Signal transducer and activator of transcription 1 (STAT1) gene mutations have broad clinical phenotypes, classified by the inheritance pattern and functional state. Individuals with autosomal dominant STAT1 deficiency are more susceptible to intracellular bacteria, the hallmark of which is Mendelian susceptibility to mycobacterial diseases (MSMDs) that are associated with increased risks of invasive disease by weakly virulent mycobacteria. We report a novel de novo heterozygous missense mutation in exon 23 of the STAT1 gene (NM_007315.4):c.2129C>T(p.Ser710Phe) (S710F), located in the transactivation domain (TAD) for two Chinese siblings, whereby the index patient presented with multifocal osteomyelitis after Bacillus Calmette-Guerin (BCG) vaccine, while the younger sibling was spared the infection, as BCG vaccination was withheld at birth. STAT1 loss-of-function was confirmed by the gamma-activated sequence reporter assay, representing the first loss-of-function mutation in the TAD of the STAT1 gene. Both parents did not have the same mutation, and this finding is suggestive of gonadal mosaicism.

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: Seafood is a common cause of food allergyand anaphylaxis, but there are limited published real-world datadescribing the clinical presentation offish and shellfish allergies. OBJECTIVE: This study aimed to examine the clinicalcharacteristics, immunological profile, and tolerance pattern tofish, crustaceans, and mollusks infish-allergic individuals. METHODS: Patients presenting with IgE-mediatedfish allergybetween 2016 and 2021 were recruited. A comprehensivesensitization profile including specific IgE and skin prick test tovariousfish and shellfish species and a detailed clinical historyincluding individuals'recent seafood consumption wereevaluated. RESULTS: A total of 249fish-allergic individuals (aged 4.2-5.8years) were recruited from 6 allergy clinics in Hong Kong, andthey had experienced theirfish-allergic reaction 2.2-3.4 yearsbefore enrollment. Seventy-five subjects (30%) reacted to eithergrass carp, salmon, grouper, or cod in oral food challenges. Weidentified an IgE sensitization gradient that corresponded to thelevel ofb-parvalbumin infish. In total, 40% offish-allergic in-dividuals reported tolerance to 1 or more types offish, morecommonly tofish with a lowerb-parvalbumin level such as tunaand salmon, compared withb-parvalbumin-richfish such ascatfish and grass carp. Despitefish and shellfish cosensitization,41% of individuals reported tolerance to crustaceans, mollusks,or both, whereas shellfish avoidance occurred in half of thefish-allergic individuals, of whom 33% lacked shellfish sensitization. CONCLUSIONS: Fish allergy commonly presents in earlychildhood. A considerable proportion offish-allergic patients areselectively tolerant to certainfish, typically those with lowerlevels ofb-parvalbumin. There is an unmet need to promoteprecision medicine for seafood allergies. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of the American Academy ofAllergy, Asthma & Immunology. This is an open access articleunder the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Signal transducer and activator of transcription (STAT)-6 is a transcription factor central to pro-allergic immune responses, although the function of human STAT6 at the whole-organism level has long remained unknown. Germline heterozygous gain-of-function (GOF) rare variants in STAT6 have been recently recognized to cause a broad and severe clinical phenotype of early-onset, multi-system allergic disease. Here, we provide an overview of the clinical presentation of STAT6-GOF disease, discussing how dysregulation of the STAT6 pathway causes severe allergic disease, and identifying possible targeted treatment approaches. Finally, we explore the mechanistic overlap between STAT6-GOF disease and other monogenic atopic disorders, and how this group of inborn errors of immunity (IEIs) powerfully inform our fundamental understanding of common human allergic disease.

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. Participants with low measles and/or rubella antibody levels as confirmed by VIDAS received an MMR booster. Antibody levels were measured at 1 month postbooster.Results Among 791 participants, the measles and rubella seroprevalence rates were 94.7% (95% confidence interval [CI], 92.9%-96.0%) and 97.3% (95% CI, 96.0%-98.3%), respectively. Lower seroprevalence rates were observed among older participants. One hundred thirteen participants who received an MMR booster acquired higher measles and rubella antibody levels at 1 month postbooster compared to baseline.Conclusions Although measles and rubella vaccine failures were observed among 5.3% and 2.7% of young adults, respectively, an MMR booster triggered a significant antibody response. Young adults in Hong Kong had failure rates of 5.3% and 2.7% to measles and rubella vaccines, respectively. One month after an MMR booster, antibody levels against measles and rubella increased significantly, even for participants who had vaccine failures.

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. To describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies. Patients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed. 99 patients with a median age of 29.02 years (IQR 12.83–37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04–8.38) which decreased over time (p = 0.004). 40

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. The immunogenicity outcomes of each patient were compared to those of three age-matched healthy control participants, ensuring a balanced comparison. Both patients that received 3 doses of BNT162b2 and 10 (90.9%) patients that received CoronaVac seroconverted against wild-type-SARS-CoV-2 virus, showing comparable antibody responses to healthy participants. After 6 months, one patient in BNT162b2 and all four patients in CoronaVac groups maintained seropositivity. The JN-1 specific binding antibody response was lower compared to wild-type virus. The use of corticosteroids did not affect seroconversion rate against wild-type virus or JN.1 variant. BNT162b2 and CoronaVac were immunogenic for neuromuscular diseases patients, maintaining durability after 6 months even for those on corticosteroids. Our data support a rapid immunization series utilizing mRNA-based and whole-virus inactivated vaccines for future pandemic.

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. These vaccines confer substantial protection.

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. Patients aged 8–18 years with no cognitive delay were invited to complete surveys in January and April 2022. Patients aged 2–21 years were enrolled for COVID-19 vaccination between June 2021 and April 2022, and they recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before and within 49 days after vaccination to measure serological antibody responses compared to healthy children and adolescents. Forty-one patients completed vaccine hesitancy surveys for both timepoints, while 22 joined the reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81–75.1, p = .010). Pain at the injection site, fatigue, and myalgia were the commonest ARs. Most ARs were mild (75.5%, n = 71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of either vaccine, similar to 280 healthy counterparts. There was lower neutralization against the Omicron BA.1 variant. BNT162b2 and CoronaVac were safe and immunogenic for patients with NMDs, even in those on low-dose corticosteroids.

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 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored. Results A homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified. Discussion The primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity.

Introduction: Telerehabilitation provides physical training to patients through telecommunication networks. We examined the feasibility, safety, and efficacy of an integrated, personalized, respiratory and motor telerehabilitation program for pediatric patients with hereditary neuromuscular disorders (NMDs). Methods: Stable pediatric patients were recruited for a 16-week home training program with personalized pulmonary, upper and lower limb exercises. Patients reviewed instructional videos at home and attended bi-weekly follow-ups through video or audio calls, text messages, or emails. The primary outcomes were respiratory function, Medical Research Council (MRC) grading, hand/pinch strength, 6-minute walk test, and Pediatric Quality-of-Life Inventory 3.0 Neuromuscular Module survey. The secondary outcomes were study compliance and user feedback. Results:Patients with spinal muscular atrophy (n = 4), congenital myasthenic syndrome (n = 2), and Duchenne muscular dystrophy (n = 2) completed the program. The median weekly exercise time was 101.3 min (range: 30.0-266.9). No extra face-to-face physiotherapy sessions were requested by the patients. No adverse events were reported. After the study, patients showed improvements in maximal expiratory pressure (35.0 vs. 47.5 cm H2O, p = .028) and maintained their MRC grade, hand/pinch strength, and walking distance. Patients also reported improvements in the Pediatric Quality-of-Life Inventory 3.0 Neuromuscular Module survey score (74.5 vs. 87.0, p = .036). Patients rated the overall program highly (mean: 4.00/5.00) and recommended it as a standard of care (mean: 4.38/5.00). Discussion: Our telerehabilitation program was feasible, safe, and possibly effective for this pilot cohort of stable pediatric patients with hereditary NMDs. Larger-scale studies for longer periods are warranted to confirm the results.

ABSTRACTBackgroundPatients with kidney diseases are at risk of severe complications from COVID-19, yet little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases.MethodsWe investigated the immunogenicity and safety of an accelerated, 3-dose primary series of COVID-19 vaccines among 64 pediatric chronic kidney disease patients (mean age 12.2; 32 male) with or without immunosuppression, dialysis, or kidney transplant. CoronaVac was given to those aged <5 years, 0.1ml BNT162b2 to those aged 5-11 years, and 0.3ml BNT162b2 to those aged 11-18 years.ResultsAntibody responses including S-RBD IgG (90.9-100% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6-94.0%) were significantly elicited by 3 doses of any vaccine. T cell responses were also elicited. Weaker neutralization responses were observed among kidney transplant recipients and non-dialysis children receiving rituximab for glomerular diseases. Neutralization was reduced against Omicron BA.1 compared to wild-type (post-dose 3 sVNT% level; 84% vs 27.2%; p<0.0001). However, T cell response against Omicron BA.1 was preserved, which likely confer protection against severe COVID-19. Hybrid immunity was observed after vaccination in infected patients, as evidenced by higher Omicron BA.1 neutralization response among infected patients receiving 2 doses than those uninfected. Generally mild or moderate adverse reactions following vaccines were reported.ConclusionsOur findings support that an accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.TRIAL REGISTRATIONClinicaltrials.govNCT04800133SIGNIFICANCE STATEMENTLittle is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. This paper describes the antibody and T cell responses of 3 doses of CoronaVac or BNT162b2, the top 2 COVID-19 vaccines distributed worldwide, by an accelerated regimen in patients with kidney diseases aged 1-18 years. Antibody and T cell responses were significantly elicited by either vaccine. Neutralization was reduced against Omicron while T cell response was preserved, which likely confer protection against severe COVID-19. Rate of severe adverse reactions was low in the study. Results confirm that accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.

There is no available data pertaining to humoral and cellular response against COVID-19 among young children with kidney diseases following inactivated vaccine.1Han B. Song Y. Li C. Yang W. Ma Q. Jiang Z. Li M. Lian X. Jiao W. Wang L. et al.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial.Lancet Infect Dis. 2021; 21: 1645-1653https://doi.org/10.1016/S1473-3099(21)00319-4Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar We therefore evaluated the immunogenicity and safety of 3-dose CoronaVac at an accelerated schedule (0.5ml; day 0, 14, 28) in a prospective study in Hong Kong (COVAC; NCT04800133) (Supplementary Methods).2Ma A.L.-T. Leung D. Chan E.Y.-H. Chim S. Cheng S. Ho F.T.-W. Lai W.-M. Tong P.-C. Lee M.H.-L. Wong W.H.-S. et al.Antibody responses to 2 doses of mRNA COVID-19 vaccine in pediatric patients with kidney diseases.Kidney International. 2022; 101: 1069-1072Abstract Full Text Full Text PDF Scopus (6) Google Scholar Sixty-four children were enrolled and five young children (median age 3.3 years, IQR 3.1-3.6; 3 females; 3 Chinese) were analyzed (glomerular disease on immunosuppression, n=2; aCKD, n=2; kidney failure, n=1). (Table S1) We tracked antibody responses in our patients against wild-type (WT) SARS-CoV-2, including S-RBD IgG for binding antibody and surrogate virus neutralization test (sVNT) for neutralization longitudinally from pre-vaccine baseline to post-dose 3 (Fig. 1A and 1B).3Rosa Duque J.S. Wang X. Leung D. Cheng S.M.S. Cohen C.A. Mu X. Hachim A. Zhang Y. Chan S.M. Chaothai S. et al.Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents.Nat Commun. 2022; 13: 3700https://doi.org/10.1038/s41467-022-31485-zCrossref PubMed Scopus (18) Google Scholar After 3 doses, all were seropositive for S-RBD IgG and had a high geometric mean sVNT% level of 94.0%, with increases in titers following successive doses. We also studied IFN-γ+ antiviral CD4+ helper and CD8+ cytotoxic T-cell responses against SARS-CoV-2 S, N and M proteins (Fig. 2). We detected a significant increase of SNM-specific IFN-γ+ CD4+ T-cell response in all 5 patients (Fig. 2B). Other T-cell responses such as IL-2 also showed an increasing trend (Fig. S1A-D). Importantly, all demonstrated S-specific or SNM-specific IFN-γ+ CD4+ and CD8+ T-cell responses. When compared with WT antibody response, we found a significantly lower sVNT% level against Omicron BA.1 (post-dose 3, 94.0% vs 17.9%, P=0.0012) (Fig. S2A), indicating partial neutralization escape. Nonetheless, IFN-γ+ T-cell responses were similar between Omicron BA.1 and WT (Fig. S2B-D).4Leung D. Cohen C.A. Mu X. Rosa Duque J.S. Cheng S.M.S. Wang X. Wang M. Zhang W. Zhang Y. Tam I.Y.S. et al.Immunogenicity against wild-type and Omicron SARS-CoV-2 after a third dose of inactivated COVID-19 vaccine in healthy adolescents.Front Immunol. 2023; 141106837https://doi.org/10.3389/fimmu.2023.1106837Crossref Scopus (0) Google Scholar In addition, we noticed comparable antibody responses between these 5 patients and healthy subjects aged 3-5 who were recruited in another subgroup of the same prospective study (Fig. S3A-B). We also found that CoronaVac was safe and tolerable in our patients, and no breakthrough infections were reported following a median of 118 days (IQR 111-132 days) after dose 3 (Supplemental text 1 and Fig. S4). In conclusion, we demonstrated that accelerated, 3-dose CoronaVac vaccination was safe, and elicited satisfactory antibody and T-cell responses in young children with kidney diseases. T-cell responses appeared preserved against Omicron BA.1, which prevent severe COVID-19. The authors declare no conflicts of interest. Y.L. Lau conceptualized the study. Y.L. Lau, M. Peiris, W. Tu, D. Leung, J.S. Rosa Duque, and X. Mu designed the study. Y.L. Lau led the acquisition of funding. Y.L. Lau, W. Tu, and M. Peiris supervised the project. S.M. Chan, D. Leung, X. Mu, S.M.S. Cheng, I.Y.S. Tam, and J.H.Y. Lam led the study administrative procedures. A.L.T. Ma, Y.L. Lau, J.S. Rosa Duque, E.Y.H. Chan, S. Chim, F.T.W. Ho, P.C. Tong, W.M. Lai, and M.H.L. Lee provided study-related clinical assessments and follow-up. D. Leung, S.M. Chan, S.T.K. Sze, J.H.Y. Lam, J.S. Rosa Duque, and Y.L. Lau collected clinical safety data. S.M.S. Cheng, L.C.H. Tsang, K.K.H. Kwan, and M. Peiris developed and performed S-RBD IgG and sVNT. X. Mu, Y. Chung, H.H.W. Wong, A.M.T. Lee, W.Y. Li, and W. Tu developed and performed the T cell assays. D. Leung, D.H.L. Lee, and J.H.Y. Lam curated, analyzed, and visualized the data. D. Leung, X. Mu, S.M.S. Cheng, J.S. Rosa Duque, D.H.L. Lee, J.H.Y. Lam, and S.M. Chan validated the data. D. Leung and E.Y.H. Chan drafted the manuscript and were supervised by A.L.T. Ma, J.S. Rosa Duque, and Y.L. Lau, with input from X. Mu, and S.M.S. Cheng. All authors reviewed and approved the final manuscript. We thank the staff at Community Vaccination Centers at Ap Lei Chau Sports Centre, Gleneagles Hospital Hong Kong, and Sun Yat-Sen Memorial Park Sports Centre, and the University of Hong Kong Health System. The investigators are grateful to all clinical research team members and laboratory staff of the Department of Pediatrics and Adolescent Medicine at the University of Hong Kong for their research support. We are most thankful to the study participants, as well as clinicians and laboratory staff who have provided clinical care and testing to the patients. FUNDING This study was supported by the research grants COVID19F02, COVID19F10, and COVID19F12 from the Hong Kong SAR Government, which was not involved in the study design, performance, interpretation, or publication of this project. DATA SHARING All requests to share the pseudonymized data underlying the conclusions of this paper from researchers will be facilitated by the authors, subject to ethics approval. Enquiries should be addressed to [email protected]. Download .pdf (2.33 MB) Help with pdf files

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 towards the identified allergens 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 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. Vaccine effectiveness (VE) of BNT162b2 and CoronaVac against BA.2 is unclear. Methods We utilize an ecological design incorporating population-level vaccine coverage statistics and territory-wide case-level SARS-CoV-2 infection surveillance data, and investigate the VE against infection during the Omicron BA.2 wave between January 1 to April 19, 2022, in Hong Kong for children and adolescents. Results We estimate VE to be 33.0% for 1 dose of BNT162b2 in children aged 5–11 and 40.8% for 2 doses of CoronaVac in children aged 3–11. We also estimate 54.9% VE for 2 doses of BNT162b2, and 55.0% VE for 2 doses of CoronaVac in adolescents aged 12–18. Conclusions Our findings support partly preserved VE against infection by variants of concerns for children and adolescents in settings with extremely low levels of prior SARS-CoV-2 circulation.

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. Methods Participants aged 11–17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13–42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. Results Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2) + CD4 + , SNM-specific IL-2 + CD8 + , S-specific IL-2 + CD8 + , N-specific IL-2 + CD4 + , N-specific IL-2 + CD8 + and M-specific IL-2 + CD4 + responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2 + CD4 + , interferon-γ + CD8 + and IL-2 + CD8 + responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines. Graphical abstract

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.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ + and IL-2 + CD8 + T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ + and IL-2 + CD4 + and CD8 + T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

ObjectiveThe coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the most rapid response and scale-up in vaccine and therapeutic development in history. We highlight the history of these amazing achievements with a focus on the description of the classification and mechanisms of allergic reactions and adverse events relevant to the allergist and immunologist that have been associated with the SARS-CoV-2 vaccines. Finally, we offer a detailed management approach in the context of a possible allergic reaction.Data SourcesUsing defined search strategy, we identified peer-reviewed articles within PubMed that were published between January 1, 2019, and December 4, 2021.Study SelectionsAll recent articles on COVID-19 published in English were reviewed with focus on the immunogenicity and allergenicity of the current existing COVID-19 vaccines.ResultsFollowing a detailed literature review, we discuss the evolution and development of the new vaccines for SARS-CoV-2. Furthermore, we provide evidence regarding the significance and mechanisms of allergic reactions associated with the vaccines and offer a management approach for those with an increased risk of presenting an allergic or other relevant vaccine reaction.ConclusionThe international rollout of COVID-19 vaccination started with reports of immediate allergic reactions. Although we still need to understand the mechanisms of these reactions, we can be reassured that patients with underlying allergic disease will not need to avoid SARS-CoV-2 vaccination. In addition, the vast majority of those with a first-dose reaction will tolerate subsequent doses.

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.

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.