In a recent study published in the New England Journal of Medicine, researchers assessed cognitive functioning among adults with varying levels of persistence of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in England.
Their results suggest that COVID-19 is associated with measurable cognitive deficits, which may persist in the long term.
Study: Cognition and Memory after Covid-19 in a Large Community Sample. Image Credit: Berit Kessler / Shutterstock
Background
The first documented cases of ‘brain fog,’ with symptoms such as poor memory, impaired concentration, and difficulty thinking, emerged as early as 2020, indicating that COVID-19 could have long-term cognitive impacts.
Though the phenomenon is well-known, what is lacking is information on how it may persist and which aspects of cognitive functioning are most affected.
About the study
In this study, researchers hypothesized that cognitive deficits after the onset of COVID-19 should be quantifiable and associated with covariates related to illness severity and duration.
Their second hypothesis was that individuals with prolonged COVID-19 symptoms should show more observable memory and executive function impairment, including brain fog and poor memory.
They conducted a cohort-based study tracking the prevalence of SARS-CoV-2 infection among 3,099,386 individuals aged over 18 years. Of these, 800,000 people were invited to complete a cognitive assessment and follow-up survey.
To be included, they should have received a positive result on a SARS-CoV-2 diagnostic test or suspected that they had COVID-19 and experienced symptoms for 12 weeks or more. Additionally, unvaccinated people with SARS-CoV-2 immunoglobulin-G antibodies and other randomly selected people from the full sample were included.
The cognitive assessment tested immediate and spatial working memory, verbal analogical reasoning, two-dimensional mental manipulation, spatial planning, word definitions, delayed memory, and information sampling. For each domain, participants were scored on accuracy; secondary information was collected on types of errors and response times.
Individuals were categorized into six groups based on SARS-CoV-2 duration. The first category included those who had never experienced an infection or had an unconfirmed one; all other categories required a positive test result.
People in the second category had asymptomatic infections, those in the third had short COVID-19 that resolved in four weeks or less, and those in the fourth had symptoms that resolved in less than 12 weeks. To be in the fifth category, individuals had symptoms that persisted for more than 12 weeks; those in the sixth had persistent symptoms continuing until the cognitive assessments.
Researchers assessed nonresponse bias to examine which factors were associated with accessing and completing the cognitive assessment. Linear regressions, factor analysis, and propensity-score matching (PSM) were used to analyze the data. Sensitivity analyses were also conducted to test the validity and robustness of the results.
Findings
Of the 800,000 people invited to participate, 34.6% completed the questionnaire, with 141,583 completing at least one cognitive testing task and 112,964 completing all eight.
Among individuals infected with SARS-CoV-2 once, being infected earlier during the pandemic was associated with greater decreases in the overall cognitive score compared to those infected later. However, the gap narrowed after adjusting for the severity of the illness.
On average, people who were ill for longer, were hospitalized, or were infected early on in the pandemic had lower overall cognitive scores than those who had never had COVID-19.
Multivariate regression results indicated that people infected during the initial stages (when the original virus or alpha variant dominated) showed higher cognitive functioning decreases than those infected with the alpha or omicron variants.
Similarly, greater decreases were seen in people with persistent and unresolved symptoms compared to those who never had COVID-19 and among people who were hospitalized compared to those who were not.
The PSM analysis showed similar trends; cognitive advantages were observed based on vaccination status, with people who received two or more doses performing best. There was, however, no significant difference based on which vaccine was taken.
Conclusions
This large-sample community-based study suggests that COVID-19 may be associated with long-term and quantifiable cognitive deficits. However, people infected with more recent variants may experience more negligible effects on cognitive functioning.
This could be because earlier strains of SARS-CoV-2 were dominant at a time when effective treatments were not available, and the health system faced heavy burdens. Repeated infections do not appear to have any effect, but vaccination (particularly two or more doses) may provide small cognitive advantages.
Limitations of this study include the possibility of participant self-selection bias and reliance on self-reported data. Certain groups were overrepresented in the sample, including White persons and women; younger people and certain underprivileged groups were underrepresented.
Further studies are required to provide information on the longer-term implications of these findings.
Journal reference:
- Cognition and memory after Covid-19 in a large community sample. Hampshire, A., Azor, A., Atchison, C., Trender, W., Hellyer, P.J., Giunchiglia, V., Husain, M., Cooke, G.S., Cooper, E., Lound, A., Donnelly, C.A., Chadeau-Hyam, M., Ward, H., Elliott, P. New England Journal of Medicine (2024). DOI: 10.1056/NEJMoa2311330, https://www.nejm.org/doi/10.1056/NEJMoa2311330
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