Abstract

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection.

Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded.

Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions.

Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

Keywords: COVID-19; brain function; fMRI; functional connectivity; symptoms.

Conflict of interest statement

SB reports payments for contract research to her institution from GE Healthcare, Eli Lilly and Company, Biogen, Genentech, Optina Diagnostics, and Roche; consulting fees and payments related to an advisory board from Roche; and payments related to an advisory board, a speaker panel, talks, and an educational session from Biogen. There were peer-reviewed grants to her institution from the Ontario Brain Institute, Canadian Institutes of Health Research, Leducq Foundation, Heart and Stroke Foundation of Canada, National Institutes of Health, Alzheimer’s Drug Discovery Foundation, Brain Canada, Weston Brain Institute, Canadian Partnership for Stroke Recovery, Canadian Foundation for Innovation, Focused Ultrasound Foundation, Alzheimer’s Association US, Department of National Defense, Montreal Medical International Kuwait, Queen’s University, Compute Canada Resources for Research Groups, CANARIE, and Networks of Centres of Excellence of Canada. She has participated on a data safety monitoring board or advisory board for the Conference Board of Canada, World Dementia Council, and University of Rochester. She has contributed to the mission and scientific leadership of the Small Vessel VCID Biomarker Validation Consortium, National Institute of Neurological Disorders and Stroke. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.