Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes
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View abstract on PubMed
Summary
This summary is machine-generated.Lethal COVID-19 involves a redefined cytokine storm, driven by immune gene and mitochondrial signaling. This leads to renin-angiotensin-aldosterone system overactivation, organ damage, and compromised lymph node function.
Area Of Science
- Immunology
- Pathology
- Genomics
Background
- Classic cytokine storm is implicated in lethal COVID-19.
- The precise mechanisms driving severe SARS-CoV-2 outcomes require further elucidation.
Purpose Of The Study
- To re-examine the cytokine storm in lethal COVID-19 using molecular and tissue analyses.
- To identify key molecular pathways and cellular changes contributing to organ damage in fatal SARS-CoV-2 infections.
Main Methods
- RNA sequencing of nasopharyngeal and autopsy tissues from COVID-19 patients.
- Immunohistochemistry of mediastinal lymph nodes.
- Analysis of SARS-CoV-2 animal models and human blood samples.
Main Results
- Upregulated noncanonical immune genes in nasal swabs correlated with organ damage (heart, lung, kidney, liver).
- These genes link to renin-angiotensin-aldosterone system (RAAS) overactivation, fibrin deposition, vascular leakage, PANoptosis, and mitochondrial dysfunction.
- Mediastinal lymph nodes showed altered architecture, fibrosis, and fibroblast infiltration.
Conclusions
- Lethal COVID-19 cytokine storm is driven by upstream immune and mitochondrial signaling.
- This signaling activates the RAAS, causing organ damage and impaired lymph node function.
- Findings were paralleled in animal models and various SARS-CoV-2 variants.
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