This story is part of a larger mosaic of stories on the neurological consequences of Covid-19 and Post-Acute Sequelae of Covid-19 (PASC), also known as Long Covid. Read parts one, two, three, four and five of this series.
Emerging studies have increasingly recognized Covid-19 as an inflammatory disease. Brain shrinkage, brain-blood barrier disruptions and neurodegeneration, as we previously reported in this series, seem to emerge as an inflammatory consequence of acute infection that for some progresses into Long Covid. Cognitive impairments are consistently reported as one of the most persistent and some of the more impairing symptoms of Long Covid. Brain fog, characterized by sluggish or slow executive function, and memory problems, for example, can severely interfere one’s ability to return to work and other daily activities. The broader implications of these symptoms could significantly disrupt the economy and society as a whole.
Although the long term effects remain unclear, the immediate repercussions are just now being uncovered. In the journal Frontiers in Aging Neuroscience, researchers from the University of Cambridge recently published their first findings from their longitudinal online study: COVID and Cognition. As Dr. Lucky Checke, a professor at the University of Cambridge’ Department of Psychology and senior author of the study, says, “”Long COVID has received very little attention politically or medically. It urgently needs to be taken more seriously, and cognitive issues are an important part of this. When politicians talk about ‘Living with COVID’ – that is, unmitigated infection, this is something they ignore. The impact on the working population could be huge,” Here, we discuss the early findings from this study, which considers how cognitive impairments associated with Long Covid may develop from acute infection regardless of disease severity.
Guo et al. reported their finding in two parts. The first asked 481 adult participants to complete questionnaires related to previous Covid-19 infections and the prevalence of ongoing symptoms. To provide a more objective measure of cognitive impairments, the second investigation employed a series of online cognitive tests to the same sample of participants. Since this data was collected between October 2020 and March 2021, infections were primarily linked to wild-type Covid-19 and alpha strain.
Although almost all the individuals sampled for this study were not hospitalized for Covid-19, Guo et al. found that more severe disease during the acute phase was associated with ongoing symptoms. In fact, ongoing symptoms were more severe among those who experienced more severe initial infections, compared to individuals who experienced mild or moderate infections. Those that reported limb weakness, in particular, were more likely to experience severe long-lasting symptoms following infection. The severity of the initial infection therefore may be a strong predictor for ongoing symptoms associated with Long Covid.
More specifically, disease severity seems to correlate with self-reported cognitive impairments. This includes fatigue and related symptoms such as headache, brain fog and dizziness, in addition to neurological symptoms such as abnormal vision, altered consciousness, delirium and disorientation. Guo et al. speculates that the presence of these symptoms may involve neurological mechanisms related to inflammation and encephalitis, consistent with previous studies.
To their surprise, investigators also found strong correlations between ongoing cognitive impairment and gastrointestinal and cardiopulmonary complications. Given that there is no evidence that SARS-CoV-2 directly infects the brain, this finding may suggest that brain injury is instead a consequence of greater systemic inflammation throughout the body. Both cardiopulmonary symptoms and fatigue, in particular, seemed to correlate with longer acute infection periods. It is possible that these symptoms manifest through similar mechanisms related to damage to blood vessels, or they may simply be two of the most commonly reported symptoms associated with long-lasting illness.
Implications for Cognitive Performance
Part two of Guo et al.’s investigation assessed the same sample of participants on cognitive tests for memory, executive function, and language. Participants were asked to complete six tasks: the Word List Recognition Memory Test, Pictorial Associate Memory Test, Category Fluency Test, Mental Rotation Test, Wisconsin Card Sorting Test, Number Counting Test, and Relational Reasoning Test.
Consistent with self-reported symptoms, individuals exposed to Covid-19 displayed significant deficits associated with memory. In fact, regardless of ongoing symptoms, those previously infected with the virus performed worse on memory tasks but not other cognitive domains. This was most evident during verbal memory tasks, during which these individuals had much slower reaction times.
Once infection severity was taken into account, those with ongoing symptoms performed worse than recovered individuals, and memory deficits once again seem to be a significant factor. Worse verbal memory, in particular, was associated with greater severity of ongoing symptoms. Those with the most severe symptoms not only had slower reaction times but also recorded fewer correct answers. Although the results for non-verbal associative memory were less clear, Guo et al. reported that individuals that had not been exposed to Covid-19 displayed a clear advantage in their performance.
A major limitation of conducting tests for cognition online is determining whether the findings actually vary with the hypothesis being tested or whether the particular participants selected for the study were simply having a “bad day.” This is made more difficult by the fact that Long Covid seems to be a cyclical illness. Although increasing reports show that the severity of symptoms change over time, we still do not know how or when cognitive symptoms may change during Long Covid. With this in mind, Guo et al. also asked participants to report if they were having a “bad day”, or the extent to which any ongoing symptoms were affecting their well-being at the time of the task. Indeed, they found that having a “bad day” did not predict cognitive performance on any tasks, thus strengthening the hypothesis that general severity of ongoing symptoms correlates with cognitive impairments.
How did the subjective reports of impaired cognitive performance compare to actual performance? Interestingly, not every self-reported cognitive symptom was confirmed by cognitive testing. While those that reported memory problems scored lower on memory tests, individuals that reported linguistic deficits did not perform any worse on language tasks. It is possible, however, that the tests selected were not sufficient to detect these deficits.
Investigators are hopeful that future publications from the COVID and Cognition Study will provide a greater understanding of how cognitive symptoms and performance change throughout Long Covid. Although these complications likely will not be permanent, it is important to recognize that “Living with Covid” will not look the same for everyone. Some people may experience more noticeable impairments in memory, executive function and attention than others. We urge lawmakers to not only consider the economic consequences but also the personal challenges associated with Long Covid. Guiding care for these individuals needs to be a political priority as this pandemic transitions into an endemic.