Trial reportFrontiers in immunology2021
Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection.
Trial report in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 4 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- The immunopathological spectrum of COVID-19: from cytokine storm to autoimmunity-a systematic review.Frontiers in medicine · 2026Pooled it
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- An updated meta-analysis of Chinese herbal medicine for the prevention of COVID-19 based on Western-Eastern medicine.Frontiers in pharmacology · 2023Pooled it
- Pitfalls in complement analysis: A systematic literature review of assessing complement activation.Frontiers in immunology · 2022Pooled it
- Recombinant C1 inhibitor in the prevention of severe COVID-19: a randomized, open-label, multi-center phase IIa trial.Frontiers in immunology · 2023Trial
- Activation of the Lectin Pathway Drives Persistent Complement Dysregulation in Long COVID.Immunology · 2026Article
- Complement Dysregulation in Kidney Diseases: Mechanisms, Biomarkers, and Emerging Targeted Therapies.International journal of molecular sciences · 2026Review
- The Complement System in the Setting of Critical Illness-A Narrative Review.Biomolecules · 2026Review
- Complement Hyperactivation Is Mediated by Alternative and Lectin Pathways During Early Phase of Severe Vaccination-Omicron BA.5 Infection.Journal of medical virology · 2026Article
- In vitro complement activation via nucleocapsid and spike proteins of SARS-CoV-2 in COVID-19 patients.Scientific reports · 2025Article
- Impact of complement system proteins on the clinical progression of hospitalized patients with COVID-19.BMC infectious diseases · 2025Article
- Rewired type I IFN signaling is linked to age-dependent differences in COVID-19.Cell reports. Medicine · 2025Article
- Is COVID-19 Coagulopathy a Thrombotic Microangiopathy? A Prospective, Observational Study.International journal of molecular sciences · 2025Observational
- CD55 upregulation in T cells of COVID-19 patients suppresses type-I interferon responses.Communications biology · 2025Article
- C3 as a predictive and prognostic biomarker in adult hemophagocytic lymphohistiocytosis: a large cohort study in China.Blood advances · 2025Article
- Host transcriptome response to Mycoplasma bovis and bovine viral diarrhea virus in bovine tissues.BMC genomics · 2025Article
- Differences in biomarker levels and proteomic survival prediction across two COVID-19 cohorts with distinct treatments.iScience · 2025Article
- Article
- Complete recovery after complement factor I deficiency associated fulminant acute hemorrhagic leukoencephalitis: a case report.Frontiers in immunology · 2025Article
- Induction of Fc-dependent functional antibodies against different variants of SARS-CoV-2 varies by vaccine type and prior infection.Communications medicine · 2024Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objectives: Uncontrolled thromboinflammation plays an important role in the pathogenesis of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus. Complement was implicated as key contributor to this process, therefore we hypothesized that markers of the complement profile, indicative for the activation state of the system, may be related to the severity and mortality of COVID-19. Methods: In this prospective cohort study samples of 102 hospitalized and 26 outpatients with PCR-confirmed COVID-19 were analyzed. Primary outcome was in-hospital, COVID-19 related mortality, and secondary outcome was COVID-19 severity as assessed by the WHO ordinal scale. Complement activity of alternative and classical pathways, its factors, regulators, and activation products were measured by hemolytic titration, turbidimetry, or enzyme-immunoassays. Clinical covariates and markers of inflammation were extracted from hospital records. Results: Increased complement activation was characteristic for hospitalized COVID-19 patients. Complement activation was significantly associated with markers of inflammation, such as interleukin-6, C-reactive protein, and ferritin. Twenty-five patients died during hospital stay due to COVID-19 related illness. Patients with uncontrolled complement activation leading to consumption of C3 and decrease of complement activity were more likely to die, than those who had complement activation without consumption. Cox models identified anaphylatoxin C3a, and C3 overactivation and consumption (ratio of C3a/C3) as predictors of in-hospital mortality [HR of 3.63 (1.55-8.45, 95% CI) and 6.1 (2.1-17.8), respectively]. Conclusion: Increased complement activation is associated with advanced disease severity of COVID-19. Patients with SARS-CoV-2 infection are more likely to die when the disease is accompanied by overactivation and consumption of C3. These results may provide observational evidence and further support to studies on complement inhibitory drugs for the treatment of COVID-19.
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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.