Measurable Cognitive Deficits Linked to Long COVID

Measurable cognitive deficits persisted after SARS-CoV-2 infection, a large observational study in England showed.

People with COVID symptoms that lasted 12 weeks or longer (i.e., long COVID) had greater deficits in global cognition than those never infected (-0.42 SD), reported Adam Hampshire, PhD, of Imperial College London, and co-authors in the New England Journal of Medicine.

This corresponded to a loss of 6 IQ points, the researchers said.

Longer hospital stays and acute illness duration predicted persistent global deficits, and those admitted to the intensive care unit had the equivalent of a 9-point loss in IQ (-0.63 SD).

People whose COVID symptoms resolved in less than 4 weeks, or at least in 12 weeks, showed a small global cognitive deficit (-0.23 SD and -0.24 SD, respectively), equivalent to a loss of 3 IQ points, the researchers said.

The greatest deficits occurred in people who had COVID when the original virus or Alpha variant was predominant. Vaccination provided a small cognitive advantage of 0.08 to 0.15 SD, depending on the number of shots.

“The potential long-term effects of COVID-19 on cognitive function have been a concern for the public, healthcare professionals, and policymakers, but until now it has been difficult to objectively measure them in a large population sample,” Hampshire said in a statement.

“By using our online platform to measure multiple aspects of cognition and memory at large scale, we were able to detect small but measurable deficits in cognitive task performance,” he added.

The deficits identified in this study have been associated with other symptoms reported by people with long COVID, observed Ziyad Al-Aly, MD, of the Veterans Affairs St. Louis Health Care System and Washington University School of Medicine in St. Louis, and Clifford Rosen, MD, of Tufts University School of Medicine in Boston, in an accompanying editorial.

“Memory, reasoning, and executive function (i.e., planning) tasks were the most sensitive indicators of impaired function, and scores on these tasks tended to correlate with brain fog,” they wrote.

“Whether these cognitive deficits persist or resolve along with predictors and trajectory of recovery should be investigated,” Al-Aly and Rosen wrote, adding that their effects on education, work performance, and other activities that need intact cognitive abilities also need to be assessed.

“SARS-CoV-2 infection happened in the context of a global pandemic that disrupted many facets of our lives; disentangling the effects of the infection from those of the pandemic (e.g., social isolation, grief, and trauma) should also be undertaken,” the editorialists noted.

Hampshire and colleagues studied data from 112,964 people who completed an online assessment tool of eight tasks on the Cognitron platform from August through December 2022.

The researchers estimated a global cognitive score across the eight tasks, which evaluated immediate memory, two-dimensional mental manipulation, spatial working memory, spatial planning, verbal analogical reasoning, word definitions, information sampling, and delayed memory.

Participants came from the REACT cohort in England and joined the study after May 2020. Overall results were similar to those that emerged in propensity score-matching analyses, Hampshire and co-authors noted.

In correspondence also published in the New England Journal of Medicine, Merete Ellingjord-Dale, PhD, of Oslo University Hospital, and co-authors reported on participants in the Norwegian COVID-19 Cohort Study who completed at least one memory function test.

Of these participants, 111,992 had documented COVID tests; about half (57,319) tested positive and half (54,673) tested negative. Participants completed the Everyday Memory Questionnaire (EMQ), a test of 13 items with scores ranging from 0 to 52, between March 2020 and April 2023.

Adjusted mean EMQ scores were numerically higher (indicating worse memory problems) after a positive COVID test than after a negative test at all time points in the study, the researchers found. The mean EMQ score among COVID-positive participants generally increased according to the number of days they had been bedridden.

“Overall, women had higher EMQ scores than men, a finding that is consistent with those from several studies that have investigated psychiatric and neurologic complications of long COVID,” Ellingjord-Dale and colleagues wrote.

Both the Norway and England studies relied on self-reported data, which was a limitation. Both may have been influenced by response bias between people who responded to the online assessment tools and those who did not.

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