Post-acute COVID-19 syndrome: prevalence of peripheral microvascular endothelial dysfunction and associations with NT-proBNP dynamics

Background: Post-acute COVID-19 syndrome (PACS) has been linked to microvascular endothelial dysfunction as a potential underlying pathomechanism and can manifest even following a mild course of the initial infection. Prevalence of microvascular endothelial dysfunction and circulating natriuretic peptides in such PACS patients remains unknown.

Methods and results: This prospective, cross-sectional cohort study enrolled 92 patients (82% females, median age 48 years) with PACS. Reactive hyperemia index (RHI) was evaluated with peripheral arterial tonometry where <1.67 was defined as microvascular endothelial dysfunction, 1.67-2.0 impaired- and >2 normal endothelial function, on average 31 months after the acute infection. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected at two different time points within over 1-year span. In total, 41% of PACS subjects had microvascular endothelial dysfunction and 20% had impaired RHI. No major differences in clinical characteristics, routine chemistry laboratory testing or symptom burden were observed across the groups. Only subjects with microvascular endothelial dysfunction and impaired endothelial function had a significant increase in NT-proBNP levels over time and those with larger increase in NT-proBNP had significantly lower RHI. There was a significant correlation between relative or absolute increase in NT-proBNP and RHI, which remained significant in a multivariable adjusted linear regression.

Conclusions: Peripheral microvascular endothelial dysfunction was prevalent in a symptomatic PACS population long after recovery from a mild acute infection. Increases in NT-proBNP levels were associated with microvascular endothelial dysfunction, suggesting a link between and providing a foundation for future studies on post viral microvascular endothelial dysfunction in PACS.