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BackgroundCOVID-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 diseases 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 findingsA 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. ConclusionsAntenatal 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.
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We detected the presence of SARS-CoV-2 specific IgA against all major VOCs in milk out to 6 weeks after D2 of BNT162b2. These likely confer some protection to the breastfed infants, who are ineligible for vaccination and are at risk of severe COVID-19. However, we detected significantly reduced milk IgA binding to VOCs, including the globally dominant Delta variant, suggesting reduced protection for breastfeeding infants. Additionally, these antibodies were significantly reduced by as early as 4-6 weeks after D2.
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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. Whats known on this subjectTwo studies reported no serious adverse effects in both mother-child dyads after mRNA COVID-19 vaccination in mothers. Up to 61.9-67% lactating women experienced minor side effects. What this study addsWe report an incidence of lymphadenopathy in our cohort at 5.7% as opposed to 0.3% from the Pfizer-BioNTech COVID-19 trial. Reassuringly, there was no change in reported milk supply after vaccination. Minimal effects related to breastfeeding were reported in this cohort; 3 (3.4%) women had mastitis with 1 person experiencing breast engorgement. The most common side effect was pain/redness/swelling at the injection site at 64.8%, which was experienced by 57 of 88 (65%) women. No adverse symptoms were reported in the breastfed children.
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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.
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INTRODUCTION@#Easy access and availability of communication tools have facilitated doctors' communication, adding new challenges. Through this study, we aimed to determine the profile of the knowledge and practices of doctors in our institution, and to identify knowledge gaps in the use of social media accounts.@*METHODS@#An anonymous survey was sent by electronic mail in March-May 2018 to 931 doctors working in National University Hospital, Singapore. It included questions on demographics; use of social media; and case-based scenarios involving professionalism, patient-doctor relationship and personal practices of social media use.@*RESULTS@#The response rate was 12.8%. The majority of the respondents owned a social media account (93.3%), had not received education on social media use in medical school (84.0%), did not own a separate work phone (80.7%) and claimed to have no medical education on this as a doctor (58.8%). Unawareness of the institution's social media policy was reported by 14.3% of the respondents. Questions on knowledge of the privacy settings of their account were incorrectly answered. Only 75.6%-82.4% of the participants responded 'no' when asked if they would post pictures of patients or their results, even if there were no patient identifiers.@*CONCLUSION@#There is inadequate knowledge regarding institutional social media policy and privacy settings of social media accounts among doctors. Regarding practices in social media use, while most agree that caution should be exercised for online posts involving patients, ambiguity still exists. The emerging knowledge deficit and potentially unsafe practices that are identified can be addressed through continuing medical education and training on social media use.
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INTRODUCTION@#As the traditional overnight call system was shown to contribute to fatigue, Singapore implemented a shift system in 2014. We aimed to compare activity levels, sleep (using a wrist actigraph), fatigue and professional quality of life between residents working on night float and those on overnight calls.@*METHODS@#All Postgraduate Year 1 (PGY1) residents at our institution were invited to participate. Participants were required to wear a wrist actigraph for four months and complete two validated surveys (Epworth Sleepiness Scale [ESS] and Professional Quality of Life [ProQOL] scale) once each at the start and end of the study.@*RESULTS@#49 residents were recruited. Night float and on-call residents showed a comparable median (range) number of steps (10,061 [1,195-15,923] vs. 10,649 [308-21,910]; p = 0.429), amount of sleep logged (361 [149-630] minutes vs. 380 [175-484] minutes; p = 0.369) and time taken to fall asleep (6 [0-14] minutes vs. 6 [range 0-45] minutes; p = 0.726), respectively. Night float residents had less efficient sleep, with 90.5% having sleep efficiency of over 85% compared to 100% of on-call residents (p = 0.127). More night float residents reported ESS scores > 10 (73.1% vs. 38.5%) and higher burnout scores on ProQOL scale (41.4% vs. 21.4%) at the start of the study. However, this was similar to the end of the study and not statistically significant.@*CONCLUSION@#Physical activity and amount of sleep were not significantly different between night float and on-call residents. Residents on night float reported comparatively more fatigue and burnout.
