Antiphospholipid Antibodies in Critically Ill Patients With COVID-19

Objective: Coagulopathy is one of the characteristics observed in critically ill patients with coronavirus disease 2019 (COVID-19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, though their role in COVID-19 remains unclear. This study was undertaken to determine the prevalence and characteristics of aPLs in patients with COVID-19. Methods: Sera collected from 66 COVID-19 patients who were critically ill and 13 COVID-19 patients who were not critically ill were tested by chemiluminescence immunoassay for anticardiolipin antibodies (aCLs), anti–β₂-glycoprotein I (anti-β₂GPI) (IgG, IgM, and IgA), and IgG anti-β₂GPI–domain 1 (anti-β₂GPI–D1) and IgM and IgG anti–phosphatidylserine/prothrombin (anti-PS/PT) antibodies were detected in the serum by enzyme-linked immunosorbent assay. Results: Of the 66 COVID-19 patients in critical condition, aPLs were detected in 31 (47%). Antiphospholipid antibodies were not present among COVID-19 patients who were not in critical condition. The IgA anti-β₂GPI antibody was the most commonly observed aPL in patients with COVID-19 and was present in 28.8% (19 of 66) of the critically ill patients, followed by IgA aCLs (17 of 66, or 25.8%) and IgG anti-β₂GPI (12 of 66, or 18.2%). For multiple aPLs, IgA anti-β₂GPI + IgA aCLs was the most common antibody profile observed (15 of 66, or 22.7%), followed by IgA anti-β₂GPI + IgA aCL + IgG anti-β₂GPI (10 of 66, or 15.2%). Antiphospholipid antibodies emerge ~35–39 days after disease onset. A dynamic analysis of aPLs revealed 4 patterns based on the persistence or transient appearance of the aPLs. Patients with multiple aPLs had a significantly higher incidence of cerebral infarction compared to patients who were negative for aPLs (P = 0.023). Conclusion: Antiphospholipid antibodies were common in critically ill patients with COVID-19. Repeated testing demonstrating medium to high titers of aPLs and the number of aPL types a patient is positive for may help in identifying patients who are at risk of developing cerebral infarction. Antiphospholipid antibodies may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID-19 may trigger the development of an autoimmune condition similar to the antiphospholipid syndrome (APS), referred to as “COVID-19–induced APS-like syndrome.” Long-term follow-up of COVID-19 patients who are positive for aPLs would be of great importance in understanding the pathogenesis of this novel coronavirus.