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Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA-antibodies

Omar Hasan Ali, David Bomze, Lorenz Risch, Silvio D Brugger, Matthias Paprotny, Myriam Weber, Sarah Thiel, Lukas Kern, Werner Albrich, Philipp Kohler, Christian R. Kahlert, Pietro Vernazza, Philipp K Bühler, Reto A Schüpbach, Alejandro Gómez-Mejia, Alexandra M Popa, Andreas Bergthaler, Josef M Penninger & Lukas Flatz

abstract

BACKGROUND
Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there is little data on possible IgA-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and if IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome (APS), 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 three independent tertiary hospitals (one in Liechtenstein, two in Switzerland). Samples were collected from April 9 th to May 1 st, 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=0.01; scCOVID, p-value<0.001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anti-Cardiolipin IgA (sdCOVID and scCOVID, p-value<0.001), anti-Cardiolipin IgM (sdCOVID, P=0.003; scCOVID, P<0.001), and anti-Beta2 Glycoprotein-1 IgA (sdCOVID and scCOVID, P<0.001). 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.
   
citation Hasan Ali O, Bomze D, Risch L, Brugger S D, Paprotny M, Weber M, Thiel S, Kern L, Albrich W, Kohler P, Kahlert C R, Vernazza P, Bühler P K, Schüpbach R A, Gómez-Mejia A, Popa A M, Bergthaler A, Penninger J M, Flatz L. Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA-antibodies. Clin Infect Dis 2020;.
   
type journal paper/review (English)
date of publishing 30-09-2020
journal title Clin Infect Dis
ISSN electronic 1537-6591
PubMed 32997739
DOI 10.1093/cid/ciaa1496