ArticleFrontiers in immunology2023
Persistence is key: unresolved immune dysfunction is lethal in both COVID-19 and non-COVID-19 sepsis.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Article
- Quantifying pathway perturbations based on gene network rewiring in sepsis progression toward death or survival.Frontiers in bioinformatics · 2026Article
- Longitudinal gene expression analysis in COVID-19 sepsis highlights dynamic immune, cellular, and metabolic dysfunction in high severity patients.Scientific reports · 2025Article
- Viral sepsis - pathophysiology and disease manifestation.Infection · 2025Review
- Molecular endotypes in sepsis: integration of multicohort transcriptomics based on RNA sequencing.Journal of intensive care · 2025Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Severe COVID-19 and non-COVID-19 pulmonary sepsis share pathophysiological, immunological, and clinical features, suggesting that severe COVID-19 is a form of viral sepsis. Our objective was to identify shared gene expression trajectories strongly associated with eventual mortality between severe COVID-19 patients and contemporaneous non-COVID-19 sepsis patients in the intensive care unit (ICU) for potential therapeutic implications. Methods: Whole blood was drawn from 20 COVID-19 patients and 22 non-COVID-19 adult sepsis patients at two timepoints: ICU admission and approximately a week later. RNA-Seq was performed on whole blood to identify differentially expressed genes and significantly enriched pathways. Using systems biology methods, drug candidates targeting key genes in the pathophysiology of COVID-19 and sepsis were identified. Results: When compared to survivors, non-survivors (irrespective of COVID-19 status) had 3.6-fold more "persistent" genes (genes that stayed up/downregulated at both timepoints) (4,289 vs. 1,186 genes); these included persistently downregulated genes in T-cell signaling and persistently upregulated genes in select innate immune and metabolic pathways, indicating unresolved immune dysfunction in non-survivors, while resolution of these processes occurred in survivors. These findings of persistence were further confirmed using two publicly available datasets of COVID-19 and sepsis patients. Systems biology methods identified multiple immunomodulatory drug candidates that could target this persistent immune dysfunction, which could be repurposed for possible therapeutic use in both COVID-19 and sepsis. Discussion: Transcriptional evidence of persistent immune dysfunction was associated with 28-day mortality in both COVID-19 and non-COVID-19 septic patients. These findings highlight the opportunity for mitigating common mechanisms of immune dysfunction with immunomodulatory therapies for both diseases.
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