A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%).

Development and validation of the Post-COVID Symptom Scale for Children/Youth (PCSS-C/Y).

This study aims to develop and validate the Post-COVID Symptom Scale for Children/Youth (PCSS-C/Y), which is a comprehensive tool for measuring the symptom burden of post-COVID-19 conditions-persistent symptoms after SARS-CoV-2 infection, commonly known as Long COVID-and its impact on health-related quality of life among children and adolescents. Parents of children and adolescents, adolescents, and young adults with and without a history of COVID-19 were invited to fill in a questionnaire from October 2022 to June 2023. There were 386 valid parent proxy-reported responses, 433 valid adolescent self-reported responses, and 324 valid young adult self-reported responses included in the final analysis.

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

Outcomes of X-Linked Agammaglobulinaemia Patients.

Background: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications.

Medium-term immunogenicity of three doses of BNT162b2 and CoronaVac in Hong Kong neuromuscular disease patients.

The durability of the immunogenicity elicited by three doses of mRNA-based BNT162b2 and whole-virus inactivated CoronaVac in patients with neuromuscular diseases, particularly those on immunosuppressive drugs and variants of concern, has not been well-established. Our goal was to evaluate medium-term humoral immunogenicity outcomes after 3 doses of these vaccines. Peripheral blood samples were collected from participants 14-49 days and 155-210 days after administration of the third vaccine dose to assess humoral immune responses through serological assays.

Seroepidemiology of Measles and Rubella Among Hong Kong Young Adults and the Humoral Responses of a Measles-Mumps-Rubella Booster Among Participants With Low Antibody Levels.

Background: Some individuals may not retain adequate immunity against measles and rubella years after 2 doses of measles, mumps, and rubella (MMR) vaccination due to vaccine failure. This study aimed to investigate the rates of vaccine failure and seroconversion by administering an MMR booster to young adults.

Methods: We first assessed measles and rubella antibody levels using the Luminex multiplex assay, Vitek Immunodiagnostic Assay System (VIDAS) immunoglobulin G assay, and plaque reduction neutralization test among individuals aged 18-30 years who had received 2 doses of MMR vaccine.

Transcriptomic features of systemic lupus erythematosus patients in flare and changes during acute in-hospital treatment.

Objectives: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies.

Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents.

Background: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.

A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection.

Background: Autosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced.

Case Presentation: Two half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.

Risk and Factors associated with disease manifestations in systemic lupus erythematosus - lupus nephritis (RIFLE-LN): a ten-year risk prediction strategy derived from a cohort of 1652 patients.

Objectives: Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients - Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus - Lupus Nephritis (RIFLE-LN).

Hesitancy, reactogenicity and immunogenicity of the mRNA and whole-virus inactivated Covid-19 vaccines in pediatric neuromuscular diseases.

The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two widely used COVID-19 vaccines that confer immune protection to healthy individuals. However, hesitancy toward COVID-19 vaccination appeared to be common for patients with neuromuscular diseases (NMDs) due to the paucity of data on the safety and efficacy in this high-risk patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for NMDs and assessed the reactogenicity and immunogenicity of these two vaccines.

Immunogenicity against wild-type and Omicron SARS-CoV-2 after a third dose of inactivated COVID-19 vaccine in healthy adolescents.

Introduction: Two doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data.

Methods: With an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.

COVID-19 vaccines versus pediatric hospitalization.

Vaccine effectiveness of BNT162b2 and CoronaVac against COVID-19-associated hospitalization and moderate-to-severe disease due to SARS-CoV-2 Omicron BA.2 is studied from the 1.36 million doses administered to 766,601 of 953,400 children aged 3-11 years and adolescents aged 12-18 years in Hong Kong as of April 2022.

Diagnostic challenge in a series of eleven patients with hyper IgE syndromes.

Hyper IgE syndromes (HIES) is a heterogeneous group of Inborn Errors of Immunity characterized by eczema, recurrent skin and lung infections associated with eosinophilia and elevated IgE levels. Autosomal dominant HIES caused by loss of function mutations in Signal transducer and activator of transcription 3 () gene is the prototype of these disorders. Over the past two decades, advent in genetic testing allowed the identification of ten other etiologies of HIES.

Effectiveness of BNT162b2 and CoronaVac in children and adolescents against SARS-CoV-2 infection during Omicron BA.2 wave in Hong Kong.

Background: The SARS-CoV-2 Omicron BA.2 subvariant replaced BA.1 globally in early 2022, and caused an unprecedented tsunami of cases in Hong Kong, resulting in the collapse of elimination strategy.

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents.

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.

Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity.

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.

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 60-180 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.