Trial reportThe Journal of clinical investigation2020
Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 530 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
530 citing papers in PubMed, 1 synthesis or guideline pooled it, 779 citations in OpenAlex.
- From immunological mechanisms to targeted therapies: a bibliometric analysis in the domain of research concerning neutrophil extracellular traps and pulmonary diseases (2006-2025).Frontiers in immunology · 2026Pooled it
- Safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of STSA-1002, recombinant anti-human C5a fully human monoclonal antibody, in a randomized, first-in-human phase I study in healthy adults.Frontiers in pharmacology · 2026Trial
- Emerging evidence of neutrophil extracellular traps in essential hypertension and target organ damage: pathophysiological insights and therapeutic implications.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- The Acute Respiratory Distress Syndrome (ARDS): epidemiology, etiology, molecular mechanisms, diagnosis and therapeutic strategies.Molecular biomedicine · 2026Review
- Spike 1 protein of SARS-CoV-2 induces endothelial inflammation and vascular dysfunction through interferon ISG15-dependent mechanisms.Cardiovascular research · 2026Article
- Review
- Diffuse alveolar damage, acute respiratory distress syndrome (ARDS), and non-cardiogenic pulmonary edema. Part 1: ARDS endotypes, including systemic inflammatory response syndrome and sepsis, with dog and cat examples.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2026Review
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Mast cells release DNA Extracellular Traps (DETs) in response to SARS-CoV-2 and its spike protein.Cell communication and signaling : CCS · 2026Article
- The role of neutrophils in the pathogenesis of abdominal aortic aneurysms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Targeting neutrophil extracellular traps (NETs): a promising immunotherapeutic approach for pulmonary diseases.Molecular biology reports · 2026Review
- The Complement System in the Setting of Critical Illness-A Narrative Review.Biomolecules · 2026Review
- "Bridging the clinical, molecular and genetic perspectives on myocarditis in post-COVID-19 era".International journal of cardiology. Cardiovascular risk and prevention · 2026Review
- Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): An Immunopathogenic Model of Dysregulated Vaccine-Triggered Immunity.Vaccines · 2026Review
- NET Biomarkers in COVID-19 and Post-COVID Syndrome: a Comprehensive Analysis.Journal of clinical immunology · 2026Article
- Exploring blood transcriptional signatures for thrombosis diagnosis in critically ill patients with COVID-19.Blood vessels, thrombosis & hemostasis · 2026Article
- Neutrophil extracellular traps in rheumatoid arthritis: biomarkers, drivers, and emerging therapeutic targets.Clinical and experimental immunology · 2026Review
- Mechanisms and impact of long COVID: pathophysiology, neuropsychiatric effects and vaccination.Frontiers in immunology · 2026Review
- Metabolic reprogramming is associated with symptomatic COVID-19: a serum proteomics and causal inference study identifying ALDOB and glycerol as candidate metabolic correlates.Frontiers in microbiology · 2026Article
470 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging data indicate that complement and neutrophils contribute to the maladaptive immune response that fuels hyperinflammation and thrombotic microangiopathy, thereby increasing coronavirus 2019 (COVID-19) mortality. Here, we investigated how complement interacts with the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 specimens, cell-based inhibition studies, and NET/human aortic endothelial cell (HAEC) cocultures. Increased plasma levels of NETs, tissue factor (TF) activity, and sC5b-9 were detected in patients. Neutrophils of patients yielded high TF expression and released NETs carrying active TF. Treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAECs. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. COVID-19 serum induced complement activation in vitro, consistent with high complement activity in clinical samples. Complement C3 inhibition with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis for a pivotal role of complement and NETs in COVID-19 immunothrombosis. This study supports strategies against severe acute respiratory syndrome coronavirus 2 that exploit complement or NETosis inhibition.
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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.