At birth, neonates are particularly vulnerable to infection and transplacental transfer of immunoglobulin G (IgG) from mother to fetus provides crucial protection in the first weeks of life. Transcytosis of IgG occurs via binding with the neonatal Fc receptor (FcRn) in the placental synctiotrophoblast. As maternal vaccination becomes an increasingly important strategy for the protection of young infants, improving our understanding of transplacental transfer and the factors that may affect this will become increasingly important, especially in low-income countries where the burden of morbidity and mortality is highest. This review highlights factors of relevance to maternal vaccination that may modulate placental transfer—IgG subclass, glycosylation of antibody, total maternal IgG concentration, maternal disease, infant gestational age, and birthweight—and outlines the conflicting evidence and questions that remain regarding the complexities of these relationships. Furthermore, the intricacies of the Ab–FcRn interaction remain poorly understood and models that may help address future research questions are described.

IntroductionRecent evidence suggests that influenza vaccination may offer protection against COVID-19 severity. Our aim was to quantify the association between influenza vaccination status and risk of hospitalisation or all-cause mortality in people diagnosed with COVID-19.MethodsA retrospective cohort study using routinely collected health records from patients registered to a General Practitioner (GP) practice in South West England within the Electronic Care and Health Information Analytics database. The cohort included 6921 people with COVID-19 during the first wave of the pandemic (1 January–31 July 2020). Data on influenza vaccination, hospitalisation and all-cause mortality were ascertained through linked clinical and demographic records. We applied propensity score methods (stabilised inverse probability of treatment weight) to quantify the association between influenza vaccination status and COVID-19 outcomes (hospitalisation or all-cause mortality).Results2613 (38%) participants received an influenza vaccination between 1 January 2019 and COVID-19 diagnosis. Receipt of influenza vaccination was associated with a significantly lower odds of hospitalisation or all-cause mortality (adjusted OR: 0.85, 95% CI 0.75 to 0.97, p=0.02), and 24% reduced odds of all-cause mortality (adjusted OR: 0.76, 95% CI 0.64 to 0.90).DiscussionInfluenza vaccination was associated with a 15%–24% lower odds of severe COVID-19 outcomes. The current UK influenza vaccination programme needs urgent expansion as an integral component of the ongoing response plans to the COVID-19 pandemic.

Compared with usual nutritional care, energy- and protein-based fortification and supplementation could be employed as an effective, well-tolerated and cost-effective intervention to improve dietary intake amongst older inpatients. This strategy may be particularly useful for patients with cognitive impairment who struggle with ONS, and clinical trials are required to compare these approaches and establish their impact on functional outcomes.

BackgroundUptake rates of influenza and pertussis vaccination in pregnancy remain suboptimal.AimTo determine the acceptability of routine vaccination among pregnant women; the confidence of maternity healthcare professionals (HCPs) discussing vaccination; and HCP opinion with regards to the optimum healthcare site for vaccine administration.MethodSeparate questionnaires for pregnant women and maternity HCPs were distributed within four NHS trusts in South England from July 2017–January 2018.ResultsResponses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives [both hospital and community], 7% unidentified) were analysed. Actual/intended uptake of influenza and pertussis vaccination was 78% and 92%, respectively. The commonest reason for declining vaccination was feared side effects for their child. White British women (79%) were significantly more accepting of influenza (odds ratio [OR] 3.25, 95% confidence interval [CI] = 1.67 to 6.32) and pertussis vaccination (OR 4.83, 95% CI = 1.77 to 13.19) compared with non-white British women. Among HCPs, 25% were not-at-all or slightly confident discussing vaccination. Obstetricians felt significantly more confident discussing pertussis vaccination than midwives (OR 2.05, 95% CI = 1.02 to 4.12). Among HCPs, 53%, 25%, and 16% thought vaccines should be administered in primary care (general practice), community midwifery, and the hospital setting, respectively.ConclusionMisconceptions exist regarding safety and efficacy of maternal vaccination, and framing information towards safety for the child may increase uptake. Education of HCPs is essential, and vaccine promotion should be incorporated into routine antenatal care, with an emphasis on women from ethnic minorities. Administration of vaccines in primary care may present a logistical barrier to women, however support for alternative sites appears low among HCPs.

Infection is responsible for over half a million neonatal deaths worldwide every year, and vaccination in pregnancy is becoming increasingly recognized as an important strategy for the protection of young infants. Increasing evidence suggests that exposure to maternal infection in utero may “prime” the developing immune system, even in the absence of infant infection. It is also possible that in utero priming may occur following maternal vaccination, with antigen-specific cellular immune responses detectable in utero and at birth. However, this remains a topic of some controversy. This review focuses on the evidence for in utero priming and the clinical implications for vaccination in pregnancy, considering whether in utero priming following vaccination could provide protection independent of antibody-mediated passive immunity, the possible effects of vaccination on subsequent infant vaccinations, their potential “non-specific” effects, and how the design and timing of vaccination might affect prenatal priming. Looking forward, we describe other possible options for quantifying antigen-specific cellular responses, including MHC tetramers, novel proliferation and cytokine-based assays, and animal models. Together, these may help us address future research questions and establish more robust evidence of fetal immune system priming.

Attitudes of pregnant women and healthcare professionals towards clinical trials and routine implementation of antenatal vaccination against respiratory syncytial virus: a multi-centre questionnaire study Wilcox,

Background Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. Objectives To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. Methods CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were selfreported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. Results A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2Á5%) or clindamycin (2Á7%) than BPO (1Á6%) or adapalene alone (1Á0%). Overall confidence in the evidence was low. Conclusions Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.What is already known about this topic?• Guidelines suggest a number of different topical preparations as first-line treatment for acne vulgaris.

ObjectiveTo review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease.DesignSystematic review.Data sourceMEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science.Study selectionAny design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression.Data extraction and synthesisMEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies.ResultsWe screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2).ConclusionsThere is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.