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

Hasan Ali, Omar; Bomze, David; Risch, Lorenz; Brugger, Silvio D; Paprotny, Matthias; Weber, Myriam; Thiel, Sarah; Kern, Lukas; Albrich, Werner C; Kohler, Philipp; Kahlert, Christian R; Vernazza, Pietro; Bühler, Philipp K; Schüpbach, Reto A; Gómez-Mejia, Alejandro; Popa, Alexandra M; Bergthaler, Andreas; Penninger, Josef M; Flatz, Lukas (2021). Severe Coronavirus Disease 2019 (COVID-19) is Associated With Elevated Serum Immunoglobulin (Ig) A and Antiphospholipid IgA Antibodies. Clinical infectious diseases, 73(9), e2869-e2874. Oxford University Press 10.1093/cid/ciaa1496

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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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Risch, Lorenz


600 Technology > 610 Medicine & health




Oxford University Press




Karin Balmer

Date Deposited:

23 Nov 2022 07:27

Last Modified:

05 Dec 2022 16:28

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

COVID-19 antiphospholipid syndrome autoimmunity immunoglobulin A thromboembolisms




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