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.

Postpartum Depression in COVID-19 Days: Longitudinal Study of Risk and Protective Factors.

COVID-19 impacted the childbirth experience and increased the rates of postpartum depression (PPD). We assessed the longitudinal effects of the pandemic on the rates of PPD and evaluated the PPD causes and symptoms among women who delivered during the first COVID-19 quarantine in Israel. The participants completed online questionnaires 3 (T1) and 6 months (T2) following delivery. We used the 'COVID-19 exposure' questionnaire, while PPD symptoms, situational anxiety, and social support were evaluated with the EPDS, STAI, and MSPSS questionnaires. The mean EPDS scores increased between T1 and T2 (6.31 ± 5.6 vs. 6.92 ± 5.9, mean difference -0.64 ± 4.59 (95% CI (-1.21)-(-0.06)); t (244) = -2.17, p = 0.031), and the STAI scores decreased (45.35 ± 16.4 vs. 41.47 ± 14.0, t(234) = 4.39, p = 0.000). Despite the exposure to an increased number of COVID-19 events (3.63 ± 1.8 vs. (6.34 ± 2.3)), the impact of exposure decreased between T1 and T2 (8.91 ± 4.6 vs. 7.47 ± 4.1), p < 0.001). In the MSPSS, significant differences were noted on the family scale between the T1 (6.10 ± 1.3) and T2 (5.91 ± 1.4) scores; t (216) = 2.68, p = 0.0008. A regression analysis showed three statistically significant variables that correlated with increased EPDS scores: the MSPSS family subscale (F (1212.00) = 4.308, p = 0.039), the STAI scores (F (1212.00) = 31.988, p = 0.000), and the impact of exposure to COVID-19 (F (1212.00) = 5.038, p = 0.026). The rates of PPD increased for women who delivered during the first COVID-19 lockdown. Further research is warranted to help reduce PPD among these women.

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.

Postpartum Depression in COVID-19 Days: Longitudinal Study of Risk and Protective Factors

COVID-19 impacted the childbirth experience and increased the rates of postpartum depression (PPD). We assessed the longitudinal effects of the pandemic on the rates of PPD and evaluated the PPD causes and symptoms among women who delivered during the first COVID-19 quarantine in Israel. The participants completed online questionnaires 3 (T1) and 6 months (T2) following delivery. We used the 'COVID-19 exposure' questionnaire, while PPD symptoms, situational anxiety, and social support were evaluated with the EPDS, STAI, and MSPSS questionnaires. The mean EPDS scores increased between T1 and T2 (6.31 ±5.6 vs. 6.92 ±5.9, mean difference −0.64 ±4.59 (95% CI (−1.21)–(−0.06));t (244) = −2.17, p = 0.031), and the STAI scores decreased (45.35 ±16.4 vs. 41.47 ±14.0, t(234) = 4.39, p = 0.000). Despite the exposure to an increased number of COVID-19 events (3.63 ±1.8 vs. (6.34 ±2.3)), the impact of exposure decreased between T1 and T2 (8.91 ±4.6 vs. 7.47 ±4.1), p < 0.001). In the MSPSS, significant differences were noted on the family scale between the T1 (6.10 ±1.3) and T2 (5.91 ±1.4) scores;t (216) = 2.68, p = 0.0008. A regression analysis showed three statistically significant variables that correlated with increased EPDS scores: the MSPSS family subscale (F (1212.00) = 4.308, p = 0.039), the STAI scores (F (1212.00) = 31.988, p = 0.000), and the impact of exposure to COVID-19 (F (1212.00) = 5.038, p = 0.026). The rates of PPD increased for women who delivered during the first COVID-19 lockdown. Further research is warranted to help reduce PPD among these women.

Evaluation of SARS-CoV-2 in the Vaginal Secretions of Women with COVID-19: A Prospective Study.

OBJECTIVE: We aimed to investigate the likelihood of vaginal colonization with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pregnant and non-pregnant women with Coronavrus Disease 2019 (COVID-19). MATERIALS AND METHODS: Vaginal swabs were taken from women diagnosed with mild to moderately acute SARS-CoV-2 infection, at Wolfson Medical Center, Israel, from March 2020 through October 2020. COVID-19 was diagnosed by real-time polymerase chain reaction (RT-PCR) performed on nasopharyngeal swabs. Vaginal swabs were tested for the presence of SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In total, 51 women diagnosed with COVID-19 were included in the study. Of the 51 women with COVID-19 enrolled in this study, 16 (31.4%) were pregnant at enrollment and 35 (68.6%) were non-pregnant. Mean age was 43.5 ± 15.3 years (range 21-74 years). Compared to the non-pregnant group, the pregnant group was characterized by a higher white blood cell and absolute neutrophil count (p = 0.02 and p = 0.027, respectively). The non-pregnant patients were more likely to have chronic diseases (p = 0.035) and to be hospitalized (p < 0.001). Only one patient (1.9%) aged 60 years tested positive for SARS-CoV-2 in vaginal secretions. Mean gestational age at the diagnosis of COVID-19 of the pregnant group was 32.3 ± 7.8 weeks. Thirteen patients delivered during the study period; all delivered at term without obstetric complications and all neonates were healthy. CONCLUSIONS: Detection of SARS-CoV-2 in the vaginal secretions of patients diagnosed with COVID-19 is rare. Vaginal colonization may occur during the viremia phase of the disease, although infectivity from vaginal colonization needs to be proven.

The use of personal protective equipment as an independent factor for developing depressive and post-traumatic stress symptoms in the postpartum period.

BACKGROUND: New recommendations regarding the use of personal protective equipment (PPE) during delivery have changed the maternal birth experience. In this study, we investigated the mental perceived impact of PPE use during delivery on the development of maternal postpartum depression (PPD) and post-traumatic stress symptoms (PTSS). METHODS: This was a multicenter, retrospective cohort study concerning women who delivered during the COVID-19 pandemic first lockdown period in Israel. Postpartum women were approached and asked to complete a comprehensive online questionnaire. Impact of PPE was graded on a scale of 1-5, and Impact of PPE ≥4 was considered high. PPD and PTSS were assessed using the EPDS and City BiTS questionnaires. RESULTS: Of 421 parturients, 36 (9%) reported high Impact of PPE. Parturients with high Impact of PPE had significantly higher PPD and PTSS scores)EPDS 8.4 ± 5.8 vs. 5.7 ± 5.3; City BiTS 9.2 ± 10.3 vs. 5.8 ± 7.8, p < 0.05 for both). Following adjustment for socio-demographic and delivery confounders and fear of COVID-19 (using Fear of COVID19 scale), Impact of PPE remained positively correlated with PPD symptoms (ß = 0.103, 95% confidence intervals [CI] 0.029-1.006, p = 0.038). CONCLUSION: When examining the risk factors for developing postpartum PTSS-experiences during labor and PPE were found to be significant variables. As the use of PPE is crucial in this era of COVID-19 pandemic in order to protect both parturients and caregivers, creative measures should be taken in order to overcome the communication gap it poses.

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.