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COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.
In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR compared with never-infected individuals.
Results also showed cerebral blood flow (CBF) was greater in never-infected vs previously infected participants, and whole-brain CVR was lower in previously infected vs never-infected participants. Although CVR was also smaller in those with vs those without post-COVID neurologic conditions, the difference was not considered significant.
“It is important to remember that while our findings were statistically significant, we had a relatively small sample size — 25 total participants — and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado School of Medicine in Aurora, told Medscape Medical News.
“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Callen said.
The findings were published online August 24 in the American Journal of Roentgenology.
Endothelial Dysfunction
The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.
Moreover, following the acute phase of infection, up to three quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.
Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.
The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.
Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted this is a population at a much higher risk of stroke compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.
Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Callen said.
“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.
This emerging evidence prompted Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity, or if we might see abnormalities using high resolution vessel wall imaging.”
In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.
The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.
All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
Imaging Data
Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs 60.5 mL/100 g/min, respectively; P = .04).
Moreover, the mean whole-brain CVR was greater in never-infected participants compared with previously infected participants (27.8 mL/100 g/min vs 19.1 mL/100 g/min; P < .001).
After adjusting for age and sex, researchers found that prior infection
was associated with a lower whole-brain CVR (-8.9 mL/100 g/min; 95% CI, 4.6 – 13.3 ml/100g/min; P < .001).
Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.
A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with vs without post-COVID neurologic symptoms (16.9 vs 21.0 mL/100 g/min; P = .22).
In addition, 40% of the previously infected participants vs 10% of the never-infected participants had at least one vessel wall imaging abnormality — but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators note.
Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”
If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
Independent Risk Factor?
Commenting on the study for Medscape Medical News, Jared Narvid, MD, associate professor of neuroradiology, University of California San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”
Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”
The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.
The study was funded by a University of Colorado Department of Radiology Faculty Development Seed Grant. The investigators and Narvid report no relevant financial relationships.
AJR Am J Roentgenol. Published online August 24, 2022. Full text
Batya Swift Yasgur, MA, LSW is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
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