ArticleEmerging microbes & infections2018
Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV.
Article in Emerging microbes & infections, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04369820 (C5a Receptor Expression in Circulating Myeloid Cells in ARDS Secondary to COVID-19), which is not on this map. Cited by 158 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
C5a Receptor Expression in Circulating Myeloid Cells in ARDS Secondary to COVID-19
Who cites it
158 citing papers in PubMed, 3 syntheses or guidelines pooled it, 204 citations in OpenAlex.
- COVID-19 and the Immune Response: A Multi-Phasic Approach to the Treatment of COVID-19.International journal of molecular sciences · 2022Pooled it
- Systemic inflammation in COVID-19 patients may induce various types of venous and arterial thrombosis: A systematic review.Scandinavian journal of immunology · 2021Pooled it
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Regional comparison of efficacy and safety for vilobelimab in critically ill, invasively mechanically ventilated COVID-19 patients.BMJ open respiratory research · 2025Trial
- Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial.The Lancet. Respiratory medicine · 2023Trial
- 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 Hyperactivation Is Mediated by Alternative and Lectin Pathways During Early Phase of Severe Vaccination-Omicron BA.5 Infection.Journal of medical virology · 2026Article
- Exploring the biological mechanisms of severe COVID-19 in the elderly: Insights from an aged mouse model.Virulence · 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
- Harnessing immunotherapeutic molecules and diagnostic biomarkers as human-derived adjuvants for MERS-CoV vaccine development.Frontiers in immunology · 2025Review
- Viral sepsis: diagnosis, clinical features, pathogenesis, and clinical considerations.Military Medical Research · 2024Review
- Total plasmaiScience · 2024Article
- Enhancing prognostic prediction of invasive candidiasis among cancer patients with a serum C5a-based scoring model.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Emerging role of complement in COVID-19 and other respiratory virus diseases.Cellular and molecular life sciences : CMLS · 2024Review
- The complement cascade in lung injury and disease.Respiratory research · 2024Review
- Review
- Complement and complement regulatory proteins are upregulated in lungs of COVID-19 patients.Pathology, research and practice · 2023Article
- C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps.The Journal of clinical investigation · 2023Article
- Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection.Nature reviews. Immunology · 2023Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a-C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.
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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.