Are antiphospholipid antibodies just a common epiphenomenon or are they causative of immune-mediated coagulopathy in COVID-19?

Abstract

The coronavirus disease 2019 (COVID-19) is the largest public health emergency in recent times. A significant number of patients develop a severe form of COVID-19 characterized by coagulopathy, organ failure, and elevated mortality. In addition, an unusually high frequency of antiphospholipid antibodies (aPLs) has been found in patients with COVID-19. These clinical and serological manifestations closely resemble those seen in the antiphospholipid syndrome (APS), especially in its catastrophic form, suggesting a role of aPLs in immune-associated coagulopathy. However, government bodies such as the American Society of Hematology have spoken out against the systematic search for aPLs in patients with COVID-19. In an attempt to bridge the gap on this hot topic, we conducted a comprehensive review of currently available cohort studies and case series systematically evaluating aPLs in COVID-19 patients. In this Perspective , we seek to identify both the frequency and the type of aPLs found in patients with COVID-19, as well as the potential association of these aPLs with vascular thrombosis and other distinctive characteristics of COVID-19. Furthermore, we investigated whether there is evidence that allows us to define the occurrence of aPLs in COVID-19 as an epiphenomenon, as has been observed in other systemic viral infections, or as antibodies against self-antigens bearing hallmarks that suggest a pathogenic role in immune-mediated thrombosis. Defining whether aPLs represent an epiphenomenon or they are actually involved in hemostatic abnormalities of COVID-19 is crucial both for uncovering novel mechanisms of immune-mediated thrombosis and for identifying potential prognostic biomarkers in this devastating disease.

Immune thrombocytopenia and COVID-19: Case report and review of literature

“…However, there is controversy about whether the appearance of these antibodies has clinical significance. 41 Be that as it may, both anticardiolipin and anti-beta-2-glycoprotein IgG were already positive in our patient before SARS-CoV-2 infection, and their titers did not increase during COVID-19 course. Therefore, in conclusion, it seems that SARS-CoV-2 itself played a major role in the ITP of our patient, even though it cannot be completely ruled out that his previous SAD might act as predisposing or facilitating factors.…”

Anti-Phospholipid Antibodies and COVID-19 Thrombosis: A Co-Star, Not a Supporting Actor

“…Some authors have proposed that the presence of aPL and thrombotic events in COVID-19 patients could represent a secondary form of APS [ 52 , 53 ]. The aPL associated with secondary APS caused by infections usually disappeared in a short period of time [ 7 , 43 , 44 , 45 ].…”

Usefulness of Easy-to-Use Risk Scoring Systems Rated in the Emergency Department to Predict Major Adverse Outcomes in Hospitalized COVID-19 Patients

“…An interesting study found that plasma levels of NET markers are associated with the need for ventilation and shortterm mortality in patients with moderate-to-severe COVID-19; all NET markers declined four months after infection [43]. Recently, the existence of an immune-mediated coagulopathy, with induction of autoantibodies (mainly antiphospholipid antibodies) parallel to hyperinflammation has been suggested [44,45].…”