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Complement activation and endothelial perturbation parallel COVID-19 severity and activity.

Authors
  • Cugno, Massimo1
  • Meroni, Pier Luigi2
  • Gualtierotti, Roberta3
  • Griffini, Samantha4
  • Grovetti, Elena4
  • Torri, Adriana4
  • Lonati, Paola2
  • Grossi, Claudia2
  • Borghi, Maria Orietta5
  • Novembrino, Cristina4
  • Boscolo, Massimo4
  • Uceda Renteria, Sara Colonia6
  • Valenti, Luca7
  • Lamorte, Giuseppe8
  • Manunta, Maria8
  • Prati, Daniele8
  • Pesenti, Antonio9
  • Blasi, Francesco10
  • Costantino, Giorgio11
  • Gori, Andrea12
  • And 3 more
  • 1 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: [email protected] , (Italy)
  • 2 Immunorheumatology Research Laboratory; IRCCS Istituto Auxologico Italiano, Milan, Italy. , (Italy)
  • 3 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. , (Italy)
  • 4 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Internal Medicine and Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy. , (Italy)
  • 5 Immunorheumatology Research Laboratory; IRCCS Istituto Auxologico Italiano, Milan, Italy; Università degli Studi di Milano, Department of Clinical Sciences and Community Health, Milan, Italy. , (Italy)
  • 6 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Virology Unit, Milan, Italy. , (Italy)
  • 7 Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Transfusion Medicine and Hematology, Milan, Italy. , (Italy)
  • 8 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Transfusion Medicine and Hematology, Milan, Italy. , (Italy)
  • 9 Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Anesthesia, Critical Care and Emergency, Milan, Italy. , (Italy)
  • 10 Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy. , (Italy)
  • 11 Università degli Studi di Milano, Department of Clinical Sciences and Community Health, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Emergency Department, Milan, Italy. , (Italy)
  • 12 Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Infectious Disease Unit, Milan, Italy. , (Italy)
Type
Published Article
Journal
Journal of Autoimmunity
Publisher
Elsevier
Publication Date
Oct 29, 2020
Pages
102560–102560
Identifiers
DOI: 10.1016/j.jaut.2020.102560
PMID: 33139116
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Animal 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. To evaluate the association among complement activation, endothelial damage and disease severity or activity in COVID-19 patients. In 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. The 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. Complement 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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