‘Brain fog’ is one of Covid-19’s most daunting symptoms. A new study measures its impact

Of all the lingering symptoms of long Covid, difficulty focusing and thinking, known as brain fog, may be the most frightening and baffling. A new study published Wednesday in the New England Journal of Medicine, which looks at how much cognition is impaired in the months after a coronavirus infection, shows that Covid-19’s impact can be measured in the equivalent of IQ points.

Researchers from Imperial College London found that even people who recovered from their Covid symptoms in four to 12 weeks had the equivalent of an IQ score three points lower than in uninfected people. Among those with long Covid — defined as symptoms lasting more than 12 weeks after testing positive — the drop was six IQ points. For people whose disease was severe enough to require hospital care, the deficit deepened to nine points.

People whose persistent symptoms had resolved by the time they took the test performed about as well as people who’d had symptoms that didn’t last very long.

“What our study shows is that brain fog can correlate with objectively measurable deficits in a person’s actual memory and executive task performance,” lead study author Adam Hampshire, professor of restorative neurosciences at Imperial College London, said Wednesday on a call with reporters.

The online tests, which entailed eight tasks, were not IQ exams, but the authors equated their results with more familiar IQ measures. They stressed that the differences they noticed in the observational study were modest and measured between groups at a single time point, not in individuals followed over time. Still, the lower test scores, even for people who have short-duration symptoms, were “a bit surprising to us,” Hampshire said. “The individuals themselves I don’t think would recognize that there’s any effect. It’s really just looking at these very large numbers and finding quite small differences.”

The study results came from more than 112,000 people in England who answered questionnaires about their infections and then took tests measuring such cognitive abilities as memory, reasoning, and planning. They are part of the much larger REACT research program, which is based on a random sample of people across England.

Testing took place when people were at different stages of their illness or recovery. People with unresolved persistent symptoms performed worse on the cognitive tests in terms of both speed and accuracy, particularly on memory and planning tasks. Those who’d been in hospital intensive care units had more and different weaknesses, such as in two-dimensional spatial processing, compared to others who’d had Covid.

“We don’t know what the clinical and cognitive long-term effects might be,” for people still living with long Covid, senior study author Paul Elliott, chair of epidemiology and public health medicine at Imperial College London, said at the press briefing. “And so following that cohort, we think, is very important in doing ongoing surveillance.”

For the current study, being vaccinated slightly narrowed gaps in cognitive performance between those who had Covid and the 40% of survey respondents who didn’t, while reinfection meant a “minimal” additional loss compared to single infections, Elliott said. People who caught the original SARS-CoV-2 strain and the Alpha strain of the virus fared worse than those infected by the Delta and Omicron variants later in the pandemic, a finding in line with other studies saying people whose Covid infections were more severe were more likely to have worse problems later.

The new study raises questions about what these IQ declines mean and if they’ll disappear, a companion editorial says. “What are the functional implications of a 3-point loss in IQ?” Ziyad Al-Aly of Washington University in St. Louis and Clifford Rosen of Tufts University School of Medicine ask. “Whether these cognitive deficits persist or resolve along with predictors and trajectory of recovery should be investigated.”

Hampshire said causation can’t be inferred directly from an observational study, and while differences are clear, the reasons for those differences aren’t.

“I was fully expecting that we would see some of these deficits in the hospitalized group. I was thinking we would likely see some cognitive deficits in people who had ongoing, long-term persistent symptoms,” Hampshire said. “I was not expecting that we would see even small cognitive differences in the shorter-duration symptom groups, and we just don’t know all the implications of that.”

While some issues remain unresolved, putting numbers to the problem is a crucial step on the way to developing any treatment, Steven Deeks, an infectious disease specialist at the University of California, San Francisco, told STAT.

“We need drug companies to get involved and make and design their own studies and fund their own studies, particularly Big Pharma,” said Deeks, who was not involved in the study. “Perhaps this paper will provide a road map to some endpoints that will make it easier to design a study, to power a study, to fund a study, to conduct a study, to interpret a study.”

Research on the mechanisms of long Covid is flourishing, said Deeks, who thinks the National Institutes of Health is making progress in its RECOVER initiative. But “where we’re making zero ground is in coming up with therapies.”

Elliott, who is also director of the REACT program, sees hopeful signs in the new study results. First, as the pandemic progressed from the original virus to Omicron, the association between symptoms and cognitive deficits weakened. Second, around a third of people with persistent cognitive symptoms saw them resolve.

“The important thing is that if they had persistent symptoms and then those symptoms resolved, they looked cognitively like the other people who’d had Covid, the short-duration people,” he said. “I think it’s encouraging that if once it resolves and you no longer report symptoms, then basically you look much more like everybody else who’d had Covid, rather than looking like the people who’ve still got ongoing symptoms.”