ArticleScience immunology2021
Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection.
Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 5 of them syntheses that pooled it.
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Who cites it
161 citing papers in PubMed, 5 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- The immunopathological spectrum of COVID-19: from cytokine storm to autoimmunity-a systematic review.Frontiers in medicine · 2026Pooled it
- Persistent inflammatory cytokine signature in long Covid-19 patients: a meta-analysis.Inflammopharmacology · 2026Pooled it
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Tissue factor in COVID-19-associated coagulopathy.Thrombosis research · 2022Pooled it
- Cumulative Evidence for the Association of Thrombosis and the Prognosis of COVID-19: Systematic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the phase 2 PANAMO trial.Respiratory research · 2022Trial
- Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy.Cell reports. Medicine · 2022Trial
- Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial.Respiratory research · 2022Trial
- Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Trial
- Complement system component dysregulation is a distinctive feature of COVID-19 disease: a prospective and comparative analysis of patients admitted to the emergency department for suspected COVID-19 disease.Journal of thrombosis and thrombolysis · 2022Trial
- Vaccination-first immune priming shapes a sustained mRNA vaccine-induced IgG4 class switch that associates with SARS-CoV-2 breakthrough infection risk.Scientific reports · 2026Article
- The Complement System and Its Role in Eosinophilic Inflammation in Respiratory Diseases.Biomedicines · 2026Review
- Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.Immunology · 2026Article
- Article
- Collectin-11, a complement pattern recognition molecule, mediates pulmonary SARS-CoV-2 neutralization and protection.PLoS pathogens · 2026Article
- Complement Hyperactivation Is Mediated by Alternative and Lectin Pathways During Early Phase of Severe Vaccination-Omicron BA.5 Infection.Journal of medical virology · 2026Article
- SARS-CoV-2 infection in brain tumors and the association with alterations in the tumor immune microenvironment.Cancer biology & medicine · 2026Article
- Cardiovascular sequelae of Long COVID: immune dysregulation inflammation as central drivers.Frontiers in immunology · 2026Review
- Common and rare variants in complement genes as biomarkers of COVID-19 infection and severity. A lesson to learn for emerging pathogens.Frontiers in immunology · 2026Article
- Investigation into the Pancreatic Pathogenesis of SFTSV across Multiple Levels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
101 more citing papers are in PubMed but not listed here.
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0 authors at 4 institutions in 1 country.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.