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

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.

Graphical abstract

Fig. 1

The impact of acute COVID-19 on endothelial function. A) Individuals hospitalized for COVID-19 had significantly worsened endothelial function as estimated by flow-mediated dilation (FMD) of brachial artery compared to a propensity score-matched control group. A1) Admission to the intensive care unit (ICU) resulted in severely decreased FMD values compared to patients hospitalized at the medical ward. A2) Lower FMD was detected in patients who died compared to COVID-19 patients who were discharged from the hospital.

Fig. 2

Follow-up evaluation of endothelial function in COVID-19 survivors. A significant improvement was observed over the follow-up duration (1 month and 6 months) in flow-mediated dilation (FMD) in patients initially hospitalized for COVID-19.

Fig. 3

Intermediate and long-term effect of COVID-19 on endothelial function. A) Follow-up evaluation of endothelial function at 1 and 6 months after hospitalization for COVID-19 demonstrated significantly impaired flow-mediated dilation (FMD) when compared to propensity score-matched controls. B) Patients hospitalized in an intensive care unit (ICU) had remarkably worse FMD compared to individuals hospitalized in a non-ICU setting at 1 and 6 months after the index admission.