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

Abstract

BackgroundMany 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.MethodsWe conducted a meta-analysis and a systematic review to examine the prevalence of aPL and its clinical impact in patients with COVID-19.Results21 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).ConclusionsaPLs 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.

Inactivated SARS-CoV-2 vaccine does not influence the profile of prothrombotic antibody nor increase the risk of thrombosis in a prospective Chinese cohort

“…Notably, the coagulopathy found in critically ill COVID-19 patients bears some similarities to the catastrophic antiphospholipid syndrome, which presented with multiple-organic thrombosis [34] , [35] . According to recent studies, there is a questionable association between aPLs and major thrombotic events considering the transient and low titers of aPLs in some COVID-19 patients [36] , [37] , [38] , [39] , [40] . Taha et al [39] conducted a meta-analysis and a systematic review including 21 studies and found that COVID patients with severe disease presented with a higher prevalence of aPL.…”

“…According to recent studies, there is a questionable association between aPLs and major thrombotic events considering the transient and low titers of aPLs in some COVID-19 patients [36] , [37] , [38] , [39] , [40] . Taha et al [39] conducted a meta-analysis and a systematic review including 21 studies and found that COVID patients with severe disease presented with a higher prevalence of aPL. However, there was no association between aPL positivity and disease outcomes, including thrombosis [39] .…”

“…Taha et al [39] conducted a meta-analysis and a systematic review including 21 studies and found that COVID patients with severe disease presented with a higher prevalence of aPL. However, there was no association between aPL positivity and disease outcomes, including thrombosis [39] . Borghi et al [40] reported that aPLs displayed different epitope specificity between COVID-19 patients and APS patients.…”

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

“…The higher prevalence of aPL reported in other studies with COVID-19 patients versus their own control population may be due to the lower mean age of the control populations with which they were compared, which evidently have a lower prevalence of autoantibodies. In the meta-analysis, carried out by Taha and Samavati, in which the prevalence of aPL in COVID-19 patients was assessed by evaluating 21 publications, all studies reported prevalence without a control group [ 22 ]. Therefore, it must be assumed that in these 21 studies, the comparisons were made using the aPL prevalence published in the literature, which are based on blood donor cohorts.…”

“…The prevalence of aPL in COVID-19 patients, with or without thrombotic events, varies between 21–70%, according to the methods used in its detection and whether the presence of LA is assessed or not [ 19 , 20 , 21 ]. In a recent meta-analysis that included 21 studies, the pooled prevalence rate of one or more aPL (aCL or anti-B2GPI IgG/M/A, or anti-PS/PT, or LA) was 46.8% [ 22 ]. In our country, the prevalence of aPL in COVID-19 patients at the time of hospital admission, excluding LA (aCL or anti-B2GPI, or anti PS/PT), is 23,6% which is higher than the 6.1% described in the control group of 201 blood donors [ 21 ] and the 5–5.5% described in other studies [ 23 , 24 ].…”