The coronavirus disease 2019 (COVID‐19) is a highly infectious disease caused by SARS‐CoV‐2. Since its first report in December 2019, COVID‐19 has evolved into a global pandemic causing massive healthcare and socioeconomic challenges. HLA system is critical in mediating anti‐viral immunity and recent studies have suggested preferential involvement of HLA‐B in COVID‐19 susceptibility. Here, by investigating the HLA‐B genotypes in 190 unrelated Chinese patients with confirmed COVID‐19, we identified a significant positive association between the B22 serotype and SARS‐CoV‐2 infection (p = 0.002, Bonferroni‐corrected p = 0.032). Notably, the B22 serotype has been consistently linked to susceptibility to other viral infections. These data not only shed new insights into SARS‐CoV‐2 pathogenesis and vaccine development but also guide better infection prevention/control.

17beta-Estradiol and progesterone were found to relax various vascular beds through multiple mechanisms. However, the exact ionic mechanisms underlying the acute relaxant responses to both hormones are incompletely understood. This study was aimed to examine the possible role of K channel activation in the relaxation induced by both hormones in isolated rat mesenteric artery rings. Isometric tension of each ring was measured with Grass force displacement transducers. In rat endothelium-denuded rings preconstricted by 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F (U46619), the relaxation induced by 17beta-estradiol was partially inhibited by tetrapentylammonium, 4-aminopyridine, iberiotoxin, BaCl, and tertiapin-Q but not by tetraethylammonium, charybdotoxin, apamin, or glibenclamide. In contrast, these putative K channel blockers, except for glibenclamide, did not affect the relaxant response to progesterone. In 4 x 10(-2) K -preconstricted rings, the K channel blockers lost their inhibitory effects on 17beta-estradiol-induced relaxation. Endothelium did not seem to be involved in the effects of K channel blockers on 17beta-estradiol-mediated relaxation. Nifedipine-induced relaxation was not inhibited but was instead enhanced by tetrapentylammonium, iberiotoxin, 4-aminopyridine, and BaCl2. The above results indicate that in rat mesenteric artery rings, nonselective activation of K channels contributes partially to the relaxation induced by 17beta-estradiol. These K channels involved in the estrogen response appeared to be sensitive to inhibition by K(Ca), K, and K(IR) channel blockers. Lack of effect of K channel blockers on progesterone-induced relaxation suggests that these K channels play little or no role. The present findings provide pharmacological evidence for an additional mechanism contributing to acute vasorelaxation induced by 17beta-estradiol.

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