It’s more than four years since the first cases of COVID-19 were identified — but many of its longer-term effects, including for those living with long COVID, remain unclear.

Now, a new study has some worrying findings that suggest COVID may have longer-term effects on cognition and memory — and that these lead to measurable differences in cognitive performance.

The study, published Thursday in the New England Journal of Medicine, found that participants who recovered from COVID symptoms had a cognitive deficit equivalent to three IQ points compared with those who were never infected, while participants suffering from unresolved COVIDc symptoms lasting 12 weeks or more experienced a loss equivalent to six IQ points.

But researchers also stressed that the greater cognitive decline associated with persistent symptoms may not be permanent, as participants in this category who had recovered by the time they took part in the study were found to have cognitive deficits comparable to those who recovered quickly. Adam Hampshire, the study’s lead author and a professor in restorative neurosciences at Imperial College London, said in a telephone interview Thursday that the improvement for those who previously had longer-term symptoms “gives us a little bit of hope that those who are struggling with long COVID at the moment — when their symptoms eventually resolve — may experience some cognitive recovery.”

Based on previous studies, researchers were “fully expecting to see cognitive deficits in people who’ve been severely ill, who’ve been in intensive care,” he said — but “we were quite surprised to see any difference at all between people who had short-duration symptoms and the no-COVID group.”

Cognitive effect greater for those infected earlier

The study involved a number of online tasks designed to measure participants’ cognitive function. More than 140,000 people completed at least one of the tasks, while almost 113,000 finished all eight.

The participants were from a cohort of more than 3 million adults who were randomly selected as part of a major English study to track the spread of COVID between May 1, 2020, and March 21, 2022.

As there is no scientific consensus around the definition of long COVID, the study instead looked at symptom duration, comparing the results of people who had not had COVID to those who were infected but recovered in less than four weeks, those who recovered between four and 12 weeks and those whose symptoms continued after that.

The study found a greater cognitive effect among people who were infected earlier in the pandemic, while those who were admitted to the intensive care unit had a particularly striking loss — equivalent to around nine IQ points compared with people who hadn’t had COVID — though the study noted that as the pandemic progressed, fewer people required intensive care.

Among those infected with COVID, the study also found “a small cognitive advantage among participants who had received two or more vaccinations” when they contracted the coronavirus, “and a minimal effect of repeat episodes.”

‘Multiple underlying factors’ may be responsible

The tests covered various aspects of cognitive performance but found that tasks involving memory, reasoning and planning “were among the most sensitive to COVID-19-related cognitive differences.”

“Our results confirmed associations of cognitive deficits with mood swings and fatigue but also with a variety of other symptoms,” it said. “Therefore, it is likely that multiple underlying factors contribute to cognitive deficits after COVID-19.”

Hampshire said the findings also broaden an understanding of brain fog, a symptom reported by many long-COVID sufferers, especially given the subjective nature of symptoms.

“What we found is that people reporting brain fog post-COVID also perform less well on tasks that measure memory and executive functions,” he explained. “So that gives us some insight into what brain fog actually is.”

“Even if cognitive deficits after COVID-19 are of small magnitude on average, a substantial minority of people have more significant deficits which are likely to affect their ability to work and function,” said Maxime Taquet, a clinical fellow in psychiatry at the University of Oxford, who was not involved in the research. “Given the scale of the pandemic and the number of people affected, this is particularly worrisome.”

We still don’t know the clinical implication of a three-point difference in IQ for people who recovered from COVID, but within that average finding “there will be substantial variability, there’s likely to be some people who were worse affected,” Hampshire said.

The study had a number of limitations. The researchers did not have information on individuals’ cognitive abilities before they were infected and therefore compared their results to those of participants who hadn’t had COVID, rather than measuring the change in their own cognition.

The authors also noted that there could have been some participant self-selection bias, as those most affected by cognitive impairment may be unable or unwilling to take part in the cognitive assessments. Women and White people were “slightly overrepresented” in the study — though the authors argued that the large sample size meant that the data was still meaningful.

An editorial about the study published Thursday in the same journal said the findings are concerning. It added that questions remain, including on the persistence of the cognitive deficits and the effect on work, education “and other activities that require intact cognitive abilities.”

The study adds to a growing body of research into the effect of long COVID, whose symptoms may include fatigue, memory loss, chest pain, diarrhea and rapid heart rates. One analysis published in August found that even mild infections can lead to a higher risk of lung problems, fatigue, diabetes and certain other health problems typical of long COVID two years later.