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

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.

Breastfeeding mother-child clinical outcomes after COVID-19 vaccination

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.

Does the introduction of a third examiner and global marking improve the generalisability of the surgical long case?

<p><b>INTRODUCTION</b>Planning a high-stake clinical examination requires the evaluation of several psychometric and logistical variables. The authors conducted generalisability and decision studies to answer the following research questions in the context of the surgical long case: (1) Does the addition of a third examiner have any added benefit, vis-à-vis reliability, to the examination? (2) Is global marking more reliable than an itemised marking template? (3) What would be the impact on reliability if there was a reduction in the number of examinees that each panel of examiners is required to assess?</p><p><b>METHODS</b>A third examiner and global marking were introduced. Separate generalisability and decision studies were carried out for both the two- and three-examiner models as well as for itemised and global scores.</p><p><b>RESULTS</b>The introduction of a third examiner resulted in a modest gain of reliability by 0.05-0.07. Gain in reliability was higher when each candidate was allowed to undertake a higher number of clinical cases. Both the global and itemised scores provided equivalent reliability (generalisability coefficient 0.74-0.89).</p><p><b>CONCLUSION</b>Our results showed that only a modest improvement in reliability of the surgical long case is achieved through the introduction of an additional examiner. Although the reliability of global scoring and the itemised marking template was comparable, the latter may provide opportunities for individualised feedback to examinees.</p>

The knowledge-attitude dissociation in geriatric education: can it be overcome?

<p><b>INTRODUCTION</b>A knowledge-attitude dissociation often exists in geriatrics where knowledge but not attitudes towards elderly patients improve with education. This study aims to determine whether a holistic education programme incorporating multiple educational strategies such as early exposure, ageing simulation and small group teaching results in improving geriatrics knowledge and attitudes among medical students.</p><p><b>MATERIALS AND METHODS</b>We administered the 18-item University of California Los Angeles (UCLA) Geriatric Knowledge Test (GKT) and the Singapore-modified 16-item UCLA Geriatric Attitudes Test (GAT) to 2nd year students of the old curriculum in 2009 (baseline reference cohort, n = 254), and before and after the new module to students of the new curriculum in 2010 (intervention cohort, n = 261), both at the same time of the year.</p><p><b>RESULTS</b>At baseline, between the baseline reference and intervention cohort, there was no difference in knowledge (UCLA-GKT Score: 31.6 vs 33.5, P = 0.207) but attitudes of the intervention group were worse than the baseline reference group (UCLA-GAT Score: 3.53 vs 3.43, P = 0.003). The new module improved both the geriatric knowledge (UCLA-GKT Score: 34.0 vs 46.0, P <0.001) and attitudes (UCLA-GAT Score: 3.43 vs 3.50, P <0.001) of the intervention cohort.</p><p><b>CONCLUSION</b>A geriatric education module incorporating sound educational strategies improved both geriatric knowledge and attitudes among medical students.</p>