Antiphospholipid antibodies in COVID-19: a meta-analysis and systematic review

BACKGROUND: Many studies reported high prevalence of antiphospholipid antibodies (aPL) in patients with COVID-19 raising questions about its true prevalence and its clinical impact on the disease course. METHODS: We conducted a meta-analysis and a systematic review to examine the prevalence of aPL and its clinical impact in patients with COVID-19. RESULTS: 21 studies with a total of 1159 patients were included in our meta-analysis. Among patients hospitalised with COVID-19, the pooled prevalence rate of one or more aPL (IgM or IgG or IgA of anticardiolipin (aCL) or anti-ß2 glycoprotein (anti-ß2 GPI) or antiphosphatidylserine/prothrombin, or lupus anticoagulant (LA)) was 46.8% (95% CI 36.1% to 57.8%). The most frequent type of aPL found was LA, with pooled prevalence rate of 50.7% (95% CI 34.8% to 66.5%). Critically ill patients with COVID-19 had significantly higher prevalence of aCL (IgM or IgG) (28.8% vs 7.10%, p<0.0001) and anti-ß2 GPI (IgM or IgG) (12.0% vs 5.8%, p<0.0001) as compared with non-critically ill patients. However, there was no association between aPL positivity and mean levels of C reactive protein (mean difference was 32 (95% CI −15 to 79), p=0.18), D-dimer (mean difference was 34 (95% CI −194 to 273), p=0.77), mortality (1.46 (95% CI 0.29 to 7.29), p=0.65), invasive ventilation (1.22 (95% CI 0.51 to 2.91), p=0.65) and venous thromboembolism (1.38 (95% CI 0.57 to 3.37), p=0.48). CONCLUSIONS: aPLs were detected in nearly half of patients with COVID-19, and higher prevalence of aPL was found in severe disease. However, there was no association between aPL positivity and disease outcomes including thrombosis, invasive ventilation and mortality. However, further studies are required to identify the clinical and pathological role of aPL in COVID-19.