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Atopic dermatitis (AD) is one of the main risk factors for infants in the development of food allergy. Oral immunotherapy (OIT) in early childhood has been found to be highly effective and safe in preschoolers with and without AD, especially in young infants. Delays in initiation of OIT in infants and children due to uncontrolled AD risk expansion of the number of foods children develop allergy to through unnecessary avoidance of multiple foods. Parents and caregivers may attribute eczema flares to OIT doses, which physicians usually ascribe to non-food triggers such as weather changes, psychological stress, and infection. There is a lack of published literature confirming OIT as a trigger of AD flares, and the degree to which OIT may be associated with AD flares needs to be further studied. We describe 8 case scenarios with varying degrees of AD flare before and during OIT. We propose management algorithms for children with preexisting concurrent AD and food allergy who are being considered for starting OIT and children with AD flares during OIT. Optimizing AD control strategies and providing adequate AD care education before starting OIT can reduce confusion for both parents and allergists if rashes arise during OIT, thus improving adherence to OIT., Competing Interests: Disclosures Dr Chua received honorarium from Pharmaniaga, Sanofi, and Menarini and is an advisory board member on maternal immunization against respiratory syncytial virus of Pfizer. Dr Mack has provided consultation and speaker services for DBV, ALK, and Alladapt and is an investigator for DBV, ALK-Abello, Dermavant, Arcutis, and Amgen. Dr Shaker is a member of the Joint Task Force on Practice Parameters, serves on the editorial board of the Journal of Allergy and Clinical Immunology In Practice, is an associate editor of Annals of Allergy, Asthma, and Immunology, and serves on the Board of Directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own). Dr Chan has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Miravo, Medexus, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma, AstraZeneca, ALK, and Alladapt; and was co-lead of the CSACI oral immunotherapy guidelines., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: LC Poon has received speaker fees and consultancy payments from Roche Diagnostics and Ferring Pharmaceuticals. Additionally, she has received in-kind contributions from Roche Diagnostics, Revvity Inc (formerly PerkinElmer Life and Analytical Sciences), Thermo Fisher Scientific, Ningbo Aucheer Biological Technology Co Ltd, and GE HealthCare. Other authors declare no conflicts of interest.

Vaccine-related myocarditis associated with the BNT162b2 vaccine is a rare complication, with a higher risk observed in male adolescents. However, the contribution of genetic factors to this condition remains uncertain. In this study, we conducted a comprehensive genetic association analysis in a cohort of 43 Hong Kong Chinese adolescents who were diagnosed with myocarditis shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. A comparison of whole-genome sequencing data was performed between the confirmed myocarditis cases and a control group of 481 healthy individuals. To narrow down potential genomic regions of interest, we employed a novel clustering approach called ClusterAnalyzer, which prioritised 2,182 genomic regions overlapping with 1,499 genes for further investigation. Our pathway analysis revealed significant enrichment of these genes in functions related to cardiac conduction, ion channel activity, plasma membrane adhesion, and axonogenesis. These findings suggest a potential genetic predisposition in these specific functional areas that may contribute to the observed side effect of the vaccine. Nevertheless, further validation through larger-scale studies is imperative to confirm these findings. Given the increasing prominence of mRNA vaccines as a promising strategy for disease prevention and treatment, understanding the genetic factors associated with vaccine-related myocarditis assumes paramount importance. Our study provides valuable insights that significantly advance our understanding in this regard and serve as a valuable foundation for future research endeavours in this field., (© 2024. The Author(s).)

Background: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis., Methods: Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and T cells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls., Findings: Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1β (IL-1β), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57 + NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57 + NK subset was particularly prominent in males and in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis., Conclusion: Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects., Funding: This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypovitaminosis D during infancy is associated with the development of chronic diseases and poor health later in life. While the effect of environmental factors on vitamin D concentration has been extensively explored, this study aimed to explore the effect of genetic factors on vitamin D concentration among Chinese infants. We conducted a multi-centre cross-sectional study in Hong Kong from July 2019 to May 2021. A candidate genetic approach was adopted to study four selected genetic variants of the vitamin D-binding protein (DBP) and vitamin D receptor (VDR) (rs4588, rs7041, rs2282679 and rs2228570) to examine their associations with measured serum 25(OH)D concentration. A total of 378 Chinese infants aged 2-12 months were recruited in this study. Peripheral blood samples were collected from the infants to measure serum 25(OH)D concentration and extract DNA. Results showed that rs7041T and rs2282679C were significantly associated with lower serum 25(OH)D concentration. Further analysis of the DBP variants revealed that the GC1F allele was significantly associated with lower 25(OH)D concentration and identified as the risk DBP isoform in infants. While our results revealed that there is no direct association between VDR-FokI genotype and serum 25(OH)D concentration, a VDR-FokI genotype-specific pattern was observed in the association between DBP isoforms and serum 25(OH)D concentration. Specifically, significant associations were observed in the DBP genotypes GC1F/F, GC1F/2 and GC1S/2 among VDR-FokI TT/TC carriers, but not in VDR-FokI CC carriers. Our findings lay down the basis for the potential of genetic screening to identify high risk of hypovitaminosis D in Chinese infants., (© 2023 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Background: Seafood is a common cause of food allergy and anaphylaxis, but there are limited published real-world data describing the clinical presentation of fish and shellfish allergies., Objective: This study aimed to examine the clinical characteristics, immunological profile, and tolerance pattern to fish, crustaceans, and mollusks in fish-allergic individuals., Methods: Patients presenting with IgE-mediated fish allergy between 2016 and 2021 were recruited. A comprehensive sensitization profile including specific IgE and skin prick test to various fish and shellfish species and a detailed clinical history including individuals' recent seafood consumption were evaluated., Results: A total of 249 fish-allergic individuals (aged 4.2 ± 5.8 years) were recruited from 6 allergy clinics in Hong Kong, and they had experienced their fish-allergic reaction 2.2 ± 3.4 years before enrollment. Seventy-five subjects (30%) reacted to either grass carp, salmon, grouper, or cod in oral food challenges. We identified an IgE sensitization gradient that corresponded to the level of β-parvalbumin in fish. In total, 40% of fish-allergic individuals reported tolerance to 1 or more types of fish, more commonly to fish with a lower β-parvalbumin level such as tuna and salmon, compared with β-parvalbumin-rich fish such as catfish and grass carp. Despite fish and shellfish cosensitization, 41% of individuals reported tolerance to crustaceans, mollusks, or both, whereas shellfish avoidance occurred in half of the fish-allergic individuals, of whom 33% lacked shellfish sensitization., Conclusions: Fish allergy commonly presents in early childhood. A considerable proportion of fish-allergic patients are selectively tolerant to certain fish, typically those with lower levels of β-parvalbumin. There is an unmet need to promote precision medicine for seafood allergies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies support the effectiveness of sesame oral immunotherapy (S-OIT) in patients >4 years old using maintenance doses of 1200 mg protein. However, tahini is often not palatable to children, and high-maintenance doses may not be possible for preschoolers., Objective: We studied the safety and effectiveness outcomes of preschoolers with sesame allergy who underwent low-dose S-OIT of 200 mg protein., Methods: Preschoolers with sesame allergy, with a history of objective reaction to sesame, and with either a positive skin prick test result (wheal diameter ≥3 mm) or sesame-specific IgE level ≥0.35 kU/L were included. Doses were escalated every 2 to 4 weeks until the maintenance dose of 200 mg of sesame protein was reached. The maintenance dose was continued daily for 1 year, followed by exit oral food challenge (OFC). Primary safety outcomes included allergic reactions grade 2 or higher and the need for epinephrine therapy during buildup. The primary effectiveness outcome was proportion of patients tolerating a minimum of 2000 mg sesame protein at exit OFC., Results: Twenty-eight preschoolers (median age, 33.5 months) were enrolled to receive S-OIT. During the buildup phase, 9 subjects (32.1%) had no reaction, and 8 (28.6%) and 11 (39.3%) had grade 1 and 2 reactions, respectively. One patient (3.57%) received epinephrine for a grade 2 reaction. Twenty-one (91.3%) of 23 eligible subjects underwent exit OFC; 18 (85.7%) of these 21 patients successfully completed exit OFC. One (4.8%) and 2 (9.5%) subjects had grade 1 and 2 reactions, respectively, during OFC., Conclusions: A lower and age-appropriate maintenance dose is safe and effective in desensitizing preschoolers with sesame allergy., (© 2023 The Author(s).)

Background: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia., Methods: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients' sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry., Results: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens., Conclusions: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients' allergic manifestations., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Genetic deficiencies of early components of the classical complement activation pathway (especially C1q, r, s, and C4) are the strongest monogenic causal factors for the prototypic autoimmune disease systemic lupus erythematosus (SLE), but their prevalence is extremely rare. In contrast, isotype genetic deficiency of C4A and acquired deficiency of C1q by autoantibodies are frequent among patients with SLE. Here we review the genetic basis of complement deficiencies in autoimmune disease, discuss the complex genetic diversity seen in complement C4 and its association with autoimmune disease, provide guidance as to when clinicians should suspect and test for complement deficiencies, and outline the current understanding of the mechanisms relating complement deficiencies to autoimmunity. We focus primarily on SLE, as the role of complement in SLE is well-established, but will also discuss other informative diseases such as inflammatory arthritis and myositis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder., (© 2023 Sharma et al.)

Allergists addressing gastrointestinal (GI) symptoms during oral immunotherapy (OIT) may be biased toward diagnoses related to OIT; however, non-OIT causes may occur. Although there is currently a lack of robust data for evidence-based treatment recommendations, we provide 3 real-world illustrative cases along with a proposed management algorithm for GI symptoms encountered during OIT. This algorithm was developed because of a significant clinical need, given the number of new-to-OIT providers that include practicing allergists, trainees transitioning into practice, and allied health care providers who manage GI symptoms in OIT patients. We developed the algorithm based on the opinions of community and academic allergy clinics across Canada with significant clinical experience offering infant, preschool, and school-aged OIT patients, with gastroenterologist input. Further research is needed to fill the knowledge gaps in the management of GI symptoms during OIT before formal recommendations can be suggested., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

In this study, we examined the clinical and electrophysiological outcomes of adolescents in Hong Kong who developed myocarditis or pericarditis following BNT162b2 vaccination for COVID-19, and followed-up for 60-180 days after their initial diagnosis. Clinical assessments included electrocardiogram (ECG) and echocardiogram at the initial admission and follow-up were compared. Treadmill testing was also performed in some cases. Between 14 June 2021 and 16 February 2022, 53 subjects were approached to participate in this follow-up study, of which 28 patients were followed up for >60 days with a median follow-up period of 100 days (range, 61-178 days) and were included in this study. On admission, 23 patients had ECG abnormalities but no high-grade atrioventricular block. Six patients had echocardiogram abnormalities, including reduced contractility, small rim pericardial effusions, and hyperechoic ventricular walls. All patients achieved complete recovery on follow-up. After discharge, 10 patients (35.7%) reported symptoms, including occasional chest pain, shortness of breath, reduced exercise tolerance, and recurrent vasovagal near-syncope. At follow-up, assessments, including ECGs, were almost all normal. Among the three patients with possible ECG abnormalities, all their echocardiograms or treadmill testings were normal. Sixteen patients (57.1%) underwent treadmill testing at a median of 117 days post-admission, which were also normal. However, at follow-up, there was a significant mean bodyweight increase of 1.81 kg (95%CI 0.47-3.1 kg, p  = 0.01), possibly due to exercise restriction. In conclusion, most adolescents experiencing myocarditis and pericarditis following BNT162b2 vaccination achieved complete recovery. Some patients developed non-specific persistent symptoms, and bodyweight changes shall be monitored.

Accruing evidence suggests an increased risk of myocarditis in adolescents from messenger RNA COVID-19 vaccines. However, other potential adverse events remain under-researched. We conducted a retrospective cohort study of adolescents aged 12-18 with a territory-wide electronic healthcare database of the Hong Kong population linked with population-based vaccination records and supplemented with age- and sex-specific population numbers. Two age- and sex-matched retrospective cohorts were formed to observe 28 days following the first and second doses of BNT162b2 and estimate the age- and sex-adjusted incidence rate ratios between the vaccinated and unvaccinated. Thirty AESIs adapted from the World Health Organization's Global Advisory Committee on Vaccine Safety were examined. Eventually, the first-dose cohort comprised 274,881 adolescents (50.25% received the first dose) and the second-dose cohort 237,964 (50.29% received the second dose). Ninety-four (34.2 per 100,000 persons) adolescents in the first-dose cohort and 130 (54.6 per 100,000 persons) in the second-dose cohort experienced ≥1 AESIs. There were no statistically significant differences in the risk of any AESI associated with BNT162b2 except myocarditis [first-dose cohort: incidence rate ratio (IRR) = 9.15, 95% confidence interval (CI) 1.14-73.16; second-dose cohort: IRR = 29.61, 95% CI 4.04-217.07] and sleeping disturbances/disorders after the second dose (IRR = 2.06, 95% CI 1.01-4.24). Sensitivity analysis showed that, with myocarditis excluded as AESIs, no significantly elevated risk of AESIs as a composite outcome associated with vaccination was observed ( P  = 0.195). To conclude, the overall absolute risk of AESIs was low with no evidence of an increased risk of AESIs except myocarditis and sleeping disturbances/disorders.

The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of <18 years old, including 34 adolescent BNT162b2 (Pfizer-BioNTech) vaccine recipients, and 15 recovered COVID-19 patients aged between 2 and 17. We demonstrated that only 38.2% of BNT162b2 vaccine recipients and 26.7% of recovered COVID-19 patients had their serum neutralization titre at or above the detection threshold in our live virus microneutralization assay. Furthermore, the neutralizing antibody titer against the Omicron variant was substantially lower than those against the ancestral virus or the Beta variant. Our results suggest that vaccine recipients and COVID-19 patients in the pediatric age group will likely be more susceptible to vaccine breakthrough infections or reinfections due to the Omicron variant than previous variants.

There has been a rapid surge of hospitalization due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants globally. The severity of Omicron BA.2 in unexposed, unvaccinated, hospitalized children is unknown. We investigated the severity and clinical outcomes of COVID-19 infection during the Omicron wave in uninfected, unvaccinated hospitalized children and in comparison with influenza and parainfluenza viral infections. This population-based study retrieved data from the HK territory-wide CDARS database of hospitalisations in all public hospitals and compared severe outcomes for the Omicron BA.2-dominant fifth wave (5-28 February 2022, n = 1144), and influenza and parainfluenza viruses (1 January 2015-31 December 2019, n = 32212 and n = 16423, respectively) in children 0-11 years old. Two deaths (0.2%) out of 1144 cases during the initial Omicron wave were recorded. Twenty-one (1.8%) required PICU admission, and the relative risk was higher for Omicron than influenza virus (n = 254, 0.8%, adjusted RR = 2.1, 95%CI 1.3-3.3, p  = 0.001). The proportion with neurological complications was 15.0% (n = 171) for Omicron, which was higher than influenza and parainfluenza viruses (n = 2707, 8.4%, adjusted RR = 1.6, 95%CI 1.4-1.9 and n = 1258, 7.7%, adjusted RR = 1.9, 95%CI 1.6-2.2, p  < 0.001 for both, respectively). Croup occurred for Omicron (n = 61, 5.3%) more than influenza virus (n = 601, 1.9%, adjusted RR = 2.0, 95%CI 1.5-2.6, p  < 0.001) but not parainfluenza virus (n = 889, 5.4%). Our findings showed that for hospitalized children who had no past COVID-19 or vaccination, Omicron BA.2 was not mild. Omicron BA.2 appeared to be more neuropathogenic than influenza and parainfluenza viruses. It targeted the upper airways more than influenza virus.

Ethnic minorities account for 8% of the Hong Kong population, most are Filipino and Indonesian domestic helpers taking care of children and the elderly. To understand the COVID-19 vaccination rates and factors associated with vaccine acceptance of ethnic minorities, we performed a cross-sectional questionnaire study recruiting Hong Kong ethnic minorities aged ≥18 years between 1 July and 18 July 2021 in public areas. Demographics, knowledge about COVID-19, vaccination status, intention and reasons to receive the vaccine, and planning to be re-vaccinated were analyzed. Continuous and categorical variables were compared using unpaired t-test and Chi-square test, respectively. Potential confounders were adjusted using multiple logistic regression. 2,012 ethnic minorities participated, with a mean age of 39 years, of which 97.6% were female, 79.5% were Filipino, and 17.5% were Indonesian. 80.6% of participants were categorized as vaccine acceptance, and 69.2% were willing to be re-vaccinated. There were significantly more Filipinos than Indonesians in the vaccine acceptance group (p < .001). Subjects in the vaccine acceptance group were more likely to have higher education (p < .001), a higher COVID-19 knowledge score (p < .001), received information from the Government website (p = .003) and not from their friends or family members (p = .02), and were more confident in judging the accuracy of the information (p < .001). Logistic regression showed the mean knowledge score (β = 3.07, p < .001) and receiving information from official Government websites (adjusted OR = 1.37, p = .03) were significant factors that positively influenced vaccine acceptance. The Hong Kong Government should improve COVID-19 vaccination acceptance among ethnic minorities through public education using official channels.

Background: The prevalence and consequences of child maltreatment are alarming, but evidence from studies with long follow-up intervals are limited. This study examined the long-term consequences of child maltreatment in relation to age of onset and follow-up interval., Methods: The exposed group comprised 63 individuals (aged 13-34 years) with a first-time diagnosis of child maltreatment between 2001 and 2010, whereas the unexposed group comprised 63 individuals who were matched upon gender, age of onset, follow-up period, and poverty status at the index hospital admission but had no medical records of maltreatment in Hong Kong. The participants completed a set of questionnaires on executive functions and mental health and provided blood samples for measurement of IL-6 and IL-10 levels during a health assessment session., Results: Compared with the unexposed group, the exposed group reported poorer maternal care during childhood (β = -4.64, p < 0.001) and had lower family support (β = -2.97, p = 0.010) and higher inflammatory responses (IL-6: β = 0.15, p = 0.001; IL-10: β = 0.11, p = 0.011) at follow-up. Additionally, the associations of childhood maltreatment exposure with family support and maternal care differed by age of onset and the length of time since exposure., Conclusions: This matched cohort study highlights childhood maltreatment as a risk factor for systemic inflammation and an indicator of suboptimal social environment, both of which could persist over a long period of time., (© 2022. The Author(s).)

There is lacking a population-based study on the fitness level of Hong Kong schoolchildren, and it seems that increasing childhood obesity prevalence has shifted the classification of healthy fitness, with 'underfit' as normal. This cross-sectional territory study aimed to develop an age- and sex-specific physical fitness reference using a representative sample of children aged 6-17 and to determine the associations with body mass index in schoolchildren. The study analyzed Hong Kong School Physical Fitness Award Scheme data covering grade 1 to grade 12 students' physical fitness and anthropometric measurements from 2017 to 2018. This reference was established without the impact due to COVID-19. Four aspects of physical fitness tests were measured using a standardized protocol, including (i) upper limb muscle strength, (ii) one-minute sit-up, (iii) sit-and-reach, and (iv) endurance run tests. The generalized additive model for location, scale, and shape was used to construct the reference charts. A Mann-Whitney U test was used to compare the mean differences in age, weight, and height, and a Pearson's chi-square test was used to examine the distributions of sex groups. A Kruskal-Wallis test was used to compare the group differences in BMI status, followed by the Dunn test for pairwise comparisons. A 5% level of significance was regarded as statistically significant. Data of 119,693 students before the COVID-19 pandemic were included in the analysis. The association between physical fitness level and BMI status varied depending on the test used, and there were significant differences in fitness test scores among BMI groups. The mean test scores of the obese group were lower in most of the tests for both boys and girls, except for handgrip strength. The underweight group outperformed the obese group in push-ups, one-minute sit-ups, and endurance run tests, but not in handgrip strength. In conclusion, a sex- and age-specific physical fitness reference value for Hong Kong Chinese children aged 6 to 17 years old is established, and this study demonstrated a nonlinear relationship between BMI status and physical fitness. The reference will help to identify children with poor physical fitness to offer support and guidance on exercise training. It also serves as a baseline for assessing the impact of the COVID-19 pandemic on Hong Kong students' physical fitness.

Context: Effect size estimates for the association between vitamin D concentrations in maternal blood during pregnancy and in cord blood vary widely across studies, but no meta-analysis has been conducted to ascertain this association., Objective: The aim of this systematic review was to estimate the pooled effect size for the association between circulating 25-hydroxyvitamin D (25[OH]D) concentrations, a marker of vitamin D status, in maternal blood during pregnancy and in cord blood., Data Sources: The PubMed, Embase, and Web of Science databases were searched from their inception to February 2021., Data Extraction: Following the application of prespecified inclusion and exclusion criteria, 94 articles were eligible for full-text review, which was conducted by 2 authors independently. A third author was consulted when necessary and consensus reached. In total, 26 articles, which comprised 30 studies and 6212 mother-infant dyads, were included. Methodological quality was assessed using a modified version of the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Correlation coefficient (r) values for the association between maternal serum 25(OH)D concentrations during pregnancy and in cord blood were extracted., Data Analysis: The r values were pooled using random-effects meta-analyses. Sensitivity and subgroup analyses were performed to investigate sources of heterogeneity. The pooled r for all studies was 0.72 (95%CI, 0.64-0.79), indicating high heterogeneity (I2 = 95%, P < 0.01). After influential and outlier studies were removed, the pooled r for 9 studies was 0.70 (95%CI, 0.66-0.74), which resulted in a substantial reduction in heterogeneity (I2 = 41%, P=0.10)., Conclusion: The findings support a positive and large correlation between maternal vitamin D concentrations during pregnancy and vitamin D concentrations in cord blood., Systematic Review Registration: PROSPERO registration number CRD42021273348., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations., Methods: Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA., Results: Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients., Conclusion: Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Recent guideline recommendations have shifted from recommending prolonged avoidance of allergenic foods in the first 3 years of life to a primary prevention approach involving the deliberate early introduction to infants at risk of developing food allergy. Despite this, some infants, especially those with severe eczema who are at highest risk for developing peanut allergy, fail to receive the preventative benefits of early peanut introduction due to hesitancy and other factors. Difficulty adhering to regular ingestion after introduction further reduces the effectiveness of primary prevention. As emerging real-world evidence has demonstrated that performing peanut oral immunotherapy (OIT) among infants is effective and safe, peanut OIT could be a treatment option for infants with peanut allergy. This review discusses the benefits, risks, and barriers to offering peanut OIT to infants who fail primary prevention strategies. We propose the novel concept that infants with peanut allergy be offered peanut OIT as soon as possible after failed peanut introduction through a shared decision-making process with the family, where there is a preference for active management rather than avoidance., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leung, Mu, Duque, Cheng, Wang, Zhang, Zhang, Tam, Lee, Lam, Chan, Cheang, Chung, Wong, Lee, Li, Chaothai, Tsang, Chua, Cheong, Au, Kwok, Chan, Chong, Lee, Ho, Lee, Tu, Peiris and Lau.)

Background: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination., Methods: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed., Results: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated., Conclusions: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose., Competing Interests: Potential conflict of interest. C. C. has received grants outside of the submitted work from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grants Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; and a personal fee from Primevigilance Ltd. A. S. Y. L. received grants outside of the submitted work from the Health and Medical Research Fund, Food and Health Bureau of the Hong Kong Government Special Administrative Region. M. Y. N. has received funding/education grants from the Food and Health Bureau of the Hong Kong Government, Radiological Society of North America, GE, Lode, Arterys, Bayer, Circle Cardiovascular Imaging and TeraRecon; honoraria for education activities from Boehringer Ingelheim; reports the following leadership roles: Vice Chair of the Education Committee for Society of Cardiovascular Magnetic Resonance and Member of the Corporate Relations Committee for Society of Cardiovascular Computed Tomography. G. C. F. C. is the CMO of Xellera and advisor of Pangenia. Y. L. L. received Government funding for COVID-19 Vaccinations in Adolescents (COVA) and is the Chairman of the Scientific Committee on Vaccine Preventable Diseases, Centre for Health Protection, HKSAR. I. W. has received research funding outside of the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Hong Kong Research Grants Council, Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, and National Health and Medical Research Council in Australia (Research grants on pharmacoepidemiology to The University of Hong Kong outside of the submitted work); consultancy fee for advising IQVIA on pharmacoepidemiology studies outside of the submitted work; payment for expert testimony from Appeal Court in Hong Kong (expert report on effects of cannabis outside of the submitted work); and speaker fees from Janssen and Medicine in the previous 3 years; reports the following leadership roles: Member of Pharmacy and Poisons Board (this is the regulatory agency in pharmaceutical product licensing), Member of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization (advise the Hong Kong Government on safety of COVID-19 vaccines), and Member of the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government (advise the Hong Kong Government on the emergency use of COVID-19 vaccines). He is also an independent nonexecutive director of Jacobson Medical in Hong Kong (salaried). P. I. has received grants outside of the submitted work from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grants Council, and Hong Kong Jockey Club Charities Trust. M. T. Y. L. reports receiving Honorarium for a talk on ADHD. W. K. C. N. reports personal honoraria for Guerbet online lecture on pediatric cardiac imaging; holds 100 shares in Moderna stock, 50 shares in Biotech stock since April, owned 100 shares in Pfizer stock from July 2020 to January 2021. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Despite concerns about the negative effects of social distancing and prolonged school closures on children's lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is lacking on the impact of the pandemic-related school closures and social distancing on children's wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns, and screen time of school-aged children during the different phases of the COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep diary, recording their daily sleep onset and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (September 2019-January 2020; n = 577), during school closures (March 2020-April 2020; n = 146), and after schools partially reopened (October 2020-July 2021; n = 227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. The later sleep onset and increased screen time documented during school closures persisted when schools partially reopened. Our findings illustrate the significant impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should urgently reinforce the importance of improving physically activity, good sleep hygiene, and regulated use of electronic devices for parents and school-aged children during this unprecedented time.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.2 sublineage has increased rapidly in Europe and Asia since January 2022. Here, we report the epidemiological and genomic analysis of a large single-source BA.2 outbreak in a housing estate., Methods: We analyzed the epidemiological information on a community outbreak of BA.2 (STY outbreak). We performed whole viral genome sequencing using the Oxford Nanopore MinION device. We calculated the doubling time of the outbreak within a housing estate., Results: The STY outbreak involved a total of 768 individuals as of 5 February 2022, including 432 residents, visitors, or staff (56.3%) from a single housing estate (KC Estate). The outbreak at the KC Estate had a short doubling time of 1.28 days (95% confidence interval: .560-1.935). The outbreak was promptly controlled with the lockdown of 3 buildings within the housing estate. Whole-genome sequencing was performed for 133 patients in the STY outbreak, including 106 residents of the KC Estate. All 133 sequences from the STY outbreak belonged to the BA.2 sublineage, and phylogenetic analysis showed that these sequences cluster together. All individuals in the STY cluster had the unique mutation C12525T., Conclusions: Our study highlights the exceptionally high transmissibility of the Omicron variant BA.2 sublineage in Hong Kong, where stringent measures are implemented as part of the elimination strategy. Continual genomic surveillance is crucial in monitoring the emergence of epidemiologically important Omicron sublineages., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Children with special educational needs (SEN) are more vulnerable during the COVID-19 pandemic with risk of poor mental wellbeing and child maltreatment., Objective: To examine the impact of COVID-19 on the mental health of children with SEN and their maltreatment risk., Participants and Setting: 417 children with SEN studying at special schools and 25,427 children with typical development (TD) studying at mainstream schools completed an online survey in April 2020 in Hong Kong during school closures due to COVID-19., Method: Emotional/behavioural difficulties, quality of life and parental stress of children with SEN were compared with typically developed children using mixed effect model. Linear regression analyses were performed to explore factors associated with child emotional/behavioural difficulties and parental stress during the pandemic. Chi-square test was performed to detect the differences in maltreatment risk before and during COVID-19., Results: Children with SEN had significantly poorer overall quality of life (68.05 vs 80.65, p < 0.01). 23.5% of children had at least one episode of severe physical assault and 1.9% experienced very severe physical assault during COVID-19. Rates of physical assault increased significantly (59.8% vs. 71.2% p < 0.001) while children with mental disorders had increased risk of severe physical assault comparing to those without mental disorders (RR = 1.58, ꭓ 2  = 5.19 p = 0.023)., Conclusion: Children with SEN had poorer mental health than typically developed children during the COVID-19 pandemic. Maltreatment risk for children with SEN is higher in comparison to pre-COVID-19 era. Surveillance of child maltreatment, continuity of medical and rehabilitation care to support children with SEN are essential during a disease pandemic., (Copyright © 2021. Published by Elsevier Ltd.)

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Wong, Leung, Yang, Fok, Mak, Yao, Ma, Mao, Zhao, Liang, Singh, Barbouche, He, Jiang, Liew, Le, Muktiarti, Santos-Ocampo, Djidjik, Belaid, Ismail, Abdul Latiff, Lee, Chen, Liu, Jin, Wang, Chien, Yu, Raj, Raj, Vaughan, Urban, Berg, Eley, Lee, Isa, Ang, Lee, Yeoh, Shek, Quynh Le, Nguyen, Phan Nguyen Lien, Capulong, Mallillin, Villanueva, Camonayan, Vera, Casis-Hao, Lobo, Foronda, Binas, Boushaki, Kechout, Phongsamart, Wongwaree, Jiratchaya, Lao-Araya, Trakultivakorn, Suratannon, Jirapongsananuruk, Chantveerawong, Kamchaisatian, Chan, Koh, Wong, Fong, Thong, Latiff, Noh, Silva, Jouhadi, Al-Saad, Vignesh, Jindal, Rawat, Gupta, Suri, Yang, Au, Kwok, Chan, Hui, Chua, Duque, Cheong, Chong, Ho, Lee, Wong, Yang, Lee, Tu, Yang and Lau.)

Legumes other than peanut are an important source of protein and consist of a wide variety of species, such as soy, peas, chickpeas, lentils, and lupin. Due to their health benefits and the rising popularity of veganism, legume consumption has increased. Legume allergy, cross-sensitization, and cross-reactivity between different species have been reported in the literature and are increasingly recognized. Unlike peanut, oral immunotherapy (OIT) for nonpeanut legumes has not been well studied and published protocols are lacking. Future studies are needed to provide real-world data on the safety and effectiveness of nonpeanut legume OIT, and whether desensitization to one legume leads to desensitization to other legumes in patients with multiple legume allergy. Nevertheless, due to the abundance of clinical trial and real-world data for peanut OIT, it is reasonable to use protocols that substitute peanut protein with other legume protein when desensitizing individuals with nonpeanut legume allergy. Clinicians who are starting to offer legume OIT in their practices may consider starting with preschoolers, an age group for whom real-world data has shown the greatest safety and effectiveness., Competing Interests: Edmond S. Chan has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Pediapharm, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma; GT Chua has no conflicts to disclose pertaining to this article, (Copyright © 2022, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N = 116) and CoronaVac (CC, N = 123) versus adults after 2 doses of the same vaccine (BB, N = 147; CC, N = 141) but not in adolescents after 1-dose BNT162b2 (B, N = 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents., (© 2022. The Author(s).)

There has been a lack of high-quality evidence concerning the association between childhood maltreatment and psychiatric diagnoses particularly for Axis II disorders. This study aimed to examine the association between childhood maltreatment exposure and Axis I and Axis II psychiatry disorders using electronic health records. In this study, the exposed group (n = 7473) comprised patients aged 0 to 19 years with a first-time record of maltreatment episode between January 1, 2001 and December 31, 2010, whereas the unexposed group (n = 26,834) comprised individuals of the same gender and age who were admitted into the same hospital in the same calendar year and month but had no records of maltreatment in the Hong Kong Clinical Data Analysis and Reporting System (CDARS). Data on their psychiatric diagnoses recorded from the date of admission to January 31, 2019 were extracted. A Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR, plus 95% CIs) between childhood maltreatment exposure and psychiatric diagnoses, adjusting for age at index visit, sex, and government welfare recipient status. Results showed that childhood maltreatment exposure was significantly associated with subsequent diagnosis of conduct disorder/ oppositional defiant disorder (adjusted HR, 10.99 [95% CI 6.36, 19.01]), attention deficit hyperactivity disorder (ADHD) (7.28 [5.49, 9.65]), and personality disorders (5.36 [3.78, 7.59]). The risk of psychiatric disorders following childhood maltreatment did not vary by history of childhood sexual abuse, age at maltreatment exposure, and gender. Individuals with a history of childhood maltreatment are vulnerable to psychiatric disorders. Findings support the provision of integrated care within the primary health care setting to address the long-term medical and psychosocial needs of individuals with a history of childhood maltreatment., (© 2022. The Author(s).)

To our best knowledge, this article presents a novel data set on Hong Kong's adolescents' attitude towards the COVID-19 vaccination, excluding their parental opinions. This research used a cross-sectional questionnaire survey, which collects data from the population at a single point in time. Our questionnaire was designed in both English and Chinese for the adolescents' convenience, using a self-designed, online questionnaire website, which was sent to 30 secondary schools across Hong Kong at the beginning of June 2021, to be completed by 31st June 2021. This gathered a total of 2609 surveys, excluding those which did not fit into the criteria. As the data has identified factors that affect vaccine hesitancy, government authorities can use the data to choose effective ways to promote the COVID-19 vaccination and to educate the general population about the benefits of receiving it., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Antimicrobial resistance is an increasingly important issue in public health as antibiotics are overused. Resistance to antimicrobial agents can pose significant challenges to infection treatment., Objectives: To evaluate risk factors associated with carriage of antimicrobial-resistant (AMR) bacteria in children in the Asia-Pacific region to consolidate evidence for future implementation of antibiotic prescribing practice., Methods: Three electronic databases-PubMed, EMBASE and Cochrane Library-were searched. Observational studies that investigated the risk factors for carriage of MRSA, penicillin-resistant Streptococcus pneumoniae , ESBL-producing Escherichia coli and Klebsiella pneumoniae among the paediatric population in community settings in the Asia-Pacific region were considered eligible. Summary statistics from the identified studies were pooled using meta-analyses., Results: From the 4145 search results, 25 papers were included in this review. Sixteen papers were included in the meta-analysis based on reported risk factors. Young age of 2-6 months compared with children aged 7-60 months (OR 2.74, 95% CI: 1.75-4.29), antibiotic use within the past 3 months (OR 2.65, 95% CI: 1.70-4.12), daycare attendance (OR 1.49, 95% CI: 1.17-1.91) and hospital admission within the past 3 months (OR 3.43, 95% CI: 2.13-5.51) were found to be significant risk factors for AMR bacterial carriage, whilst breastfeeding (OR 0.69, 95% CI: 0.60-0.81) and concurrent colonization of S. pneumoniae (OR 0.59, 95% CI: 0.38-0.91) are protective factors., Conclusions: The findings support that there are a number of significant risk factors associated with carriage of AMR bacteria in the Asia-Pacific paediatric population. To combat antimicrobial resistance in the future, these risk factors should be considered, and measures taken to mitigate associated carriage., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still's disease with atypical lung disease. We sought to characterise features of patients with Still's disease with DRESS compared with drug-tolerant Still's controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort., Methods: In a case/control study, we collected a multicentre series of patients with Still's disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still's controls (n=65). We retrospectively analysed clinical data from all Still's subjects and typed 94/131 for HLA. European Still's-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still's cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still's-DRESS cases (n=64) compared with drug-tolerant Still's controls (n=30). KD subjects (n=19) were similarly studied., Results: Still's-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still's-DRESS (64%) versus drug-tolerant Still's (3%; p=1.2×10 -14 ). We found striking enrichment for HLA-DRB1*15 haplotypes in Still's-DRESS cases versus INCHARGE Still's controls (p=7.5×10 -13 ) and versus self-identified, ancestry-matched Still's controls (p=6.3×10 -10 ). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions., Conclusions: DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted., Competing Interests: Competing interests: VES, GD, report personal fees from Novartis, SP reports fees from Novartis outside the current work, SC reports personal fees from Novartis and grants from AB2 Bio, EDM reports grants from Novartis and JAH reports grant from Genentech. Drug Hypersensitivity Consortium: SL, GSS, SS and MS report personal fees from Novartis, AAG reports grants and personal fees from Novartis and grants from NovImmune. INCHARGE Consortium: No conflicts of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Vaccines against COVID-19 are now available for adolescents in Hong Kong but vaccine hesitancy is a major barrier to herd immunity. This survey study explores Hong Kong adolescents' attitudes towards the COVID-19 vaccination. 2609 adolescents from across Hong Kong completed an online survey focused on the intent to vaccinate and the reasons for their choice. 39% of adolescents intended to take the COVID-19 vaccination and significant factors for this decision include: having at least one parent vaccinated, knowing somebody diagnosed with COVID-19 and receiving the influenza vaccine. Adolescents' major concerns were either the safety and efficacy of the vaccine or the risk of infection. This study has proved that even in adolescents the vaccine hesitancy model is prominent with adolescents' intentions highly related to confidence in the vaccine and perception of disease risk. Future interventions should target these specific concerns to ensure adolescents are well educated to overcome vaccine hesitancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: HLA-B*15:11 is associated with carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited in Chinese. Routine HLA-B*15:02 screening is mandatory before CBZ commencement, however, SCARs related to CBZ were still observed in non-HLA*B-15:02 carriers., Objective: We aimed to find out the prevalence of HLA-B*15:11 in Chinese patients and its associations with CBZ-induced SCARs., Method: We screened 8,328 blood samples collected for HLA allele typing before CBZ commencement during the period of January 2014 to December 2019. In HLA-B*15:02 negative Chinese patients, HLA-B*15:11 status were further screened, and the incidence of SCARs in the CBZ group was compared with the control group without CBZ use., Result: In this cohort, 1416 out of 8328 patients (17%) tested HLA-B*15:02 positive and were advised to avoid CBZ, while 80 (0.96%) were found to be HLA-B*15:11 positive. In 6911 (83%) patients who tested HLA-B*15:02 negative, 70 (1.01%) were HLA-B*15:11 positive. Five out of 70 (7.14%) patients had SCARs. The incidence of SCARs in HLA-B*15:11 carriers who received CBZ was significantly higher than those without CBZ (17.4% [4/23] vs. 2.13% [1/47], P = 0.037*). The odds ratio was 9.68 (95% CI 1.02-92.4, P = 0.048*). These included: one Stevens-Johnson syndrome (SJS), two DRESS, and one MPE after CBZ use, while one developed MPE after phenytoin use in control., Conclusion: HLA-B*15:11 is a potential risk factor of CBZ-induced SCARs in HLA-B*15:02 negative Chinese patients. Further screening of HLA-B*15:11 status in those HLA-B*15:02 negative patients is recommended to avoid undesirable SCARs., (© 2021 the International Society of Dermatology.)

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI), characterised by recurrent bacterial and fungal infections. It is inherited either in an X-linked (XL) or autosomal recessive (AR) mode. Phenome refers to the entire set of phenotypes expressed, and its study allows us to generate new knowledge of the disease. The objective of the study is to reveal the phenomic differences between XL and AR-CGD by using Human Phenotype Ontology (HPO) terms., Methods: We collected data on 117 patients with genetically diagnosed CGD from Asia and Africa referred to the Asian Primary Immunodeficiency Network (APID network). Only 90 patients with sufficient clinical information were included for phenomic analysis. We used HPO terms to describe all phenotypes manifested in the patients., Results: XL-CGD patients had a lower age of onset, referral, clinical diagnosis, and genetic diagnosis compared with AR-CGD patients. The integument and central nervous system were more frequently affected in XL-CGD patients. Regarding HPO terms, perianal abscess, cutaneous abscess, and elevated hepatic transaminase were correlated with XL-CGD. A higher percentage of XL-CGD patients presented with BCGitis/BCGosis as their first manifestation. Among our CGD patients, lung was the most frequently infected organ, with gastrointestinal system and skin ranking second and third, respectively. Aspergillus species, Mycobacterium bovis , and Mycobacteirum tuberculosis were the most frequent pathogens to be found., Conclusion: Phenomic analysis confirmed that XL-CGD patients have more recurrent and aggressive infections compared with AR-CGD patients. Various phenotypic differences listed out can be used as clinical handles to distinguish XL or AR-CGD based on clinical features., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with the authors DL, HM, SS, PPL and YLL., (Copyright © 2022 Chiu, Leung, Chan, Yeung, Wong, Mao, He, Vignesh, Liang, Liew, Jiang, Chen, Chen, Tao, Xu, Yu, Terblanche, Lung, Li, Chen, Tian, Eley, Yang, Yang, Chiang, Lee, Suri, Rawat, Gupta, Singh, Wong, Chua, Duque, Cheong, Chong, Ho, Lee, Yang, Lee and Lau.)

A growing body of research suggests an association between attention deficit hyperactivity disorder (ADHD) and allergic disorders, but little work has been done to explore the role of external factors such as parental smoking at home in the development of comorbid ADHD and allergic disorders. This study aimed to examine the association between allergic diseases and ADHD adjusted for exposure to parental smoking at home in early adolescents. We recruited 250 male (41.7%) and 350 female (58.3%) adolescents (mean [SD] age, 13.29 [0.52] years) via chain-referral sampling. Their ADHD symptoms were assessed by the parent proxy-report version of the Chinese Strengths and Weaknesses of Attention-Deficit/Hyperactivity-symptoms and Normal-behaviours (SWAN) rating scale. Data on the participants' history of clinician-diagnosed allergic diseases, family socio-demographics, and parental smoking habit were collected using a parent-completed questionnaire. Regression analyses were performed to examine the associations of interest. The levels of ADHD symptoms were comparable between allergic and non-allergic participants after controlling for child and family demographics and parental smoking at home. Notably, the risk of probable ADHD was particularly high in participants with food allergies (odd ratio = 4.51, p = 0.011) but not in those with allergic rhinitis after adjusting for parental smoking at home. Our findings suggest that second-hand smoke exposure at home is a potential risk factor underlying the link between ADHD and allergic diseases. Current management guidelines should emphasize the importance of early identification and cessation of tobacco smoke exposure for prevention of comorbidity of ADHD and allergic disorders. Clinical Trial Registration (if any): NA., Competing Interests: Conflict of InterestAll authors have indicated they have no potential conflicts of interest to disclose., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)