Long-COVID patients with neuropsychiatric symptoms such as brain fog showed abnormal brain activity on magnetic resonance imaging (MRI) while completing memory tests, with a shift from activity in brain areas normally used for memory to other brain regions, shows a study published yesterday in Neurology.
From February 2021 to February 2022, University of Maryland School of Medicine (UMSOM) researchers conducted functional MRI on 29 participants who had persistent symptoms after a COVID-19 diagnosis at least 6 weeks earlier and 21 never-infected matched controls. Among the COVID patients, the average interval between diagnosis and enrollment was 7 months.
Nine long-COVID patients were hospitalized for treatment of their infections, and 19 required supplemental oxygen or other treatments. The study was conducted primarily during the period of SARS-CoV-2 Delta predominance.
Participants completed three National Institutes of Health tests for cognitive and emotional health and movement, as well as tests from the Patient-Reported Outcomes Measurement Information System (PROMIS) on depression, anxiety, fatigue, and pain. They underwent MRI as they completed working-memory tasks.
The average age was 42 years in the long-COVID group and 41 in the control group, and 65% and 57%, respectively, were women.
Cognitive test scores similar
Long-COVID participants reported a high rate of problems with concentration (92.9%) and memory (78.6%), confusion (64.3%), headaches (57.1%), visual disturbances (50%), gait disturbances (50%), burning sensations in the extremities (42.9%), and incoordination (39.3%).
Loss of taste or smell persisted in 28.6% of long-COVID-19 patients. This group also had a high rate of new-onset fatigue (85.7%), depression or anxiety (67.9%), impaired sleep (64.3%), muscle pain (60.7%), lightheadedness (46.4%), and urinary issues (27.6%).
While long-COVID patients' cognitive test scores were similar to those of never-infected participants, those with persistently compromised memory and concentration and lingering fatigue had greater brain activation on MRI while completing working-memory tests.
Long-COVID patients also had lower scores on tests for dexterity and motor endurance than controls and reported more anger, sadness, stress, depression, anxiety, fatigue, and pain and lower life satisfaction, meaning, and purpose. Those in the long-COVID group who had more brain-activity changes were more likely to have lower test scores.
Possible brain reorganization
"Their [long-COVID patients'] brain activity differed from those without prior COVID-19, indicating that their brains compensated for their deficits by reorganizing the networks to maintain their performance," lead author Linda Chang, MD, said in a press release from the American Academy of Neurology, which publishes the journal.
The authors emphasize that the findings don't prove that SARS-CoV-2 caused the brain changes but rather only an association.
"The greater activity occurred outside of the normal working memory brain network," Chang said in a University of Maryland press release. "We often see such changes in patients with a brain injury: Deficits in the default mode network of the brain leads to an increase in activity in other regions to help maintain brain function."
Chang is a professor of diagnostic radiology and nuclear medicine and an associate member of the Institute of Human Virology at UMSOM.
Deficits in the default mode network of the brain leads to an increase in activity in other regions to help maintain brain function.
The researchers say their findings may not apply to infections with more recent variants such as the now-predominant Omicron. They recommend that physicians consider referring long-COVID patients who have neuropsychiatric symptoms for neurorehabilitation or psychiatric treatment.
"While this study provides crucial information on brain function in those who suffer neuropsychiatric symptoms from long COVID, we now need longitudinal follow-up studies to determine whether or when these abnormal imaging patterns will normalize and whether that correlates to a resolution in symptoms," UMSOM Dean Mark Gladwin, MD, who was not involved in the study, said in the university release.