While severe COVID-19 has typically been viewed as a result of an inflammatory “cytokine storm,” in which the immune response becomes overly aggressive, it inundates the bloodstream and tissues with immune signaling proteins at concentrations that cause inflammation in the lungs and other associated symptoms.
A study by researchers from Weill Cornell Medicine, Johns Hopkins Medicine, Children’s Hospital of Philadelphia, the University of Pittsburgh School of Medicine, and other members of the COVID-19 International Research Team suggests that severe COVID-19 may be partly caused by the SARS-CoV-2 virus’s impact on mitochondria.
The findings enhance our understanding of how molecular pathways drive this storm.
The team used RNA sequencing and other laboratory techniques on patient and animal model tissue samples to identify these processes in great detail.
The researchers found that SARS-CoV-2 infection causes significant damage to mitochondria in infected cells, activating the immune system and contributing to the inflammatory response. One key finding was the overactivation of the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure.
This overactivation is linked to abnormal blood clotting, a prominent feature of severe COVID-19, as well as scarring in lymph nodes and dysfunction of immune cells. These immune cell dysfunctions may explain the impaired immune response in severe COVID-19 cases.
Dr. Robert Schwartz, associate professor of medicine, said, “One of the suggestions of these findings is that there is, early in the process, profound mitochondrial dysfunction and damage, which is then driving RAAS overactivation, which in turn contributes to the multi-organ damage of severe COVID-19.”
“We’re also concerned that these processes underlying acute COVID-19 may not always return to normal afterward.”
Journal Reference:
- Michael J. Topper, Joseph W. Guarnieri, Jeffrey A. Haltom et al. Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2401968121
