• Massimo Cugno, Pier Luigi Meroni, Roberta Gualtierotti, Samantha Griffini, Elena Grovetti, Adriana Torri, Paola Lonati, Claudia Grossi, Maria Orietta Borghi, Cristina Novembrino, Massimo Boscolo, Sara Colonia Uceda Renteria, Luca Valenti, Giuseppe Lamorte, Maria Manunta, Daniele Prati, Antonio Pesenti, Francesco Blasi, Giorgio Costantino, Andrea Gori, Alessandra Bandera, Francesco Tedesco, and Flora Peyvandi.
• Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy. Electronic address: massimo.cugno@unimi.it.
• J. Autoimmun. 2021 Jan 1; 116: 102560.

BackgroundAnimal models and few clinical reports suggest the involvement of the complement system in the onset of severe manifestations of coronavirus disease-2019 (COVID-19). However, complement contribution to endotheliopathy and hypercoagulability has not been elucidated yet.ObjectiveTo evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients.MethodsIn this single-centre cohort study, 148 patients with COVID-19 of different severity were evaluated upon hospital admission and 30 days later. Markers of complement activation (SC5b-9 and C5a) and endothelial perturbation (von Willebrand factor [vWF], tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1], soluble thrombomodulin [sTM], and soluble endothelial selectin [sE-selectin]) were measured in plasma.ResultsThe patients had high plasma levels of SC5b-9 and C5a (p = 0.0001 for both) and vWF, t-PA and PAI-1 (p = 0.0001 for all). Their SC5b-9 levels correlated with those of vWF (r = 0.517, p = 0.0001) and paralleled disease severity (severe vs mild p = 0.0001, severe vs moderate p = 0.026 and moderate vs mild p = 0.001). The levels of sE-selectin were significantly increased only in the patients with severe disease. After 30 days, plasma SC5b-9, C5a and vWF levels had significantly decreased (p = 0.0001 for all), and 43% of the evaluated patients had normal levels.ConclusionsComplement activation is boosted during the progression of COVID-19 and dampened during remission, thus indicating its role in the pathophysiology of the disease. The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy.Copyright © 2020. Published by Elsevier Ltd.

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