Daily Respiratory Research Analysis

BACKGROUND: A respiratory syncytial virus (RSV) vaccination programme for older adults using bivalent pre-F vaccine was introduced in England from Sept 1, 2024. Although vaccine effectiveness has been reported against all-cause RSV-associated respiratory hospital admissions, data are scarce on vaccine effectiveness against different presentations of RSV-associated illness, such as exacerbation of chronic illness. METHODS: This multicentre, test-negative, case-control study used data from a national, hospital-based, acute respiratory infection sentinel surveillance (HARISS) system across 14 hospitals in England. Eligibility criteria were vaccine-eligible adults aged 75-79 years admitted to hospital with acute respiratory infection (ARI) for ≥24 h and tested with molecular diagnostic assays within 48 h of admission. Cases were RSV positive, and controls were negative for RSV, influenza, and SARS-CoV-2. Vaccination status and data on sex were obtained from the National Immunisation Information System. The primary outcome was hospital admission due to RSV-associated ARI, which was tested for using nasopharyngeal or combined nose and throat swabs. Clinical data were collected using a structured questionnaire. FINDINGS: Between Oct 1, 2024, and March 31, 2025, 1006 older adults were admitted to hospital with ARI; 173 were RSV positive (cases) and 833 were RSV negative (controls). 526 (52·3%) of 1006 individuals were female and 480 (47·7%) were male. Mean age was 77·8 years (SD 1·4) in individuals who were RSV positive and 77·6 years (SD 1·3) in those who were negative for RSV, influenza, and SARS-CoV-2. Vaccine effectiveness was 82·3% (95% CI 70·6-90·0) against hospitalisation for any RSV-associated ARI and 86·7% (75·4-93·6) in those with severe disease including oxygen supplementation. Vaccine effectiveness was 88·6% (75·6-95·6) among individuals admitted due to lower respiratory tract infection, including pneumonia, 77·4% (42·4-92·8) due to exacerbation of chronic lung disease, and 78·8% (47·8-93·0) due to exacerbation of chronic heart disease, lung disease, and/or frailty. In individuals with immunosuppression, vaccine effectiveness was 72·8% (39·5-89·3). INTERPRETATION: This study provides evidence that the RSV pre-F vaccine is highly effective against RSV-associated hospital admissions, including exacerbations of chronic disease, and in adults with immunosuppression. FUNDING: UK Health Security Agency.

Systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to extrapulmonary tissues has been observed following acute infections. Autopsy studies further indicate tissue-specific virus diversity, including in immune-privileged sites. Questions remain on the viral dynamics leading to the tissue tropism of SARS-CoV-2, including evolutionary trajectories and functional adaptations that could impact persistence and transmission. In this study, we characterized SARS-CoV-2 genomes from 27 distinct tissues collected from an autopsy case where the patient had a primary immune deficiency. We identified tissue-specific virus genotypes, in some instances coexisting within the same sites, with mutations primarily in the receptor-binding domain of the spike protein. Protein simulations and isolation of infectious virus indicate combinations of spike substitutions that would lead to increased protein stability and stronger binding of the virus to host cells. This highlights the importance of studying patients with weakened immune responses where potential tissue reservoirs provide an environment permissive for SARS-CoV-2 evolution and diversification.IMPORTANCEPersistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised individuals are considered a potential source of new viral variants. Beyond the respiratory tract, the virus can spread within days to organs like the brain, heart, and kidneys, where distinct tissue microenvironments may further drive viral evolution and the emergence of new mutations. In this study, we compared the genetic diversity of SARS-CoV-2 genomic RNA isolated from 27 distinct tissue sites collected from an individual with a weakened immune system. By linking viral population dynamics across these tissue sites, we defined the extent of compartmentalization during multi-organ spread, highlighting how non-respiratory tissues can impact SARS-CoV-2 diversification.

PURPOSE: Subphenotype classifiers for acute respiratory distress syndrome (ARDS) dichotomise patients into hyperinflammatory versus hypoinflammatory subgroups. These models demonstrated prognostic and predictive values but were developed primarily in Caucasian populations. Generalisability of these models in Asian patients, who experience worse clinical outcomes, has not been established. We aimed to profile host responses in Asian patients with ARDS and evaluate the generalisability of established classifiers in this understudied population compared with a Caucasian cohort. METHODS: We prospectively enrolled patients with ARDS from medical intensive care units in Beijing, China, and Pittsburgh, Pennsylvania, USA. In the Beijing cohort, 37 protein biomarkers were measured, with 10 overlapping biomarkers measured in the Pittsburgh cohort. Six established subphenotype models were assessed for generalisability and intermodel agreement. Sensitivity analyses, including latent class analysis, were conducted to explore biological heterogeneity within Asians. RESULTS: Between 2011 and 2020, a total of 356 patients with ARDS (83% meeting the Berlin Definition; the rest on high-flow nasal cannula (HFNC) meeting the New Global Definition) were enrolled across Beijing (97% Han Asian) and Pittsburgh (90% Caucasian) sites, with comparable baseline hypoxaemia severity but disparate outcome. While the proportion of hyperinflammatory versus hypoinflammatory subphenotypes was predicted to be overall similar across different cohorts per each model, we observed poor intermodel agreement. We observed heightened inflammation in Berlin patients with ARDS compared with HFNC-ARDS within our Asian cohort. CONCLUSION: Established subphenotype classifiers demonstrated similar distribution of subphenotypes in Asian patients with ARDS. However, poor intermodel agreement highlights the need for further investigation into model variability with models coming closer to bedside implementation. TRIAL REGISTRATION NUMBER: NCT02975908.