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

COVID-19 antiphospholipid syndrome autoimmunity immunoglobulin A thromboembolisms

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
02 11 2021
Historique:
received: 18 08 2020
accepted: 29 09 2020
pubmed: 1 10 2020
medline: 9 11 2021
entrez: 30 9 2020
Statut: ppublish

Résumé

Severe 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). In 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. Clinical 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. Higher 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.

Sections du résumé

BACKGROUND
Severe 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).
METHODS
In 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.
RESULTS
Clinical 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.
CONCLUSIONS
Higher 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.

Identifiants

pubmed: 32997739
pii: 5913451
doi: 10.1093/cid/ciaa1496
pmc: PMC7543315
doi:

Substances chimiques

Antibodies, Antiphospholipid 0
Immunoglobulin A 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2869-e2874

Subventions

Organisme : Swiss National Science Foundation
ID : PP00P3_157448
Pays : Switzerland
Organisme : Research Fund of the Kantonsspital
Organisme : Promedica Foundation
ID : 1449/M

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Auteurs

Omar Hasan Ali (O)

Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

David Bomze (D)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Lorenz Risch (L)

Labormedizinisches Zentrum Dr. Risch, Vaduz, Liechtenstein.
Center of Laboratory Medicine, University Institute of Clinical Chemistry, University of Bern, Bern, Switzerland.

Silvio D Brugger (SD)

Department of Infectious Diseases and Hospital Hygiene, University Hospital Zurich, Zurich, Switzerland.

Matthias Paprotny (M)

Department of General Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein.

Myriam Weber (M)

Department of General Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein.

Sarah Thiel (S)

Department of General Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein.

Lukas Kern (L)

Department of Pulmonology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Werner C Albrich (WC)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Philipp Kohler (P)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Christian R Kahlert (CR)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Department of Infectious Diseases and Hospital Epidemiology, Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.

Pietro Vernazza (P)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Philipp K Bühler (PK)

Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.

Reto A Schüpbach (RA)

Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland.

Alejandro Gómez-Mejia (A)

Department of Infectious Diseases and Hospital Hygiene, University Hospital Zurich, Zurich, Switzerland.

Alexandra M Popa (AM)

Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Andreas Bergthaler (A)

Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Josef M Penninger (JM)

Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

Lukas Flatz (L)

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Department of Dermatology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

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