ArticlePLoS computational biology2021
A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes' interactions points to Neutrophil extracellular traps as mediators of thrombosis in COVID-19.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed, 28 citations in OpenAlex.
- Unbiased characterization of COVID-19 endotypes leads to prognostication of high-risk individuals using routine blood tests.Communications medicine · 2026Article
- DENetwork unveils non-differentially expressed genes with functional relevance across conditions through information flow perturbation.Nucleic acids research · 2025Article
- Fatal Cytokine Collision: HLH-AIHA in Advanced AIDS-Case Report and Literature Review.Reports (MDPI) · 2025Article
- Efficient and scalable construction of clinical variable networks for complex diseases with RAMEN.Cell reports methods · 2025Article
- Multisystem inflammatory syndrome in children (MIS-C): Implications for long COVID.Inflammopharmacology · 2023Review
- The central role of neutrophil extracellular traps (NETs) and by-products in COVID-19 related pulmonary thrombosis.Immunity, inflammation and disease · 2023Review
- Article
- Circulating biomarkers of inflammaging as potential predictors of COVID-19 severe outcomes.Mechanisms of ageing and development · 2022Review
- Pulmonary embolism after dexamethasone treatment for COVID-19: a case report.BMC infectious diseases · 2022Article
- Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children.Biology · 2022Article
- Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States.Cells · 2022Article
- On the Origin of Neutrophil Extracellular Traps in COVID-19.Frontiers in immunology · 2022Review
- Identification of transcriptional regulatory network associated with response of host epithelial cells to SARS-CoV-2.Scientific reports · 2021Article
- Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children.Current opinion in pediatrics · 2021Review
- Innate immunology in COVID-19-a living review. Part II: dysregulated inflammation drives immunopathology.Oxford open immunology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal coagulation and an increased risk of thrombosis are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis in severe COVID-19 in children and adults. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic and metabolic disorders.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.