Persistent COVID-19 Symptoms Objectively Linked to Worse Cognition

Patients with COVID-19 could have objective cognitive deficits, according to the results of a recent study published in the New England Journal of Medicine. Contracting an earlier variant of COVID-19, having long-term symptoms, or being hospitalized from the illness were factors that were linked most strongly with global cognitive deficit.

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There are few objective data which measure the impact of COVID-19 on cognitive performance and how long it lasts, despite many patients reporting worse memory and difficulty thinking or concentrating (also called brain fog) post-infection. Therefore, investigators conducted a large community-based study to understand the impact of COVID-19 on objectively measurable cognitive deficits.

Participants (n=112,964) completed an online assessment of 8 tasks so investigators could measure cognitive function; this cohort was originally part of an 800,000-person study in England. Investigators hypothesized that individuals with persistent symptoms of COVID-19, or symptoms lasting 12 weeks or longer, would have objective global cognitive deficits in memory and executive functioning impairment.

Patients hospitalized with this virus had medium- to large-scale cognitive deficits compared withpatients who were not hospitalized. In addition, patients with persistent symptoms had an objective cognitive deficit compared with individuals who never had COVID-19.

Investigators had hypothesized that patients with persistent symptoms would score more poorly on memory and executive function tasks, and they observed just that. Individuals with persistent symptoms struggled with tasks relating memory, executive functioning, and reasoning. These patients had lower scores related to verbal analogical reasoning accuracy, spatial working memory maximum span, and immediate memory accuracy.

“We found small associations between specific task scores and reports of poor memory or brain fog in the previous 2 weeks,” authors wrote in the paper.

Individuals who were infected with the wild type or alpha variants also had larger objective cognitive deficits than individuals infected with more recent variants. In addition, it is interesting to note that patients with quick symptom recovery still appeared to experience acute cognitive deficiencies.

Those who recovered from COVID-19 in fewer than 4 weeks (or within 12 weeks) experienced small deficits in global cognition; however, these deficits were similar to those observed in people who never had COVID-19 or had unconfirmed infection (−0.23 SD [95% confidence interval {CI}, −0.33 to −0.13] and −0.24 SD [95% CI, −0.36 to −0.12], respectively).

“[This] suggests that persons with unresolved persistent symptoms may have some cognitive improvement once symptoms resolve,” authors wrote in the paper.

The trial’s limitations include participant self-selection bias, subjective reporting of symptoms, lack of an established long COVID diagnosis, lack of evaluation of cognitive change, and overrepresentation of certain groups (mainly women, older individuals, and White participants). Further research is needed to evaluate global cognitive deficits associated with infection.

“The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance,” authors wrote in the paper.

REFERENCE

Hampshire A, Azor A, Atchison C, et al. Cognition and Memory after Covid-19 in a Large Community Sample. N Engl J Med 2024; 390:806-818, DOI: 10.1056/NEJMoa2311330