Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients

Abstract

BackgroundReports of severe COVID-19 being associated with thrombosis, antiphospholipid antibodies (APLA), and antiphospholipid syndrome have yielded disparate conclusions. Studies comparing patients with COVID-19 with contemporaneous controls of similar severity are lacking.Methods22 COVID-19+ and 20 COVID-19– 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 anticardiolipin (aCL), anti-β2glycoprotien 1 (β2GP1), antidomain 1 β2GP1 and antiphosphatidyl serine/prothrombin complex. Antinuclear antibodies (ANAs) were detected by immunofluorescence and antibodies to cytokines by a commercially available multiplexed array. Analysis of variance 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.ResultsAPLAs were predominantly IgG aCL (48%), followed by IgM (21%) in all patients, with a tendency towards higher frequency among the COVID-19+. aCL was not associated with surrogate markers of thrombosis but IgG aCL was strongly associated with worse disease severity and higher ANA titres regardless of COVID-19 status. An association between aCL and anticytokine autoantibodies tended to be higher among the COVID-19+.ConclusionsPositive APLA serology was associated with more severe disease regardless of COVID-19 status.Trial registration numberNCT04747782

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

“…Some have found no consistent association of antiphospholipid antibodies and thrombosis or disease severity [46,49,51,53,64,69,71]. Whether detected at the time of first patient presentation or shortly thereafter, such antibody status is time-accrued, maximizes in over 1 month after infection onset, and tends to be transient [49,68,70]. The timing of antibody detection therefore must be considered in comparing one study to another.…”

“…Borghi and colleagues examined reactivity to specific ß2-glycoprotein-I domains but found a low prevalence [46]. Others find that the presence of such antibodies correlates with severity of COVID-19 [55,61,68]. There is a high frequency of antiphospholipid antibodies among patients in intensive care [51,58,62,68,74].…”

“…Others find that the presence of such antibodies correlates with severity of COVID-19 [55,61,68]. There is a high frequency of antiphospholipid antibodies among patients in intensive care [51,58,62,68,74]. An association of such antibodies with stroke risk has been suggested [45,50].…”

“…Among patients with lupus anticoagulant, one study of critically ill patients found an association of IgM anticardiolipin antibodies with thrombosis [70]. Antibodies to phosphatidyl serine/prothrombin complex and/or prothrombin appear to be much less common in some but not all studies [68,69,73]. Zuo et al assessed purified immunoglobulin from such patients and found it to promote venous thrombosis in a murine model [67].…”

“…From the research detailed above, it is safe to say that a conclusive role of antiphospholipid antibodies in the course of COVID-19 is yet to be defined. The rise of antiphospholipid antibodies during COVID-19 infection must be seen in a larger context of the potential rise in autoantibodies generally [32,61,68,70,72].…”