New research highlights a complex relationship between COVID-19 and cognitive function, suggesting that even mild infections can lead to subtle memory and attention deficits lasting at least a year.
Adam Hampshire, PhD, professor of cognitive and computational neuroscience.
Image credit: Imperial College London
Recent studies indicate a connection between COVID-19 and ongoing cognitive issues, though the causal relationship, duration, and specificity remain unclear. Factors such as baseline cognitive abilities, individual vulnerabilities, virus variants, vaccination status, and treatment options complicate this picture. Research suggests that even mild SARS-CoV-2 infections can lead to subtle cognitive and memory changes lasting at least a year.
In a study involving 18 volunteers confirmed to have SARS-CoV-2 via qPCR, those infected, mostly with mild illness, showed significantly lower global cognitive scores compared to uninfected individuals (mean difference = −.8631, 95% CI = −1.3613 to −.3766). This difference was consistent even after accounting for community respiratory infections. Notably, none of the participants reported persistent subjective cognitive symptoms.1
In an online interview, Adam Hampshire, PhD, discussed potential biological mechanisms behind these cognitive changes with Contagion, “There are a number of theories regarding biological mechanisms that underlie the observed cognitive changes, but we do not have a definitive answer yet. An important clue is that the largest differences are for immediate memory performance. Given that we do not see accelerated forgetting over time (which is what we see for the same tests in early stage and prodromal dementia for example), This could relate to the cognitive mechanisms underlying encoding, that is, the interplay of attention and memory systems. I note that this view is somewhat speculative.”
In this controlled study, 34 healthy volunteers were inoculated with Wildtype SARS-CoV-2. Researchers examined cognitive performance and physiological measures during quarantine and follow-up at 30, 90, 180, 270, and 360 days. While mild COVID-19 resulted in subtle cognitive differences, none of the participants reported lasting issues.1
Hampshire continues to discuss how the long-term trajectories of cognitive deficits beyond the 360-day mark, "Based on our previous cross-sectional work in the REACT cohort, we still see cognitive differences in people who had mild illness due to the Wildtype virus several years post infection. That is the current time limit to which we have been able to measure."
Hampshire also highlighted which cognitive domains exhibited the most significant changes and their implications for vulnerable populations, “Memory, attention, and executive functions showed the most pronounced differences. The scale of the differences was small/subtle, we could only detect them as we used highly sensitive computerized tests that have much more precision than typical pen and paper assessments and applied analyses comparing people for multiple days pre and post-inoculation. None of the participants reported lasting cognitive problems.”
To address variability in baseline cognitive abilities among different populations, Hampshire stated, “Unless there is explicit pre-infection cognitive data where we can individually baseline correct, then we have to test large populations and apply rigorous corrections based on demographic and other confounding factors, alongside careful sensitivity analyses where we stratify data according to potentially confounding factors in order to provide greater confidence in results. This is the approach that we have taken in some of our past studies.”
Cognitive Deficits in Severe Cases
Hampshire further noted that more severe illness is associated with broader and more pronounced cognitive deficits. In a recent article published in Nature Medicine, findings indicated that cognitive impairments following moderate to severe COVID-19 may be linked to immune-mediated brain injury.
In the study, findings that cognitive impairments following moderate to severe COVID-19 may be linked to immune-mediated brain injury. The study found cognitive deficits correlated with elevated serum markers of brain injury and a reduction in anterior cingulate cortex volume after one year. Patients with more severe initial infections, psychiatric symptoms, or a history of encephalopathy exhibited more significant cognitive impairments.2
Additionally, a correlation was observed between subjective reports of cognitive decline and objective assessments, with longitudinal data from 106 patients indicating a trend toward cognitive recovery over the year.2
Conducted as a national study, researchers analyzed cognitive performance, serum biomarkers, and neuroimaging results from 351 hospitalized COVID-19 patients, comparing them to 2,927 age and sex matched normative controls. Follow-up assessments helped monitor cognitive recovery over time, evaluating the impact of infection severity and psychiatric symptoms on cognitive outcomes.2
Hampshire also addressed the role of vaccination in cognitive outcomes, stating, “We examined this in the NEJM article. Cross sectionally, people who were vaccinated at least twice prior to infection score better than those who were not. Severity and duration of illness predict cognitive differences and vaccination helped to mitigate both.”
The ongoing research into the cognitive effects of COVID-19 underscores the complexity of the virus's impact on brain health. As studies continue to evolve, a clearer understanding of the relationship between infection and cognitive outcomes will be essential for guiding future interventions and support for affected individuals.
