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INTRODUCTION: Coronavirus disease 2019 (COVID-19) still has a high mortality rate when it is severe. Regdanvimab (CT-P59), a neutralizing monoclonal antibody that has been proven effective against mild to moderate COVID-19, may be effective against severe COVID-19. This study was conducted to determine the effectiveness of the combined use of remdesivir and regdanvimab in patients with severe COVID-19. METHODS: From March to early May 2021, 124 patients with severe COVID-19 were admitted to Ulsan University Hospital (Ulsan, Korea) and received oxygen therapy and remdesivir. Among them, 25 were also administered regdanvimab before remdesivir. We retrospectively compared the clinical outcomes between the remdesivir alone group [n = 99 (79.8%)] and the regdanvimab/remdesivir group [n = 25 (20.2%)]. RESULTS: The oxygen-free days on day 28 (primary outcome) were significantly higher in the regdanvimab/remdesivir group [mean ± SD: 19.36 ± 7.87 vs. 22.72 ± 3.66, p = 0.003]. The oxygen-free days was also independently associated with use of regdanvimab in the multivariate analysis, after adjusting for initial pulse oximetric saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio (severity index). Further, in the regdanvimab/remdesivir group, the lowest SpO2/FiO2 ratio during treatment was significantly higher (mean ± SD: 237.05 ± 89.68 vs. 295.63 ± 72.74, p = 0.003), and the Kaplan-Meier estimates of oxygen supplementation days in surviving patients (on day 28) were significantly shorter [mean ± SD: 8.24 ± 7.43 vs. 5.28 ± 3.66, p = 0.024]. CONCLUSIONS: In patients with severe COVID-19, clinical outcomes can be improved by administering regdanvimab, in addition to remdesivir.
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In this in vitro study we examined the effects of diazepam on a phenylephrine-induced contraction in rat aorta and determined the associated cellular mechanism focusing on the endothelium-derived vasodilators. The concentration-response curves for phenylephrine and potassium chloride were generated in the presence or absence of diazepam. Phenylephrine concentration-response curves were generated from the endothelium-intact rings pretreated independently with N(W)-nitro-L-arginine methyl ester, PK 11195, tetraethylammonium, and indomethacin in the presence or absence of diazepam. Diazepam (7 x 10(-7) M) attenuated the phenylephrine-induced contraction in the endothelium-intact rings, whereas a large dose (5 x 10(-6) M) of diazepam attenuated the phenylephrine-induced contraction in the aortic rings with or without the endothelium. A pretreatment with the N(W)-nitro-L-arginine methyl ester completely abolished the diazepam (7 x 10(-7) M)-induced attenuation of the phenylephrine concentration-response curve, as well as the diazepam (5 x 10(-6) M)-induced attenuation of the maximal contractile response to phenylephrine. The N(W)-nitro-L-arginine methyl ester (10(-4) M)-induced contraction was enhanced in the rings pretreated with diazepam (5 x 10(-6) M). These results indicate that a supraclinical concentration of diazepam attenuates phenylephrine-induced contraction by increasing endothelial nitric oxide activity and directly affecting vascular smooth muscle.
