COVID-19 mRNA vaccination status and concerns among pregnant women in Japan: a multicenter questionnaire survey.

BACKGROUND: mRNA vaccination is an effective, safe, and widespread strategy for protecting pregnant women against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, information on factors such as perinatal outcomes, safety, and coverage of mRNA vaccinations among pregnant women is limited in Japan. Therefore, this study aimed to investigate the perinatal outcomes, coverage, adverse effects, and short-term safety of mRNA vaccination as well as vaccine hesitancy among pregnant women. METHODS: We conducted a multicenter online survey of postpartum women who delivered their offspring at 15 institutions around Tokyo from October 2021 to March 2022. Postpartum women were divided into vaccinated and unvaccinated groups. Perinatal outcomes, COVID-19 prevalence, and disease severity were compared between the two groups. Adverse reactions in the vaccinated group and the reasons for being unvaccinated were also investigated retrospectively. RESULTS: A total of 1,051 eligible postpartum women were included. Of these, 834 (79.4%) had received an mRNA vaccine, while 217 (20.6%) had not, mainly due to concerns about the effect of vaccination on the fetus. Vaccination did not increase the incidence of adverse perinatal outcomes, including fetal morphological abnormalities. The vaccinated group demonstrated low COVID-19 morbidity and severity. In the vaccinated group, the preterm birth rate, cesarean section rate, and COVID-19 incidence were 7.2%, 33.2%, and 3.3%, respectively, compared with the 13.7%, 42.2%, and 7.8% in the unvaccinated group, respectively. Almost no serious adverse reactions were associated with vaccination. CONCLUSIONS: mRNA vaccines did not demonstrate any adverse effects pertaining to short-term perinatal outcomes and might have prevented SARS-CoV-2 infection or reduced COVID-19 severity. Concerns regarding the safety of the vaccine in relation to the fetus and the mother were the main reasons that prevented pregnant women from being vaccinated. To resolve concerns, it is necessary to conduct further research to confirm not only the short-term safety but also the long-term safety of mRNA vaccines.

Declaration of emergency state due to COVID-19 spread in Japan reduced maternal transports without reduction in preterm delivery.

INTRODUCTION: To clarify whether the declaration of an emergency state due to the spread of COVID-19 in Japan affected the number of maternal transports and premature births. METHODS: A questionnaire-based descriptive study was conducted in perinatal centers throughout Japan in 2020. The incidence of maternal transport and preterm delivery rates every month after the COVID-19 spread in 2020 were compared with those in 2019. RESULTS: Participants were recruited from 52 perinatal centres. The maternal transport rate (maternal transports per number of deliveries) was 10.6% in April and 11.0% in June 2020, compared with 12.5% in 2019 (P < 0.05). The maternal transport rate due to preterm labor was 4.8% in April 2020 and 5.8% in 2019 (P < 0.05). The maternal transport rate during the declaration of emergency state decreased by 21% in April 2020 in non-emergency-declared prefectures, and decreased by 17% in May 2020 in emergency-declared prefectures. However, there was no significant difference in the preterm delivery rate between 2020 and 2019, regardless of the prefecture and gestational period. CONCLUSION: Declaration of the emergency status due to COVID-19 spread in Japan reduced maternal transport due to preterm labor, but did not reduce preterm delivery itself.

Risk factors for severe disease and impact of severity on pregnant women with COVID-19: a case-control study based on data from a nationwide survey of maternity services in Japan.

OBJECTIVE: To identify independent risk factors for severe COVID-19 in pregnant women and to evaluate the impact of disease severity on preterm birth. DESIGN: A case-control study based on data from a nationwide questionnaire-based survey of maternity services in Japan. SETTING: A questionnaire was mailed to all 2135 delivery institutions in Japan between July and August 2021. A total of 1288 institutions responded (60% of all delivery institutions in Japan). 566 facilities reported having cared for pregnant women with COVID-19, and 722 facilities reported having had no such patients. PARTICIPANTS: One thousand and forty-three hospitalised and non-hospitalised pregnant women diagnosed with COVID-19 between July 2020 and 30 June 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was progression to severe COVID-19. The secondary outcome was preterm birth due to COVID-19 infection. RESULTS: 56 cases (5.4%) were severe, and 987 (94.6%) were non-severe. Multivariable logistic regression analysis showed that gestational age≥24 weeks (adjusted OR (aOR) 6.68, 95% CI 2.8 to 16.0) and maternal age≥32 years (aOR 2.40, 95% CI 1.3 to 4.3) were independently associated with severe cases. Using the Kaplan-Meier method, the probability of continued pregnancy at 14 days after diagnosis for severe cases was 0.57 between 24 and 31 weeks' gestation and 0.27 between 32 and 36 weeks' gestation. The probability for non-severe cases was 1.0 between 24 and 31 weeks' gestation and 0.8 between 32 and 36 weeks' gestation. Among the patients with COVID-19 in the preterm period, preterm birth due to infection was significantly more common in severe than non-severe cases (48% vs 6%, p< 0.0001). CONCLUSIONS: Severe COVID-19 in pregnant women was associated with gestational age≥24 weeks and maternal age≥32. The rate of preterm delivery due to the infection was significantly higher in severe COVID-19 cases.

Maternal death due to serious group A streptococcal toxic shock syndrome reduced after the coronavirus disease pandemic in Japan.

Purpose: Serious group A streptococcal (GAS) infections and toxic shock syndrome (TSS) are rare conditions, but their rapid progression often results in death. The purpose of the present study was to clarify recent trend after the coronavirus disease (COVID-19) pandemic of GAS infection in Japan.Materials and Methods: Maternal death statistics were analyzed by the Japan Maternal Death Exploratory Committee.Results: Maternal deaths due to GAS-TSS accounted for 4.2% (n = 22) of all maternal deaths in Japan (n = 525) in the last 12 years. GAS-TSS remains one of the leading causes of maternal death after obstetric hemorrhage and hypertensive disorder. However, no maternal deaths due to GAS-TSS have been reported since the COVID-19 pandemic in Japan after the last death occurred in February 2020.Conclusions: The major change during this period was that most Japanese people wore facemasks at all times and did frequent disinfection. It is considered that the reduction in the incidence of GAS infections itself reduced the number of serious GAS-related maternal deaths. Wearing facemasks and frequent disinfection during pregnancy might to be recommended to prevent various infectious diseases including serious GAS infection, even after the COVID-19 pandemic era.

Physical Characteristics of Injection Site Pain After COVID-19 mRNA BNT162b2 Vaccination.

BACKGROUND: BNT162b2, an mRNA COVID-19 vaccine, was launched in many countries as an intramuscular vaccination for COVID-19 infection. Few studies have assessed the physical indications of pain at the immunization site. This study aimed to characterize pain at the injection site and investigate morphological attributes using ultrasound. METHODS: Forty-three of 211 healthcare workers who received a second dose of BNT162b2 between February 2021 and March 2021 were enrolled in the study. The mean age of the subjects was 40 years. We evaluated patients' pain at the injection site using the Numerical Rating Pain Scale (NRPS). We also assessed the thickness of the deltoid muscle fascia at the injection site by ultrasound. Bayesian robust correlation was employed to explore the relationship between the pain intensity scores and ultrasound measurements. RESULTS: All eligible subjects complained of pain at the injection site. A median pain onset of 8 hours post-vaccination and a median peak intensity score of 4 were reported. Onset of relief occurred after 2 days. Ultrasound images demonstrated a 2.5-fold increase in fascia thickness at the injection site without intramuscular echogenicity change in all subjects. A correlation was established between the NRPS score and the non-injection-to-injection-side ratio of fascia thickness at the injection site (rho = 0.66). CONCLUSION: A sore arm was the most prevalent side effect of BNT162b2 vaccination and could be attributed to temporal fasciitis.

Predictive Model for Adverse Events and Immune Response Based on the Production of Antibodies After the Second-Dose of the BNT162b2 mRNA Vaccine.

BACKGROUND: The BNT162b mRNA vaccine for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mimics the immune response to natural infection. Few studies have predicted the adverse effects (AEs) after the second-dose vaccination. We present a predictive model for AEs and immune response after the second-dose of the BNT162b mRNA vaccine. METHODS: To predict AEs, 282 healthcare workers (HCWs) were enrolled in this prospective observational study. The classification and regression tree (CART) model was established, and its predictive efficacy was assessed. To predict immune response, 282 HCWs were included in the analysis. Moreover, the factors affected by anti-SARS-CoV-2 spike protein RBD antibody (s-IgG) were evaluated using serum samples collected 2 months after the second-dose vaccination. The s-IgG level was assessed using Lumipulse G1200. Multiple regression analyses were conducted to evaluate variables associated with anti-s-IgG titer levels. RESULTS: The most common AEs after the second-dose vaccination were pain (87.6%), redness (17.0%) at the injection site, fatigue (68.8%), headache (53.5%), and fever (37.5%). Based on the CART model, headache after the first-dose vaccination and age < 30 years were identified as the first and second discriminators for predicting the headache after the second-dose vaccination, respectively. In the multiple linear regression model, anti-s-IgG titer levels were associated with age, female sex, and AEs including headache and induration at the injection site after the second-dose vaccination. CONCLUSION: Headache after the first-dose vaccination can be a predictor of headache after the second-dose vaccination, and AEs are indicators of immune response.

Clinical characteristics of pregnant women with COVID-19 in Japan: a nationwide questionnaire survey.

BACKGROUND: Few reports have presented an overall view of pregnant women with coronavirus disease 2019 (COVID-19) across an entire country and throughout the entire gestation period. Furthermore, no such reports are available for Japan. We examined the clinical characteristics and outcomes of pregnant women with COVID­19 on a national scale in Japan. METHODS: A nationwide questionnaire-based survey for all 2,185 maternity services in Japan was conducted between July and August 2020. Information regarding maternal characteristics and epidemiological, clinical, treatment, and perinatal outcomes of pregnant women diagnosed with COVID-19 between 16 January and 30 June 2020 were collected. Main outcome measures were incidence of pregnant women with COVID-19 and infant infection, positive rate of the universal screening test for asymptomatic pregnant women, identification of infection route and rates of maternal death, and severe cases. RESULTS: Responses from 1,418 institutions were assessed (65% of all delivery institutions in Japan). Seventy-two pregnant women were reported to have been diagnosed with COVID-19. The positive rate of the universal screening test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic pregnant women was 0.03% (2/7428). The most common route of infection was familial (57%). Fifty-eight pregnant women with COVID-19 were symptomatic, of whom five (8.6%) had a severe infection and one died (a tourist). Severe respiratory symptoms, oxygen administration, and pneumonia were frequently reported in the third trimester and postpartum period compared with in early pregnancy (22.2% vs 2.5% [P = 0.03], 38.9% vs 7.5% [P = 0.01], and 50.0% vs 7.5% [P < 0.001], respectively). All pregnant women with COVID-19 underwent caesarean sections, regardless of symptoms. There were no SARS-CoV-2 transmissions to newborns. CONCLUSIONS: In Japan, the number of cases of COVID-19 infection in pregnant women is very low. Compared with early pregnancy, late pregnancy may be a risk factor for exacerbation of symptoms and familial transmission is the most common route of infection. The importance of infection prevention should be emphasised, especially in women in late pregnancy, their families, and any cohabitants.

Current status of community-acquired infection of COVID-19 in delivery facilities in Japan.

A nationwide questionnaire survey about community-acquired infection of coronavirus disease 2019 (COVID-19) was conducted in July 2020 to identify the characteristics of and measures taken by Japanese medical facilities providing maternity services. A case-control study was conducted by including medical facilities with (Cases) and without (Control) community-acquired infection of COVID-19. Responses from 711 hospitals and 707 private clinics were assessed (72% of all hospital and 59% all private clinics provided maternity service in Japan). Seventy-five COVID-19-positive pregnant women were treated in 52 facilities. Community-acquired infection was reported in 4.1% of the facilities. Of these, 95% occurred in the hospital. Nine patients developed a community-acquired infection in the maternity ward or obstetric department. Variables that associated with community-acquired infection of COVID-19 (adjusted odds ratio [95% confidence interval]) were found to be state of emergency prefecture (4.93 [2.17-11.16]), PCR test for SARS-CoV-2 on admission (2.88 [1.59-5.24]), and facility that cannot treat COVID-19 positive patients (0.34 [0.14-0.82]). In conclusion, community-acquired infection is likely to occur in large hospitals that treat a higher number of patients than private clinics do, regardless of the preventive measures used.