Prevalence, specificity, and clinical association of anti-phospholipid antibodies in COVID-19 patients: are the antibodies really guilty?

Borghi, M. O.; Beltagy, A.; Garrafa, E.; Curreli, D.; Cecchini, G.; Bodio, C.; Grossi, C.; Blengino, S.; Tincani, A.; Franceschini, F.; Andreoli, L.; Lazzaroni, M. G.; Piantoni, S.; Masneri, S.; Crisafulli, F.; Brugnoni, D.; Muiesan, M. L.; Salvetti, M.; Parati, G.; Torresani, E.; Mahler, M.; Heilbron, F.; Pregnolato, F.; Pengo, M.; Tedesco, F.; Pozzi, N.; Meroni, P. L.

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-{beta}2GPI and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-{beta}2GPI antibodies was not reported. Aim. 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-{beta}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-{beta}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 {beta}2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-{beta}2GPI nor with thrombosis. Conclusion. 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 {beta}2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome.