Even ‘mild’ COVID is linked to significant brain changes, study finds

(ORDO NEWS) — One of the largest brain imaging studies to date on COVID-19 patients has shed a disturbing light on the impact of the disease on our brains.

Even in people with mild to moderate severity, SARS-CoV-2 infection has been associated with “significant” neurological changes and loss of gray matter.

The study looked at brain scans of 785 UK residents aged 51 to 81. The scans were performed an average of 38 months apart and along with cognitive tests.

“To our knowledge, this is the first longitudinal imaging study of SARS-CoV-2 in which participants were initially scanned prior to infection,” the researchers, led by Gwenael Duo from the University of Oxford in the UK, write.

“Our longitudinal analysis revealed significant detrimental effects associated with SARS-CoV-2.”

The early results of this study were published in a preprint and have now been peer-reviewed and published in the journal Nature.

The structural changes appeared to be persistent – on average, scans were taken 5 months (141 days) after a person became ill with COVID-19 – although how long they last and whether they are reversible should be the subject of future research.

That SARS-CoV-2 affects our brains is not new: We already had evidence that infection with the virus can lead to structural changes and inflammation in the brain.

But this study is unique in that it compares, for the first time, images of the brains of people before and after COVID-19, minimizing the possibility that any damage could have occurred before infection.

The researchers also compared brain scans of people who were not infected with the SARS-CoV-2 virus during the study period, thus creating a control group. The researchers were able to do this by accessing data from the UK Biobank, which holds medical data and images taken from volunteers over the years.

Of the 785 subjects who underwent the initial scan, 401 tested positive for COVID-19 before they returned for further tests. The remaining 384 people did not test positive for COVID-19 during the study and served as controls.

Compared to the first brain scan, those infected showed marked tissue damage in the piriform cortex, olfactory tubercle, and anterior olfactory nucleus—brain regions associated with smell and taste, as well as memory.

These people also had markedly lower scores on cognitive tests than before and showed atrophy of the cerebellum, a region of the brain associated with cognition.

In particular, SARS-CoV-2 infection has been associated with a loss of 0.7 percent of gray matter in affected areas of the brain. For comparison, the authors compare this to the roughly 0.2 percent of gray matter that adults typically lose each year in middle age.

To make sure the results were specific to COVID-19, the researchers also ran a control analysis on another, smaller group of 11 people who had experienced non-COVID-19 pneumonia and found that these brain effects were not observed. in patients with a common respiratory illness.

Importantly, many of those who contracted COVID-19 during the study did not have severe disease. Even when 15 people hospitalized with COVID-19 were excluded from the results, the effects of the virus were still visible in the brain.

“The results of the study are amazing,” said neurologist Sarah Hellewell of Curtin University in Australia, who was not involved in the study.

“The authors show that people who had a mild COVID-19 infection an average of five months prior had thinning of brain tissue in several key areas of the brain.”

Of course, despite the strengths of this study, there remain big unanswered questions.

First, the study had no data on how severe each person’s case of COVID-19 was, other than whether they were hospitalized. For example, it is not clear what level of oxygen they had throughout the infection.

It’s also important to note that the scans were conducted between March 2020 and April 2021, so it’s unlikely that any of the participants had the Delta or Omicron options currently in circulation – so we need to keep that in mind when considering whether how these findings may be related to later infections.

In addition, these results were analyzed as a group sample, so the results may not be directly applicable to individuals.

“People should not panic if they have had COVID-19. The observed changes in the brain were relatively small and at the group level, so not everyone had the same effects,” adds Hellewell.

“More research is needed to find out if these changes persist, change or worsen over time, and if there are treatments that can help.”

Importantly, the study could give us more information about how SARS-CoV-2 infection damages the brain in the first place, something scientists still don’t understand.

In their study, Duo and her team propose three possible damage mechanisms.

One is the degenerative spread of COVID-19 along olfactory pathways in the brain. Alternatively, the virus itself may not enter the brain, but affect it in other ways: either through a general inflammation of the nervous system; or causing loss of sensory input due to loss of smell.


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