Pregnant patients with severe COVID-19 more frequently require intensive care and may receive antiviral therapy such as remdesivir. Because antivirals can have tissue-specific toxicities, this study investigated whether intravenous remdesivir affects the uterine endometrium and markers of endometrial receptivity in a pregnant mouse model.
Thirty female Naval Medical Research Institute (NMRI) mice were used and allocated into five groups. The control group received no treatment. The sham group received remdesivir solvent, dimethyl sulfoxide (DMSO). Three remdesivir dose groups received intravenous remdesivir at 2 mg, 4 mg, or 8 mg. Treatment continued for 10 days prior to mating.
After the treatment period the mice were mated; the presence of a vaginal plug was counted as gestational day 1. On gestational day 4.5 the animals underwent assessment for endometrial outcomes. The timeline was designed to evaluate early implantation-window effects on uterine tissue and circulating hormones.
Remdesivir was given intravenously at the three specified dose levels (2 mg, 4 mg, 8 mg). The sham group received the vehicle (dimethyl sulfoxide). The duration of exposure was 10 days, with mating performed after completion of treatment. The abstract does not provide dosing frequency or exact administration schedule beyond total dose per group and route.
Primary measured outcomes reported in the abstract were:
All outcomes were assessed on gestational day 4.5. The abstract reports some findings for estradiol and IL-6 but does not provide detailed numeric results or full reporting for interleukin-1β.
Remdesivir exposure was associated with a dose-dependent decrease in serum estradiol levels. The study also found a dose-dependent reduction in endometrial IL-6 expression following remdesivir treatment. In addition, remdesivir-treated mice exhibited a reduced number of uterine pinopodes compared with control and sham groups.
The authors reported that these changes reached statistical significance where indicated (p<0.05) for the reported endpoints. Exact quantitative values for estradiol concentrations, IL-6 expression levels, and pinopode counts are not provided in the abstract.
Histological analysis of endometrial tissue demonstrated evidence of tissue injury in remdesivir-treated animals. The abstract states this injury and the reduction in pinopodes and IL-6 expression were statistically significant (p<0.05). Details on the specific histologic features observed (for example, epithelial disruption, stromal changes, inflammation severity) and grading criteria are not described in the abstract and would require the full text for clarification.
The authors conclude that in this pregnant mouse model, intravenous remdesivir reduced serum estradiol levels, decreased the number of endometrial pinopodes, and suppressed endometrial interleukin-6 expression. They suggest these effects indicate potential adverse impacts on the endometrium that could compromise implantation.
However, the authors note that direct functional validation is required. In other words, the observed changes in markers and histology do not by themselves confirm impaired implantation or altered pregnancy outcomes; studies measuring implantation rates or subsequent pregnancy progression are necessary to establish functional reproductive toxicity.
The abstract does not provide detailed numerical results (exact estradiol concentrations, IL-6 fold-changes, pinopode counts), dosing frequency, or administration schedule beyond total doses and route. Results for interleukin-1β expression were mentioned as an outcome but specific findings are not reported in the abstract. Likewise, specific histologic descriptors and grading methods are not provided.
Functional endpoints such as implantation success, fetal outcomes, or longer-term reproductive assessment were not reported and the authors explicitly state that direct functional validation remains necessary. For full methodological details, statistical analyses, and comprehensive results, consult the full manuscript.
These preclinical findings are presented in the context of remdesivir use for COVID-19 in pregnant patients. While the study raises a potential safety signal regarding endometrial receptivity in mice, translation to humans requires caution: species differences, dose equivalence, administration schedules, and comprehensive reproductive outcome data must be considered. The abstract serves to highlight an area for further investigation rather than to provide definitive clinical guidance.