A new British study has found that even mild cases of Covid-19 can cause subtle tissue damage, accelerated brain volume loss, and brain regions related to smell within the first few months after a coronavirus attack. Mild Covid can also be associated with cognitive function deficiencies.
These are the striking results of a new University of Oxford study. This study is of particular importance to leading Covid researchers as it is the first study of coronavirus' potential effect on the brain. It is based on brain scans that were taken before and after participants received the virus.
"This study design overcomes many of the major limitations of most brain studies of Covid-19 up to now, which rely upon analysis and interpretation at one time point in people with Covid-19," Dr. Serena S. Spudich of Yale University School of Medicine said. She was not involved in the research.
This published Monday by Nature also stands out as the majority of participants had mild Covid, which is the most common outcome from coronavirus infection. The majority of brain-related research in this area has focused on people with moderate to severe Covid.
Gwenaelle Doaud is an associate professor at Oxford's Nuffield Department of Clinical Neurosciences and lead author of the paper. She said that the brain volume loss she and her colleagues saw in brain scans of hundreds of British people was equivalent to at most one additional year of normal aging.
She said, "It's brain damage, but it's possible that it can be reversible." It is still quite scary, however, because it only affected mildly infected individuals.
Douaud and her colleagues relied on a rich source of data: the United Kingdom Biobank. This vast database had tens to thousands of brain MRIs from people across Britain before the Covid pandemic. It also included responses to surveys about diets, lifestyles, and cognitive function test results.
Investigators examined 401 people aged 51-81 who tested positive for Covid based on clinical data from the Biobank study. The coronavirus was detected in the brains of 401 people aged 51-81 years old. The majority of the participants were not affected by covid and only 15 were admitted to hospital.
These scans were compared to those of a 384 U.K. control group. Biobank participants were not tested for Covid. They were matched according the Covid-positive group’s obesity, blood pressure, smoking, and diabetes rates, as well their socioeconomic status and age.
The researchers noticed a striking trend in Covid patients who had MRIs separated by an average time of three years. They saw a greater loss in gray matter, also an increase in abnormalities in brain tissue. Gray matter is composed of neurons and other cells.
Researchers note that it is normal for adults in the study to lose some brain tissue over three years. However, Covid patients experienced an additional 0.2 to 2 percent brain tissue loss in areas that are most closely associated with sense of smell, specifically in the parahippocampal Gyrus and the orbitofrontal cortex.
Covid patients had a 0.3 percent decrease in brain volume than those who did not have the disease.
These brain-related declines were more severe in older participants.
This study does not indicate whether Covid vaccinations would reduce the risk of such changes. Participants were tested for the disease between March 2020 - April 2021, just before vaccines were widely available in Britain.
Covid-related cognitive function deficits were evident in those with slower processing speeds and lower scores on executive function tests. This umbrella measure measures the brain's ability manage complex tasks. These Covid-linked deficits were even more evident in older people.
Dr. Avindra NATH, the clinical director of National Institute of Neurological Disorders and Stroke, stated that these findings have "long-term implications" because they raise concerns about similar cognitive dysfunctions in large populations around the world.
He said, "It is necessary to determine if these patients can further deteriorate over time."
Investigators did not have access to any Covid-related symptoms that participants might have experienced. They don't know whether the participants lost their senses of smell or if they have suffered long-term effects from the disease. Others may have had only asymptomatic cases.
However, the loss in smell was more common among coronavirus-infected people during the first two waves of the pandemic. When certain brain regions are not used, they can atrophy. The study's authors are unsure if the coronavirus caused the loss or brain damage.
What is the average lifespan of brain changes in Covid?
In February, a study published by Cell found that coronavirus infections of different cells in the nasal cavity can cause inflammation that impairs the function of smell-receptor protein on nerve cells. This causes smell loss.
Douaud stated that Covid's association with declines in smell-related brain areas does not negate the possibility of other effects on the brain in non-smell related regions. It has been shown that the severity of Covid can vary from one patient to another. Other studies have also identified other ways in which it might cause brain damage. The study found that the most consistent brain-related trend to Covid was in the study cohort's changes to the smell-related areas.
It is not clear if these changes will last long-term. Douaud hopes to conduct a third round brain scans.
She said, "The brain can reorganize itself and heal itself." This is true even for older people.
Long Covid experts praised Douaud’s paper.
"This study provides the most conclusive clinical data to date that SARS/CoV-2 directly or indirect damages nerves, and that this can have systemic effects including brain changes," said Dr. Steven Deeks a veteran HIV researcher at University of California, San Francisco. It supports the emerging theme that nerve damage was common in the initial waves of the pandemic.
Deeks is leading a large cohort study of people with persistent symptoms after a coronavirus infected. He noted one limitation to the new study. He pointed out that Covid patients had different baseline cognitive functions and some initial brain scan results than those who didn't get the disease.
He said that it was possible, but not likely, for those at higher risk of becoming infected to be more rapid in brain changes due to other unmeasured factors.
Douaud and her coworkers were able to use the brain scans of both before and after the infection to identify brain abnormalities that may have been present prior to people developing Covid. They are therefore able to rule out any possible connection between the disease and brain abnormalities.