Impaired endothelial glycocalyx, vascular dysfunction and myocardial deformation four months after COVID-19 infection are partially improved at twelve months
Authors: Ikonomidis I , Kountouri A , Mitrakou A , Katogiannis K , Thymis J , Korakas E , Pavlidis G , Andreadou I , Chania C , Bamias A , Thomas K , Antoniadou A , Lambadiari V , Filippatos G 
Published: October 2022

Abstract

Introduction
COVID-19 patients present impaired subclinical markers of cardiovascular and endothelial function. Subclinical myocardial and vascular dysfunction during COVID-19 disease have been associated with worse outcomes and higher mortality risk.

Purpose
We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function at four and twelve months after the infection

Methods
We recruited 70 patients who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four and twelve months after a confirmed COVID-19 infection and 70 healthy individuals with similar clinical characteristics. At four and twelve months we measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) malondialdehyde (MDA), an oxidative stress marker.

Results
At four months, COVID-19 patients displayed higher values of PBR5–25 compared to control group (p&lt;0.001) which increased at twelve months (p&lt;0.001). FMD, PWV and cSBP values were similar between 4 and 12 months (p&gt;0.05 for all the comparisons) and higher than those in controls (p&lt;0.001, p=0.057, p=0.003 respectively). At four months, COVID-19 patients presented impaired CFR and LVGLS values which were improved at twelve months (p=0.002, p=0.069 respectively), though remained impaired compared to controls (p=0.003 for all the comparisons). At four months, COVID-19 patients had impaired RVGLS values which were significantly improved at twelve months (p=0.001,) and showed no statistically significant difference compared to controls (p&gt;0.05). COVID-19 patients at four months display higher myocardial wasted work and decreased myocardial efficiency compared to controls (p=0.01, p=0.006 respectively). There was a modest improvement in GWW and GWE at twelve months,(p=0.043, p=0.001, respectively); however, these markers remained impaired compared to controls (p&gt;0.05). At four months, MDA was higher in COVID-19 patients compared to control group and significantly decreased at twelve months (p&lt;0.001); however, these values remain higher than in controls (p=0.002) (Table 1).

Conclusions
SARS-CoV-2 causes endothelial and cardiovascular dysfunction which are partially restored at twelve months after the infection.

Funding Acknowledgement
Type of funding sources: None.