Complement Activation in the Disease Course of Coronavirus Disease 2019 and Its Effects on Clinical Outcomes

Author:

de Nooijer Aline H1,Grondman Inge1,Janssen Nico A F1,Netea Mihai G12,Willems Loek3,van de Veerdonk Frank L1,Giamarellos-Bourboulis Evangelos J4,Toonen Erik J M3,Joosten Leo A B15ORCID,Jaeger Martin,Dijkstra Helga,Lemmers Heidi,van Emst Liesbeth,Schraa Kiki,Jacobs Cor,Hijmans Anneke,Jansen Trees,Weren Fieke,Fransman Liz,Gerretsen Jelle,van de Maat Josephine,Nijman Gerine,Moorlag Simone,Taks Esther,Debisarun Priya,Kouijzer Ilse,Wertheim Heiman,Hopman Joost,Rahamat-Langendoen Janette,Bleeker-Rovers Chantal,ten Oever Jaap,van Crevel Reinout,Hoogerwerf Jacobien,de Mast Quirijn,van der Hoeven Hans,Pickkers Peter,Kox Matthijs,Frenzel Tim,Schouten Jeroen,Hemelaar Pleun,Beunders Remi,van der Velde Sjef,Kooistra Emma,Waalders Nicole,Claassen Wout,Heesakkers Hidde,van Schaik Tirsa,van der Eng Hetty,Rovers Noortje,Klop-Riehl Margreet,

Affiliation:

1. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands

2. Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany

3. R&D Department, Hycult Biotechnology, Uden, the Netherlands

4. Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece

5. Núcleo de Pesquisa da Faculdade da Polícia Militar do Estado de Goiás, Goiânia, Goiás, Brazil

Abstract

Abstract Background Excessive activation of immune responses in coronavirus disease 2019 (COVID-19) is considered to be related to disease severity, complications, and mortality rate. The complement system is an important component of innate immunity and can stimulate inflammation, but its role in COVID-19 is unknown. Methods A prospective, longitudinal, single center study was performed in hospitalized patients with COVID-19. Plasma concentrations of complement factors C3a, C3c, and terminal complement complex (TCC) were assessed at baseline and during hospital admission. In parallel, routine laboratory and clinical parameters were collected from medical files and analyzed. Results Complement factors C3a, C3c, and TCC were significantly increased in plasma of patients with COVID-19 compared with healthy controls (P < .05). These complement factors were especially elevated in intensive care unit patients during the entire disease course (P < .005 for C3a and TCC). More intense complement activation was observed in patients who died and in those with thromboembolic events. Conclusions Patients with COVID-19 demonstrate activation of the complement system, which is related to disease severity. This pathway may be involved in the dysregulated proinflammatory response associated with increased mortality rate and thromboembolic complications. Components of the complement system might have potential as prognostic markers for disease severity and as therapeutic targets in COVID-19.

Funder

Netherlands Organization for Scientific Research

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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