Severe COVID May Cause Brain Changes Similar to Aging

Severe COVID May Cause Brain Changes Similar to Aging

Nature

Key genes that are active in the brains of older people are also active in the brains of people who developed serious COVID

Credit: Panther Media GmbH/Alamy Stock Photo

Severe COVID-19 is linked to changes in the brain that mirror those seen in old age, according to an analysis of dozens of post-mortem brain samples.

The analysis revealed brain changes in gene activity that were more extensive in people who had severe SARS-CoV-2 infections than in uninfected people who had been in an intensive care unit (ICU) or had been put on ventilators to assist their breathing–treatments used in many people with serious COVID-19.

The study, published on 5 December in Nature Aging, joins a bevy of publications cataloguing the effects of COVID-19 on the brain. Marianna Bugiani, a neuropathologist at Amsterdam University Medical Centers, says that this study opens up a lot of questions that are crucial for understanding the disease and preparing society for the possible consequences. These consequences might not be obvious for years .”

COVID on the brain

Maria Mavrikaki, a neurobiologist at the Beth Israel Deaconess Medical Center in Boston, Massachusetts, embarked on the study about two years ago, after seeing a preprint, later published as a paper, that described cognitive decline after COVID-19. She decided to continue her research to determine if there were any brain changes that could trigger these effects.

She and her colleagues studied samples taken from the frontal cortex–a region of the brain closely tied to cognition–of 21 people who had severe COVID-19 when they died and one person with an asymptomatic SARS-CoV-2 infection at death. The team compared these with samples from 22 people with no known history of SARS-CoV-2 infection. A third control group consisted of nine people with no history of infection, but who had been on a ventilator or in an ICU. These interventions can have serious side effects.

The team found that genes associated with inflammation and stress were more active in the brains of people who had had severe COVID-19 than in the brains of people in the control group. In contrast, genes that are linked to cognition and the formation connections between brain cells were less active.

The scientists also analysed brain tissue from 20 further uninfected people: 10 who were 38 years old or younger at death, and 10 who were 71 or older. A comparison revealed that people in the older group had brain changes that were similar to those seen in people with severe COVID-19.

The work is preliminary and will need confirmation using complementary approaches, according to Daniel Martins-de-Souza (head of proteomics at University of Campinas, Brazil). But it is an informative study, he says, and such research could ultimately guide treatment for people who have lingering cognitive difficulties after COVID-19.

Inflammatory effect

Mavrikaki suspects that COVID-19’s effects on gene activity are caused indirectly, by inflammation, rather than by viral infiltration of the brain. She and her colleagues discovered that the activity of subsets of the aging-related genes was affected by exposing laboratory-cultured neurons protein that promote inflammation.

But it is possible that this response could also be triggered other infections, she states. And the study could not fully control for obesity or other conditions that might both increase a person’s chances of developing severe COVID-19 and generate an inflammatory state that affects gene expression in the brain.

Another key question is whether the changes in gene expression are associated only with severe cases of COVID-19, or if milder disease can also cause them, says Bugiani. In March, a study of hundreds of brain images collected by the UK Biobank found that even mild disease could cause changes in the brain, including damage to the regions involved in smell and taste.

It will take time to determine if the changes seen in the study are temporary or permanent, Bugiani states. She says, “The pandemic has been long enough for us to see these things, but not enough to know if they are permanent.” “We don’t know yet .”

what their true consequences will be

This article is reproduced with permission and was first published on December 5 2022.

ABOUT THE AUTHOR(S)

    Heidi Ledford works for Nature magazine.

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