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. 2025 Jun;138(6):1019-1028.
doi: 10.1016/j.amjmed.2024.10.012. Epub 2024 Oct 16.

Post-Acute COVID-19 Syndrome: Prevalence of Peripheral Microvascular Endothelial Dysfunction and Associations With NT-ProBNP Dynamics

Marcus Ståhlberg  1 , Katarina Fischer  1 , Maged Tahhan  1 , Allan Zhao  2 , Artur Fedorowski  1 , Michael Runold  3 , Malin Nygren-Bonnier  4 , Mikael Björnson  5 , Lars H Lund  1 , Judith Bruchfeld  5 , Liyew Desta  1 , Frieder Braunschweig  1 , Ali Mahdi  6
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Free article

Post-Acute COVID-19 Syndrome: Prevalence of Peripheral Microvascular Endothelial Dysfunction and Associations With NT-ProBNP Dynamics

Marcus Ståhlberg et al. Am J Med. 2025 Jun.
Free article

Abstract

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: 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 as impaired function, 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 2 different time points within over a 1-year span.

Results: 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.

Keywords: Microvascular endothelial dysfunction; Natriuretic peptides; Post-acute COVID-19 syndrome.

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