ArticleImmunity2022
Functional proteomic profiling links deficient DNA clearance with increased mortality in individuals with severe COVID-19 pneumonia.
Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Exercise intensity and training alter the innate immune cell type and chromosomal origins of circulating cell-free DNA in humans.Proceedings of the National Academy of Sciences of the United States of America · 2025Trial
- Trial
- RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation.Science (New York, N.Y.) · 2026Article
- GRP78 in viral pneumonia: dual regulatory mechanisms and translational prospects.Clinical and experimental medicine · 2026Review
- Neutrophil extracellular traps associated with severity and prognosis of community-acquired pneumonia.Clinical and experimental medicine · 2025Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Unraveling NETs in Sepsis: From Cellular Mechanisms to Clinical Relevance.International journal of molecular sciences · 2025Review
- Kinetics of DNases after hematopoietic stem cell transplant.Blood vessels, thrombosis & hemostasis · 2025Article
- Neutrophil extracellular traps capture the human pathogen, Candida albicans, in blood and delay hyphal transformation.Journal of leukocyte biology · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Neutrophils restricted contribution ofHeliyon · 2025Article
- A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation.Nature communications · 2024Article
- Development of a Clonal and High-Yield Mammalian Cell Line for the Manufacturing of a Hyperactive Human DNase I with Extended Plasma Half-Life Using PASylationPharmaceutics · 2024Article
- Review
- Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality.The Journal of clinical investigation · 2024Observational
- Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease.Journal of translational medicine · 2024Article
- NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease.Circulation research · 2023Review
- Plasma Proteomic Variables Related to COVID-19 Severity: An Untargeted nLC-MS/MS Investigation.International journal of molecular sciences · 2023Article
- Visualization of Nuclease- and Serum-Mediated Chromatin Degradation with DNA-Histone Mesostructures.International journal of molecular sciences · 2023Article
- You are what you eat and how you digest it! A discussion on inflammatory efferocytosis.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
The factors that influence survival during severe infection are unclear. Extracellular chromatin drives pathology, but the mechanisms enabling its accumulation remain elusive. Here, we show that in murine sepsis models, splenocyte death interferes with chromatin clearance through the release of the DNase I inhibitor actin. Actin-mediated inhibition was compensated by upregulation of DNase I or the actin scavenger gelsolin. Splenocyte death and neutrophil extracellular trap (NET) clearance deficiencies were prevalent in individuals with severe COVID-19 pneumonia or microbial sepsis. Activity tracing by plasma proteomic profiling uncovered an association between low NET clearance and increased COVID-19 pathology and mortality. Low NET clearance activity with comparable proteome associations was prevalent in healthy donors with low-grade inflammation, implicating defective chromatin clearance in the development of cardiovascular disease and linking COVID-19 susceptibility to pre-existing conditions. Hence, the combination of aberrant chromatin release with defects in protective clearance mechanisms lead to poor survival outcomes.
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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.