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A new study revealed that mild infections led to subtle memory and attention deficits lasting at least 12 months, providing further evidence of the complex relationship between COVID-19 and cognitive function.
Adam Hampshire, PhD
(Credit: Imperial College London)
This story was originally published by our sister publication, ContagionLive.
Recent research has indicated a connection between COVID-19 and ongoing cognitive issues, though its causal relationship, duration, and specificity have previously remained unclear. Contributing factors including baseline cognitive abilities, individual vulnerabilities, virus variants, vaccination status, and treatment options have complicated this picture even more. In a recent study published in eClinicalMedicine, results showed that even mild SARS-CoV-2 infections led to subtle cognitive and memory changes lasting at least a year.1
The study involved 18 volunteers with confirmed SARS-CoV-2 via quantitative polymerase chain reaction, those infected, mostly with mild illness, displayed significantly lower global cognitive scores compared with uninfected patients (mean difference = −.8631; 95% CI, −1.3613 to −.3766). This difference showed consistency even after accounting for community respiratory infections. Notably, none of the patients in the study experienced persistent subjective cognitive symptoms.1
In a recent interview with ContagionLive, Adam Hampshire, PhD, visiting professor in the department of brain sciences at Imperial College London, shared his viewpoint on the potential biological mechanisms behind these cognitive changes, stating “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. Investigators assessed cognitive performance and physiological measures during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Authors noted that although mild COVID-19 resulted in subtle cognitive differences, none of the patients reported lasting issues.1
Hampshire continued to explain 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 underscored 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 said, “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.”
Hampshire additional highlighted that more severe illness was associated with broader and more pronounced cognitive deficits. In a recent article published in Nature Medicine, results demonstrated that cognitive impairments after moderate to severe COVID-19 were linked to immune-mediated brain injury.
In this study, researchers observed that cognitive deficits correlated with elevated serum markers of brain injury and a reduction in anterior cingulate cortex volume after 1 year. Participants with more severe initial infections, psychiatric symptoms, or a history of encephalopathy displayed more significant cognitive impairments. Additional findings revealed a correlation between reports of cognitive decline and objective assessments, with longitudinal data from 106 patients that indicated a trend toward cognitive recovery over the year.2
Conducted as a national study, investigators evaluated cognitive performance, serum biomarkers, and neuroimaging results from 351 hospitalized COVID-19 patients, comparing them with 2927 age and sex matched normative controls. Follow-up assessments aided with monitoring cognitive recovery over time, assessing the impact of infection severity and psychiatric symptoms on cognitive outcomes.2
Hampshire also addressed the role of vaccination in cognitive outcomes, in which he stated, “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 better understanding of the relationship between infection and cognitive outcomes will be important for guiding future interventions and support for affected patients.
