Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study

Evangelos Oikonomou; Nektarios Souvaliotis; Stamatios Lampsas; Gerasimos Siasos; Garyphallia Poulakou; Panagiotis Theofilis; Theodore G Papaioannou; Anna-Bettina Haidich; Georgia Tsaousi; Vasileios Ntousopoulos; Vissaria Sakka; Georgios Charalambous; Vasiliki Rapti; Sylvia Raftopoulou; Konstantinos Syrigos; Costas Tsioufis; Dimitris Tousoulis; Manolis Vavuranakis

doi:10.1016/j.vph.2022.106975

Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study

Vascul Pharmacol. 2022 Jun:144:106975. doi: 10.1016/j.vph.2022.106975. Epub 2022 Mar 3.

Authors

Evangelos Oikonomou¹, Nektarios Souvaliotis², Stamatios Lampsas², Gerasimos Siasos³, Garyphallia Poulakou⁴, Panagiotis Theofilis⁵, Theodore G Papaioannou⁵, Anna-Bettina Haidich⁶, Georgia Tsaousi⁷, Vasileios Ntousopoulos⁴, Vissaria Sakka⁴, Georgios Charalambous⁸, Vasiliki Rapti⁴, Sylvia Raftopoulou⁹, Konstantinos Syrigos⁴, Costas Tsioufis⁵, Dimitris Tousoulis⁵, Manolis Vavuranakis²

Affiliations

¹ 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece; 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece. Electronic address: boikono@med.uoa.gr.
² 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece.
³ 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece; 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece.
⁴ 3rd Department of Medicine, Medical School, Sotiria Chest Disease Hospital, National and Kapodistrian University of Athens, Athens, Greece.
⁵ 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece.
⁶ Department of Hygiene, Social-Preventive Medicine and Medical Statistics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁷ Department of Anesthesiology and ICU, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
⁸ Emergency Department, "Hippokration" General Hospital, Athens, Greece.
⁹ Intensive Care Unit, Sotiria Chest Disease Hospital, Athens, Greece.

Abstract

Background: Coronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function.

Methods: In this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages.

Results: Seventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge.

Conclusion: COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.

Keywords: COVID-19; Endothelial function; Endothelium; Flow-mediated dilation.

MeSH terms

COVID-19* / complications
Cohort Studies
Endothelium, Vascular
Humans
Post-Acute COVID-19 Syndrome
Prospective Studies
Vasodilation / physiology