A recent New England Journal of Medicine study assessed whether cognitive deficits can be measured after severe acute respiratory syndrome (SARS-CoV-2) infection, the causal agent of the coronavirus disease 2019 (COVID-19) pandemic.
This study further explored the period for which these symptoms persist.
Study: Cognition and Memory after Covid-19 in a Large Community Sample. Image Credit: Orawan Pattarawimonchai/Shutterstock.com
Background
Brain fog is the common name for problems associated with thinking, concentrating, or memory. It has been observed frequently in patients recovered from COVID-19, but there is a dearth of objective data on cognitive performance.
Furthermore, it is not clear which cognitive functions are most vulnerable and how long such deficits persist.
About the study
The primary hypothesis in this observational study was that cognitive deficits after COVID-19 were measurable and scalable regarding illness severity and duration.
The secondary hypothesis was that objective impairments in memory and executive functions would be noted in patients showing prolonged symptoms.
These hypotheses were tested using data from the Real-Time Assessment of Community Transmission (REACT) cohort in England.
Eight hundred thousand adults were invited to complete an online assessment of cognitive function.
Across eight tasks, a global cognitive score was estimated. These tasks helped test immediate memory, verbal analogical reasoning, two-dimensional mental manipulation, verbal analogical reasoning, spatial working memory, word definitions, delayed memory, spatial planning, and information sampling.
Individuals who were invited to participate in this study were SARS-CoV-2 test positive or with persistent COVID-19 symptoms for at least 12 weeks.
The eligible participants were categorized into six groups based on the duration of SARS-CoV-2 infection.
The categories were defined as follows:
- Category 1: No infection with SARS-CoV-2 detected.
- Category 2: Infected with SARS-CoV-2, but no symptoms developed (asymptomatic infection).
- Category 3: Experienced a brief infection period, with symptoms lasting less than four weeks.
- Category 4: The period of infection lasted between 4 and 12 weeks.
- Category 5: Symptoms were resolved at least 12 weeks after the onset of the infection.
- Category 6: Symptoms persisted for more than 12 weeks after the infection began and were present during the cognitive assessment.
Study findings
This community-based study noted that COVID-19 and long-term objectively measurable cognitive deficits were associated with each other.
The difference in the cognitive score between the no-COVID group and the group of participants whose symptoms had resolved was small. The difference was, however, large for participants who experienced unresolved symptoms.
The probability of task performance was below the cut-off point in the case of moderate impairment.
Relative to the no-COVID group, larger cognitive differences were noted in the group where ICU admission was needed. This finding is consistent with the ones documented in previous studies where medium-to-large-scale cognitive deficits were observed in patients who were hospitalized in a critical care unit.
It was noted that with the progression of the pandemic, the association between cognitive deficits and COVID-19 attenuated.
Smaller cognitive declines were noted among those infected with newer variants, compared to the original strain or the Alpha strain. Individuals who had received two or more vaccine doses were seen to have a small cognitive advantage.
A progressive decline in cognitive deficits was observed among those infected during the pandemic's first wave.
The observation that patients whose persistent symptoms had resolved had experienced global cognitive deficits similar in nature to patients with shorter-duration symptoms is indicative of the fact that individuals with persistent symptoms could experience some degree of cognitive improvement once symptoms resolve.
The executive, memory, and reasoning tasks were the most sensitive to COVID-19. The performance was dependent on hospitalization and illness duration.
The scores were also weakly correlated with recent brain fog or poor memory. The results documented here validated the associations between mood swings, fatigue, and cognitive deficits, besides a variety of other symptoms.
Limitations of the study
A key limitation centers around subjective reporting to identify patients with persistent symptoms.
Linking these results to the literature is difficult owing to the lack of definitive criteria for post–COVID-19 syndromes. Furthermore, causality could not be inferred owing to the observational nature of the data.
The global cognitive score calculation adjusted for demographic characteristics and pre-existing health conditions. However, some residual confounding could have remained due to the observational nature of the data.
To mitigate this bias, the propensity score matching method was used to show a highly consistent pattern of results.
As with any study requiring active participant engagement, self-selection bias could not be ruled out.
Patients with the most severe cognitive impairment may not have been willing or able to take a cognitive assessment.
Additionally, some groups were less representative compared to the base population. Individuals from deprived backgrounds and younger persons were underrepresented.
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