Association Between Time Interval from COVID-19 Vaccination to In Vitro Fertilization and Pregnancy Rate After Fresh Embryo Transfer.

Importance: There is a lack of information regarding the need to postpone conception after COVID-19 vaccination. Objective: To investigate the time interval between the first dose of inactivated COVID-19 vaccine and in vitro fertilization (IVF) treatment as well as the rate of pregnancy after a fresh embryo transfer. Design, Setting, and Participants: This cohort study was conducted at a single public IVF center in China. Female patients aged 20 to 47 years and undergoing IVF treatment were consecutively registered from May 1 to December 22, 2021, with follow-up until March 31, 2022. Patients with SARS-CoV-2 infection before or during IVF treatment and those who underwent 2 or more IVF treatments, received the noninactivated or unknown COVID-19 vaccine, or did not have a fresh embryo transfer were excluded from this study. Exposures: The vaccinated group (subdivided into 4 subgroups of time interval from first vaccination to fertilization treatment: ≤30 days, 31-60 days, 61-90 days, and ≥91 days) and nonvaccinated group. Main Outcomes and Measures: Risk ratios (RRs) for the association between the time interval and ongoing pregnancy (pregnancy continued at least 12 weeks). Results: A total of 3052 female patients (mean [SD] age, 31.45 [3.96] years) undergoing IVF treatment were analyzed in this study. There were 667 vaccinated patients receiving IVF (35 were vaccinated ≤30 days, 58 were vaccinated 31-60 days, 105 were vaccinated 61-90 days, and 469 were vaccinated ≥91 days before fertilization treatment), and 2385 unvaccinated patients receiving treatment. The ovarian stimulation and laboratory parameters were similar among all groups. Ongoing pregnancy was significantly lower in the 30 days or less subgroup (34.3% [12 of 35]; adjusted RR [aRR], 0.61; 95% CI, 0.33-0.91) and the 31 to 60 days' subgroup (36.2% [21 of 58]; aRR, 0.63; 95% CI, 0.42-0.85). A slightly but not statistically lower rate was found in the 61 to 90 days' subgroup, and no reduced risk for ongoing pregnancy in the 91 days or more subgroup was observed (56.3% [264 of 469]; aRR, 0.96; 95% CI, 0.88-1.04) compared with the unvaccinated group (60.3% [1439 of 2385], as reference). Conclusions and Relevance: Findings of this study suggest that receipt of the first inactivated COVID-19 vaccine dose 60 days or less before fertilization treatment is associated with a reduced rate of pregnancy. In patients undergoing IVF treatment with a fresh embryo transfer, the procedure may need to be delayed until at least 61 days after COVID-19 vaccination.

Dynamics of binding ability prediction between spike protein and human ACE2 reveals the adaptive strategy of SARS-CoV-2 in humans.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. High adaptive plasticity on the spike protein of SASR-CoV-2 enables it to transmit across different host species. In the present study, we collected 2092 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny. We also analyzed the polymorphic interaction between spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 suggests that SARS-CoV-2 is probably originated from a recombination event on the spike protein between a bat coronavirus and a pangolin coronavirus that endows it humans infectivity. Compared with other regions in the S gene of SARS-CoV-2, the direct-binding sites of the receptor-binding domain (RBD) is more conserved. We focused on 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 and simulated their differential stability and binding affinity to hACE2 (S19-D615). The results indicate no preference for SARS-CoV-2 infectivity on people of different ethnic groups. The variants in the spike protein of SARS-CoV-2 may also be a good indicator demonstrating the transmission route of SARS-CoV-2 from its natural reservoir to human hosts.

A Thermostable mRNA Vaccine against COVID-19.

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.