ArticleThe Journal of clinical investigation2023
C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Novel interactions between the C5-C5aR1 Axis and IF1: Implications for kidney mitochondrial physiology and ischemia-reperfusion injury.Physiological reports · 2026Article
- Blood Coagulation in COVID-19: Systems-Biology Evidence, Clinical Implications, and Therapeutic Opportunities in an Evolving Pandemic.ACS omega · 2026Article
- C/EBP-β-regulated complement hyperactivation in spleen of SFTSV-infected mice: A clue to targeted complement therapy.PLoS pathogens · 2026Article
- The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.Cellular and molecular neurobiology · 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
- Immune-endothelial-coagulation crosstalk as a driver of multi-organ dysfunction in severe viral pneumonia.Frontiers in immunology · 2026Review
- Spatial proteomics for the analysis of host-pathogen interactions in mice lungs infected withmicroLife · 2026Article
- Dysregulation of complement components associated with inflammation and coagulation in virally suppressed people living with HIV.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Targeted Blockade of Terminal C5a Is Critical to Management of Sepsis and Acute Respiratory Distress Syndrome: The Mechanism of Action of Vilobelimab.International journal of molecular sciences · 2025Review
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Neutrophil extracellular traps potentiate effector T cells via endothelial senescence in uveitis.JCI insight · 2025Article
- Identification and validation of key biomarkers of the glycolysis-ketone body metabolism in heart failure based on multi-omics and machine learning.Frontiers in cardiovascular medicine · 2025Article
- Therapeutic targeting of alternative pathway and C5 but not C5a protects from disease development in a preclinical model of autoimmune blistering dermatosis.Frontiers in immunology · 2025Article
- Complement-mediated and direct activation of human neutrophils induced byFrontiers in immunology · 2025Article
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- Hexamerization: explaining the original sin of IgG-mediated complement activation in acute lung injury.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
44 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions and plays immunopathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill patients with COVID-19 compared with patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular traps-dependent (NETs-dependent) immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonists of C5aR1 could be useful for COVID-19 treatment.
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Registered trials
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.