Complement activation in COVID-19 and targeted therapeutic options: A scoping review

Endry Hartono Taslim Lim; Rombout Benjamin Ezra van Amstel; Vieve Victoria de Boer; Lonneke Alette van Vught; Sanne de Bruin; Matthijs Christian Brouwer; Alexander Petrus Johannes Vlaar; Diederik van de Beek

doi:10.1016/j.blre.2022.100995

Complement activation in COVID-19 and targeted therapeutic options: A scoping review

Blood Rev. 2023 Jan:57:100995. doi: 10.1016/j.blre.2022.100995. Epub 2022 Jul 30.

Authors

Endry Hartono Taslim Lim¹, Rombout Benjamin Ezra van Amstel², Vieve Victoria de Boer³, Lonneke Alette van Vught⁴, Sanne de Bruin², Matthijs Christian Brouwer⁵, Alexander Petrus Johannes Vlaar⁶, Diederik van de Beek⁵

Affiliations

¹ Amsterdam UMC location University of Amsterdam, Department of Intensive Care Medicine, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Amsterdam, the Netherlands; Amsterdam UMC location University of Amsterdam, Department of Neurology, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands.
² Amsterdam UMC location University of Amsterdam, Department of Intensive Care Medicine, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Amsterdam, the Netherlands.
³ Amsterdam UMC location University of Amsterdam, Department of Intensive Care Medicine, Meibergdreef 9, Amsterdam, the Netherlands.
⁴ Amsterdam UMC location University of Amsterdam, Department of Intensive Care Medicine, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Amsterdam, the Netherlands.
⁵ Amsterdam UMC location University of Amsterdam, Department of Neurology, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam Neuroscience, Amsterdam, the Netherlands.
⁶ Amsterdam UMC location University of Amsterdam, Department of Intensive Care Medicine, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam UMC Location University of Amsterdam, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Amsterdam, the Netherlands. Electronic address: a.p.vlaar@amsterdamumc.nl.

Abstract

Increasing evidence suggests that activation of the complement system plays a key role in the pathogenesis and disease severity of Coronavirus disease 2019 (COVID-19). We used a systematic approach to create an overview of complement activation in COVID-19 based on histopathological, preclinical, multiomics, observational and clinical interventional studies. A total of 1801 articles from PubMed, EMBASE and Cochrane was screened of which 157 articles were included in this scoping review. Histopathological, preclinical, multiomics and observational studies showed apparent complement activation through all three complement pathways and a correlation with disease severity and mortality. The complement system was targeted at different levels in COVID-19, of which C5 and C5a inhibition seem most promising. Adequately powered, double blind RCTs are necessary in order to further investigate the effect of targeting the complement system in COVID-19.

Keywords: COVID-19; Complement cascade; Complement inhibition; Review; SARS-CoV-2.

Publication types

Review

MeSH terms

COVID-19*
Complement Activation
Humans
Randomized Controlled Trials as Topic
SARS-CoV-2