tetano
Editor, Senior Moderator
Clin Infect Dis
. 2020 Sep 30;ciaa1496.
doi: 10.1093/cid/ciaa1496. Online ahead of print.
Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA-antibodies
Omar Hasan Ali[SUP] 1 2 3 [/SUP], David Bomze[SUP] 3 4 [/SUP], Lorenz Risch[SUP] 5 6 [/SUP], Silvio D Brugger[SUP] 7 [/SUP], Matthias Paprotny[SUP] 8 [/SUP], Myriam Weber[SUP] 8 [/SUP], Sarah Thiel[SUP] 8 [/SUP], Lukas Kern[SUP] 9 [/SUP], Werner C Albrich[SUP] 10 [/SUP], Philipp Kohler[SUP] 10 [/SUP], Christian R Kahlert[SUP] 10 11 [/SUP], Pietro Vernazza[SUP] 10 [/SUP], Philipp K B?hler[SUP] 12 [/SUP], Reto A Sch?pbach[SUP] 12 [/SUP], Alejandro G?mez-Mejia[SUP] 7 [/SUP], Alexandra M Popa[SUP] 13 [/SUP], Andreas Bergthaler[SUP] 13 [/SUP], Josef M Penninger[SUP] 1 14 [/SUP], Lukas Flatz[SUP] 2 3 15 16 [/SUP]
Affiliations
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.
Keywords: COVID-19; antiphospholipid syndrome; autoimmunity; immunoglobulin A; thromboembolisms.
. 2020 Sep 30;ciaa1496.
doi: 10.1093/cid/ciaa1496. Online ahead of print.
Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA-antibodies
Omar Hasan Ali[SUP] 1 2 3 [/SUP], David Bomze[SUP] 3 4 [/SUP], Lorenz Risch[SUP] 5 6 [/SUP], Silvio D Brugger[SUP] 7 [/SUP], Matthias Paprotny[SUP] 8 [/SUP], Myriam Weber[SUP] 8 [/SUP], Sarah Thiel[SUP] 8 [/SUP], Lukas Kern[SUP] 9 [/SUP], Werner C Albrich[SUP] 10 [/SUP], Philipp Kohler[SUP] 10 [/SUP], Christian R Kahlert[SUP] 10 11 [/SUP], Pietro Vernazza[SUP] 10 [/SUP], Philipp K B?hler[SUP] 12 [/SUP], Reto A Sch?pbach[SUP] 12 [/SUP], Alejandro G?mez-Mejia[SUP] 7 [/SUP], Alexandra M Popa[SUP] 13 [/SUP], Andreas Bergthaler[SUP] 13 [/SUP], Josef M Penninger[SUP] 1 14 [/SUP], Lukas Flatz[SUP] 2 3 15 16 [/SUP]
Affiliations
- PMID: 32997739
- DOI: 10.1093/cid/ciaa1496
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.
Keywords: COVID-19; antiphospholipid syndrome; autoimmunity; immunoglobulin A; thromboembolisms.