A new study found that COVID-19 infection can cause cognitive deficits that persist for over a year and lower IQ scores in severe cases. Those with persistent symptoms that resolved had small cognitive deficits similar to those with a shorter illness duration.
In a large-scale observational study published on Feb. 29 in the New England Journal of Medicine (NEJM), researchers invited 800,000 people with varying levels of COVID-19 exposure and duration to take an online cognitive assessment and follow-up survey. Cognitive difficulties have been implicated in numerous syndromes following COVID-19, including long COVID, suggesting infection may have lasting effects on the mental processes of the brain.
The study’s authors hypothesized there would be measurable cognitive deficits after COVID-19 that would scale with the severity and duration of the illness. They also speculated that objective impairments in executive and memory function, especially poor memory and brain fog, would be observable in those with persistent symptoms.
Using an assessment tool for cognitive function, researchers estimated global cognitive scores among participants with a history of previous SARS-CoV-2 infection who had symptoms for at least 12 weeks—whether resolved or not—and among a control group of uninfected participants. While cognitive and memory deficits were small for people with mild infection who recovered from COVID-19 quickly, impairments were more pronounced in those with severe disease.
Greater Impairment With More Severe Disease
Of 112,964 participants who completed the survey, those who recovered from COVID-19 with symptoms that resolved in less than four weeks or by 12 weeks post-infection had similar small deficits in global cognition compared with those who had never had COVID-19.
Participants who had mild COVID-19 with resolved symptoms experienced a 3-point drop in IQ compared to uninfected participants. Those with unresolved persistent symptoms had a 6-point loss in IQ, and those with COVID-19 admitted to the intensive care unit experienced a 9-point loss in IQ. Reinfection with SARS-CoV-2 caused an additional loss in IQ of nearly 2 points compared to those who were not reinfected. An IQ, or intelligence quotient, is a number used to represent the relative intelligence of an individual.
According to the study, memory, reasoning, and executive function tasks were the strongest indicators of impaired cognitive function, and these scores correlated with brain fog symptoms reported by participants. More significant deficits were seen in those with unresolved persistent symptoms and those infected with earlier variants of the SARS-CoV-2 virus compared with those who never had COVID-19. Additionally, study participants who were hospitalized had greater deficits in cognitive function compared to those who were not hospitalized.
“By using an innovative cognitive test which has also been completed by people who did not have COVID-19, this important and well-conducted study provides the first accurate quantification of the scale of cognitive deficits in people who had COVID-19,” Maxime Taquet, a fellow in psychiatry at the National Institute for Health and Care Research at the University of Oxford, said in a statement.
Mr. Taquet said researchers found a small but obvious association between COVID-19 and cognition that was more pronounced at extremes.
“The risk of having more severe cognitive problems was almost twice as high in those who had COVID-19 compared to those who did not, and three times as high in those who were hospitalized with COVID-19,” he noted.
In an editorial published Feb. 29 in the NEJM, Drs. Ziyad Al-Aly and Clifford Rosen said the study’s results are concerning and have broad implications that require further evaluation to determine the functional impact of a 3-point loss in IQ and why one group of participants was more severely affected than another.
“Whether these cognitive deficits persist or resolve along with predictors and trajectory of recovery should be investigated. Will Covid-19-associated cognitive deficits confer a predisposition to a higher risk of Alzheimer’s disease or other forms of dementia later in life? The effects on educational attainment, work performance, accidental injury, and other activities that require intact cognitive abilities should also be evaluated,” they wrote.
Study Implications for People With Long COVID
The study’s participants were part of a larger community sample of nearly 3 million people in the Real-time Assessment of Community Transmission (REACT) study assessing SARS-CoV-2 transmission in England. Although the researchers did not say whether participants in the study had long COVID, people with long COVID frequently report persistent cognitive impairment.
There is no accepted universal definition for the condition, but the Centers for Disease Control and Prevention (CDC) broadly defines long COVID as “signs, symptoms, and conditions that continue to develop after acute COVID-19 infection” that can last for “weeks, months, or years.” The term “long COVID” also includes post-acute sequelae of SARS-CoV-2 infection, long-haul COVID, and post-acute COVID-19.
Nearly 7 percent of U.S. adults surveyed by the CDC in 2022 said they’ve experienced long COVID. Although U.S. regulatory agencies claim vaccinating against COVID-19 can reduce the risk of developing long COVID and the current paper suggests vaccination with two or more doses may provide a slight cognitive advantage, a recent paper published in the Journal of Clinical Medicine did not find a significant link between the presence of comorbidities or infection severity and the emergence of long COVID symptoms.
The NEJM study has several limitations, including reliance on subjective reporting to identify individuals with ongoing symptoms and self-selection bias. People with long COVID may have enrolled in the study, but those with more severe impairments may not have been able to participate in the survey. Additionally, certain groups were overrepresented in the study compared with the base population. Baseline cognitive data before SARS-CoV-2 infection was also unavailable, so researchers could not assess cognitive change or infer causality.
