The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination.

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-1ß (IL-1ß), 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).

Natural history of infants with vitamin D deficiency in Hong Kong.

BACKGROUND AND OBJECTIVES: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD. METHODS AND STUDY DESIGN: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected. RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L). CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Does obesity persist from childhood to adolescence? A 4-year prospective cohort study of chinese students in Hong Kong.

BACKGROUND: Little is known about the progression of obesity from childhood to adolescence. This study aimed to longitudinally examine the obesity status in a cohort of children across their childhood and adolescence, and to identify the factors associated with persistent obesity. METHODS: The study used data from School Physical Fitness Award Scheme (SPFAS), a population-based programme in Hong Kong primary and secondary schools. Students were included if they participated in the SPFAS in both 2014 (Primary 1 and 2) and 2018 (Primary 5 and 6). Their anthropometric and physical fitness parameters were analyzed. RESULTS: A total of 18,863 students were included. The baseline prevalence of obesity was 5.7 %. After 4 years, the prevalence increased to 6.7 %. Among those with obesity at baseline, 35.3 % remained obese after 4 years. The addition of baseline physical fitness level did not improve the prediction for persistent obesity. CONCLUSIONS: One-third of obese students in junior primary school remained to be obese into adolescence. Their baseline physical fitness level did not improve the predictive value for future obesity. Further studies should investigate the prognostic factors that may influence the natural course of childhood obesity.

Effect of Pokémon Go on Self-Harm Using Population-Based Interrupted Time-Series Analysis: Quasi-Experimental Study.

BACKGROUND: Pokémon Go is a very popular location-based augmented reality game with widespread influences over the world. An emerging body of research demonstrates that playing Pokémon Go can lead to improvements in physical activity and psychosocial well-being; however, whether Pokémon Go reduces self-harm incidence at the population-level is still questionable. OBJECTIVE: This study aimed to quantify how the launch of Pokémon Go in Hong Kong affected the incidence of self-harm using a quasi-experimental design. METHODS: An interrupted time-series design with Poisson segmented regression adjusted for time and seasonality trends was used on data from 2012 to 2018 to detect any changes in the number of accident and emergency attendances due to self-harm, after Pokémon Go was launched. The findings were validated using a baseline control period and using other intentional injuries and minor noninjuries as control outcomes. We also assessed intervention effects by age group. RESULTS: From January 1, 2012 to July 31, 2018, there were 13,463 accident and emergency attendances due to self-harm in Hong Kong. During the period after launching Pokémon Go, self-harm attendances dropped by 34% (adjusted incidence rate ratio: 0.66, 95% CI 0.61-0.73). When analyzed by age group, a reduction in self-harm incidence was only apparent in adults (18 to 24 years of age: adjusted incidence rate ratio: 0.78, P=.02; 25 to 39 years of age: adjusted incidence rate ratio: 0.75, P<.001; 40 years of age and older: adjusted incidence rate ratio: 0.57, P<.001). CONCLUSIONS: Self-harm incidence in the population, particularly in adults, showed a significant decline in the period after Pokémon Go was launched. Augmented reality games such as Pokémon Go show great promise as a tool to enhance psychosocial well-being and improve mental health.

A prospective cohort study to investigate parental stress and child health in low-income Chinese families: protocol paper.

INTRODUCTION: Chronic stress has adverse effects on health. Adults and children from low-income families are subject to multiple sources of stress. Existing literature about economic hardship mostly focuses on either adults or children but not both. Moreover, there is limited knowledge on the relationship between parental generalised stress and child health problems. This study aims to explore the bidirectional relationship between parental stress and child health in Chinese low-income families and to identify other modifiable factors influencing this relationship. METHODS AND ANALYSIS: This prospective cohort study will sample 254 low-income parent-child pairs and follow them up for 24 months with assessments at three time points (baseline, 12 and 24 months) on parental stress, health-related quality of life (HRQOL) and child health and behaviour using both subjective measures and objective physiological parameters. This study will collect data using standardised measures on HRQOL and behaviours of children as well as on HRQOL, mental health and stress levels of parents along with physiological tests of allostatic load and telomere length. The mediating or moderating effect of family harmony, parenting style and neighbourhood conditions will also be assessed. Data will be analysed using latent growth modelling and cross-lagged path analysis modelling to examine the bidirectional effect of parental stress and child health over time. Mediation and moderation analysis will also be conducted to examine the mechanism by which the variables relate. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the University of Hong Kong-the Hospital Authority Hong Kong West Cluster, reference no: UW 16-415. The study findings will be disseminated through peer-reviewed publications and international conferences. TRIAL REGISTRATION NUMBER: NCT03185273; Pre-results.

Fall-related attendance and associated hospitalisation of children and adolescents in Hong Kong: a 12-year retrospective study.

OBJECTIVES: The present study aimed to examine the trends and characteristics of fall-related attendance in accident and emergency department (AED) by injury type and the trend in associated average length of stay (LOS) among children and adolescents in Hong Kong. DESIGN: A retrospective approach was adopted. SETTING: AED, involving all local public emergency departments from 2001 to 2012. PARTICIPANTS: 63 557 subjects aged 0-19 years with fall injury record were included in the analysis. PRIMARY OUTCOME MEASURES: Fall-related injury number and rates were calculated and reported. Poisson and negative binomial regression models were used to study the trends of injury incidence rate at different body regions. RESULTS: AED fall-related attendance rate increased significantly with an annual percentage change of 4.45 (95% CI 3.43 to 5.47%, p<0.0001). The attendance number of male subjects was persistently higher than female subjects. The standardised rate of fracture injury increased by 1.31% (95% CI 0.56 to 2.05%, p<0.0001) and that of non-fracture injury increased by 9.23% (95% CI 7.07 to 11.43%, p<0.0001) annually. Upper limb was the most frequently fractured location. It included forearm/elbow, shoulder/upper arm and wrist/hand with descending order of frequency. On the contrary, head was the most frequent non-fracture location, followed by forearm/elbow. CONCLUSIONS: The rates of fall-related attendance have been increasing and still remain high. There were significant increases in non-fracture injuries. Fractures were most frequently found in the upper extremity of a child while the most common non-fracture location was head. It appears that more efforts should be made and preventive measures should be implemented for children and adolescents in Hong Kong.

Prenatal Tobacco Exposure Shortens Telomere Length in Children.

INTRODUCTION: Preliminary evidence suggests a possible association between prenatal tobacco exposure and telomere length in children. This study was conducted to investigate whether maternal smoking during pregnancy was associated with telomere shortening in their children and whether prenatal and childhood exposure to environmental tobacco had any impact on this association. METHODS: This is a population-representative study on the association between prenatal tobacco exposure and telomere length in children. Ninety-eight Hong Kong Chinese children aged under 15 years with prenatal tobacco exposure and 98 age- and gender-matched controls were recruited from a population health study with stratified random sampling. RESULTS: Telomere length in children with prenatal tobacco exposure was significantly shorter than in those with no exposure (mean T/S ratio = 24.9 [SD = 8.58] in exposed vs. 28.97 [14.15] in control groups; P = 0.02). A negative dose-response relationship was observed between the T/S ratio and tobacco exposure duration: the longer the duration of maternal smoking in pregnancy, the shorter the child's telomere length. The association between the child's telomere length and prenatal tobacco exposure remained significant after considering the influence of family socioeconomic status and exposure to environmental tobacco smoke during pregnancy and childhood. CONCLUSIONS: Prenatal tobacco exposure was associated with telomere shortening in children. As this may impose significant health impacts through fetal genetic programming, more efforts should be made to reduce fetal tobacco exposure by educating pregnant women to not smoke and motivating smokers to quit in early pregnancy. IMPLICATIONS: As reflected by telomere shortening, prenatal tobacco exposure in children can cause premature aging and increased health risks, which we suggest is entirely preventable. Not smoking during pregnancy or quitting smoking is critical to improving the health outcome of our future generations as prenatal tobacco exposure may affect children's biological programming.