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Multi-Institution Study Identifies Cause of Deadly Hyperinflammatory Response in Cases of COVID-19

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Multi-Institution Study Identifies Cause of Deadly Hyperinflammatory Response in Cases of COVID-19
December 3, 2024

As part of the COVID-19 International Research Team, scientists from Children’s Hospital of Philadelphia, the Johns Hopkins Kimmel Cancer Center, the University of Pittsburgh, and Weill Cornell Medicine have identified mitochondrial dysfunction as a key driver of cytokine storm, the extreme inflammatory response linked to increased mortality in COVID-19.

The study, published this week in Proceedings of the National Academy of Sciences, employed advanced multi-omics approaches to analyze hundreds of human and animal COVID-19 specimens. These included analyzing autopsy tissues from the lungs, heart, liver, kidneys, and lymph nodes of 40 deceased patients, as well as nasopharyngeal swabs, blood, peripheral blood mononuclear cells (PBMCs), and samples from SARS-CoV-2-infected animal model tissues.

By mapping metabolic and immune changes across all stages of COVID-19—from early infection to severe disease and autopsy—the researchers uncovered widespread mitochondrial and immune dysfunction, alongside hyperactivation of the renin-angiotensin-aldosterone system (RAAS) in multiple tissues, including those not directly infected by the virus. This dysfunction was particularly prominent in the lymph nodes, where immune dysregulation and sustained damage created a harmful environment that exacerbated severe disease and increased vulnerability to secondary infections and tumor growth after infection because of decreased immune response.

Prolonged immune and mitochondrial dysregulation in other tissues, notably the lungs, heart, and kidneys, also has significant implications for understanding long COVID, a chronic condition characterized by symptoms such as fatigue, respiratory issues, heart palpitations, and joint pain. Currently, the COV-IRT is pursuing follow-up studies to investigate long-term immune and mitochondrial changes and their connections to long COVID and cancer predisposition. Click here to read the full announcement.

 

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