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Complement activation in COVID-19 and targeted therapeutic options: A scoping review
Endry Hartono Taslim Lim1, Rombout Benjamin Ezra van Amstel2, Vieve Victoria de Boer3
1Amsterdam 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.
Insights
Complement activation significantly contributes to Coronavirus disease 2019 (COVID-19) severity. Inhibiting C5 and C5a shows promise, but further clinical trials are needed to confirm effectiveness in treating COVID-19.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Growing evidence links complement system activation to COVID-19 pathogenesis.
- The complement system's role in disease severity and mortality is increasingly recognized.
Purpose of the Study:
- To provide a comprehensive overview of complement activation in COVID-19.
- To identify promising therapeutic targets within the complement system for COVID-19.
Main Methods:
- Systematic scoping review of 157 articles from PubMed, EMBASE, and Cochrane.
- Analysis of histopathological, preclinical, multiomics, observational, and clinical interventional studies.
Main Results:
- Evidence confirms complement activation via all three pathways in COVID-19.
- Complement activation correlates with increased disease severity and mortality.
- C5 and C5a inhibition emerged as the most promising therapeutic strategies.
Conclusions:
- Targeting the complement system is a potential therapeutic avenue for COVID-19.
- Further adequately powered, double-blind randomized controlled trials are essential to validate complement inhibition therapies.
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.
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