Preventive allergen immunotherapy with inhalant allergens in children.

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen-specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell-mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen-based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head-to-head comparative paediatric studies are scarce. Additionally, there are fewer placebo-controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well-designed studies.

Limited role of children in transmission of SARS-CoV-2 virus in households-Immunological analysis of 26 familial clusters.

BACKGROUND: The impact of children on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. This study provides an insight into distinct patterns of SARS-CoV-2 household transmission in case of pediatric and adult index cases as well as age-dependent susceptibility to SARS-CoV-2 infection. METHODS: Immune analysis, medical interviewing, and contact tracing of 26 families with confirmed SARS-CoV-2 infection cases have been conducted. Blood samples were analyzed serologically with the use of a SARS-CoV-2-specific IgG assay and virus neutralization test (VNT). Uni- and multivariable linear regression and mixed effect logistic regression models were used to describe potential risk factors for higher contagiousness and susceptibility to SARS-CoV-2 infection. RESULTS: SARS-CoV-2 infection could be confirmed in 67 of 124 family members. Fourteen children and 11 adults could be defined as index cases in their households. Forty of 82 exposed family members were defined as secondarily infected. The mean secondary attack rate in households was 0.48 and was significantly higher in households with adult than with pediatric index cases (0.85 vs 0.19; p < 0.0001). The age (grouped into child and adult) of index case, severity of disease, and occurrence of lower respiratory symptoms in index cases were significantly associated with secondary transmission rates in households. Children seem to be equally susceptible to acquire a SARS-CoV-2 infection as adults, but they suffer milder courses of the disease or remain asymptomatic. CONCLUSION: SARS-CoV-2 transmission from infected children to other household members occurred rarely in the first wave of the pandemic, despite close physical contact and the lack of hygienic measures.

Long-Lived Immunity in SARS-CoV-2-Recovered Children and Its Neutralizing Capacity Against Omicron.

SARS-CoV-2 infection is effectively controlled by humoral and cellular immune responses. However, the durability of immunity in children as well as the ability to neutralize variants of concern are unclear. Here, we assessed T cell and antibody responses in a longitudinal cohort of children after asymptomatic or mild COVID-19 over a 12-month period. Antigen-specific CD4 T cells remained stable over time, while CD8 T cells declined. SARS-CoV-2 infection induced long-lived neutralizing antibodies against ancestral SARS-CoV-2 (D614G isolate), but with poor cross-neutralization of omicron. Importantly, recall responses to vaccination in children with pre-existing immunity yielded neutralizing antibody activities against D614G and omicron BA.1 and BA.2 variants that were 3.9-fold, 9.9-fold and 14-fold higher than primary vaccine responses in seronegative children. Together, our findings demonstrate that SARS-CoV-2 infection in children induces robust memory T cells and antibodies that persist for more than 12 months, but lack neutralizing activity against omicron. Vaccination of pre-immune children, however, substantially improves the omicron-neutralizing capacity.

Characterization of the antibody response to SARS-CoV-2 in a mildly affected pediatric population.

BACKGROUND: While children usually experience a mild course of COVID-19, and a severe disease is more common in adults, the features, specificities, and functionality of the SARS-CoV-2-specific antibody response in the pediatric population are of interest. METHODS: We performed a detailed analysis of IgG antibodies specific for SARS-CoV-2-derived antigens S and RBD by ELISA in 26 SARS-CoV-2 seropositive schoolchildren with mild or asymptomatic disease course, and in an equally sized, age- and gender-matched control group. Furthermore, a detailed mapping of IgG reactivity to a panel of microarrayed SARS-CoV-2 proteins and S-derived peptides was performed by microarray technology. The capacity of the antibody response to block RBD-ACE2 binding and virus neutralization were assessed. Results were compared with those obtained in an adult COVID-19 convalescent population. RESULTS: After mild COVID-19, anti-S and RBD-specific IgG antibodies were developed by 100% and 84.6% of pediatric subjects, respectively. No difference was observed in regards to symptoms and gender. Mounted antibodies recognized conformational epitopes of the spike protein and were capable to neutralize the virus up to a titer of ≥80 and to inhibit the ACE2-RBD interaction by up to 65%. SARS-CoV-2-specific IgG responses in children were comparable to mildly affected adult patients. CONCLUSION: SARS-CoV-2 asymptomatic and mildly affected pediatric patients develop a SARS-CoV-2-specific antibody response, which is comparable regarding antigen, epitope recognition, and the ability to inhibit the RBD-ACE2 interaction to that observed in adult patients after mild COVID-19.

Case Report: Maintenance of Desensitization to Nebulized Colomycin Over 10 Years.

Drug desensitization can be achieved successfully by gradual drug dose increases in different protocols. Most protocols are designed to obtain temporal tolerance. The data on long-term maintenance of drug tolerance is scarce. Based on an IgE-mediated colomycin allergy we describe the maintenance of drug tolerance to nebulized drug for the period of 10 years in a 15-year-old cystic fibrosis patient, proceeded by successful rush intravenous desensitization protocol. The mechanism of drug tolerance is largely speculative; however, long-term maintenance of it seems achievable by continuous local drug application.

Lessons from low seroprevalence of SARS-CoV-2 antibodies in schoolchildren: A cross-sectional study.

BACKGROUND: Children are discussed as hidden SARS-CoV-2 virus reservoir because of predominantly mild or even asymptomatic course of disease. The objective of this cross-sectional study in May-July 2020 was to assess the prevalence of SARS-CoV-2 antibodies and virus RNA in schoolchildren, consistent with previous infection by contact tracing. METHODS: School authorities approached parents for voluntary participation. Interested families were contacted by the study team. A nasal and oropharyngeal swab, a blood sample, and a questionnaire were employed. Primary endpoint was the frequency of SARS-CoV-2 real-time PCR (RT-PCR) and antibody-positive children. Antibody positivity was assessed by a highly sensitive first-line ELISA, and a neutralization assay and two other immunoassays as confirmatory assays. RESULTS: Of 2069 children (median age 13 years, IQR 10-15), 2 cases (0.1%) tested positive for SARS-CoV-2 RNA and 26 cases (1.3%) tested positive for specific antibodies. SARS-CoV-2-specific antibodies exhibited detectable virus-neutralizing activity in 92% (24 of 26 samples). Seropositivity was associated with a history of mild clinical symptoms in 14 children (53.8%), while 12 children (46.2%) remained asymptomatic. Among 13 seropositive children being tested concomitantly with their siblings, only one pair of siblings was seropositive. Contact tracing revealed adult family members and school teachers as potential index cases. CONCLUSION: In schoolchildren, the infection rate with SARS-CoV-2 is low and associated with a mild or asymptomatic course of disease. Virus spreading seemed to occur more likely in intergenerational contacts than among siblings in the same household. The presence of neutralizing SARS-CoV-2 antibodies in children may reflect protective adaptive immunity.