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[Preprint]. 2020 Jul 16:2020.06.17.20134114. Originally published 2020 Jun 19. [Version 3] doi: 10.1101/2020.06.17.20134114

Anti-phospholipid antibodies in COVID-19 are different from those detectable in the anti-phospholipid syndrome

Maria Orietta Borghi, Asmaa Beltagy, Emirena Garrafa, Daniele Curreli, Germana Cecchini, Caterina Bodio, Claudia Grossi, Simonetta Blengino, Angela Tincani, Franco Franceschini, Laura Andreoli, Maria Grazia Lazzaroni, Silvia Piantoni, Stefania Masneri, Francesca Crisafulli, Dulio Brugnoni, Maria Lorenza Muiesan, Massimo Salvetti, Gianfranco Parati, Erminio Torresani, Michael Mahler, Francesca Heilbron, Francesca Pregnolato, Martino Pengo, Francesco Tedesco, Nicola Pozzi, Pier Luigi Meroni
PMCID: PMC7310661  PMID: 32588001

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-β2GPI) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-β2GPI 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-β2GPI 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-β2GPI 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 β2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β2GPI 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 β2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.

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