ArticleJCI insight2021
Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 2 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
145 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.European journal of neurology · 2025Pooled it
- Stress and circulating cell-free mitochondrial DNA: A systematic review of human studies, physiological considerations, and technical recommendations.Mitochondrion · 2021Pooled it
- Multicenter randomized trial assessing efficacy and safety of aerosolized dornase Alfa in COVID-19 ARDS.Scientific reports · 2025Trial
- Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality.The Journal of clinical investigation · 2021Trial
- Lower mitochondrial DNA copy number in ATTRV50M Swedish carriers.Orphanet journal of rare diseases · 2026Article
- Article
- DAMP Laden Extracellular Vesicles From the Airways of Patients With Severe SARS-CoV-2 Respiratory Infection Compromise Inflammation and Cellular Metabolism.Journal of extracellular vesicles · 2026Article
- Cell-free nucleic acids as a non-invasive biomarker for predicting COVID-19 disease severity and outcome: a retrospective cohort study.BMC infectious diseases · 2026Article
- Rethinking Mitochondria: The Extracellular Dimension.Circulation research · 2026Review
- Mitochondria in SARS-CoV-2 infection: Immune interactions and molecular approaches in the Post COVID-19 condition.Genetics and molecular biology · 2026Article
- Convergent hub pathways targeted by IAV, SARS-CoV-2, and RSV in type II alveolar epithelial cells: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Circulating cell-free mitochondrial DNA as a candidate marker of hyperinflammation and immune activation in pre-adolescents, adolescents and young adults with COVID-19 and comorbidities.Revista do Instituto de Medicina Tropical de Sao Paulo · 2026Article
- The cGAS-STING pathway in pulmonary infectious and sterile inflammation: differences, connections, and therapeutic implications.Frontiers in immunology · 2026Review
- Mitochondrial DNA efflux as a potential amplifier of systemic inflammatory network rewiring in heart failure with preserved ejection fraction.Frontiers in immunology · 2026Review
- Innate immune activation and mitochondrial ROS induce acute and persistent cardiac conduction system dysfunction after COVID-19.JCI insight · 2025Article
- Kidney mitochondrial DNA contributes to systemic IL-6 release in sepsis-associated acute kidney injury.JCI insight · 2025Article
- Mitochondrial function is impaired in long COVID patients.Annals of medicine · 2025Observational
- Wide-spectrum profiling of plasma cell-free RNA and the potential for health-monitoring.RNA biology · 2025Article
- Hyperinflammation by Human Macrophages Induced by SARS-CoV-2 Anti-Spike IgG Is Dependent on Glucose and Fatty Acid Metabolism.European journal of immunology · 2025Article
- Extracellular mitochondrial DNA activates complement and is associated with complement activation in patients with out-of-hospital cardiac arrest.Scientific reports · 2025Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19.ResultsCirculating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy.ConclusionThese results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.FundingWashington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345.
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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.