Реферат
Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence: E0300201.).
Реферат
Background: The mortality rate of coronavirus disease 2019 (COVID-19) in patients with rheumatic and musculoskeletal disease (RMD) is as high as approximately 10% [1]. Therefore, vaccination promotion is a critical issue. However, there are few reports on the psychological aspects of patient vaccine acceptance. Objectives: To investigate the intention of patients with RMD to receive the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine and explore the psychological factors related to vaccine acceptance. Methods: We conducted a questionnaire-based survey of 406 outpatients with RMD at Shiga General Hospital from July to October 2021. The questionnaire included the following sections: (1) vaccination status;(2) expectation of susceptibility to severe COVID-19;(3) expectation of vaccine efficacy;and (4) anxiety about the vaccine, which included concerns on I) the diminishing effect of the vaccine due to current treatment and II) the influence of vaccination on: i) primary disease status, ii) treatment, and iii) adverse reaction. Results: There were 305 vaccinated and 101 unvaccinated individuals. Unvacci-nated individuals were classifed into the acceptance group (n=60) and hesitancy group (n=41) according to their vaccination status (Figure 1). We compared the backgrounds and awareness of the patients on vaccination between the two groups. Univariate analysis did not show any difference in the backgrounds. The expectation of susceptibility to severe COVID-19 was similar in both groups. There were also no signifcant differences in the vaccine-related anxiety levels. However, the expectation of vaccine efficacy was higher in the acceptance group and signifcantly influenced vaccination intention as revealed by multivariate analyses (Table 1). Conclusion: The perception of vaccine efficacy is strongly correlated with vaccine acceptance. In order to promote vaccination in patients with RMDs, this study suggests that emphasizing the efficacy of the vaccine may be more effective than alleviating anxiety about the adverse effects of the vaccine.