Vascular Thrombosis in COVID-19: A Potential Association with Antiphospholipid Antibodies

Abstract

Background: Vascular thrombosis is common in patients with coronavirus disease 2019 (COVID-19). Etiologies underlying this complication are unclear. Purpose: To determine the prevalence of antiphospholipid (aPL), including lupus anticoagulant, anti-cardiolipin and anti-β2-glycoprotein-1 antibodies, and its possible association with thrombotic manifestations of COVID-19. Data Sources: We searched MEDLINE indexed journals on September 24, 2020 using the tool LitCovid and the pre-print server medRxIV. Study Selection: Original investigations (cross-sectional studies, cohort studies, case series, and research letters) on COVID-19 and thrombosis were included. Data Extraction: Data were independently extracted, and compiled into spreadsheets based on the PRISMA principles. Data Synthesis: Hospitalized patients with COVID-19 showed a higher prevalence of lupus anticoagulant compared to non-COVID-19 patients. Temporally, lupus anticoagulant was generally positive early in the course of illness, whereas anti-cardiolipin and anti-β2-glycoprotein-1 antibodies appeared to emerge later in the disease. Some patients who were aPL-negative at an early time-point after disease onset became aPL-positive at a later time-point. Lupus anticoagulant was independently associated with thrombosis in 60 COVID-19 patients in New York had who had 32 thrombotic events (8 arterial and 24 venous). In 88 patients in Wuhan, who had more than 20 each of arterial and venous thrombotic events, medium/high positivity for multiple aPL was significantly associated with arterial thrombosis. However, the association of aPL with thrombosis was not evident in reports that had an overall lower number of or predominantly venous thrombotic events. Analysis of pooled patients revealed that aPL were significantly more frequent in COVID-19 patients with stroke than stroke patients in the general population. Furthermore, injection of IgG aPL fractions from COVID-19 patients into mice accelerated venous thrombosis. Limitation: Limited data and paucity of prospective studies. Conclusion: The aPL are prevalent in patients with COVID-19 and their presence is associated with thrombosis. Importantly, these antibodies may be a key mechanism of thrombosis in COVID-19. Follow-up studies are required to understand the relationship between aPL and the spectrum of vascular thrombosis during and after infection with SARS-CoV-2.