COVID-19 Linked to Significant Brain Changes, Shrinkage

Even a mild COVID-19 infection can change the brain. People infected had a greater reduction in brain volume and performed worse on cognitive tests than those who did not contract COVID-19.

While the vast majority of people who contract COVID-19 recover, a new study finds even a mild infection can damage the brain.

The study, published in Nature, examined the long-term neurological effects of COVID-19 infection. The investigators noted they were moved to do so in resulting from the consistent disturbance in olfactory and gustation in COVID-19 patients (loss of smell and taste). This longitudinal brain imaging study was the first to scan patients before any had contracted COVID-19.

The investigators explored brain changes in 785 Biobank participants in the United Kingdom. The participants ranged from 51-81 years of age and were scanned twice, with an average of 3 years in between scans. Enrollment closed on May 31, 2021, meaning that all patients who tested positive for COVID-19 contracted the Alpha variant.

Notably, 401 participants tested positive for COVID-19 in between their first and second brain scans, reducing the risk of the investigators interpreting pre-existing conditions as COVID-19-induced brain abnormalities. There were 384 participants in the control group, and the cohorts were matched for age, sex, ethnicity, and time between their 2 scans.

The investigators looked for longitudinal effects when comparing the group that had contracted COVID-19 to the group that had not. They identified differences including: “(i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex, and (iii) greater reduction in global brain size.”

In short, the virus significantly impacted the central nervous system. The multimodal brain imaging data revealed COVID-19-related damage to the brain, including greater atrophy and increased tissue damage in cortical areas directly attached to the primary olfactory cortex. Additionally, there were decreases in the global measurements of brain and cerebrospinal fluid volume.

Overall, the people infected with COVID-19 had a greater reduction in brain volume and performed worse on cognitive tests. COVID-19 infection could cause the region of the brain linked to smell to shrink, with a decrease in size comparable to a year of natural aging. The greater atrophy in the COVID-19-positive patients was mostly located in limbic regions, but the increase in cerebrospinal fluid and decrease in brain volume indicates there may have been an additional loss of grey matter.

The 15 most severely ill and hospitalized COVID-19 patients had the most marked brain changes. The older patients also had more severe changes than younger participants. However, even a mild infection in an otherwise healthy person may irreparably change the brain.

Narrowly perceiving COVID-19 as a respiratory infection that causes mainly mild infections overlooks the long-term neurological effects. Due to the relatively short amount of time we have lived with COVID-19, we cannot know the full effects of “long COVID.” The investigators concluded, “Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.”