In a first, researchers have discovered that severe Covid-19 is linked with molecular signatures of brain ageing, suggesting that many biological pathways that change with natural ageing in the brain also changed in patients with severe Covid.
Neurological symptoms have already been described in many Covid patients, including in recovered individuals. Patients report symptoms including brain fog or lack of focused thinking, memory loss and depression.
In a series of experiments published in Nature Aging, scientists at Beth Israel Deaconess Medical Center (BIDMC) in Boston in the US found that gene usage in the brains of patients with Covid-19 is similar to those observed in ageing brains.
Using a molecular profiling technique called RNA sequencing to measure the levels of every gene expressed in a particular tissue sample, the scientists assessed changes in gene expression profiles in the brains of Covid-19 patients and compared them to those changes observed in the brains of uninfected individuals.
The team’s analysis, published in Nature Aging, suggested that many biological pathways that change with natural aging in the brain also changed in patients with severe COVID-19.
“Ours is the first study to show that Covid-19 is associated with the molecular signatures of brain ageing,” said Maria Mavrikaki, an instructor of pathology at BIDMC and Harvard Medical School.
“We found striking similarities between the brains of patients with Covid-19 and aged individuals.”
Mavrikaki and colleagues analysed a total of 54 postmortem human frontal cortex tissue samples from adults 22 to 85 years old.
Of these, 21 samples were from severe Covid-19 patients and one from an asymptomatic Covid patient who died.
“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,” said Jonathan Lee, a postdoctoral research fellow at BIDMC and Harvard Medical School.
Genes that were upregulated in ageing 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. This suggests that this inflammation may contribute to the aging-like effects observed in the brains of patients with Covid-19 and long Covid,” Lee explained.
Better understanding of the molecular mechanisms underlying brain ageing and cognitive decline in Covid-19 could lead to the development of novel therapeutics to address cognitive decline observed in such patients.