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Post-COVID microvascular dysfunction in hospitalized COVID-19 survivors is associated with acute disease severity and
Noa van der Knaap1, Simona Klinkhammer2, Alida A Postma3
1Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, the Netherlands; Department of Intensive Care, Maastricht University Medical Center, the Netherlands; Mental Health & Neuroscience Research Institute (MHeNs), Maastricht University, the Netherlands.
Insights
COVID-19 survivors from intensive care units show more widespread cerebral microvascular dysfunction than general ward patients. This dysfunction in white matter is linked to persistent cognitive complaints, even without objective cognitive deficits.
Area of Science:
- Neurology
- Radiology
- Infectious Diseases
Background:
- Coronavirus disease 2019 (COVID-19) can affect brain vasculature, potentially leading to persistent vascular and cognitive issues post-infection.
- The specific pathological pathways contributing to post-COVID cognitive dysfunction remain unclear.
Purpose of the Study:
- To investigate cerebral microvascular properties in COVID-19 survivors.
- To correlate these properties with acute systemic blood markers and post-COVID cognitive function and complaints.
Main Methods:
- An observational cohort study compared 108 hospitalized COVID-19 survivors (53 general ward, 55 ICU).
- Multi-b-value diffusion MRI assessed cerebral microvascular properties (fmv, fmv·Dmv) in cortical gray matter (cGM), normal-appearing white matter (NAWM), and white matter hyperintensities (WMH) approximately 9 months post-infection.
Main Results:
- ICU survivors exhibited significantly lower microvascular perfusion volume fraction (fmv) and blood flow (fmv·Dmv) in cGM, NAWM, and WMH compared to general ward survivors.
- Lower fmv in NAWM correlated with increased subjective cognitive complaints, independent of objective cognitive performance.
- In ICU survivors, higher blood lactate levels during hospitalization were associated with reduced fmv and fmv·Dmv in NAWM.
Conclusions:
- COVID-19 intensive care unit survivors present with more extensive post-infection cerebral microvascular dysfunction.
- Microvascular dysfunction in NAWM may result from cerebral tissue hypoxia during acute infection.
- This dysfunction is associated with persistent subjective cognitive complaints, even without objective cognitive impairment.
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 (fmv) and blood flow-related measure (fmv·Dmv) 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 fmv 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 fmv (p = .031) and fmv·Dmv (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.
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