Gene Changes Caused by Severe COVID-19 Infection Can Make Brain Age Faster, Study Says

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Changes in the gene activity inside the brains of severe COVID-19 patients are “strikingly similar” to those seen in people of old age, a new study suggests.

Published this week in Nature Aging, the study focused on genes that are expressed in the frontal cortex, a region in the brain critically responsible for cognition. Age-related deficits in cognitive function have long been attributed to changes within this region.

For the study, a research team led by neurologist Maria Mavrikaki at Beth Israel Deaconess Medical Center of Harvard Medical School examined frontal cortex tissue samples taken from 21 patients who died of severe COVID-19, as well as one patient who died of asymptomatic COVID-19 infection.

These samples were then compared with their corresponding age- and sex-matched uninfected controls with no history of neurological or psychiatric disease. Another control group comprised nine individuals who never had COVID-19 but had spent time on a ventilator or in an ICU, which can cause long-term problems with brain function.

The comparison, according to the study, found 6,993 differentially expressed genes. Of those, 3,330 were more actively expressed, or upregulated; and 3,663 were less actively expressed, or downregulated.

In particular, genes associated with inflammation and stress were found to be more upregulated in the brains of severe COVID-19 patients than in the uninfected controls.

Researchers said this pattern mirrors what happens to the brains of older people.

“We observed that gene expression in the brain tissue of patients who died of COVID-19 closely resembled that of uninfected individuals 71 years old or older,” coauthor Jonathan Lee, a postdoctoral research fellow at Beth Israel and Harvard Medical School, said in a news release. “Genes that were upregulated in aging were upregulated in the context of severe COVID-19. Likewise, genes downregulated in aging were also downregulated in severe COVID-19.”

“While we did not find evidence that the SARS-CoV-2 virus was present in the brain tissue at the time of death, we discovered inflammatory patterns associated with COVID-19,” Lee added. “This suggests that this inflammation may contribute to the aging-like effects observed in the brains of patients with COVID-19 and long COVID.”

In addition, researchers noted “significant associations” of cellular response to DNA damage, mitochondrial function, regulation of response to stress and oxidative stress, vesicular transport, calcium homeostasis and insulin signaling/secretion pathways previously associated with aging processes and brain aging.

“Ours is the first study to show that COVID-19 is associated with the molecular signatures of brain aging,” Mavrikaki said in the release. “We found striking similarities between the brains of patients with COVID-19 and aged individuals.”