The complement system and human autoimmune diseases

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

Cardiac Involvement related to COVID-19 Infection and Vaccination in Children and Adolescents – Hong Kong's Perspective

Myocarditis and Pericarditis have many virological and immunological causes. This article described the SARS-CoV involvement to the heart in children and adolescents, also the entity Multisystem Inflammatory Syndrome in Children (MIS-C), a rare but severe consequence of SARS-CoV2 infection. Hong Kong case definition of MIS-C was listed. The consensus from overseas experts was that MIS-C should be managed by multidisciplinary team with a structured long-term follow-up to monitor the functioning of various organs and ascertain the prognosis. The side effect mRNA vaccination causing myocarditis and pericarditis is also concern of paediatricians worldwide. Hong Kong published local epidemiology of acute myocarditis and pericarditis among adolescents following Comirnaty vaccination, the local and overseas data were used in fine-tuning the COVID vaccination program in children and adolescents. To prevent severe and fatal outcome of COVID-19 diseases, it is important to educate the public and to promote COVID-19 vaccination in the community, also to continue monitoring the safety of the available vaccines

Evidence of individual differences in the long-term social, psychological, and cognitive consequences of child maltreatment

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

Associations between childhood maltreatment and psychiatric disorders: analysis from electronic health records in Hong Kong

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

Adverse events of special interest following the use of BNT162b2 in adolescents: a population-based retrospective cohort study

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

Medium-term Outcomes of Myocarditis and Pericarditis following BNT162b2 Vaccination among Adolescents in Hong Kong

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 to 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 1.81kg (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

Association of early nutritional status With child development in the Asia Pacific region

Importance: Stunting was used as a proxy for underdevelopment in early childhood in previous studies, but the associations between child development and other growth and body composition parameters were rarely studied. Objective: To estimate the association between malnutrition and early child development (ECD) at an individual level. Design, Setting, and Participants: This population-based, cross-sectional study used data from the East Asia Pacific Early Child Development Scales, a population-representative survey of children aged 3 to 5 years old, conducted in 2012 to 2014 in communities in Cambodia, China, Mongolia, Papua New Guinea, and Vanuatu. Data analysis was performed from November 2019 to April 2021. Exposures: Stunting (height-for-age [HFA] z score less than −2), wasting (weight-for-height z score less than −2), overweight (weight-for-height z score greater than 2), body mass index (BMI)–for-age z score, and body fat proportion based on existing growth standard and formula. Main Outcomes and Measures: ECD directly assessed using the validated East Asia–Pacific ECD Scales. Results: A total of 7108 children (3547 girls; mean [SD], age 4.48 [0.84] years) were included in this study. The prevalence of stunting was 27.1% (range across countries, 1.2%-55.0%), that of wasting was 13.7% (range, 5.4%-35.9%), and that of overweight was 15.9% (range, 2.2%-53.7%). Adjusted for country variations, age, sex, urbanicity, family socioeconomic status, and body fat proportion, ECD was linearly associated with HFA (β, 1.57; 95% CI, 1.35-1.80) and BMI-for-age (β, 0.64; 95% CI, 0.45-0.82). After adjustment for BMI and height, better ECD was associated with low body fat proportion (β, 0.93; 95% CI, 0.45-1.42). The association of HFA was more pronounced in Southeast Asia and the Pacific region than in East Asia, and the association of fat proportion was specific to children living in urban environments. Conclusions and Relevance: HFA, BMI-for-age, and body fat proportion were independently associated with ECD, and these findings suggest that future studies should consider using these parameters to estimate the prevalence of child underdevelopment; nutritional trials should examine to what extent the associations are causal

Age- and sex-specific physical fitness reference and association with body mass index in Hong Kong Chinese schoolchildren

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

Vaccine Potential of Nipah Virus-Like Particles

Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease