COVID-19’s Double Blow: Mitochondrial Damage Fuels Complicated Health Outcomes
A groundbreaking study published in the Proceedings of the National Academy of Sciences sheds light on the devastating path COVID-19 takes through the body, offering crucial insight into why some survivors experience lasting complications.
"Our study resolves some of the long-standing unanswered questions about how the SARS-CoV-2 virus impacts the body. The findings point to new avenues for developing therapies to prevent or mitigate severe COVID-19 outcomes and possibly reduce the risk of long COVID," said Afshin Beheshti, Ph.D., co-senior author of the study and professor of surgery and computational and systems biology at the University of Pittsburgh School of Medicine.
Researchers, collaborating from institutions like Johns Hopkins University and Weill Cornell Medicine, analyzed gene expression in nasal swab samples from COVID-19 patients, comparing them to healthy individuals. They uncovered a surprising link between the virus and the mitochondria, the powerhouses of our cells. SARS-CoV-2 disrupted the mitochondria, causing them to release distress signals that triggered a complex immune response.
This response involved the renin-angiotensin-aldosterone system (RAAS), a critical regulator of blood pressure. Overactivated, RAAS acts like a runaway train, fueling a cascade of damaging events. When combined with mitochondrial stress, it intensifies a hyperactive immune reaction known as a "cytokine storm" frequently observed in severe COVID-19 cases.
The team’s examination of autopsy samples revealed the devastating fallout. The combined assault of overactive RAAS and cytokine storms unleashed severe inflammation, leading to organ damage. This encompassed heart failure, lung scarring, and kidney disease—conditions frequently found in individuals with long COVID.
"Notably, we also found that activation of RAAS caused substantial damage to the lymph nodes, which hasn’t been shown in COVID-19 before," explained Beheshti, who also heads the McGowan Institute’s Center for Space Biomedicine.
"This could explain the long-lasting immune dysregulation seen in survivors of COVID-19 and may contribute to long COVID."
Beheshti suggests that this damage to lymph nodes could have far-reaching consequences, potentially hindering the body’s ability to detect and eliminate cancerous cells. This finding might explain the recent rise in cancer cases observed post-pandemic.
Based on these findings, researchers believe therapies targeting RAAS overactivation and supporting mitochondrial function could hold immense promise in preventing or mitigating the severity of COVID-19 and potentially reduce the risk of long COVID.
Source:
Journal reference:
Topper, M. J., et al. (2024). Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2401968121.
