Predicting vaccine hesitancy among parents towards COVID-19 vaccination for their children in Singapore

Background There was a considerably slower uptake among children despite the high COVID-19 vaccination uptake amongst adults and adolescents in Singapore. This was concerning as unvaccinated children are at risk of severe COVID-19 infections and a source and reservoir of infections. We sought to understand the impact of social media on parental vaccine hesitancy and to determine the risk factors associated with vaccine hesitancy. Methods An electronic survey conducted from November 2021 to March 2022. Data on the demographic profiles of respondents and to classify them based on their vaccine hesitancy status. Data including the choice of social media used to obtain information on the COVID-19 pandemic, frequency of use were collected. Statistical significance was defined as p < 0.05. Results Six hundred and twenty-eight parents participated. 66.9% of parents were not vaccine hesitant. About a third (27.2%) considered themselves somewhat vaccine hesitant. Fathers were more vaccine hesitant than mothers. Vaccine hesitancy was also associated with having a lower household income, unvaccinated parents, knowing someone with an adverse reaction to the Covid 19 vaccine and having a low level of trust in their child's doctor. There was no significant difference with high usage of social media between parents who were not vaccine hesitant vs. those who were vaccine hesitant. Despite high usage of social media, about two thirds (62.7%) of parents preferred print material to obtain COVID-19 related information. Parental trust in their child's doctor was the most significant factor in determining vaccine hesitancy amongst parents. When the variables of gender, household income status, vaccine status were further analysed with a multinomial logistic regression model, vaccine hesitancy in a parent could be predicted with a 70% accuracy, and non-vaccine hesitancy with a 92.4% accuracy. Conclusion Newspapers and print media were the primary sources used in obtaining information on COVID-19 vaccine safety and efficacy, especially amongst parents with a higher household income. Healthcare providers should continue to establish rapport amongst parents, in particular the group with a lower household income to encourage higher paediatric COVID-19 vaccine uptake as well as correct COVID-19 related vaccine misconceptions or vaccine hesitancy, if present.

Immune and pathophysiologic profiling of antenatal coronavirus disease 2019 in the GIFT cohort: A Singaporean case-control study

COVID-19 can be severe in pregnant women, and have adverse consequences for the subsequent infant. We profiled the post-infectious immune responses in maternal and child blood as well as breast milk in terms of antibody and cytokine expression and performed histopathological studies on placentae obtained from mothers convalescent from antenatal COVID-19. Seventeen mother-child dyads (8 cases of antenatal COVID-19 and 9 healthy unrelated controls;34 individuals in total) were recruited to the Gestational Immunity For Transfer (GIFT) study. Maternal and infant blood, and breast milk samples were collected over the first year of life. All samples were analyzed for IgG and IgA against whole SARS-CoV-2 spike protein, the spike receptor-binding domain (RBD), and previously reported immunodominant epitopes, as well as cytokine levels. The placentae were examined microscopically. The study is registered at clinicaltrials.gov under the identifier NCT04802278. We found high levels of virus-specific IgG in convalescent mothers and similarly elevated titers in newborn children. Thus, antenatal SARS-CoV-2 infection led to high plasma titers of virus-specific antibodies in infants postnatally. However, this waned within 3–6 months of life. Virus neutralization by plasma was not uniformly achieved, and the presence of antibodies targeting known immunodominant epitopes did not assure neutralization. Virus-specific IgA levels were variable among convalescent individuals’ sera and breast milk. Antibody transfer ratios and the decay of transplacentally transferred virus-specific antibodies in neonatal circulation resembled that for other pathogens. Convalescent mothers showed signs of chronic inflammation marked by persistently elevated IL17RA levels in their blood. Four placentae presented signs of acute inflammation, particularly in the subchorionic region, marked by neutrophil infiltration even though > 50 days had elapsed between virus clearance and delivery. Administration of a single dose of BNT162b2 mRNA vaccine to mothers convalescent from antenatal COVID-19 increased virus-specific IgG and IgA titers in breast milk, highlighting the importance of receiving the vaccine even after natural infection with the added benefit of enhanced passive immunity.

Correlation between parents’ social media use, educational level, COVID-19 vaccination status and vaccine hesitancy for their children in Singapore

AimsAfter the approval of the paediatric COVID-19 vaccines, the uptake was slower compared to the teenagers and adults in Singapore. Studies have shown that parents with higher social media usage are more hesitant to vaccinate their children. Our research aims to determine: (1) correlation between profile of parents in Singapore and source of information versus vaccine hesitancy, (2) their opinions towards paediatric COVID-19 vaccines.MethodsA prospective, anonymous, and voluntary electronic survey was performed in Singapore from 14/Nov/2021 for 12 weeks. Demographic data was obtained. Time spent on social media (Facebook, YouTube, Twitter, Weibo, Instagram) and total device usage per week were divided into high and low usage: high usage being more than 12 hours/week of social media and/or 6 hours/day of device use. Vaccine hesitancy was a self-assessed variable by the participants. Results were analysed using Chi-square and Fisher’s exact tests with SPSS. Statistical significance was defined to be 2-sided p <.05.ResultsWe surveyed 628 parents (mean (SD) of 39.1(6.7) years old), with 69.1% being mothers, with a median of 2 children each. 90.1% had at least pre-university education. Majority (99.2%) had received at least 1 dose of the COVID-19 vaccine. 61.4% had at least 1 child eligible for paediatric COVID-19 vaccine and 27.6% had at least 1 teenager. Respondents spent a mode of 1 to 12 hours per week on social media and 1 to 6 hours per day on digital devices. 85.8% and 61.0% believed that mRNA COVID-19 vaccines were most effective, and safest against COVID-19, respectively. The most read source for health information was from print material such as health pamphlets (50.8%) rather than social media (35.7%).Contrary to other studies, parents with high usage of digital devices were more willing to give mRNA vaccines to their teenagers (84.0% vs 16.0%, p<.001). COVID-19 unvaccinated parents were also more childhood vaccine hesitant. (100% vs 18.3%, p< .001). Comparing to lower educated parents, parents with at least pre-university education were less vaccine hesitant (30.5% vs 56.5%, p<.001). They were more likely to receive COVID-19- related information via other print material (91.2% vs 8.8%, p=.010). Among parents with at least pre-university education, 53.0% obtained most of their COVID-19 related information from print material compared to social media (35.1%). Parents who personally knew someone with a bad reaction to the COVID-19 vaccine correlates to hesitancy towards childhood vaccines (18.9% vs 14.2%, p<.001).ConclusionVaccine hesitancy is correlated with low device and social media usage, parents’ unvaccinated status, low education status. Despite high usage of social media and digital devices, parents with a higher level of education were more likely to obtain information regarding COVID-19 vaccines from print material rather than social media. Health education regarding vaccine safety through print media may encourage more parents to vaccinate their children and may help to reassure them that benefits overweigh the risks to increase uptake.

Human Milk Antibodies after BNT162b2 Vaccination Exhibit Reduced Binding against SARS-CoV-2 Variants of Concern.

SARS-CoV-2-specific antibody responses are engendered in human milk after BNT162b2 vaccination. However, the emergence of variants of concern (VOCs) raises concerns about the specificity of and potential cross-protection mediated by milk antibody responses, which are crucial for passive immunity transferred from breastfeeding mothers to their infants. In this study, we collected milk samples at three different time points pre- and post-vaccination, and measured milk IgA antibody binding to the receptor binding domain (RBD) of the original Wuhan-Hu-1 strain, and the four VOCs, namely Alpha, Beta, Gamma and Delta. We report a significant level of anti-RBD IgA in milk collected at 4-6 weeks after the second dose of vaccination compared to pre-vaccination. We observed around a 30% reduction in binding to most VOCs, including the major circulating Delta variant, compared to the original Wuhan-Hu-1 strain. As COVID-19 vaccines may take some time to be approved for infants, these individuals remain at risk for severe disease and rely mainly on transferred passive immunity. Our findings support the current recommendations for vaccinating lactating women with the aim of transferring mucosal immunity to breastfeeding infants.

Breastfeeding Mother and Child Clinical Outcomes After COVID-19 Vaccination.

BACKGROUND: Pre-approval clinical trials of the Pfizer/BioNTech messenger RNA COVID-19 vaccine, BNT162b2 did not include participants who were breastfeeding. Therefore, there is limited evidence about outcomes of breastfeeding mother-child dyads and effects on breastfeeding after vaccination. RESEARCH AIMS: To determine: (1) solicited adverse effects (e.g., axillary lymphadenopathy, mastitis, and breast engorgement), which are unique to lactating individuals; and (2) systemic and local adverse effects of COVID-19 mRNA vaccine on mothers and potential effects on their breastfed infants. METHOD: This was a prospective cohort study of lactating healthcare workers (N = 88) in Singapore who received two doses of BNT162b2 vaccination (Pfizer/BioNTech). The outcomes of mother-child dyads within 28 days after the second vaccine dose were determined through a participant-completed questionnaire. RESULTS: Minimal effects related to breastfeeding were reported by this cohort; three of 88 (3.4%) participants had mastitis, one (1.1%) participant experienced breast engorgement, five of 88 (5.7%) participants reported cervical or axillary lymphadenopathy. There was no change in human milk supply after vaccination. The most common side effect was pain/redness/swelling at the injection site, which was experienced by 57 (64.8%) participants. There were no serious adverse events of anaphylaxis or hospital admissions. There were no short-term adverse effects reported in the infants of 67 lactating participants who breastfed within 72 hr after BNT162b2 vaccination. CONCLUSIONS: BNT162b2 vaccination was well tolerated in lactating participants and was not associated with short-term adverse effects in their breastfed infants. STUDY PROTOCOL REGISTRATION: The study protocol was registered at clinicaltrials.gov (NCT04802278).

Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees.

Lactating women can produce protective antibodies in their milk after vaccination, which has informed antenatal vaccination programs for diseases such as influenza and pertussis. However, whether SARS-CoV-2-specific antibodies are produced in human milk as a result of COVID-19 vaccination is still unclear. In this study, we show that lactating mothers who received the BNT162b2 vaccine secreted SARS-CoV-2-specific IgA and IgG antibodies into milk, with the most significant increase at 3-7 days post-dose 2. Virus-specific IgG titers were stable out to 4-6 weeks after dose 2. In contrast, SARS-CoV-2-specific IgA levels showed substantial decay. Vaccine mRNA was detected in few milk samples (maximum of 2 ng/ml), indicative of minimal transfer. Additionally, infants who consumed post-vaccination human milk had no reported adverse effects up to 28 days post-ingestion. Our results define the safety and efficacy profiles of the vaccine in this demographic and provide initial evidence for protective immunity conferred by milk-borne SARS-CoV-2-specific antibodies. Taken together, our study supports recommendations for uninterrupted breastfeeding subsequent to mRNA vaccination against COVID-19.

Titres and neutralising capacity of SARS-CoV-2-specific antibodies in human milk: a systematic review.

OBJECTIVE: Synthesise evidence on production of SARS-CoV-2 antibodies in human milk of individuals who had COVID-19, and antibodies' ability to neutralise SARS-CoV-2 infectivity. DESIGN: A systematic review of studies published from 1 December 2019 to 16 February 2021 without study design restrictions. SETTING: Data were sourced from PubMed, MEDLINE, Embase, CNKI, CINAHL and WHO COVID-19 database. Search was also performed through reviewing references of selected articles, Google Scholar and preprint servers. Studies that tested human milk for antibodies to SARS-CoV-2 were included. PATIENTS: Individuals with COVID-19 infection and human milk tested for anti-SARS-CoV-2 neutralising antibodies. MAIN OUTCOME MEASURES: The presence of neutralising antibodies in milk samples provided by individuals with COVID-19 infection. RESULTS: Individual participant data from 161 persons (14 studies) were extracted and re-pooled. Milk from 133 (82.6%) individuals demonstrated the presence of anti-SARS-CoV-2 immunoglobulin A (IgA), IgM and/or IgG. Illness severity data were available in 146 individuals; 5 (3.4%) had severe disease, 128 (87.7%) had mild disease, while 13 (8.9%) were asymptomatic. Presence of neutralising antibodies in milk from 20 (41.7%) of 48 individuals neutralised SARS-CoV-2 infectivity in vitro. Neutralising capacity of antibodies was lost after Holder pasteurisation but preserved after high-pressure pasteurisation. CONCLUSION: Human milk of lactating individuals after COVID-19 infection contains anti-SARS-CoV-2-specific IgG, IgM and/or IgA, even after mild or asymptomatic infection. Current evidence demonstrates that these antibodies can neutralise SARS-CoV-2 virus in vitro. Holder pasteurisation deactivates SARS-CoV-2-specific IgA, while high-pressure pasteurisation preserves the SARS-CoV-2-specific IgA function.

Childhood vaccinations: Hidden impact of COVID-19 on children in Singapore.

Although the direct health impact of Coronavirus disease (COVID-19) pandemic on child health is low, there are indirect impacts across many aspects. We compare childhood vaccine uptake in three types of healthcare facilities in Singapore - public primary care clinics, a hospital paediatric unit, and private paediatrician clinics - from January to April 2020, to baseline, and calculate the impact on herd immunity for measles. We find a 25.6% to 73.6% drop in Measles-Mumps-Rubella (MMR) uptake rates, 0.4 - 10.3% drop for Diphtheria-Tetanus-Pertussis-inactivated Polio-Haemophilus influenza (5-in-1), and 8.0-67.8% drop for Pneumococcal conjugate vaccine (PCV) across all 3 sites. Consequent herd immunity reduces to 74-84% among 12-month- to 2-year-olds, well below the 95% coverage that is protective for measles. This puts the whole community at risk for a measles epidemic. Public health efforts are urgently needed to maintain efficacious coverage for routine childhood vaccines during the COVID-19 pandemic.