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

By Uriel Trahtemberg, Robert Rottapel, Claudia C dos Santos, Arthur S Slutsky, Andrew J Baker, Marvin J Fritzler

Posted 23 Feb 2021
medRxiv DOI: 10.1101/2021.02.19.21252113

BackgroundReports 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. Methods22 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}2glycoprotien 1 ({beta}2GP1), anti-domain 1 beta2 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 Fishers exact test was used for categorical variables with =0.05 and the false discovery rate at q=0.05. ResultsAPLA 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+. ConclusionsPositive APLA serology was associated with more severe disease regardless of COVID-19 status. KEY MESSAGESO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LICOVID-19 is associated with coagulopathy and high morbidity and mortality. C_LIO_LICOVID-19 shares some of these clinical features with anti-phospholipid syndrome. C_LIO_LIReports 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. C_LI What does this study add?O_LIAnti-phospholipid syndrome serology assessed longitudinally was predominantly anticardiolipin IgG autoantibodies, in 48% of patients. C_LIO_LIAnticardiolipin serology was associated with worse disease severity in both COVID-19 positive and negative patients. C_LI How might this impact on clinical practice or future developments?O_LIThe 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. C_LI

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