Viruses have a history of effecting the human brain. For example, it’s been long understood that HIV/AIDs can cause “progressive cerebral volume loss,” and measle infections can lead to encephalitis or inflammation of the brain. Given this context, the recent reports of how COVID-19 effects the brain are unsurprising, though nonetheless, concerning.

“A lot of people have long-term cognitive problems, even if their virus is well under control,” says Avindra Nath, Clinical Director of the National Institute of Neurological Disorders and Stroke.

“What effects the brain can be extremely devastating because it can affect your personality, your ability to think and concentrate, your mood, and those things that make us a person as a whole.” 

Oxford study finds brain shrinkage and cognitive decline in Covid patients

One of the most widely cited studies on the matter was conducted by Oxford University and published in the science journal Nature in Mar. 2022. The study analyzed brain changes in 785 subjects aged 51-81 years from UK Biobank, an organization conducting long-term bioresearch. The subjects were imaged via magnetic resonance once before and once after the onset of the pandemic.

Of the 785 participants, 401 tested positive for COVID-19 between their scans, 15 of which were hospitalized, with an average of 141 days separating their diagnoses from their second brain scan. The remaining 384 individuals, the control group, were never infected with COVID-19.

Before diving into the findings, the study refers to the “strong evidence” of Covid’s ability to invade, live in, or otherwise effect the brain. One consistent symptom that is particularly evident of this is “the disturbance in olfaction and gustation,” or the loss or impairment of taste and smell.

“Such loss of sensory olfactory inputs to the brain could lead to a loss of grey matter in olfactory-related brain regions,” reads the study’s introduction.

Upon examining the before and after images, researchers were able to identify Covid’s significant effects on the brain, including a greater reduction in grey matter thickness (by roughly 2%) and tissue contrast in areas of the brain responsible for emotion, decision-making, and memory, known as the orbitofrontal cortex and parahippocampal gyrus.

The study also found tissue damage in regions of the brain connected to the primary olfactory cortex, a part of the brain involved in the sense of smell, and a reduction in “global brain size” in subjects that had tested positive for Covid.

Lastly, participants that had been infected demonstrated a “greater cognitive decline between the two time points” than the control group, though it should be noted that the difference is described as only being “slightly lower.”

The researchers clarified that these findings still occurred when the 15 hospitalized patients with Covid were removed from the data, suggesting even milder cases could damage the brain.  

What is unknown about COVID-19’s effect on the brain

As informative as the Oxford study is, there are still many questions left unanswered. For example, it is still unknown if it is possible to reverse Covid’s effects. “Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up,” the study states.

However, there are clinics attempting to do exactly that. Here in Snohomish County, the University of Washington’s (UW) Post-Covid-19 Rehabilitation and Recovery Clinic at Harborview is currently helping to reverse the toll long-Covid has had on millions of Americans.

“Long-Covid” is a somewhat ambiguous term for Covid-related symptoms that persist beyond a certain window of time. According to the Center for Disease Control (CDC), individuals experiencing symptoms four weeks after the initial infection are considered to have long-Covid. These symptoms can range from the cognitive decline noted in the Oxford study, also known as “brain fog,” to tiredness and fatigue.   

The World Health Organization (WHO) refers to the condition as “Post-COVID-19” and cites the same symptoms noted by the CDC. However, the WHO’s timetable slightly differs from the CDC’s, stating that individuals experiencing symptoms “3 months from the onset of COVID-19” are considered to have long-Covid or Post-COVID-19.

According to the UW Rehabilitation and Recovery Clinic, “The most common symptoms of post-COVID-19 are daytime fatigue, tiring easily (especially with activity) and difficulty thinking or ‘brain fog.’ But there are many different symptoms that may effect your body, mind, mood and ability to function.”

Does being vaccinated help? Do different variants have different effects?

Another aspect that’s unclear is whether or not vaccinated Covid patients’ brains fair better than unvaccinated and if every variant has the same effect. 

As the Oxford study completed gathering its data in May 2021, it’s unlikely that the majority of patients were vaccinated. According to ourworldindata.com, only 1.2% of the UK’s population had been fully inoculated when the study began in February 2021, and only 37% by the end of the study.

Given this timetable, the data collected primarily came from the Alpha variant, so it’s unclear if other variants, like Delta and Omicron, effect the brain differently. 

Why Covid-19 effects the brain?

It is still unclear exactly why the virus is causing these long-term symptoms. According to Akiko Iwasaki, Immunologist and Investigator at Howard Hughes Medical Institute, there are three hypotheses that might explain how Covid can effect the brain.

“One is a direct infection of the virus of some cells in the nervous system or supportive structures in the brain,” Iwasaki beings. 

“Second hypothesis is that there are autoimmune responses that are attacking parts of the brain that could obviously trigger lots of different systems, and long duration of such responses because once the autoimmune cells are activated, it’s very hard to deactivate them.”

“The third possibility,” he continues, “is that there is distal inflammation happening, such as in the lung, that could stimulate cells within the brain and trigger a long term changes in those cells.”

Iwasaki concludes that brain fog and long-Covid may result from a combination of these things or possibly a “sequential event of things that happen and they all contribute to these brain, neurologic issues.”

A more direct take on how exactly Covid effects the brain comes from Clinical Director of the National Institute of Neurological Disorders Avindra Nath. From the autopsies he’s conducted on brains of patients who have died from severe Covid cases, Nath discovered damaged blood vessels, antibodies stuck to blood vessels in the brain, inflammatory cells around the brain, and immune cells in the brain itself.

While Nath’s findings may support one or two of Iwasaki’s hypotheses, he surprisingly did not find the SARS-COVID-2 virus in the brain. “I had expected to see a lot of virus in the brain,” Nath admits, “because the virus effects the nose.”

“To our surprise, we didn’t find the virus in the brain. Now there are a few people that have reported detection of virus in the brain, but they find very, very small amounts.”

Who is effected?

The U.S. Government Accountability Office (GAO) estimates that between 7.7 and 23 million Americans have developed long-Covid, and it is clear that the severity of infection does not correlate with its onset. In fact, more than 75% of long-Covid patients were never hospitalized from their initial infection.

“Many, many people who’ve had mild initial infections with Covid-19 end up getting long-Covid,” says Pam Belluck, a health and science writer for the New York Times. “So you do not have to have been hospitalized with your initial infection to end up having lasting, very debilitating symptoms for months.”

The demographics most at risk of developing long-Covid appear to be middle-aged women. An analysis of over 75,000 health insurance claims across the states revealed that people in their mid-thirties to mid-sixties made up two-thirds of long-Covid patients. And 60% of those insurance claims were female patients. This demographic trend is observed across multiple studies cited by The New York Times and The Guardian.

If you suspect you’re suffering from long-Covid and would like to learn more about symptoms and treatments, visit UW’s Post-Covid-19 Rehabilitation and Recovery Clinic website by clicking here.