Severe COVID-19 associated with molecular signatures of brain aging

Abstract: Gene usage in the brains of those who suffered severe COVID-19 infections was similar to that observed in the aging brain. Researchers say that COVID-19 is linked to molecular signatures of brain aging.

Source: BIDMC

Although COVID-19 is primarily a respiratory disease, neurological symptoms have been described in many patients with COVID-19, including those who have recovered.

Patients report symptoms including brain fog or a lack of focused thinking, memory loss and depression, and scientists have shown that patients with severe COVID-19 show cognitive decline that mimics accelerated aging. But molecular evidence of the aging effects of COVID-19 on the brain is lacking.

In a series of experiments, scientists at Beth Israel Deaconess Medical Center (BIDMC) found that gene usage in the brains of patients with COVID-19 is similar to that seen in brain aging.

Using a molecular profiling technique called RNA sequencing to measure the levels of each gene expressed in a given tissue sample, the scientists assessed changes in gene expression profiles in the brains of patients with COVID-19 and compared them to changes seen in the brains of uninfected individuals.

Team analysis, published in Aging of naturesuggested that many of the biological pathways that change with natural aging in the brain were also altered in patients with severe COVID-19.

“Ours is the first study to show that COVID-19 is associated with molecular signatures of brain aging,” said first and co-author Maria Mavrikaki, PhD, instructor of pathology at BIDMC and Harvard Medical School. “We found striking similarities between the brains of patients with COVID-19 and the elderly.”

Mavrikaki and colleagues analyzed a total of 54 postmortem tissue samples of the human frontal cortex of adults aged 22 to 85 years. Of these, 21 samples were from a severe patient with COVID-19 and one from an asymptomatic patient with COVID-19 who died. These samples were age- and sex-matched with uninfected controls without a history of neurological or psychiatric disease.

The scientists also included an age- and sex-matched uninfected Alzheimer’s disease case for analysis as a control for a COVID-19 case who had comorbid Alzheimer’s disease, as well as an additional independent control group of uninfected individuals with a history of intensive care or ventilator treatment.

“We observed that gene expression in the brain tissue of patients who died of COVID-19 was very similar to that of uninfected individuals aged 71 years or older,” said first author Dr. Jonathan Lee, a postdoctoral researcher at BIDMC and Harvard Medical. School.

“Genes that were up-regulated in aging were up-regulated in the context of severe disease of COVID-19; likewise, genes that are downregulated during aging were also downregulated in severe COVID-19 disease.

“Although we found no evidence that the SARS-CoV-2 virus was present in brain tissue at the time of death, we did detect 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-term COVID.”

“Given these findings, we advocate for neurological monitoring of patients who have recovered from COVID-19,” said senior and co-author Dr. Frank Slack, director of the Institute for RNA Medicine at BIDMC and the Shields Warren Mallinckrodt Professor of Medical Research. at Harvard Medical School.

“We also highlight the potential clinical value in modifying factors associated with dementia risk—such as weight control and reducing excessive alcohol consumption—to reduce the risk or delay the development of age-related neurological pathologies and cognitive decline.”

A better understanding of the molecular mechanisms underlying brain aging and cognitive decline in COVID-19 could lead to the development of new therapies to address the cognitive decline seen in patients with COVID-19. The team is now trying to understand what triggers the effects of aging in the brains of patients with COVID-19.

Financing: Isaac H. Solomon, MD, PhD, Brigham and Women’s Hospital, also contributed to this work, which was supported by the National Institute on Aging (NIA; R01 AG058816). The authors declare that there is no conflict of interest.

About this news about research into the disease COVID-19 and brain aging

Author: Chloe Meck
Source: BIDMC
Contact: Chloe Meck – BIDMC
Picture: The image is in the public domain

Original research: Closed access.
“Severe COVID-19 is associated with molecular signatures of aging in the human brain” Jonathan Lee et al. Aging of nature

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Abstract

Severe COVID-19 is associated with molecular signatures of aging in the human brain

Since both coronavirus disease 2019 (COVID-19) and aging are accompanied by cognitive decline, we hypothesized that COVID-19 could lead to age-like molecular signatures.

We performed a whole-transcriptome analysis of the frontal cortex, a critical region for cognitive function, in individuals with COVID-19, uninfected age- and sex-matched control subjects, and uninfected individuals on intensive care unit/ventilator treatment.

Our findings show that COVID-19 is associated with molecular signatures of brain aging and highlight the value of neurological monitoring in recovered individuals.