Long COVID Fatigue Linked to Reduced Brain Blood Flow

Brain Blood Flow and Cognitive Performance in Long COVID

Patients experiencing post-COVID-19 condition show reduced cerebral perfusion alongside slower reaction times during tasks requiring sustained attention, according to the study led by researchers at the Cognitive Post-COVID Outpatient Clinic at Danderyd Hospital. “Our findings show that people with post-COVID-19 condition not only report more fatigue, but also perform more slowly on a task that requires sustained attention,” says Sonia Miri Hedberg, doctoral student at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, and first author of the study.

Using functional magnetic resonance imaging, the research team identified differences in blood flow through the brain. Participants with long COVID exhibited slightly lower average cerebral blood flow than healthy control groups. More pronounced reductions appeared specifically in brain regions tied to attention, sensory processing, and cognitive control. Further statistical analysis connected these slower reaction times directly to lower regional brain blood flow.

Patients with post-COVID-19 condition also displayed greater fluctuation in reaction times throughout the testing process. Researchers note that this specific variability pattern mirrors mental fatigue seen in other neurological conditions. “The study suggests that changes in brain blood flow may be part of the explanation for the fatigue and concentration difficulties described by many patients,” Hedberg says.

Methodology and Limitations of the fMRI Findings

While the fMRI results offer concrete physiological data, the study authors emphasize that the research cannot establish direct cause and effect. The investigation involved a relatively small participant sample, meaning findings require validation through larger cohort studies. Additionally, the fMRI imaging technique cannot completely differentiate between reduced blood flow directly inside brain tissue and alterations in blood transport through smaller cerebral blood vessels.

The research project was conducted at Danderyd Hospital in collaboration with Karolinska Institutet and Karolinska University Hospital, with funding provided by Promobilia. The study authors reported no conflicts of interest, aside from one researcher receiving research funding from Promobilia.

Broader Context of Long COVID Fatigue and Brain Fog

The Karolinska findings arrive alongside growing longitudinal data regarding the persistence of post-infection symptoms. According to data from the multi-centre COVIDOM–NAPKON-POP cohort published in eClinicalMedicine, cognitive deficits and debilitating fatigue remain major challenges years after initial infection. Longitudinal follow-up data showed that significant numbers of patients experience persistent fatigue and cognitive impairment months and years post-infection, though symptoms can be transient for others.

Standardizing the definition of long COVID remains a priority for researchers. A consensus definition published by the National Academies of Sciences, Engineering, and Medicine describes long COVID as an infection-associated chronic condition occurring after SARS-CoV-2 infection that persists for at least three months. Identifying shared and distinct pathophysiological mechanisms—such as the cerebral perfusion differences isolated in the Karolinska Institutet study—remains essential for developing precision medicine treatments for patients suffering from long-term neurological and systemic symptoms.