Post-COVID microvascular dysfunction in hospitalized COVID-19 survivors is associated with acute disease severity and persistent cognitive complaints

Objective: Coronavirus disease 2019 (COVID-19) is known to have adverse effects on the brain's vasculature in some patients. After recovery of the infection, vascular abnormalities may persist, but it remains unclear which pathological pathways play a role in post-COVID vascular and cognitive dysfunction and may contribute to post-COVID cognitive complaints. Methods: In this observational cohort study, 108 previously hospitalized COVID-19 survivors (general ward: n = 53; intensive care unit (ICU): n = 55) were compared. Cerebral microvascular properties in the cortical gray matter (cGM), normal-appearing white matter (NAWM), and white matter hyperintensities (WMH) were assessed using multi-b-value diffusion MRI around 9 months post-infection and related to acute systemic blood markers and post-COVID cognitive performance and complaints. Results: A lower microvascular perfusion volume fraction (f_mv) and blood flow-related measure (f_mv·D_mv) were found in ICU compared to general ward patients in the cGM (p = .032; p = .021), NAWM (p = .008; p = .006), and WMH (p = .014; p = .035). No associations were found between diffusion/perfusion metrics and cognitive performance, but a lower f_mv in the NAWM was found in those with more cognitive complaints (p = .047). In ICU survivors, higher median blood lactate levels during ICU admission were associated with lower f_mv (p = .031) and f_mv·D_mv (p = .044) in the NAWM. Interpretation: Significantly more widespread post-COVID cerebral microvascular dysfunction was found in COVID-19 ICU compared to general ward survivors. Post-COVID microvascular dysfunction in the NAWM may be due to more severe cerebral tissue hypoxia at time of the infection and is associated with persisting subjective cognitive complaints, even in absence of objective cognitive problems.