'Brain Fog' Persists After Mild COVID-19

Young adults performed worse on memory and attention tests several months after an acute case of mild COVID-19, according to a small study that may support the "brain fog" reported by many.

Most cognitive abilities tested -- including working memory, executive function, and planning -- were normal, but COVID-19 patients displayed significantly worse episodic memory for up to 6 months after infection and a greater decline in vigilance on a sustained task for up to 9 months than uninfected people, reported Sijia Zhao, PhD, of the University of Oxford, England, and co-authors in Brain Communications.

These deficits in memory and concentration were not significantly different from normal after 6 or 9 months, suggesting people recover over time, Zhao and colleagues noted.

"We found that COVID survivors who had no or mild symptoms showed impaired memory and declined ability to sustain attention over minutes," Zhao told MedPage Today.

"Importantly, these participants did not consider themselves as having long COVID," Zhao continued. "These cognitive deficits could not be explained by the participants' age, socioeconomic status, education level, employment status, smoking history, or familiarity with the cognitive tests."

"Our findings highlight that cognitive reductions are not limited to patients who had prolonged neurological manifestations after recovery, but might exist more widely in a subclinical form among COVID-19 survivors who would not consider themselves as requiring any post-COVID treatment," she added.

The study evaluated adults with a mean age of 29, comparing 53 participants with previous self-reported mild COVID-19 (usually confirmed by PCR test) and 83 participants who reported not having COVID-19. People who were hospitalized with COVID-19 or had symptoms that affected their daily life were excluded from the analyses, as were people with severe long COVID symptoms.

All participants were recruited from the Prolific online research platform, where the study was advertised as a brain game to test how well people could perform. COVID patients participated an average of 163 days after COVID-19 diagnosis, and about 43% were women.

Participants completed questionnaires and were tested on sustained attention, memory, motor control, planning, semantic reasoning, mental rotation (spatial thinking), and spatial-visual attention. After each minute during testing, they were asked to report their level of fatigue and motivation on a visual analogue scale.

Questionnaire measures of fatigue, forgetfulness, motivation, sleep abnormality, depression, and anxiety levels were not statistically different between COVID patients and age-matched controls. But people who had been infected with SARS-CoV-2 had significantly larger vigilance decrement and faster fatigue during a task that demanded attention for 9 minutes. They also had significantly worse episodic memory decline over time, comparable to that of healthy people in their 60s.

"Notably, both deficits scaled with the time from COVID-19 diagnosis suggesting a strong relation with COVID-19 itself," Zhao and co-authors wrote.

"In the present study, COVID-19 survivors began with apparently normal behavioral performance followed by a gradual decline away from age-matched controls, suggesting reduced ability to attentively track and maintain information over time," they added.

The analysis had certain limitations, observed Stephen Burgess, PhD, of the University of Cambridge, England, who wasn't involved with the study.

"The exposure was not assigned randomly, it was not blinded from participants, and it may associate with various confounding factors, such as lifestyle and social position," Burgess posted on the Science Media Centre. "At all stages of the pandemic, there are likely to be many systematic differences on average between individuals who had a positive COVID-19 test versus those who did not."

"However, despite this, differences between the COVID and non-COVID groups in terms of several specific measures of cognitive ability looked at in this study were striking, particularly in terms of delayed memory tasks and ability to perform tasks accurately when fatigued," he continued. "Despite the limitations of non-randomized research, it seems unlikely that these results can be explained by systematic differences between the groups unrelated to COVID infection."

Though more people need to be studied, the analysis "raises the possibility that COVID-19 infection could be a causal factor for these measures of reduced cognitive ability in some people, at least in the short- to medium-term following infection," Burgess noted.

The study also was limited by its reliance on self-reported data, Zhao and co-authors acknowledged. The small sample mostly included young and very few older people, and results may not be generalizable.

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