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

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.