ArticleJCI insight2021
Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity.
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 63 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Carbohydrates Metabolic Signatures in Immune Cells: Response to Infection.Frontiers in immunology · 2022Pooled it
- Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.Molecular systems biology · 2021Pooled it
- Host metabolic responses to SARS-CoV-2 and influenza viruses: parallels and contrasts.Metabolomics : Official journal of the Metabolomic Society · 2026Review
- SARS-CoV-2 Nsp15 facilitates immune evasion and viral replication by limiting multiple host innate immune pathways, including cGAS-STING.The Journal of general virology · 2026Article
- Lactiplantibacillus plantarum GUANKE ameliorates influenza a virus-induced inflammation and lung barrier dysfunction through enhancing mitophagy and improving oxidative phosphorylation.Cellular and molecular life sciences : CMLS · 2026Article
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- Article
- Differential DNA methylation 7 months after SARS-CoV-2 infection.Clinical epigenetics · 2025Article
- Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19.BMC medical genomics · 2025Article
- Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.EClinicalMedicine · 2025Review
- Polyunsaturated Fatty Acid Imbalance-A Contributor to SARS CoV-2 Disease Severity.Journal of nutrition and metabolism · 2025Review
- Salivary cortisol in long COVID: a marker of broader stress system and circadian rhythm dysregulation.Frontiers in cellular and infection microbiology · 2025Article
- COVIDomics: Metabolomic Views on COVID-19.Metabolites · 2024Article
- Bone-marrow macrophage-derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair.Nature cardiovascular research · 2024Article
- Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.Biomolecules & therapeutics · 2024Review
- CCL2-mediated endothelial injury drives cardiac dysfunction in long COVID.Nature cardiovascular research · 2024Article
- The emerging role of SARS-CoV-2 nonstructural protein 1 (nsp1) in epigenetic regulation of host gene expression.FEMS microbiology reviews · 2024Review
- SARS-CoV-2 Nsp15 antagonizes the cGAS-STING-mediated antiviral innate immune responses.bioRxiv : the preprint server for biology · 2024Article
- PKM2 regulates metabolic flux and oxidative stress in the murine heart.Physiological reports · 2024Article
- Persistent Post COVID-19 Endothelial Dysfunction and Oxidative Stress in Women.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Article
3 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
24 authors at 7 institutions in 3 countries.
Funding
Abstract
Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2-induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.
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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.