COVID-19 and Antiphospholipid Antibodies: Time for a Reality Check?

Abstract

Antiphospholipid antibodies (aPL) comprise a panel of autoantibodies that reflect a potential prothrombotic risk in several autoimmune conditions, most notably antiphospholipid (antibody) syndrome (APS). aPL can be divided into those that form part of the laboratory criteria for APS, namely, lupus anticoagulant (LA), as well as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) of the immunoglobulin G and M classes, and those that form a group considered as “noncriteria antibodies.” The noncriteria antibodies include, for example, antiphosphatidylserine antibodies (aPS), antiprothrombin antibodies (aPT), and antiphosphatidylserine/prothrombin complex antibodies (aPS/PT). COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of various aPL being present in COVID-19 patients. There have also been similarities drawn between some of the pathophysiological features of COVID-19 and APS, in particular, the most severe form, catastrophic APS (CAPS). In this review, we critically appraise the literature on aPL and COVID-19. This is a companion piece to a separate review focused on LA. In the current review, we primarily concentrate on the so-called solid phase identifiable aPL, such as aCL and aβ2GPI, but also reflect on noncriteria aPL. We conclude that aPL positivity may be a feature of COVID-19, at least in some patients, but in general, identified “solid-phase” aPL are of low titer and not able to be well-linked to the thrombotic aspects of COVID-19. Also, most publications did not assess for aPL persistence, and where persistence was checked, the findings appeared to represent transient aPL. Importantly, high-titer aPL or multiple aPL positivity (including double, triple) were in the minority of COVID-19 presentations, and thus discount any widespread presence of APS, including the most severe form CAPS, in COVID-19 patients.

Persistent Antiphospholipid Antibodies Are Not Associated With Worse Clinical Outcomes in a Prospective Cohort of Hospitalised Patients With SARS-CoV-2 Infection

“…In this study, LAC was not tested. Finally, in a narrative review, Favarolo et al (16) found a median incidence of reported cases positive for aPL of 33% (with an interquartilic range of 11% to 52%).…”

The Impact of SARS-CoV-2 Infection on Blood Coagulation and Fibrinolytic Pathways: A Review of Prothrombotic Changes Caused by COVID-19

“…[73][74][75] A role for lupus anticoagulant and antiphospholipid antibodies has been suggested for pathogenesis of COVID-19-associated coagulopathy. 52,[76][77][78][79][80] In severely infected patients, immobility under conditions of quarantine or hospitalization is another predisposing factor of thrombosis. 81,82 Modification of the equilibrium between clot formation and degradation in favor of hypercoagulability and hypofibrinolysis, impaired endothelial function, platelet hyperactivation, and excessive immune response are emerging as major contributors to the thrombotic complications.…”

COVID-19: autoimmunity, multisystemic inflammation and autoimmune rheumatic patients

“…Primarily antinuclear antibody (ANA) and antibodies against elements of the coagulation cascade, such as antiphospholipid (APLA), anti-prothrombin and anti-heparin antibodies have been described. However, anti-citrullinated protein (ACPA), anti-neutrophil cytoplasmic antigen (ANCA), anti-SS-A/Ro antibodies and rheumatoid factor production has also been described with SARS-CoV-2 infection (12,(36)(37)(38). Some studies have also analysed histological changes induced by SARS-CoV-2 infection.…”