TSLP-elicited basophils promote epicutaneous sensitization to food antigens and subsequent IgE-mediated food allergy through IL-4. Strategies to target the TSLP-basophil-IL-4 axis in patients with AD might lead to innovative therapies that can prevent the progression of allergies to distant mucosal sites.

The SARS-CoV-2 Delta variant, corresponding to the Pangolin lineage B.1.617.2, was first detected in India in July 2020 and rapidly became dominant worldwide. The ARTIC v3 protocol for SARS-CoV-2 whole-genome sequencing, which relies on a large number of PCR primers, was among the first available early in the pandemic, but may be prone to coverage dropouts that result in incomplete genome sequences. A new set of primers (v4) was designed to circumvent this issue in June 2021. In this study, we investigated whether the sequencing community adopted the new sets of primers, especially in the context of the spread of the Delta lineage, in July 2021. Because information about protocols from individual laboratories is generally difficult to obtain, the aims of the study were to identify whether large under-sequenced regions were present in deposited Delta variant genome sequences (from April to August 2021), to investigate the extent of the coverage dropout among all the currently available Delta sequences in six countries, and to propose simple PCR primer modifications to sequence the missing region, especially for the first circulating Delta variants observed in 2021 in Switzerland. Candidate primers were tested on few clinical samples, highlighting the need to further pursue primer optimization and validation on a larger and diverse set of samples.

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4 and CD8 T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.

Background Testing and contact tracing (CT) can interrupt transmission chains SARS-CoV-2. Whole genome sequencing (WGS) can potentially strengthen these investigations and provide insights on transmission. Methods We included all laboratory-confirmed COVID-19 cases diagnosed between June 4 to July 26, 2021, in a Swiss canton. We defined CT clusters based on epidemiological links reported in the CT data and genomic clusters as sequences with no single nucleotide polymorphism (SNP) differences between any two pairs of sequences being compared. We assessed the agreement between CT clusters and genomic clusters. Results Of 359 COVID-19 cases, 213 were sequenced. Overall, agreement between CT and genomic clusters was low (Kappa coefficient=0.13). Out of 24 CT clusters with at least two sequenced samples, 9 (37.5%) were also linked based on genomic sequencing but in four of these, WGS found additional cases in other CT clusters. Household was most often reported source of infection (101, 28.1%) and home addresses coincided well with CT clusters: In 44 out of 54 CT clusters containing at least two cases (81.5%), all cases of the cluster had the same home address. However, only a quarter of household transmission was confirmed by WGS (6 out of 26 genomic clusters, 23.1%). A sensitivity analysis using ≤1 SNP differences to define genomic clusters resulted in similar results. Conclusions WGS data supplemented epidemiological CT data, supported the detection of potential additional clusters missed by CT, and identified misclassified transmissions and sources of infection. Household transmission was overestimated by CT.

Rationale: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infancy, potentially aided by an inappropriate immune response. Sparse information is available for the distal lung, mostly because data arose from non-invasive samplings of peripheral blood and nasal aspirates. Objectives: To determine the neonatal immune response to RSV in the bronchoalveolar space and better understand why neonates are at greater risk of developing severe disease. Methods: We used the newborn lamb, a state-of-the-art translational model of human RSV infection, offering ease sampling and full accessibility to lower airways. Using a multiparameter flow cytometry assay, we evaluated the frequency and activation/maturation state of the major subsets of the developing T-cell compartment. Measurements and Main Results: The T-cell compartment of the healthy developing lung was very distinct to that seen in adults. We observed a high frequency of type 2 CD4+ (Th2) and CD8+ (Tc2) T-cells, both being a large source of IL-4, which declined progressively over time. Remarkably, RSV infection exacerbated this pro-type 2 environment, rather than inducing a type 2 response per se. Neonatal regulatory T-cell (Treg) suppressive functions occurred very early to dampen those Th2 and Tc2 responses, while γδ T-cells dropped and failed to produce IL-17. The disease severity was related to the magnitude of these T-cell responses. Conclusion: The atypical neonatal immune response to RSV consists of distinct T-cell subsets that tightly cooperate, namely a combined bronchoalveolar influx of Treg, Th2 and Tc2 cells, associated with a depletion of γδ T-cells.