期刊
SCIENCE IMMUNOLOGY
卷 6, 期 59, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abh2259
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资金
- Barnes-Jewish Hospital Foundation
- Siteman Cancer Center grant from the National Cancer Institute of the National Institutes of Health (NIH) [P30 CA091842]
- Washington University Institute of Clinical and Translational Sciences grant from the National Center for Advancing Translational Sciences of the NIH [UL1TR002345]
- Rheumatic Diseases Core Center [NIH WLC6313040077]
- NIH [K08HL148510, T32HL007317, R35GM136352, R01EYE028602, R01HL094601, P01AI116501, R01HL126094, R01HL142818]
- Emergency Medicine Foundation
- Children's Discovery Institute
- Washington University Institute of Clinical Translational Sciences (ICTS) SPIRIT award
- Rheumatic Diseases Research Resource-Based Center [P30AR073752]
- Alexion Pharmaceuticals
- Clark Family/Clayco Foundation International Cerebroretinal Vasculopathy (CRV) Research Award
- Washington University ICTS COVID-19 Research Program
- Jacqueline G. and William E. Maritz Endowed Chair in Immunology and Oncology
- Patterson Trust Award in Clinical Research
- Yale University CTSA SPIRIT award
- American Heart Association Transformative Research Project
- DeLuca Foundation
Complement activation is elevated in patients with COVID-19 and is associated with severe illness, endothelial injury, and hypercoagulability, serving as a distinctive feature of COVID-19 and providing specific targets for risk prognostication and drug discovery.
Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19 and whether it is associated with certain features of COVID-19, such as endothelial injury and hypercoagulability. Hence, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers: Washington University School of Medicine (n = 134) and Yale School of Medicine (n = 49). We compared our patients with two non-COVID cohorts: (i) patients hospitalized with influenza (n = 54) and (ii) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV; n = 22). We demonstrate that circulating markers of complement activation are elevated in patients with COVID-19 compared with those with influenza and to patients with non- COVID-19 respiratory failure. Furthermore, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission or IMV. Moreover, the results indicate that enhanced activation of the alternative pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., angiopoietin-2) and hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19 and provide specific targets that may be used for risk prognostication, drug discovery, and personalized clinical trials.
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