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.

Reactogenicity of mRNA- and Non-mRNA-Based COVID-19 Vaccines among Lactating Mother and Child Dyads.

The aims of the study are to: (a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA (Oxford-AstraZeneca, Sinovac) vaccines among lactating mother and child pairs, and (b) Compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site, and the largest minority of respondents, 49.6% (780/1571), reported experiencing worse symptoms when receiving the second dose compared to the first dose. Respondents reported no major adverse effects or behavioural changes in the breastfed children for the duration of the study period. Among respondents who received non-mRNA COVID-19 vaccines, a majority reported no change in lactation, but those who did more commonly reported changes in the quantity of milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breast milk supply quantity and pain in the breast) for the non-mRNA vaccines were similar to those of respondents who received mRNA vaccines. Our study, with a large, racially diverse cohort, further augments earlier reported findings in that the COVID-19 vaccines tested in this study did not cause any serious adverse events in our population for the duration of our survey period, although long-term effects are yet to be studied.

Reactogenicity of mRNA and non-mRNA Based COVID-19 Vaccines Among Lactating Mother and Baby Dyads (preprint)

The aims of the study are: a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA vaccines (Oxford-AstraZeneca, Sinovac) among lactating mother and baby pairs; and b) compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site; the largest minority of respondents, 43.7% (780/1784), reported experiencing worse symptoms when receiving the second dose compared to the first dose. There were no major reported adverse effects or behavioural changes in the breastfed infants. Among the respondents who received non-mRNA COVID-19 vaccinations, a majority reported no change in lactation but those who did more commonly reported an increase in milk supply, decrease in milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breastmilk supply and pain in the breast) for the non-mRNA vaccines were similar to that of respondents who received mRNA vaccines. Our study, with a large cohort and wide geographical and racial mix, further augments earlier reported findings that COVID-19 vaccines are safe for breastfeeding mothers and her children.

Immune and pathophysiologic profiling of antenatal COVID-19 in the GIFT cohort: A Singaporean case-control study. (preprint)

Background COVID-19 has been a major public health threat for the past two years, with disproportionate effects on the elderly, immunocompromised, and pregnant women. While much has been done in delineating immune dysfunctions and pathogenesis in the former two groups, less is known about the disease's progression in expectant women and children born to them. To address this knowledge gap, we profiled the immune responses in maternal and child sera 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. Methods and findings A total of 17 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 sera, 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, with conventional ELISA approaches. Cytokine levels were quantified in maternal sera using multiplex microbead-based Luminex arrays. The placentae were examined microscopically. We found high levels of virus-specific IgG in convalescent mothers and similarly elevated titers in newborn children. Virus-specific IgG in infant circulation waned within 3-6 months of life. Virus-specific IgA levels were variable among convalescent individuals' sera and breast milk. Convalescent mothers also showed a blood cytokine signature indicative of a persistent pro-inflammatory state. Four placentae presented signs of acute inflammation 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. Conclusions Antenatal SARS-CoV-2 infection led to high plasma titres of virus-specific antibodies in infants postnatally. However, this was not reflected in milk; milk-borne antibody levels varied widely. Additionally, placentae from COVID-19 positive mothers exhibited signs of acute inflammation with neutrophilic involvement, particularly in the subchorionic region. Virus neutralisation by plasma was not uniformly achieved, and the presence of antibodies targeting known immunodominant epitopes did not assure neutralisation. 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. A single dose of the Pfizer BNT162b2 mRNA vaccine provided significant boosts to milk-borne virus-specific antibodies, highlighting the importance of receiving the vaccine even after natural infection with the added benefit of enhanced passive immunity. The study is registered at clinicaltrials.gov under the identifier NCT04802278.

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.

Breastfeeding mother-child clinical outcomes after COVID-19 vaccination (preprint)

This is a prospective cohort study of 88 lactating women in Singapore who received two doses of BNT162b2 vaccination (Pfizer/BioNTech), whereby outcomes of mother-child dyads within 28 days after the second vaccine dose were determined through a structured questionnaire. Minimal effects related to breastfeeding were reported in this cohort; 3 of 88 (3.4%) women had mastitis with 1 of 88 (1.1%) women experiencing breast engorgement. We report an incidence of lymphadenopathy in our cohort at 5 of 88 (5.7%). Reassuringly, there was no change in reported breastmilk supply after vaccination. The most common side effect was pain/redness/swelling at the injection site, which was experienced by 57 of 88 (64.8%) women. There were no serious adverse events of anaphylaxis and hospital admissions. No adverse symptoms were reported in 67 of 88 (76.1%) breastfed children.

Online survey on healthcare skin reactions for wearing medical-grade protective equipment against COVID-19 in Hubei Province, China.

With the spread of Coronavirus Disease 2019 globally, more than 40,000 healthcare staff rushed to Wuhan, Hubei Province to fight against this threatening disease. All staff had to wear personal protective equipment (PPE) for several hours when caring for patients, which resulted in adverse skin reactions and injuries. In this study, we used an online questionnaire to collect the self-reported skin damages among the first-line medical staff in the epidemic. The questionnaire was designed by four front-line wound care nurses and then revised through Delphi consultants. Items mainly focused on the adverse skin reactions and preventive strategies. The survey was distributed through phone application from March 15th to March 20th and received 275 responses in total. The prevalence of skin reactions (212, 77.09%) was high in both head and hands. The common clinical symptoms of skin reactions were redness, device-like mark, and burning pain in face; and dryness, dermatitis, and itch/irritation in hands. Three risk factors included gender, level of protection, and daily wearing time of PPE were identified that caused skin reactions among medical staff. 150 of 275 (54.55%) participants took preventive strategies like prophylactic dressings, however, more than 75% users had little knowledge about dressings. We suggest the frontline staff strengthened the protection of skin integrity and reduced the prevalence of adverse skin reactions after professional education.

BNT162b2 vaccination induces SARS-CoV-2 specific antibody secretion into human milk with minimal transfer of vaccine mRNA (preprint)

ImportanceTo examine the impact of SARS-CoV-2 vaccination of lactating mothers on human milk Objective(1) To quantify SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in human milk of lactating mothers who received the BNT162b2 vaccine, with reference to a cohort convalescent from antenatal COVID-19, and healthy lactating mothers. (2) To detect and quantify vaccine mRNA in human milk after BNT162b2 vaccination. DesignGestational Immunity For Transfer 2 (GIFT-2) is a prospective cohort study of lactating mothers who were due to receive two doses of BNT162b2 vaccine, recruited between 5th February 2021 and 9th February 2021. SettingLactating healthcare workers living in Singapore ParticipantsConvenience sample of ten lactating healthcare workers. Human milk samples were collected at four time points: pre-vaccination, 1-3 days after dose one, 7-10 days after dose one, and 3-7 days after dose two of the BNT162b2 vaccine. ExposureTwo doses of the BNT162b2 vaccine 21 days apart. Main Outcome and Measure(i) SARS-CoV-2-specific IgA and IgG in human milk of lactating mothers who received BNT162b2 vaccine, (ii) Detection and quantification of vaccine mRNA in human milk after BNT162b2 vaccination. ResultsTen lactating healthcare workers aged 32.5 years (range 29 - 42) were recruited, with 40 human milk samples collected and analysed. SARS-CoV-2-specific IgA was predominant in human milk of lactating mothers who received BNT162b2 vaccine. The sharpest rise in antibody production was 3 -7 days after dose two of the BNT162b2 vaccine, with medians of 1110 picomolar of anti-SARS-CoV-2 spike and 374 picomolar of anti-Receptor Binding Domain IgA. Vaccine mRNA was detected only on rare occasions, at a maximum concentration of 2 ng/mL. Conclusions and RelevanceIn this cohort of ten lactating mothers following BNT162b2 vaccination, nine (90%) produced SARS-CoV-2 IgA, and ten (100%) produced IgG in human milk with minimal amounts of vaccine mRNA. Lactating individuals should continue breastfeeding in an uninterrupted manner after receiving mRNA vaccination for SARS-CoV-2. Trial RegistrationRegistered at clinicaltrials.gov (NCT04802278). Key PointsO_ST_ABSQuestionC_ST_ABSDoes BNT162b2 (i) induce the production and secretion of SARS-CoV-2 specific antibodies into human milk, and/or (ii) get secreted into human milk? FindingsIn this cohort that included ten lactating healthcare workers following BNT162b2 vaccination, 90% produced SARS-CoV-2 immunoglobulin A, and 100% produced immunoglobulin G in human milk, with minimal amounts of vaccine mRNA transfer. MeaningLactating individuals should continue breastfeeding in an uninterrupted manner after receiving SARS-CoV-2 mRNA vaccination.