Investigating the effects of Long COVID upon cerebrovascular reactivity via multimodal fMRI

Long COVID (LC) is characterised by persistent symptoms such as fatigue and cognitive issues (“brain fog”) after acute SARS-CoV-2 infection. Emerging evidence links long COVID to cerebrovascular changes, including microclots, inflammation, and blood–brain barrier disruption, but brain haemodynamics remain poorly understood since previous studies have focused on resting-state or structural metrics.

This pilot MRI study examined task-evoked neurovascular responses in individuals with long COVID (n = 23) and matched controls (n = 24). Participants completed three tasks of increasing difficulty: passive visual, visual with hand grip, and a visual attention. Using BOLD fMRI and vascular space occupancy (VASO) cerebral blood volume (CBV) measurements, haemodynamics were assessed in primary visual (V1) and motor (M1) cortices, chosen for their well-established response profiles. Whole-brain BOLD and structural MRI analyses complemented these measures. Symptom severity was assessed with the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm).

Due to the small sample, most group differences were not statistically significant. Nevertheless, compared to controls, long COVID V1 BOLD responses shifted from lower amplitude and longer latency in the easiest task to larger and faster in the hardest task, while LC M1 responses were consistently smaller and slower, and finger-press reaction times were significantly slower. Whole-brain analyses showed reduced task-related activation in LC across dorsal parietal/precuneus, early visual, inferior frontal, and premotor areas.

VASO CBV responses were obtained from only a subset of participants, indicating the need for imaging protocol optimisation aligned well with those from the dedicated BOLD scans. Structural MRI showed no significant group differences in V1, M1, or whole-brain cortical thickness, though exploratory analyses using less stringent statistical thresholds suggested possible regional variations.

While limited by sample size, this study demonstrates the feasibility of combining task-based BOLD and VASO MRI to explore neurovascular function in long COVID, laying groundwork for larger future studies.