Research from University of Southern California shows that the effects of COVID-19 on the immune system appear to be due to suppression of the cells’ mitochondria
New research has helped to shed light on the effects that COVID-19 has on the immune system. Since the early months of the pandemic, it has been known that COVID-19 can suppress and evade the immune system; however, the way in which this occurs has only recently begun to be understood.
Research on how COVID-19 evades the immune system took a significant step forward in late May when Israeli researchers discovered multiple genetic changes that COVID-19 causes to suppress early immune system signaling (See New Research From Israel Provides Insights Into Unknown Immune System Evasion Capabilities of COVID-19). Additionally, new research out of the University of Southern California (USC) Leonard Davis School of Gerontology has further expanded the base of knowledge on this topic.
The USC Leonard Davis School of Gerontology study, published in the Nature journal Scientific Reports, demonstrates that SARS-CoV-2 specifically affects genetic expression in the mitochondria of cells. Mitochondria play a key role in how cells generate energy and other aspects of cell metabolism. Researchers also found that the effects of SARS-CoV-2 on mitochondria were significantly different than other viruses.
“We already knew that our immune response was not mounting a successful defense to COVID-19, but we didn’t know why,” stated lead author Brendan Miller for SciTechDaily. Miller is a senior doctoral student at the USC Leonard Davis School. “What we did differently was look at how the virus specifically targets mitochondria, a cellular organelle that is a crucial part of the body’s innate immune system and energy production.”
One Key Effect of SARS-CoV-2 on Mitochondria
Researchers found that one of the key effects of SARS-CoV-2 on mitochondria was that it reduced the levels of a group of proteins called Complex One. This reduction leads to suppression of the cell’s normal metabolism and reduces the cell’s normal ability to create an inflammatory response that would normally kill the virus.
“COVID-19 is reprogramming the cell to not make these Complex One-related proteins. That could be one way the virus continues to propagate,” said Miller, emphasizing that continued experimentation would be necessary to validate the team’s findings.
New Finding May Explain Age-Related Responses to COVID-19
This finding helps to explain why people who are older or who have diseases such as diabetes are more at risk for developing severe COVID-19 symptoms. Advanced age or certain diseases can naturally suppress the normal function of mitochondria, predisposing patients to the apparent mitochondrial effects of COVID-19. If a patient already has pathologically suppressed mitochondria, further suppression from the effects of SARS-CoV-2 would result in even more severe suppression of the natural immune response.
“If you already have mitochondrial and metabolic dysfunction, then you may, as a result, have a poor first line of defense against COVID-19,” added Pinchas Cohen, MD, Professor of Gerontology, Medicine and Biological Sciences and Dean of the USC Leonard Davis School of Gerontology. “Future work should consider mitochondrial biology as a primary intervention target for SARS-CoV-2 and other coronaviruses.”
What USC Leonard Davis School Study Adds to COVID-19 Research
“This study adds to a growing body of research on mitochondrial-COVID interactions and presents tissue and cell-specific effects that should be carefully considered in future experiments,” Cohen summed up.
The discovery that COVID-19 may primarily affect the immune system through its effects on the mitochondria provides researchers with potential testing and treatment applications. Treatments that promote and maintain mitochondrial health may help to reduce the severity of disease in those who develop a COVID-19 infection.
Testing that provides indications about mitochondrial health may also provide healthcare professionals with better indications about the expected severity of a COVID-19 infection and could allow them to better predict which patients would require more intensive early treatments. While there is still much research to be done in this area, the USC Leonard Davis School may provide clinicians with new tools to fight COVID-19 infection.
—By Caleb Williams, Editor, STAT Intelligence Briefings