Anti-Phospholipid Antibodies in COVID-19 Are Different From Those Detectable in the Anti-Phospholipid Syndrome
María Orietta Borghi, Asmaa Beltagy, Emirena Garrafa, Daniele Curreli, Germana Cecchini, Caterina Bodio, C. Grossi, Simonetta Blengino, Anǵela Tincani, Franco Franceschini, Laura Andréoli, Maria Grazia Lazzaroni, Silvia Piantoni, Stefania Masneri, Francesca Crisafulli, Duilio Brugnoni, María Lorenza Muiesan, Massimo Salvetti, Gianfranco Parati, Erminio Torresani, Michael Mähler, Francesca Heilbron, Francesca Pregnolato, Martino F. Pengo, Francesco Tedesco, Nicola Pozzi, Pier Luigi Meroni
Abstract
Background. Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPL) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-2GPI antibodies was not reported. Objective. To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-2GPI antibodies. Methods. ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events. Results. Anti-2GPI IgG/IgA/IgM were the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM were detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of 2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-2GPI nor with thrombosis. Conclusions. aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against 2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.