New Delhi,: Organ damage and death due to severe COVID-19 could be because of disruption to the mitochondria, or a cell’s “energy-producing factory”, which contributes to ‘cytokine storm’ — or excessive inflammation commonly seen in these patients, a new study has found.
Researchers found that the damage or stress in mitochondria can trigger immune responses, specifically those that activate the renin-angiotensin-aldosterone system, or ‘RAAS’, network of hormones, proteins and enzymes.
The network is known to be essential for regulating blood pressure, but when overactivated, can trigger a string of processes causing organ damage, the researchers, including those at the University of Pittsburgh, US, said.
They explained that overactivation of the RAAS network and stress in mitochondria intensify an “out-of-control” immune response, known as a ‘cytokine storm’ — a common feature of severe COVID-19 and also considered a main contributor to long Covid.
The findings, published in the journal Proceedings of the National Academy of Sciences, shed light on the biological processes driving organ damage and death in severe COVID-19 and helps explain why survivors can experience long-term complications.
“Notably, we also found that activation of RAAS caused substantial damage to the lymph nodes (part of the immune system), which hasn’t been shown in COVID-19 before,” co-senior author Afshin Beheshti, a professor of surgery and computational and systems biology at the University of Pittsburgh, said.
“This could explain the long-lasting immune dysregulation seen in survivors of COVID-19 and may contribute to long COVID,” Beheshti said.
For the study, the researchers analysed genomes in autopsy samples obtained from 40 patients who died due to the viral infection. The samples were taken from multiple organs, including nasal cavity (nose), lungs, heart and liver.
The team observed an increased expression of about 50 genes involved in the functioning of one’s immune system in the samples obtained from nasal swabs. Information in one’s genes translate into observable behaviour and traits through the process of ‘gene expression’.
The authors wrote, “In total, these data suggest that overactivation of RAAS signalling and mitochondrially mediated inflammation activation holistically comprise the cytokine storm that causes lethal COVID-19.” “Our study resolves some of the long-standing unanswered questions about how the SARS-CoV-2 virus impacts the body,” Beheshti said.
“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,” Beheshti said.
