Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection

Lina Ma, Sanjaya K. Sahu, Marlene Cano, Vasanthan Kuppuswamy, Jamal Bajwa, Ja'Nia McPhatter, Alexander Pine, Matthew L. Meizlish, George Goshua, C. Hong Chang, Hanming Zhang, Christina Price, Parveen Bahel, Henry Rinder, Tingting Lei, Aaron Day, Daniel Reynolds, Xiaobo Wu, Rebecca Schriefer, Adriana M. RauseoCharles W. Goss, Jane A. O'Halloran, Rachel M. Presti, Alfred H. Kim, Andrew E. Gelman, Charles S. Dela Cruz, Alfred I. Lee, Philip A. Mudd, Hyung J. Chun, John P. Atkinson, Hrishikesh S. Kulkarni

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Article numbereabh2259
JournalScience immunology
Volume6
Issue number59
DOIs
StatePublished - May 2021

Fingerprint

Dive into the research topics of 'Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection'. Together they form a unique fingerprint.

Cite this