Persistent Endothelial Dysfunction in Post-Acute COVID-19 Syndrome: A Case-Control Study.

Pasquale Ambrosino,Matteo Nicola Dario Di Minno,Ilenia Calcaterra,Antonio Molino,Roberta Lupoli,Giorgio Alfredo Spedicato,Pasquale Moretta,Antimo Papa,Mauro Maniscalco,Andrea Motta

doi:10.3390/biomedicines9080957

Pasquale Ambrosino, Matteo Nicola Dario Di Minno + Show 8 more

Open Access

https://doi.org/10.3390/biomedicines9080957

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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

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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