Previous COVID infection linked to lower brain oxygen levels, cognitive problems: study

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In a new Canadian study, researchers found that not only did participants who previously had COVID-19 perform worse on two specific cognitive tasks, but brain imaging showed that during these tasks, there was a lack of oxygen reaching the sections of the brain that would normally be fully engaged.

The results shed new light on how COVID-19 impacts the brain, with serious implications for the field of long COVID.

"We are the first to show reduced oxygen uptake in the brain during a cognitive task in the months following a symptomatic COVID-19 infection," Dr. Peter Hall, researcher in the School of Public Health Sciences at Waterloo and lead author of the study, said in a press release. "This is important because a lack of sufficient oxygen supply is thought to be one of the mechanisms by which COVID-19 may cause cognitive impairment."

The study, published in January in the peer-reviewed journal Brain, Behaviour & Immunity, utilized two sets of data: a national population survey of Canadians in 2021 and 2022, and a laboratory study in which participants performed cognitive tests while having their brains imaged.

The two separate studies were compared to create a greater picture of how COVID-19 affects the brain.

In the laboratory study, 120 participants from 18-84 years old performed three cognitive tests, one measuring executive function, another looking at impulsive decision making and the third looking at reaction time.

Although there were no clear associations with reaction time and a history of COVID-19, that wasn't the case for the other two tests.

During the task measuring executive function, those with a history of COVID-19 performed significantly worse at the test itself, the study found.

There was also a clear lack of oxygen saturation in a region of the brain specific to that task in participants who had a history of COVID-19, compared with those who had never been infected with the virus.

Neither the survey nor the laboratory test looked at whether Omicron or later variants created any markedly different effects.

The survey which made up the second portion of the larger study looked at 2,000 Canadians between the ages of 18 to 56 years old, and asked respondents about their history with COVID-19, as well as cognitive performance and psychiatric symptoms that they had experienced in 2021 and 2022.

Those who said they had previously had COVID-19 were more likely to also report problems with concentrating and inhibition, as well as higher levels of anxiety and depression.

This link was slightly stronger among unvaccinated participants who had previously had COVID-19, and persisted even when the data was controlled for how long ago the infection had taken place.

"It appears that, regardless of gender and other demographic factors, COVID-19 infection at baseline is correlated with increased problems with emotion regulation six months later: depression, anxiety and agitation. In some cases, we are talking about symptom levels that are at or above recommended as cut-off scores for psychiatric diagnoses," Hall said in the release.

Hall added that in the results of the laboratory study, older women experienced less oxygen saturation during the cognitive tests than any other group in connection to previous cases of COVID-19.

"We don't know for sure why this was the case, but there have been other studies showing that older women are especially impacted by some post-COVID-19 syndrome symptoms," Hall said.

The laboratory study, which was carried out between the start of May 2022 and mid-November 2022, only included fully vaccinated individuals.

One of the tests was a flanker test, a test of executive function in which participants are told to relay information presented in the middle of the screen in front of them, while distracting answers are displayed at the sides of the screen. In this iteration of the test, participants had to identify the centre letter in a string of letters where the other letters were either the same or all different (i.e., HHHHHHH or CCCHCCC).

It's a test to evaluate how well and how quickly the brain can shut out distractions, with both accuracy and speed as measurements.

During this test, those with a history of COVID-19 had significantly less oxygen saturation in part of the frontal lobe called the superior frontal gyrus.

In a second test measuring decision making, those with a history of COVID-19 had a higher level of delay compared to participants who had never had COVID-19, with symptomatic cases of COVID-19 among older women highly predictive of a slower performance.

Several other studies have demonstrated a link between poorer performance on cognitive tests in connection with long COVID or with having had COVID-19 previously, but researchers say that this new evidence of a lower level of oxygen in the brain brings the issue into greater relief.

It opens up new possibilities for the mechanisms linking COVID-19 to brain injury. Theories that have been previously proposed include vascular damage, blood clots or hyperactive immune cells.

The brain uses around a fifth of the total oxygen supply that the human body needs to function, and when parts of the brain are starved of oxygen, it means signals and messages get sent out more slowly, or not at all. And if the brain doesn't get enough oxygen, brain cells can begin to die.

More research needs to be done to figure out how a lack of oxygen in the brain is triggered by or connected to COVID-19, and if this is a factor in those who present with long COVID.

"Our two studies, using very different methods, highlight the need to understand the full range of harms of COVID-19 illness," Hall said. "We still need to know more about how factors like vaccination affect the course of long COVID. We also need to know about how some physical conditions like diabetes, obesity and hypertension might impact these mechanisms and outcomes."