Abstract

Background: Endothelial dysfunction has a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its disabling complications. We designed a case-control study to assess the alterations of endothelium-dependent flow-mediated dilation (FMD) among convalescent COVID-19 patients. Methods: COVID-19 patients referred to a Pulmonary Rehabilitation Unit within 2 months from swab test negativization were consecutively evaluated for inclusion and compared to controls matched for age, gender, and cardiovascular risk factors. Results: A total of 133 convalescent COVID-19 patients (81.2% males, mean age 61.6 years) and 133 matched controls (80.5% males, mean age 60.4 years) were included. A significantly lower FMD was documented in convalescent COVID-19 patients as compared to controls (3.2% ± 2.6 vs. 6.4% ± 4.1 p < 0.001), confirmed when stratifying the study population according to age and major clinical variables. Among cases, females exhibited significantly higher FMD values as compared to males (6.1% ± 2.9 vs. 2.5% ± 1.9, p < 0.001). Thus, no significant difference was observed between cases and controls in the subgroup analysis on females (6.1% ± 2.9 vs. 5.3% ± 3.4, p = 0.362). Among convalescent COVID-19 patients, FMD showed a direct correlation with arterial oxygen tension (rho = 0.247, p = 0.004), forced expiratory volume in 1 s (rho = 0.436, p < 0.001), forced vital capacity (rho = 0.406, p < 0.001), and diffusing capacity for carbon monoxide (rho = 0.280, p = 0.008). Overall, after adjusting for major confounders, a recent COVID-19 was a major and independent predictor of FMD values (β = −0.427, p < 0.001). Conclusions: Post-acute COVID-19 syndrome is associated with a persistent and sex-biased endothelial dysfunction, directly correlated with the severity of pulmonary impairment.

Highlights

  • The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 [1], culminating in a worldwide health emergency with a pandemic declaration in March 2020 [2]

  • No significant difference in age, gender, presence of CV risk factors, and ongoing CV therapies was documented between cases and matched controls

  • Our results suggest the presence of persistent endothelial dysfunction among COVID19 patients within 2 months from swab test negativization

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Summary

Introduction

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 [1], culminating in a worldwide health emergency with a pandemic declaration in March 2020 [2]. SARS-CoV-2 may be responsible for the coronavirus disease 2019 (COVID-19) [3], a syndrome with a plethora of clinical manifestations, ranging. Convalescent COVID-19 patients may experience fatigue, muscular weakness, and a decline in quality of life [5], with a persistent pulmonary impairment potentially lasting for months after the acute phase [6]. Endothelial dysfunction has a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its disabling complications. A significantly lower FMD was documented in convalescent COVID19 patients as compared to controls (3.2% ± 2.6 vs 6.4% ± 4.1 p < 0.001), confirmed when stratifying the study population according to age and major clinical variables. Conclusions: Postacute COVID-19 syndrome is associated with a persistent and sex-biased endothelial dysfunction, directly correlated with the severity of pulmonary impairment

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