SARS-CoV-2 variants show temperature-dependent enhancedpolymerase activity in the upper respiratory tract and high transmissibility

With the convergent global emergence of SARS-CoV-2 variants of concern (VOC), a precise comparison study of viral fitness and transmission characteristics is necessary for the prediction of dominant VOCs and the development of suitable countermeasures. While airway temperature plays important roles in the fitness and transmissibility of respiratory tract viruses, it has not been well studied with SARS-CoV-2. Here we demonstrate that natural temperature differences between the upper (33{degrees}C) and lower (37{degrees}C) respiratory tract have profound effects on SARS-CoV-2 replication and transmission. Specifically, SARS-COV-2 variants containing the P323L or P323L/G671S mutation in the NSP12 RNA-dependent RNA polymerase (RdRp) exhibited enhanced RdRp enzymatic activity at 33{degrees}C compared to 37{degrees}C and high transmissibility in ferrets. MicroScale Thermophoresis demonstrated that the NSP12 P323L or P323L/G671S mutation stabilized the NSP12-NSP7-NSP8 complex interaction. Furthermore, reverse genetics-derived SARS-CoV-2 variants containing the NSP12 P323L or P323L/G671S mutation displayed enhanced replication at 33{degrees}C, and high transmission in ferrets. This suggests that the evolutionarily forced NSP12 P323L and P323L/G671S mutations of recent SARS-CoV-2 VOC strains are associated with increases of the RdRp complex stability and enzymatic activity, promoting the high transmissibility.

Comparison of Midazolam versus Midazolam/Meperidine during Colonoscopy in a Prospective, Randomized, Double-Blind Study / 대한소화기학회지

BACKGROUND/AIMS: Colonoscopy is a painful procedure. Therefore conscious sedation is often used. However, the value of adding analgesics to sedatives has not been well evaluated. METHODS: The double blind, randomized controlled trial was carried out to compare patients' and endoscopist' assessments in both groups of patients: MP (Midazolam/Placebo) group (n=49) received midazolam plus placebo and MM (Midazolam/Meperidine) group (n=51) received midazolam plus meperidine. RESULTS: There was no significant difference of baseline characteristics except previous operation history. There were no significant difference of grade of tolerance, pain and willingness to another colonoscopy between the two groups. In endoscopist' satisfaction, the degree of difficulty was higher in MP group than in MM group (39.0 vs. 31.7,p<0.05). After the colonoscopy, systolic blood pressure, oxygen saturation, and pulse rate were significantly decreased (p<0.05) in both groups. However, there was no difference in the degree of decrease between the two groups. The incidence of adverse effect was not different in the two groups. However, one case of orthostatic hypotension with presyncope was noted in MM group. CONCLUSIONS: Adding meperidine to the midazolam before the colonoscopy does not seem to bring more beneficial effect to patients, whereas endoscopist favored the use of both medications.