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

Nishijima, Yoshinori; Hader, Shelby; Zhang, David; Gutterman, David; Beyer, Andreas

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 H(2)O). 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 H(2)O: 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.