dis, 20, 1135, 10.1016/S1473-3099(20)30434-5

Wise, 2020, COVID-19 and thrombosis: what do we know about the risks and treatment?, BMJ, 369, m2058, 10.1136/bmj.m2058

Klok, 2020, Incidence of thrombotic complications in critically ill ICU patients with COVID-19, Thromb Res, 191, 145, 10.1016/j.thromres.2020.04.013

Zhang, 2020, Coagulopathy and antiphospholipid antibodies in patients with COVID-19, N Engl J Med, 382, e38, 10.1056/NEJMc2007575

Schreiber, 2018, Antiphospholipid syndrome, Nat Rev Dis Primers, 4, 17103, 10.1038/nrdp.2017.103

Corman, 2020, Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR, Euro Surveill, 25, 2000045, 10.2807/1560-7917.ES.2020.25.3.2000045

Pfefferle, 2020, Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system, Euro Surveill, 25, 2000152, 10.2807/1560-7917.ES.2020.25.9.2000152

World Health Organization, 2020

Pilette, 2001, Lung mucosal immunity: immunoglobulin-A revisited, Eur Respir J, 18, 571, 10.1183/09031936.01.00228801

Yao, 2020, D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study, J Intensive Care, 8, 49, 10.1186/s40560-020-00466-z

Yu, 2020, Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis, J Thromb Thrombolysis, 50, 548, 10.1007/s11239-020-02171-y

Zhang, 2020, Profile of natural anticoagulant, coagulant factor and anti-phospholipid antibody in critically ill COVID-19 patients, J Thromb Thrombolysis, 50, 580, 10.1007/s11239-020-02182-9

Aringer, 2019, 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus, Arthritis Rheumatol, 71, 1400, 10.1002/art.40930

Shoenfeld, 2006, Infectious origin of the antiphospholipid syndrome, Ann Rheum Dis, 65, 2, 10.1136/ard.2005.045443

Cervera, 2004, Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients, Ann Rheum Dis, 63, 1312, 10.1136/ard.2003.014175

Mendoza-Pinto, 2018, Role of infectious diseases in the antiphospholipid syndrome (including its catastrophic variant), Curr Rheumatol Rep, 20, 62, 10.1007/s11926-018-0773-x

Fessler, 2016, Surfactant lipids at the host-environment interface. Metabolic sensors, suppressors, and effectors of inflammatory lung disease, Am J Respir Cell Mol Biol, 54, 624, 10.1165/rcmb.2016-0011PS

Nkadi, 2009, An overview of pulmonary surfactant in the neonate: genetics, metabolism, and the role of surfactant in health and disease, Mol Genet Metab, 97, 95, 10.1016/j.ymgme.2009.01.015

Kanduc, 2020, On the molecular determinants of the SARS-CoV-2 attack, Clin Immunol, 215, 108426, 10.1016/j.clim.2020.108426

Horby, 2020, Dexamethasone in hospitalized patients with COVID-19–preliminary report, N Engl J Med

Imai, 2008, Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury, Cell, 133, 235, 10.1016/j.cell.2008.02.043

Laplante, 2016, Antiphospholipid antibody-mediated effects in an arterial model of thrombosis are dependent on Toll-like receptor 4, Lupus, 25, 162, 10.1177/0961203315603146

Toubiana, 2020, Kawasaki-like multisystem inflammatory syndrome in children during the COVID-19 pandemic in Paris, France: prospective observational study, BMJ, 369, m2094, 10.1136/bmj.m2094

Verdoni, 2020, An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study, Lancet, 395, 1771, 10.1016/S0140-6736(20)31103-X

Dietz, 2017, Dissecting Kawasaki disease: a state-of-the-art review, Eur J Pediatr, 176, 995, 10.1007/s00431-017-2937-5

Rowley, 1997, IgA plasma cells in vascular tissue of patients with Kawasaki syndrome, J Immunol, 159, 5946, 10.4049/jimmunol.159.12.5946

Rowley, 2000, IgA plasma cell infiltration of proximal respiratory tract, pancreas, kidney, and coronary artery in acute Kawasaki disease, J Infect Dis, 182, 1183, 10.1086/315832

Thông tin
Thông tin xuất bản

Clinical Infectious Diseases

Tập 73 Số 9

e2869-e2874

Thông tin tác giả