Maternal third dose of BNT162b2 mRNA vaccine and risk of infant COVID-19 hospitalization.

Infants are at a higher risk of Coronavirus Disease 2019 (COVID-19)-related hospitalizations compared to older children. In this study, we investigated the effect of the recommended third maternal dose of BNT162b2 COVID-19 vaccine during pregnancy on rates of infant COVID-19-related hospitalizations. We conducted a nationwide cohort study of all live-born infants delivered in Israel between 24 August 2021 and 15 March 2022 to estimate the effectiveness of the third booster dose versus the second dose against infant COVID-19-related hospitalizations. Data were analyzed for the overall study period, and the Delta and Omicron periods were analyzed separately. Cox proportional hazard regression models estimated hazard ratios and 95% confidence intervals (CIs) for infant hospitalizations according to maternal vaccination status at delivery. Among 48,868 live-born infants included in the analysis, rates of COVID-19 hospitalization were 0.4%, 0.6% and 0.7% in the third-dose, second-dose and unvaccinated groups, respectively. Compared to the second dose, the third dose was associated with reduced infant hospitalization with estimated effectiveness of 53% (95% CI: 36-65%). Greater protection was associated with a shorter interval between vaccination and delivery. A third maternal dose during pregnancy reduced the risk of infant hospitalization for COVID-19 during the first 4 months of life, supporting clinical and public health guidance for maternal booster vaccination to prevent infant COVID-19 hospitalization.

Boosting Dose of Pfizer-BioNtech mRNA Vaccine Against SARS-CoV-2 Does Not Affect Reproductive Outcomes in In-Vitro Fertilization Patients: A Cohort Study.

Background: Since the introduction of anti-COVID-19 mRNA vaccination, few studies have shown that reproductive outcomes in artificial reproductive technology (ART) treatments are not impaired, after receiving the two-dose regimen. Our aim was to investigate whether a boosting dose of the Pfizer-BioNtech mRNA vaccine affects reproductive outcomes in ART patients. Materials and Methods: This is a prospective observational study, including 157 consecutive in-vitro fertilization (IVF) cycles between October 1, 2021, and November 24, 2021, in a single university affiliated IVF unit. We included female patients going through an ART procedure and male partners in cases of utilization of a fresh sperm sample. The study population was divided into four groups according to exposure status: vaccinated and boosted patients (three total doses of Pfizer-BioNtech mRNA vaccine), patients who were vaccinated without the booster dose (one or two vaccine doses), PCR-confirmed convalescent COVID-19 patients, and unvaccinated nonconvalescent patients. Main outcome measure was clinical pregnancy rate. Results: In total, 99 (63%) female patients were vaccinated three times, 24 (15.3%) were vaccinated without the booster dose, 21 (13.4%) were convalescent, and 13 were (8.3%) unexposed. Although age differed between study groups, vaccination exposure status did not affect treatment outcome: clinical pregnancy rates, maximal estradiol levels, and number of oocytes retrieved did not differ significantly between study groups (p = 0.78, 0.50, and 0.97, respectively). Vaccinated patients who received a boosting vaccine dose were treated within 43.3 ± 30.9 days after receiving the last dose, whereas vaccinated, nonboosted, or convalescent patients were treated 168.7 ± 53 and 209.6 ± 85.1 days after their last exposure, respectively. We stratified the male cohort according to boosting vaccine dose status. Sperm concentration and motility did not differ significantly after boosting (p = 0.49 and 0.49, respectively). Conclusions: Our results provide further reassurance that IVF outcomes are not affected by the anti-SARS-CoV-2 Pfizer-BioNtech mRNA vaccine, in particular the three-dose regimen.

Boosting maternal and neonatal anti-SARS-CoV-2 humoral immunity using a third mRNA vaccine dose.

BACKGROUND: To minimize COVID-19 pandemic burden and spread, 3-dose vaccination campaigns commenced worldwide. Since patients who are pregnant are at increased risk for severe disease, they were recently included in that policy, despite the lack of available evidence regarding the impact of a third boosting dose during pregnancy, underscoring the urgent need for relevant data. We aimed to characterize the effect of the third boosting dose of mRNA Pfizer BNT162b2 vaccine in pregnancy. METHODS: We performed a prospective cohort study of anti-SARS-CoV-2 antibody titers (n = 213) upon delivery in maternal and cord blood of naive fully vaccinated parturients who received a third dose (n = 86) as compared with 2-dose recipients (n = 127). RESULTS: We found a robust surge in maternal and cord blood levels of anti-SARS-CoV-2 titers at the time of delivery, when comparing pregnancies in which the mother received a third boosting dose with 2-dose recipients. The effect of the third boosting dose remained significant when controlling for the trimester of last exposure, suggesting additive immunity extends beyond that obtained after the second dose. Milder side effects were reported following the third dose, as compared with the second vaccine dose, among the fully vaccinated group. CONCLUSION: The third boosting dose of mRNA Pfizer BNT162b2 vaccine augmented maternal and neonatal immunity with mild side effects. These data provide evidence to bolster clinical and public health guidance, reassure patients, and increase vaccine uptake among patients who are pregnant. FUNDING: Israel Science Foundation KillCorona grant 3777/19; Research grant from the "Ofek" Program of the Hadassah Medical Center.

Effectiveness of a third BNT162b2 mRNA COVID-19 vaccination during pregnancy: a national observational study in Israel.

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses' vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83-96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26-99%), and 48% (95% CI 37-57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes.

Mild COVID-19 Was Not Associated with Impaired IVF Outcomes or Early Pregnancy Loss in IVF Patients.

Data collection regarding the effects of COVID-19 on reproduction is ongoing. This study examined the effect of COVID-19 on IVF cycle parameters and early pregnancy outcomes. It included two arms: the first compared non-exposed cycles to post-SARS-CoV-2 IVF cycles. Sperm parameters were also compared. The second, prospective arm compared pregnancy outcomes among IVF patients who contracted COVID-19 during early pregnancy to those who did not. None of the patients were vaccinated against SARS-CoV-2. The first arm included 60 treatment cycles of women with confirmed COVID-19, compared to 60 non-exposed cycles (either the same patient before exposure or matched non-exposed patients). The outcomes of the treatment cycles did not differ significantly between exposed and non-exposed groups, including number of oocytes, endometrial thickness, fertilization rate and number of top-quality embryos. In 11 cycles, the male partner had also recently recovered: sperm concentration was lower post-exposure: 6.27 million/mL vs. 16.5 pre-exposure (p = 0.008). In 189 patients with IVF-achieved pregnancies, pregnancy loss and hospital admissions did not differ between exposed and non-exposed groups. IVF treatment outcomes and the rate of early pregnancy loss appears to be unaffected by SARS-CoV-2 disease, despite a minor decline in sperm concentration among recent recoverees.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose.

BACKGROUND: Post-COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti-SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients. STUDY DESIGN: Serum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction-confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction-confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction-confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti-SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes. RESULTS: A total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy. CONCLUSION: Postinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine.

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.