Today the New England Journal of Medicine posted a study by Imperial College London researchers showing that COVID-19 patients recovering from short-term symptoms experienced similar small deficits in memory, thinking, or concentrating ("brain fog") as those who had longer-term symptoms.
The investigators calculated a global cognitive score across eight tasks using online self-reports of cognitive function among 112,964 adults participating in a study in England. They compared the results of COVID-19 survivors with those of their uninfected counterparts.
"Objective data on cognitive performance are largely lacking, and how long such deficits may persist and which cognitive functions are most vulnerable are unclear," the study authors wrote.
Virus strain, infection severity
A multiple regression analysis showed that COVID-19 survivors whose symptoms had resolved in less than 4 weeks or at least 12 weeks had comparable small deficits in cognitive function—or the ability to think—compared with uninfected participants (−0.23 and −0.24 standard deviations [SD], respectively). COVID-19 survivors demonstrated greater deficits than uninfected controls (−0.42 SD).
Mild cognitive decline was noted after infection with the wild-type virus and with each variant, including B.1.1.529 (Omicron). Relative to uninfected participants, cognitive deficit (3-point loss in IQ) was seen even in participants who had had completely recovered from mild COVID-19.
Participants with persistent symptoms had the equivalent of a 6-point loss in IQ, while those who had been admitted to an intensive care unit (ICU) experienced the equivalent of a 9-point loss in IQ.
Participants who contracted COVID-19 during the periods of wild-type and Alpha variant predominance exhibited larger deficits than those infected with later variants (eg, −0.17 SD for B.1.1.7 vs B.1.1.529). Similar findings were observed in hospitalized versus unhospitalized participants (eg, ICU admission, −0.35 SD) and in those with longer periods of acute illness and hospital stays.
The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance.
A comparison of the group with unresolved persistent symptoms with the uninfected group revealed that memory, reasoning, and executive function tasks were associated with the greatest cognitive deficits (−0.33 to −0.20 SD). These tasks had a weak correlation with recent symptoms, including impaired memory and brain fog.
COVID-19 vaccination provided a small cognitive benefit, while reinfection was tied to an IQ loss of nearly 2 points, compared with no reinfection.
"The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance," the researchers wrote.
Understanding the functional implications
In a related editorial, Ziyad Al-Aly, MD, of the Veterans Affairs St. Louis Health Care System, and Clifford Rosen, MD, of Tufts University, said the study findings are concerning and require further exploration.
"For example, what are the functional implications of a 3-point loss in IQ?" they asked. "Whether these cognitive deficits persist or resolve along with predictors and trajectory of recovery should be investigated."
Al-Aly and Rosen noted that millions of people around the world have long COVID, many of whom had or still have cognitive difficulties. "A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations," they concluded.
