Antiphospholipid Autoantibodies and Thrombosis in Patients With COVID‐19: Comment on the Article by Bertin et al
Authors: T. Frapard, S. Hue, C. Rial, N. de Prost, A. Mekontso Dessap
Journal: Arthritis & Rheumatology (2020)

To the Editor: We read with great interest the letter by Bertin et al (1) on their study exploring the involvement of antiphospholipid antibodies (aPLs) in a cohort of patients with severe acute respiratory syndrome coronavirus 2 (SARS–COV-2). Bertin and colleagues observed that levels of IgG anticardiolipin antibodies (aCLs) were significantly associated with severe coronavirus disease 2019 (COVID-19) manifestations (odds ratio [OR] 6.50; P = 0.009). Helms et al reported that a significant number of patients with COVID-19–related acute respiratory distress syndrome (ARDS) developed life-threatening thrombotic complications, with 25% of computed tomography pulmonary angiography findings showing pulmonary embolism (2). They also reported that 88% of patients tested were positive for lupus anticoagulant (LAC) during their intensive care unit (ICU) stay. Bowles et al also described abnormal coagulation test results, in particular the presence of LAC in 31 of 34 COVID-19 patients tested (91%) (3). Moreover, Zhang et al described 3 COVID-19 patients with thrombosis and an atypical pattern of aPLs, including IgA aCL and IgA anti–β2-glycoprotein I (anti-β2GPI) without LAC (4). The significance of IgA antibodies is not fully understood. Positivity of aPLs may favor thrombotic events in patients with COVID-19–related ARDS via endothelial injury (5). We assessed the association between thrombotic complications during COVID-19–related ARDS and the presence of aPLs, including IgA aCL and IgA anti-β2GPI. Levels of aPLs were measured using enzyme-linked immunosorbent assay (Inova Diagnostics), according to the manufacturer's instructions. We conducted an observational single-center study, which included all patients with COVID-19–related ARDS confirmed by reverse transcriptase–polymerase chain reaction (n = 37), consecutively admitted to our ICU between March 8, 2020, and March 30, 2020. Patients with pneumonia-associated ARDS who were previously included in a single-center prospective cohort between January 2014 and December 2018 were used as controls (non–COVID-19–related ARDS group, n = 31). Levels of aPLs and biomarkers were measured within 48 hours of ICU admission. The thromboembolic events were retrospectively recorded. Data on patient characteristics, aPL levels, and outcomes are shown in Table 1. Compared with patients with non–COVID-19–related ARDS, patients with COVID-19–related ARDS did not show significant differences regarding age, sex, associated comorbidities (except for more frequent obesity), severity scores (i.e., Sequential Organ Failure Assessment score and Simplified Acute Physiology Score II), and invasive mechanical ventilation support upon admission to the ICU. More thrombotic complications (including pulmonary embolism) were diagnosed in patients with COVID-19–related ARDS than in patients with non–COVID-19–related ARDS. Overall, the prevalence of aPLs did not differ significantly between patients with COVID-19–related ARDS and patients with non–COVID-19–related ARDS (11 [30%] versus 9 [29%], P = 0.950), no matter the type of antibody considered. The rate of thromboembolic events was similar in patients with versus those without aPLs (9 [45%] versus 23 [48%], P = 0.83), and these findings were similar when the type of aPL (IgA versus IgG/IgM) or the type of thrombotic event was separately considered (data not shown). COVID-19–related ARDS (n = 37) Non–COVID-19–related ARDS (n = 31) In conclusion, we also observed that patients with COVID-19–​related ARDS experienced more thrombotic events than patients with non–COVID-19–related ARDS. However, the occurrence of aPLs was of similar magnitude in patients with COVID-19–related ARDS and patients with non–COVID-19–related ARDS, with no significant association with thrombosis. The findings of Bertin et al could be related to the severity of the pulmonary condition regardless of the SARS–COV-2 infection (6). The pathophysiology of thrombosis in patients with COVID-19–related ARDS warrants further research.