Anti-cardiolipin and other anti-phospholipid antibodies in critically ill COVID-19 positive and negative patients

Trahtemberg, U.; Rottapel, R.; DosSantos, C.; Slutsky, A. S.; Baker, A. J.; Fritzler, M. J.

Background: Reports of severe COVID-19 being associated with thrombosis, anti-phospholipid antibodies (APLA), anti-phospholipid syndrome (APS) have yielded disparate conclusions. Studies comparing COVID-19 patients with contemporaneous controls of similar severity are lacking. Methods: 22 COVID+ and 20 COVID- patients with respiratory failure admitted to intensive care were studied longitudinally. Demographic and clinical data were obtained from the day of admission. APLA testing included anti-cardiolipin (aCL), anti-{beta}2glycoprotein 1 ({beta}2GP1), anti-domain 1 {beta}2 glycoprotein 1 ({beta}2GP1) and anti-phosphatidyl serine/prothrombin complex (PS/PT). Anti-nuclear antibodies (ANA) were detected by immunofluorescence and antibodies to cytokines by a commercially available multiplexed array. ANOVA was used for continuous variables and Fisher exact test was used for categorical variables with =0.05 and the false discovery rate at q=0.05. Results: APLA were predominantly IgG aCL (48%) followed by IgM (21%) in all patients, with a tendency toward higher frequency among the COVID+. aCL was not associated with surrogate markers of thrombosis but IgG aCL was strongly associated with worse disease severity and higher ANA titers regardless of COVID-19 status. An association between aCL and anti-cytokine autoantibodies tended to be higher among the COVID+ cohort. Conclusions: Positive APLA serology was associated with more severe disease regardless of COVID-19 status.