Most of what we know about how COVID can affect the brain has come from studies of severe infection. In people with severe COVID, inflammatory cells from outside the brain can enter brain tissue and spread inflammation. There may be changes to blood vessels. Brain cells can even have changes similar to those seen in people with Alzheimer’s disease.

For the first time, a new study has investigated the effects of mild COVID (that is, infection that doesn’t lead to a hospital admission) on the brain. The findings may further explain some of the brain changes contributing to long COVID.

Brain scans and tests show changes

Many people who have had COVID report feelings of “brain fog”, fatigue and problems with concentration and memory long after their initial symptoms resolve. These problems, collectively referred to as “long COVID”, may last for months even after mild infection.

Long COVID is very common, and may affect more than half of the people who catch COVID, even if they have a mild case.

Scientists collected data as part of the massive UK Biobank database. They looked at brain magnetic resonance imaging (MRI) scans and tests of brain function in 785 volunteers who were assessed before the pandemic. They then compared this to the same data collected three years later, when about half of those participants had mild COVID infection, and the other half had not caught COVID. This allowed the scientists to determine the specific effects of mild COVID infection on brain structure and function.

The group who had mild COVID an average of five months beforehand had thinning of brain tissue in several brain regions, ranging from 0.2% to around 2% compared to their pre-COVID scan. This is equivalent to between one and six years of normal brain ageing. Affected brain regions included the parahippocampal gyrus (an area related to memory) and the orbitofrontal cortex, which is located at the front of the brain and is important for smell and taste.

The post-COVID group also showed a reduction in overall brain size between their MRI scans that wasn’t seen in the non-COVID group, and had altered connections between different brain regions in the olfactory cortex, an area related to smell.

They performed worse in a test for attention and mental flexibility, a finding that was associated with volume reductions within a part of the cerebellum related to smell and social relationships.

Comparing to other illnesses

To show these changes were specific to COVID and not just related to having a respiratory illness, the scientists also looked at a group of people who had pneumonia. They did not see the same changes, confirming they are related to COVID.

Decreases in brain volume are common to many brain diseases and disorders associated with degeneration, and have been found in people with mild cognitive impairmentAlzheimer’s diseasedepression and traumatic brain injury, among others.

Problems with memory and attention are also frequent for people with these diseases and disorders, indicating mild COVID infection may accelerate brain degeneration. These changes could explain the reported symptoms of long COVID, such as brain fog.

The study did not look at the mechanisms of mild COVID in the brain. However, the authors suggest this could be due to inflammation, degeneration which spreads through the brain pathways associated with smell, or sensory deprivation due to loss of smell.

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