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

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-β2glycoprotien 1 (β2GP1), anti-domain 1 beta2 glycoprotein 1 (β2GP1) 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’s exact test was used for categorical variables with α=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 + . Conclusions Positive APLA serology was associated with more severe disease regardless of COVID-19 status. KEY MESSAGES What is already known about this subject? COVID-19 is associated with coagulopathy and high morbidity and mortality. COVID-19 shares some of these clinical features with anti-phospholipid syndrome. Reports of an association of anti-phospholipid antibodies with high risk COVID-19 have yielded disparate conclusions, but they lacked longitudinal follow up and control groups of similar severity. What does this study add? Anti-phospholipid syndrome serology assessed longitudinally was predominantly anticardiolipin IgG autoantibodies, in 48% of patients. Anticardiolipin serology was associated with worse disease severity in both COVID-19 positive and negative patients. How might this impact on clinical practice or future developments? The use of anti-phospholipid antibodies tests in the COVID-19 clinical setting needs to be taken in context; whereas they are associated with more serve disease, they do not discriminate between COVID-19 positive and negative patients.