Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study.

Salma Charfeddine,Imen Touil,Nedia Moussa,Aiman Ghrab,Leila Abid,Nesrine Kallel,Sami Milouchi,Salma Kraiem,Amine Bahloul,Salem Abdessalem,Slim Torjmen,Kamel Bouslama,Jihen Jdidi,Hassen Ibn Hadj Amor,Jamel Elghoul,Zineb Meddeb,Rania Hammami,Yamina Thabet,Samir Kammoun

doi:10.3389/fcvm.2021.745758

Abstract

The COVID-19 disease is a multisystem disease due in part to the vascular endothelium injury. Lasting effects and long-term sequelae could persist after the infection and may be due to persistent endothelial dysfunction. Our study focused on the evaluation of endothelial quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long-covid 19 symptoms are associated with endothelial dysfunction. This is a cross-sectional multicenter observational study with prospective recruitment of patients. A total of 798 patients were included in this study. A total of 618 patients (77.4%) had long COVID-19 symptoms. The mean EQI was 2.02 ± 0.99 IC95% [1.95–2.08]. A total of 397 (49.7%) patients had impaired EQI. Fatigue, chest pain, and neuro-cognitive difficulties were significantly associated with endothelium dysfunction with an EQI <2 after adjustment for age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease, and the severity of acute COVID-19 infection. In multivariate analysis, endothelial dysfunction (EQI <2), female gender, and severe clinical status at acute COVID-19 infection with a need for oxygen supplementation were independent risk factors of long COVID-19 syndrome. Long COVID-19 symptoms, specifically non-respiratory symptoms, are due to persistent endothelial dysfunction. These findings allow for better care of patients with long COVID-19 symptoms.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) was detected in China in December 2019 [1, 2]
SARS-CoV-2 infects the host using the angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in several organs, including the lung, heart, kidney, intestine, and expressed by endothelial cells, causing a distinguishable and distinct systemic endotheliitis [5, 19]
While it is well established that endothelial dysfunction is associated with poor prognosis in acute phase COVID19, its link with long COVID 19 symptoms is still questionable

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) was detected in China in December 2019 [1, 2]. Lasting effects and long-term sequelae could persist after the infection, affecting patients’ return to work and quality-of-life [6]. Some studies suggest that Long-COVID 19 symptoms may be due to persistent endothelial dysfunction [12]. The SARSCoV-2 infection of endothelial cells is associated with changes in cell morphology and endothelial cells apoptosis that could persist several weeks after the acute infection. The Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provided a Position Statement on the importance of the endothelial function study in convalescent patients for early detection and prevention of long-term cardiovascular complications [4]

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Results

Conclusion