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IntroductionVaccine-related myocarditis is recognized as a rare but important complication, especially after mass-scale mRNA COVID-19 vaccination. Knowledge regarding how to minimize the risk is limited. As NK cells can mediate acute myocarditis after mRNA COVID-19 vaccination and vitamin D may inhibit NK cells via cytokine modulation, we hypothesize that the myocarditis side effect is related to a hypovitaminosis D – mRNA vaccine – hypercytokinemia – NK cell axis, which is amendable to clinical intervention.MethodsBiochemical, immunophenotypic and genotyping assays were performed to examine vitamin D status and immune profiles in 60 patients who had BNT162b2 vaccine-related acute myocarditis.ResultsA high incidence of hypovitaminosis D (73.3%) was observed in these individuals with vaccine-related myocarditis, particularly in those presented with chest pain or intensive care unit (ICU) admission. Moreover, vitamin D level was negatively associated with peak serum cardiac troponin T level during vaccine-related myocarditis. Genotypically, the GC (vitamin D binding protein) rs4588T allele which encoded the GC2 isoform of vitamin D binding protein was a risk allele, whereas the GC1S isoform was protective. Mechanistically, hypovitaminosis D was associated with higher levels of cytokines pivotal for natural killer (NK) cells (particularly interleukin-1β (IL-1β), IL-12, Interferon-γ (IFN-γ), and IL-8) and higher percentage of CD69+ NK cells in blood, which in turn correlated with chest pain presentation.ConclusionThese data support the hypothesis that vitamin D plays a crucial role in mitigating mRNA vaccine-related myocarditis by modulating proinflammatory cytokine milieu and subsequent unfavorable NK cell activation, laying a groundwork for preventive and treatment strategies.

Background: Adverse effects following immunizations (AEFIs) can contribute to vaccine hesitancy. Objective: We evaluated clinical outcomes of AEFIs subsequent to administration of the coronavirus disease 2019 (COVID-19) vaccine at 2 pediatric allergy centers. Methods: Data on pediatric patients referred for COVID-19 AEFI concerns between March 2021 and October 2022 were reviewed. The collected data included patient demographics, clinical characteristics, outcomes of prior COVID-19 vaccination, recommendations after consultation, and outcomes of revaccination. Results: The 163 patients were separated into 2 groups based on the absence (n = 89 [54.6%]) or presence (n = 74 [45.4%]) of prior COVID-19–related AEFIs. The most common reason for referral without a prior AEFI was another suspected drug allergy (n = 58 [35.6%]). All patients in this group were recommended for COVID-19 vaccination. Of the 163 patients, 82 (92.1%) proceeded with vaccination, with 77 of them (93.9%) tolerating vaccination. Most of those with a prior COVID-19–related AEFI had a delayed cutaneous reaction (n = 60 [37.0%]); 1 patient (0.6%) had suspected anaphylaxis. In this group, 6 (8.1%) were advised to postpone COVID-19 vaccination until their debilitating skin conditions had improved in response to further treatment, whereas 45 (77.6%) tolerated subsequent vaccination to the same or an alternate COVID-19 vaccine type. The most common AEFI on revaccination was urticaria (in 8 of 11 patients [72.7%]). AEFI on revaccination was significantly associated with a history of spontaneous urticaria or angioedema (relative risk = 3.6 [95% CI = 1.30-9.99]; P = .020) and urticaria following COVID-19 vaccination previously (relative risk = 4.12 [95% CI = 1.22-13.87]; P = .017). Conclusions: Children with a history of urticaria or angioedema related or unrelated to prior COVID-19 vaccination were at higher risk of a COVID-19–related AEFI on revaccination, although most were able to complete the vaccination series under the management of our immunology/allergy service.

Background: Chronic urticaria (CU), in both inducible and spontaneous forms, is associated with a substantial burden in the Asia-Pacific region (APAC). Patient-centred care recognises patients desire to be involved in decisions regarding their health. Although patient-centred approaches have previously not been studied in the context of CU management, they have demonstrated benefits in the management of other chronic conditions. Methods: Information and opinions regarding the barriers and solutions to the implementation of patient-centred approaches to the management of CU were gathered from a group of 13 expert dermatologists and allergist/immunologists from APAC through surveys and a face-to-face meeting. Results: Barriers identified there included a lack of awareness of CU amongst patients, delays in consulting healthcare providers, financial constraints, and low adherence. Particular issues raised included a lack of suitable online information for patients (83% of experts), and patients accessing oral corticosteroids without a prescription. Compliance issues were also identified as key reasons for inadequate responses to treatments (67% of experts). Solutions proposed by the authors were improving patients' knowledge about their condition (92% strongly agree, 8% agree), physicians’ consideration of patient characteristics when choosing treatments (92% strongly agree, 8% agree), implementing shared decision-making (85% strongly agree, 15% agree), and using patient-reported outcome measures (70% strongly agree, 23% agree). Conclusion: Expert opinion within APAC supports the use of patient-centred approaches to improve the management of CU. We provide several recommendations focusing on patient education and involvement in disease management as well as disease monitoring methods that can be implemented by physicians in APAC.

Abstract Background Food ladders are tools designed to facilitate home-based dietary advancement in children with food allergies through stepwise exposures to increasingly allergenic forms of milk and egg. Several studies have now documented safety and efficacy of food ladders. In 2021, we published a Canadian adaptation of the previously existing milk and egg ladders originating in Europe using foods more readily available/consumed in Canada. Our study adds to the growing body of evidence supporting food ladder use and provides safety and effectiveness data for our Canadian adaptation of the milk and egg ladders. Methods Surveys were distributed to families of children using the Canadian Milk Ladder and/or the Canadian Egg Ladder at baseline, with follow up surveys at 3 months, 6 months, and 12 months. Data were analyzed using REDCap and descriptive and inferential statistics are presented. Results One hundred and nine participants were started on milk/egg ladders between September 2020 and June 2022. 53 participants responded to follow up surveys. Only 2 of 53 (3.8%) participants reported receiving epinephrine during the study. Severe grade 4 reactions (defined according to the modified World Allergy Organization grading system) were not reported by any participants. Minor cutaneous adverse reactions were common, with about 71% (n = 10/14) of respondents reporting cutaneous adverse reactions by 1 year of food ladder use. An increasing proportion of participants could tolerate most foods from steps 2–4 foods after 3, 6, and 12 months of the food ladder compared to baseline. Conclusion The Canadian food ladders are safe tools for children with cow’s milk and/or egg allergies, and participants tolerated a larger range of foods with food ladder use compared to baseline.

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.

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.

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

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.

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

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.

Abstract 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

Abstract A food ladder is a form of home-based dietary advancement therapy that gradually increases exposure to an allergenic food through the gradual introduction of egg or milk containing food with increasing quantity and allergenicity from extensively heated forms, such as baked goods, to less processed products. While widely considered safe, the food ladder is not risk-free and most of the egg and milk ladder studies only included preschoolers with mild egg and milk allergies, and with no or well-controlled asthma. We propose a Food Ladder Safety Checklist to assist with patient selection using “4 A's” based on available evidence for food ladders, including Age, active or poorly controlled Asthma, history of Anaphylaxis, and Adherence.

There are adverse events associated with COVID-19 vaccines, such as myocarditis for adolescents following receipt of SARS-CoV-2 mRNA vaccines. Here the authors compare the immunogenicity and reactogenicity of two widely available SARS-CoV-2 vaccines (BNT162b2, an mRNA vaccine, and CoronaVac, a whole-virus inactivated vaccine) in healthy adolescents.

Abstract 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.

Objectives: Meningitis in neonates and young infants leads to significant morbidity and mortality worldwide. This study aimed to investigate pathogens, antibiotic resistance and secular change of incidence in Hong Kong. Methods: A retrospective search was performed on meningitis in neonates and infants aged

Abstract Asparaginase is an important drug to treat childhood haematological malignancies. Data on the association between human leukocyte antigens (HLA) and asparaginase hypersensitivity among Chinese are lacking. We conducted a retrospective study to identify HLA alleles associated with asparaginase hypersensitivity among Chinese children with acute lymphoblastic leukaemia (ALL), mixed phenotype leukaemia and non-Hodgkin lymphoma (NHL), who received asparaginases with HLA typing performed between 2009 and 2019. 107 Chinese patients were analysed. 66.3% (71/107) developed hypersensitivity to at least one of the asparaginases. HLA-B*46:01 (OR 3.8, 95% CI 1.4–10.1, p

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

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.

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.

Background Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking.Methods Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19.Findings 91 patients were included between March and August 20 20. NPS and saliva viral loads were correlated (r = 0.315, p = 0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r = −0.532, p

Abstract Background Complement C4A or C4B deficiency has never been reported in autoantibody-associated encephalitides patient. Here we present a case of anti-N-methyl- D-aspartate (NMDA) receptor encephalitis associated with homozygous C4B deficiency, who did not respond to intravenous immunoglobulin and pulse methylprednisolone but plasmapheresis and rituximab. Case presentation A fourteen-year-old boy presented to our unit with subacute onset of behavioral changes and confusion, and was later confirmed to be anti-NMDA receptor encephalitis. He was initially managed with intravenous immunoglobulin (IVIG) and pulse methylprednisolone but did not achieve any clinical improvement. Seven sessions of plasmapheresis was commenced with remarkable improvement after the second session, and was followed by four doses of rituximab. His neurological and cognitive functioning gradually returned to baseline. Immunological investigations demonstrated persistently low C4 levels below 8 mg/dL. A more in-depth complement analysis of the patient and his family showed that he has homozygous C4B deficiency. Genetic analysis revealed that the index patient has homozygous deficiency in complement C4B and he carries one non-functioning mutant C4B gene inherited from his mother. Conclusions Low levels of serum C4 correlate with reduced functions of the classical and lectin pathways, leading to the impairment of immune-complexes removal. Plasmapheresis ameliorates complement deficiency and removes the offending immune-complexes leading to clinical improvement that was not achieved by IVIG and steroids. We postulate that serum C4 levels may serve as a biomarker for the need of plasmapheresis upfront rather than only after non-response to steroid and IVIG in treating anti-NMDA-receptor encephalitis.

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.

X-linked lymphoproliferative disease (XLP1) is an inborn error of immunity (IEI) with severe immune dysregulation caused by a mutation in the SH2D1A gene resulting in the absence or dysfunction of signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). The severe acute respiratory syndrome (SARS) caused by SARS-coronavirus (CoV), a highly pathogenic CoV, has been shown to only cause mild diseases in Asian children. We report on a 5-year-old Nepalese boy with agammaglobulinemia and probable SARS who died of diffuse alveolar damage 22 days after admission amid the SARS outbreak. The index patient and his younger brother were genetically confirmed to have XLP1. In the current coronavirus disease 2019 (COVID-19) pandemic, most children also had mild disease only. Children with severe COVID-19 would warrant investigations for underlying IEI, particularly along the pathways leading to immune dysregulation.

Amphipod crustacean diversity and zonation are described from the large Mississippi Canyon that extends from the continental shelf across the entire continental margin. Benthic amphipods were sampled on four cruises from 2000 to 2004 from six locations in the Mississippi Canyon from depths of 480 through 2,750 m, and compared with five locations in a second transect on the open continental slope approximately 100 km west of the canyon to assess the canyon effect on the structure and composition of amphipod assemblages. Five replicates were collected from each location using 0.2 m–2 GOMEX box corer. Amphipods amounted to 40% of the total faunal abundance within the canyon compared to only 4% in the non-canyon samples. Of the seventy-two species (19 families) collected, 61 were encountered in the canyon compared to 38 on the non-canyon transect. The trough-like head of the canyon (480 m) supported high densities (4,446–26,933 ind./m2) of the filter feeding, tube dwelling ampeliscid amphipod (Ampelisca mississippiana), the highest densities sampled compared to any other single species, at any other location, either within or outside the canyon, reflecting extreme flux of organic detritus from the continental shelf. The dominance by this single species suppressed the within – habitat (alpha) diversity and evenness, compared to relatively high diversity within the 1,000–1,500 m depths interval both in and outside the canyon. The species richness and alpha diversity exhibited mid-depth maxima at ca. 1,100 m both in and out of the canyon. High species richness (61) over the entire length of the canyon is presumed to be a function of greater topographic complexity and intermittent mass wasting of sediment down the canyon axis. The absence of nestedness is attributed to the amphipod reproductive pattern that lacks dispersive larval stages and brooding comparatively small numbers of eggs in this taxon. Despite depressed diversity at the head of the canyon, the fact that the number of amphipod species in the Mississippi Canyon was 1.5 times their numbers on the adjacent slope suggests that this physiographic feature enriches geographic-scale species diversity.

BackgroundChronic 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.MethodsWe 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.ResultsXL-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.ConclusionPhenomic 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.

We report this rare case of cerebral phaeohyphomycosis in a previously healthy Chinese boy, who was found to have caspase recruitment domain family member 9 (CARD9) deficiency. Initial radiological features suggested a neoplastic cerebral lesion, while histopathological examination supplemented by internal transcribed sequencing (ITS) of cerebral tissue confirmed the diagnosis of phaeohyphomycosis. He was treated with intravenous (IV) liposomal amphotericin B and voriconazole, guided by plasma and cerebrospinal fluid (CSF) level monitoring at drug initiation. At the 1 year follow-up, the patient demonstrated near complete neurological and radiological recovery.

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged

Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or C4B isotypes. We demonstrated the diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease, such as type 1 diabetes, systemic lupus erythematosus (SLE) and encephalitis. We identified subjects with (a) the fastest migrating C4B allotype, B7, or (b) a deficiency of C4B protein caused by genetic mutation in addition to gene copy-number variation. Those variants and mutants were characterized, sequenced and specific techniques for detection developed. Novel findings were made in four case series. First, the amino acid sequence determinant for C4B7 was likely the R729Q variation at the anaphylatoxin-like region. Second, in healthy White subject MS630, a C-nucleotide deletion at codon-755 led to frameshift mutations in his single C4B gene, which was a private mutation. Third, in European family E94 with multiplex lupus-related mortality and low serum C4 levels, the culprit was a recurrent haplotype with HLA-A30, B18 and DR7 that segregated with two defective C4B genes and identical mutations at the donor splice site of intron-28. Fourth, in East-Asian subject E133P with anti-NMDA receptor encephalitis, the C4B gene had a mutation that changed tryptophan-660 to a stop-codon (W660x), which was present in a haplotype with HLA-DRB1*04:06 and B*15:27. The W660x mutation is recurrent among East-Asians with a frequency of 1.5% but not detectable among patients with SLE. A meticulous annotation of C4 sequences revealed clusters of variations proximal to sites for protein processing, activation and inactivation, and binding of interacting molecules.

ABSTRACTAs another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p

The coronavirus disease 2019 (COVID-19) pandemic has led to the deprioritization of non-emergency services, such as oral food challenges and the initiation of oral immunotherapy (OIT) for food-allergic children. Recent studies have suggested that home-based peanut OIT could be a safe and effective option for low-risk peanut-allergic children. In the period between September 1, 2020, and January 31, 2021, nine preschoolers with a history of mild allergic reactions to peanut underwent home-based peanut OIT. Eight of them (88.9%) completed the build-up phase at home in 11–28 weeks, tolerating a daily maintenance dose of 320 mg peanut protein. During the build-up, six patients (75.0%) reported urticaria, three (33.3%) reported gastrointestinal tract symptoms, and one (14.3%) reported oral pruritis. None of the patients developed anaphylaxis, required epinephrine, or attended emergency services related to OIT. One or two virtual follow-up visits were completed per patient during the build-up phase. Our case series shows that home-based OIT could be offered to the low-risk preschoolers during the COVID-19 pandemic when non-emergency services are limited and could be considered beyond the pandemic, especially for the families living in the rural or remote areas that may otherwise be unable to access OIT.

Haematological and immunological data of children with COVID-19 infection is lacking. Between 21st January and 20th March 2020, 244 children who were confirmed to have COVID-19 infection and admitted to the Wuhan Children's Hospital, China were retrospectively reviewed. 193 children were considered as symptomatic, which was defined as having either the presence of clinical symptoms or the presence of CT thorax abnormalities. Their haematological and immunological profiles, including complete blood counts, lymphocyte subsets (T, B and NK cell counts), immunoglobulin (Ig) profiles (IgG, IgA and IgM) and cytokine profiles were analysed and compared between the symptomatic and asymptomatic groups. The median values and the interquartile ranges were calculated. Comparison was made using the Mann–Whitney U test. Children with symptomatic COVID-19 infection had significantly lower haemoglobin levels, but higher absolute lymphocyte and monocyte counts, IgG and IgA levels, as well as interleukin 6 (IL-6), IL-10, tumour necrosis factor alpha and interferon gamma levels. The obtained data will be utilized for further studies in comparing children and adults with COVID-19 infections in other parts of the world and with different severity .

Background: The Asia Pacific Society for Immunodeficiencies (APSID) conducted nine primary immunodeficiency (PID) Schools in 5 years since inauguration to provide PID care training for early career physicians in Asia Pacific, a region with divergent needs in PID resources and training.Objective: To identify differences in PID patient care resource and training needs across Asia Pacific and propose a corresponding action plan.Methods: The Human Development Index (HDI) indicates the degree of socio-economic development in each country/region. Information related to investigations and learning issues were extracted from the abstracts and personal statements from all Schools and mapped onto resource and training needs. Correlations between HDI and country/region-specific parameters were tested by two-tailed Pearson correlation.Results: A total of 427 abstracts were received in nine Schools between 2015 and 2020, predominantly on immunodeficiencies affecting cellular and humoral immunity. Genetic confirmation was described in 61.8% of abstracts, and its absence negatively correlated with HDI (r = −0.696, p = 0.004). Essential immunologic and genetic tests were not available in 25.4 and 29.5% of abstracts, respectively, and their absence negatively correlated with HDI (r = −0.788, p < 0.001; r = −0.739, p = 0.002). HDI positively correlated with average testing level (r = 0.742, p = 0.002). Cases from medium-HDI countries/regions focused on learning how to investigate a patient for PIDs in cases of severe or atypical infections, whereas those from very-high-HDI countries/regions, from which most faculty members originated, listed hematopoietic stem cell transplantation and gene therapy, newborn screening, and research as learning issues more frequently.Conclusion: There are unique HDI-related PID resource and training needs in each country/region. APSID proposes HDI group-specific strategies to improve PID care and education in her member countries/regions. Further quantitative analysis of needs in PID care in Asia Pacific is needed for lobbying governments to increase their support for PID care and research.

Abstract Background Patients with Alzheimer's disease (AD) demonstrate the narrowing of retinal veins and decreased retinal venous blood flow compared with control subjects. We assessed whether these abnormalities are present in patients with mild cognitive impairment (MCI). Methods After the determination of the global clinical dementia rating, 52 subjects (10 AD, 21 MCI, and 21 normal controls) underwent retinal hemodynamic profiling. Blood column diameter, blood speed, and blood flow were measured in a major temporal retinal vein using retinal laser Doppler flowmetry. In addition, peripapillary retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography. Results Blood column diameter in AD was narrower than in both MCI (P = .004) and controls (P = .002). However, blood speed in both AD (P = .024) and MCI (P = .005) was lower than in controls. As a result, the differences in blood flow between AD and MCI (P = .036), AD and controls (P

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.

Author(s): Rosa S. Wong [sup.1] [sup.2] [sup.3] , Keith T. S. Tung [sup.1] , Hugo E. Leung [sup.1] , Reena Chow [sup.1] , Gilbert T. Chua [sup.1] , Macro H. [...], 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&apos; 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.

Introduction: Vaccine-related myocarditis is recognized as a rare but important complication, especially after mass-scale mRNA COVID-19 vaccination. Knowledge regarding how to minimize the risk is limited. As NK cells can mediate acute myocarditis after mRNA COVID-19 vaccination and vitamin D may inhibit NK cells via cytokine modulation, we hypothesize that the myocarditis side effect is related to a hypovitaminosis D – mRNA vaccine – hypercytokinemia – NK cell axis, which is amendable to clinical intervention. Methods: Biochemical, immunophenotypic and genotyping assays were performed to examine vitamin D status and immune profiles in 60 patients who had BNT162b2 vaccine-related acute myocarditis. Results: A high incidence of hypovitaminosis D (73.3%) was observed in these individuals with vaccine-related myocarditis, particularly in those presented with chest pain or intensive care unit (ICU) admission. Moreover, vitamin D level was negatively associated with peak serum cardiac troponin T level during vaccine-related myocarditis. Genotypically, the GC (vitamin D binding protein) rs4588T allele which encoded the GC2 isoform of vitamin D binding protein was a risk allele, whereas the GC1S isoform was protective. Mechanistically, hypovitaminosis D was associated with higher levels of cytokines pivotal for natural killer (NK) cells (particularly interleukin-1β (IL-1β), IL-12, Interferon-γ (IFN-γ), and IL-8) and higher percentage of CD69+ NK cells in blood, which in turn correlated with chest pain presentation. Conclusion: These data support the hypothesis that vitamin D plays a crucial role in mitigating mRNA vaccine-related myocarditis by modulating proinflammatory cytokine milieu and subsequent unfavorable NK cell activation, laying a groundwork for preventive and treatment strategies. [ABSTRACT FROM AUTHOR]