TY - JOUR
T1 - The complement system in COVID-19
T2 - Friend and foe?
AU - Java, Anuja
AU - Apicelli, Anthony J.
AU - Kathryn Liszewski, M.
AU - Coler-Reilly, Ariella
AU - Atkinson, John P.
AU - Kim, Alfred H.J.
AU - Kulkarni, Hrishikesh S.
N1 - Funding Information:
The authors would like to thank Ben Palanca, Kristen Sanfilippo, and Anthony Chang for informative discussions that helped to shape the manuscript. Figures were partially created using BioRender. AJ is supported by the Barnes Jewish Hospital Foundation Fund and is a coinvestigator on a multicenter study funded by Alexion (NCT04369469). JPA is supported by NIH/National Institute of General Medical Sciences (R35-GM136352-01 and 2R01-GM99111-23). AHJK is supported by NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30-AR073752) and the Rheumatology Research Foundation. HSK is funded by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (PD-FR-2020-867), the NIH (K08-HL148510), and the American Lung Association (RG-575308). HSK is currently a principal investigator on a multicenter study funded by Alexion on the use of complement inhibitors in severe COVID-19 (NCT04369469). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding Information:
The authors would like to thank Ben Palanca, Kristen Sanfilippo, and Anthony Chang for informative discussions that helped to shape the manuscript. Figures were partially created using BioRender. AJ is supported by the Barnes Jewish Hospital Foundation Fund and is a coinvestigator on a multicenter study funded by Alexion (NCT04369469). JPA is supported by NIH/National Institute of General Medical Sciences (R35-GM136352-01 and 2R01-GM99111-23). AHJK is supported by NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30-AR073752) and the Rheumatology Research Foundation. HSK is funded by the Children?s Discovery Institute of Washington University and St. Louis Children?s Hospital (PD-FR-2020-867), the NIH (K08-HL148510), and the American Lung Association (RG-575308). HSK is currently a principal investigator on a multicenter study funded by Alexion on the use of complement inhibitors in severe COVID-19 (NCT04369469). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.
PY - 2020/8/6
Y1 - 2020/8/6
N2 - Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19–related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.
AB - Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19–related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.
UR - http://www.scopus.com/inward/record.url?scp=85089203661&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.140711
DO - 10.1172/jci.insight.140711
M3 - Article
C2 - 32554923
AN - SCOPUS:85089203661
SN - 2379-3708
VL - 5
JO - JCI insight
JF - JCI insight
IS - 15
M1 - e140711
ER -