Prolonged Endothelial Dysfunction in Human Arterioles with SARS-CoV-2

ABSTRACT

The vascular endothelium plays a crucial role to regulate vascular tone. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is known to cause vascular endothelial dysfunction. However, the long-term effects of SARS-CoV-2 in resistance vessels remains unknown. This study is designed to test whether endothelium-dependent vasodilation in human arterioles remains impaired after clearance of SARS-CoV-2 virus. Fresh human adipose tissues were obtained as discarded surgical specimens from control subjects (n=15, no SARS-CoV-2 exposure, 46.7±4 years) and previously SARS-CoV-2 positive subjects (PSPSs n=8, 35.8±3.8 years). Among PSPSs, the time between positive and negative SARS-CoV-2 test results was ≤3 months (n=6) or 8 months (n=2). Isolated arterioles (100-200 µm) were cannulated under 60 mmHg and examined for diameter changes to acetylcholine (ACh;10?9 to 10?5 M) and sodium nitroprusside (SNP 10?9 to 10?4 M) using videomicroscopy. Flow-mediated dilation (FMD) was recorded at steady-state during graded increases in intraluminal pressure gradients (5-100 cm H2O). Dilation to ACh and FMD in arterioles from PSPSs was significantly reduced (ACh max. dilation at 10?5 M 60±6% vs. 92.8±3.9% in control, n=7-8, P<0.001;FMD max. dilation at 100 cm H2O 39.9±5.7% vs. 85.8±1.8% in control, n=6-8, P<0.001, Fig.1) while endothelial-independent dilation in response to SNP was not different between groups (max. dilation at 10-4 M 86.6±2.7% vs. 92.3±2.1% in control, n=5). To compare time-dependent effects of previous SARS-CoV-2 infection, we compared max. dilator capacity vs. time after exposure (Fig. 2). At ≤3 months post exposure, FMD was significantly impaired (% max. dilation 26.7±7.4, n=5) whereas at 8 months endothelial function began to normalize (% max. dilation 41.8±17.6, n=2). In conclusion, we observed significantly reduced endothelial-dependent dilation months after exposed to SARS-CoV-2. Our data suggests SARS-CoV-2 may cause long-term endothelial dysfunction in human arterioles.