For some people, the worst is not over once their COVID-19 infection subsides. An October 2021 study from Penn State found that more than half of the 236 million people who have been diagnosed with COVID-19 worldwide since December 2019 experience post-COVID symptoms, more commonly known as long-COVID.
Long-COVID is typically characterized by brain fog, fatigue, memory loss and attention problems for up to one year post-infection. Thus far, no underlying pathophysiology has been identified, and scientists are concerned as they continue to work to understand the long-term implications of this unprecedented pandemic—which has killed 5 million people globally as of Monday.
In a study just published in the Journal of Nuclear Medicine, however, researchers with the University of Freiburg (Germany) offer tentatively good news for long-COVID sufferers—cognitive problems may be a result of fatigue rather than pathological changes in the brain.
The study cohort comprised 31 patients who were admitted to the University Hospital Freiburg between June 2020 and January 2021 due to lasting neurocognitive symptoms three months after COVID-10 infection.
First, all patients participated in a battery of neuropsychological tests. All patients complained of difficulties in attention, memory and multitasking abilities, with 77% mentioning extreme fatigue. However, almost half (49%) of the patients presented unimpaired in the tests, to the point where the average group results showed no cognitive impairment. Mild deficits were observed in some patients—about 23%—on the single-subject level for verbal and visual memory tests.
Next, the team recommended 18F-FDG PET imaging for all patients, with 14 of 31 agreeing to proceed. Clinical assessment of each patient’s scan revealed no distinct pathological findings. When the scans were compared to those of the control group, no significant differences were noted, either. Additionally, the PET scans suggested no alternative diagnoses—such as encephalitis or neurodegenerative dementia—is any case.
“The lack of significant findings on 18F-FDG PET scans and only mild impairments on neuropsychological testing is in contrast to the severe and lasting disability self-reported by the patients. Fatigue, however, was particularly prevalent in the group, reported by 61% of study participants,” write the researchers.
Thus—with molecular imaging ruling out regional brain dysfunction in at least this small sample—the German research team believes fatigue is behind many long-COVID symptoms.
“Fatigue is a common sequel of systemic viral infections, systemic inflammatory diseases and has been related to immune dysregulation processes, [including] systemic inflammatory response and cytokine release in COVID-19. Fatigue has also been linked to myalgic encephalomyelitis/chronic fatigue syndrome in long-COVID, which is characterized by functional impairment (e.g., disability to work) in a considerable number of patients,” the researchers conclude.
The research team says future studies should include a larger sample size, and longitudinal studies are needed to define the prognosis of neurocognitive symptoms in patients with long-COVID. They suggest 18F-FDG PET imaging for this research due to its lack of long-lasting alterations to cerebral functioning.
Photo: 18F-FDG PET in patients with long-COVID syndrome. A and B: Transaxial sections of group averaged, spatially normalized 18F-FDG PET scans in patients with long-COVID syndrome (A) and control patients (B). C: The pattern expression score (PES; *adjusted for age and sex, for illustration purposes) of the previously established COVID-19-related spatial covariance pattern was not significantly different between patients with long-COVID syndrome and control patients. Credit: Dressing et al., Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.