ArticleProceedings of the National Academy of Sciences of the United States of America2024
Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- An integrated machine learning and mendelian randomization approach identifies SERPING1 as a prognostic biomarker associated with CD8 + T-cell infiltration in DLBCL.Discover oncology · 2026Article
- Exacerbated Hepatic Stress and Systemic Metabolic Disruption Driven by SARS-CoV-2 P.1 Variant in K18-hACE2 Mice.Immunity, inflammation and disease · 2026Article
- Immunomodulatory activities of bovine host defense peptides (HDPs): context-dependent roles in inflammation and immune priming.BMC veterinary research · 2026Article
- Inflammatory and Molecular Mechanisms of Adenomyosis Associated Pain: Insights from Multiple Analytic Approaches.Journal of pain research · 2026Article
- Multi-omics analysis of long COVID (post-COVID-19 condition) reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune dysregulation.Frontiers in immunology · 2026Article
- Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis.Molecular biology and evolution · 2025Article
- Severe acute respiratory syndrome coronavirus 2-mediated dysregulation of drug processing genes is dependent on pathogenic variants, target site of infection, age, and sex.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Revisiting the monocrotaline-treated rat as a model of inflammatory lung disease: COVID-19 and future pandemic threats?Animal models and experimental medicine · 2025Review
- Anatomical Region-Specific Transcriptomic Signatures and the Role of Epithelial Cells in Pterygium Inflammation: A Multi-Omics Analysis.Translational vision science & technology · 2025Article
- IL-1β drives SARS-CoV-2-induced disease independently of the inflammasome and pyroptosis signalling.Cell death and differentiation · 2025Article
- Risk of acute kidney injury and mortality in patients vaccinated against COVID-19.International journal of medical sciences · 2025Article
- Article
- Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- RAAS Overactivation and Mitochondrial Damage Signaling as Key Players in Lethal COVID-19.Current drug targets · 2025Article
- Mitochondrial antioxidants abate SARS-COV-2 pathology in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multi-System-Level Analysis with RNA-Seq on Pterygium Inflammation Discovers Association between Inflammatory Responses, Oxidative Stress, and Oxidative Phosphorylation.International journal of molecular sciences · 2024Article
- RNA-Seq of an LPS-Induced Inflammation Model Reveals Transcriptional Profile Patterns of Inflammatory Processes.Life (Basel, Switzerland) · 2024Article
- Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.International journal of molecular sciences · 2024Article
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60 authors.
Funding
Abstract
Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes. Twenty-two of these are "noncanonical" immune genes, which we link to components of the renin-angiotensin-activation-system that manifest as increased fibrin deposition, leaky vessels, thrombotic tendency, PANoptosis, and mitochondrial dysfunction. Immunohistochemistry of mediastinal lymph nodes reveals altered architecture, excess collagen deposition, and pathogenic fibroblast infiltration. Many of the above findings are paralleled in animal models of SARS-CoV-2 infection and human peripheral blood mononuclear and whole blood samples from individuals with early and later SARS-CoV-2 variants. We then redefine cytokine storm in lethal COVID-19 as driven by upstream immune gene and mitochondrial signaling producing downstream RAAS (renin-angiotensin-aldosterone system) overactivation and organ damage, including compromised mediastinal lymph node function.
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