Long COVID Linked to Lower Brain Oxygen Levels, Cognitive Problems and Psychiatric Symptoms

Summary: Long COVID is linked to reduced oxygen uptake in the brain, a new study reports. Researchers say the finding is significant as a lack of sufficient oxygen supply may be one of the mechanisms that cause brain fog, cognitive problems, and an increased risk of depression and anxiety in long COVID patients.

Source: University of Waterloo

Long COVID is associated with reduced brain oxygen levels, worse performance on cognitive tests and increased psychiatric symptoms such as depression and anxiety, according to new research studying the impacts of the disease.  

Researchers from the University of Waterloo combined the results of two new parallel studies: a laboratory study involving cognitive testing and imaging of oxygen levels in the brain, and a national population survey of Canadians in 2021 and 2022. 

The laboratory study found that individuals who had experienced symptomatic COVID-19 illness performed worse on two computer tasks. One is measuring inhibition and another impulsive decision-making.

Compared to those who had not been infected, people who had been infected showed a lack of increase in oxygen saturation in an area of the brain that is normally engaged during one of the tasks.  

“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,” said Dr. Peter Hall, lead author and researcher in the School of Public Health Sciences at Waterloo.

“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 second study in this paper, a population survey of more than 2,000 Canadians aged 18 to 56, examined the relationships among COVID, cognitive function and psychiatric symptoms.

Respondents who had COVID reported difficulty concentrating and problems with inhibition, as well as increased symptoms of anxiety and depression. These effects appeared to be marginally stronger among unvaccinated individuals and were still detectable after controlling for how long ago respondents were infected. 

Previous studies have shown a link between COVID and test performance, self-reported cognitive symptoms and differences in brain structure measured by MRI, but not oxygenation changes in the brain. 

Older women were more affected than others in the case of the brain imaging outcomes. “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. 

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Compared to those who had not been infected, people who had been infected showed a lack of increase in oxygen saturation in an area of the brain that is normally engaged during one of the tasks. Image is in the public domain

In the case of the population study, “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. 

The studies were conducted during earlier waves of the pandemic. The researchers did not examine whether Omicron and later variants have the same effects on the brain as earlier variants. 

“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.” 

About this long COVID and cognition research news

Author: Pamela Smyth
Source: University of Waterloo
Contact: Pamela Smyth – University of Waterloo
Image: The image is in the public domain

Original Research: Open access.
Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies” by Peter Hall et al. Brain Behavior and Immunity


Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies


The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric symptoms using cognitive task performance, functional brain imaging, and a prospective population survey.


Study 1 was a laboratory study conducted between 3 May 2022 and 16 Nov 2022 involving 120 fully vaccinated community dwelling adults between 18 and 84 years of age (Mage = 31.96 (SD = 20.71), 63.3% female). In this cross-sectional study we examined the association between symptomatic COVID-19 infection history and performance on three computer tasks assessing cognitive function (Flanker interference, delay discounting and simple reaction time) and measured oxygen saturation within the prefrontal cortex using functional near infrared spectroscopy (fNIRS). Study 2 was a 2-wave population survey undertaken between 28 September 2021 and 21 March 2022, examining the prospective relationship between symptomatic COVID-19 and self-reported symptoms of cognitive dysfunction, depressive symptoms, anxiety symptoms, and agitation at 6-month follow up. The sample (N = 2,002, Mage = 37.0, SD = 10.4; 60.8% female) was collected using a quota process to ensure equal numbers of vaccinated and unvaccinated individuals. Structural equation modelling with latent variables was performed on the population-level data, evaluating the fit of the proposed mediational model of symptomatic COVID-19 to psychiatric symptoms through cognitive dysfunction.


Findings from Study 1 revealed significant effects of symptomatic COVID-19 history on Flanker interference and delay discounting. Effects on flanker performance were significantly stronger among older adult women (effect: 9.603, SE = 4.452, t = 2.157, p = .033), and were accompanied by task-related changes cerebral oxygenation at the right superior frontal gyrus (F (1, 143.1) = 4.729, p = .031). Additionally, those with a symptomatic COVID-19 infection history showed evidence of amplified delay discounting (coefficient = 0.4554, SE = 0.2208, t = 2.0629, p = .041). In Study 2, baseline symptomatic COVID-19 history was associated with self-reported cognitive dysfunction and a latent variable reflecting psychiatric symptoms of anxiety, depression and agitation at follow-up. Mediational analyses revealed evidence of cognitive mediation of clinically significant psychiatric outcomes: depression (indirect effect = 0.077, SE = 0.026, p = .003) and generalized anxiety (indirect effect = 0.060, SE = 0.021, p = .004).


Converging findings from laboratory and population survey data support the conclusion that symptomatic COVID-19 infection is associated with task-related, functional imaging and self-reported indices of cognitive dysfunction as well as psychiatric symptoms. In some cases, these findings appear to be more amplified among women than men, and among older women than younger.

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