Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection
| Autor: | Jane A. O’Halloran, C-Hong Chang, Rachel M. Presti, Xiaobo Wu, Rebecca E Schriefer, Alfred H.J. Kim, Vasanthan Kuppuswamy, Hanming Zhang, Parveen Bahel, Henry M. Rinder, John P. Atkinson, George Goshua, Andrew E. Gelman, Sanjaya Kumar Sahu, Hyung J. Chun, Phillip Mudd, Tingting Lei, Lina Ma, Aaron Day, Christina Price, Hrishikesh S. Kulkarni, Alexander B Pine, Charles S. Dela Cruz, Daniel Reynolds, Charles W. Goss, Adriana M Rauseo, Matthew L Meizlish, Ja’Nia McPhatter, Jamal Bajwa, Marlene Cano, Alfred Ian Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Critical Illness Immunology Thrombomodulin Article law.invention Cohort Studies Pathogenesis 03 medical and health sciences 0302 clinical medicine Von Willebrand factor law Humans Medicine Prospective Studies Prospective cohort study Complement Activation Research Articles Aged biology business.industry R-Articles Patient Acuity COVID-19 Thrombosis General Medicine Middle Aged Intensive care unit Complement (complexity) Complement system Coronavirus Treatment Outcome 030104 developmental biology Respiratory failure 030220 oncology & carcinogenesis biology.protein Alternative complement pathway Female Endothelium Vascular business Biomarkers |
| Zdroj: | bioRxiv Science Immunology |
| Popis: | 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 if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, 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 to two non-COVID cohorts: (a) patients hospitalized with influenza (n=54), and (b) 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 to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., angiopoietin-2) as well as 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 utilized for risk prognostication, drug discovery and personalized clinical trials. Increased complement activation is observed in COVID-19 compared to non-COVID respiratory illness, and is a key marker of organ failure. |
| Databáze: | OpenAIRE |
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