Respiratory syncytial virus (RSV) is a leading cause of hospitalisation in infants worldwide. New immunoprophylactic products, including long-acting monoclonal antibodies and maternal vaccines, have demonstrated high efficacy in prelicensure clinical trials. Understanding how these interventions perform outside controlled trials, and how viral evolution or host factors influence protection, is essential for sustaining confidence in RSV prevention programmes.

We will conduct a 5-year, test-negative case–control study among infants ≤12 months of age who present with acute respiratory illness (ARI) within a large healthcare delivery network serving a demographically diverse population. Cases will be infants testing positive for RSV by PCR, and controls will be RSV-negative infants meeting the same ARI criteria. Data will be obtained from electronic health records, structured caregiver surveys and state immunization registries to ensure accurate classification of exposures and covariates. Vaccine effectiveness will be estimated using multivariable logistic regression controlling for potential confounding. RSV-positive specimens will undergo full-genome sequencing to identify variant lineages and potential immune-escape mutations. A subset of participants will provide acute and convalescent blood samples for single-cell immune profiling to define innate and adaptive responses associated with breakthrough infection.

The study protocol has been approved by the Yale Human Investigation Committee (HIC #2000036550). Written informed consent will be obtained from all parents or legal guardians prior to participation. Study findings will be disseminated through peer-reviewed publications, scientific meetings and public repositories, with fully de-identified participant data to protect privacy and confidentiality. Viral genomic data will be shared in accordance with the National Institutes of Health Genomic Data Sharing Policy, and analytical code will be made publicly available to ensure reproducibility.

NCT06172660.

Mothers’ mental health and life satisfaction may have been negatively affected due to challenges during the COVID-19 pandemic. Given the risk of future crises, knowledge of possible mitigating factors in this population is essential. This study aims to examine whether the pandemic affected the level of protective factors such as social support, physical activity and employment situation, and how these factors are associated with mental distress and life satisfaction.

Longitudinal cohort study.

Primary outcomes were mental distress (measured by the eight-item version of the Hopkins Symptom Checklist) and life satisfaction (measured by the Satisfaction With Life Scale). As the first step, we investigated changes in the levels of social support (defined by the number and frequency of social contact), physical activity (average hours of physical activity during a week), employment situation (actively working vs sick leave or unemployed), alcohol consumption (measured by the Alcohol Use Disorders Identification Test-Consumption) and relationship satisfaction (measured by the five-item version of the Relationship Satisfaction Scale).

We analysed data from two waves of the Norwegian Mother, Father and Child Cohort Study (n=~18 000 mothers); one pre-pandemic wave and one wave where half of the sample responded after the onset of the pandemic, with pandemic exposure being defined by questionnaire response timing rather than cohort recruitment. To assess changes in protective factors over time and pandemic exposure, we used difference-in-differences analyses and regression discontinuity design. Associations between protective factors with mental distress and life satisfaction, and possible moderation by pandemic exposure, were investigated using multiple regression models with interaction terms adjusted for potential confounders.

Apart from physical activity, which declined less across time in the pandemic group (B=0.09, 99% CI 0.05 to 0.12), protective factors did not change during the pandemic. Social support, employment situation and relationship satisfaction were associated with mental distress and life satisfaction, whereas physical activity showed a unique relationship with mental distress. Most associations were similar across pandemic exposure groups, except employment situation which appeared to have a stronger protective effect in the pandemic group (β=–0.12, 99% CI –0.24 to –0.00).

Changes over time in self-reported levels of protective factors were generally consistent among mothers independent of the pandemic. These factors appear to play an equally important role for mental distress and life satisfaction both under ordinary circumstances and during public health crises. Our findings enhance the understanding of how potential protective factors among mothers are associated with mental distress and life satisfaction in the context of a global stressor. Future studies should investigate additional mitigating factors that may be particularly relevant during global crises and explore the causal relationship between protective factors, mental health and life satisfaction.

Total diet replacements (TDRs) and weight loss medications (WLMs) have proven effective in producing substantial weight loss for individuals with obesity. Evidence is lacking on whether combining these treatments is effective and cost-effective in primary care for adults with obesity class I (body mass index (BMI) 30–34.9) or uncomplicated obesity class II or higher (BMI≥35 without obesity-related disease).

LightCARE is a 2-year 1:1 randomised, parallel-group, clinical superiority trial with blinded outcome assessment evaluating the benefits and harms of an intensive weight loss (IWL) intervention compared with usual care for adults with obesity in Denmark and the UK. The trial will include 400 participants aged 18–60 years with obesity class I or uncomplicated obesity class II or higher. The IWL programme aims to achieve and maintain a weight loss of ≥20% through a flexible and individualised combination of TDR, behavioural support, including physical activity and sleep guidance, and WLM if needed and will continue for 2 years. The control group will receive usual care offered in each country, typically consisting of brief behavioural support for weight loss. The primary outcome is body weight 2 years after randomisation. Secondary outcomes will include the proportion of participants achieving ≥20% weight loss, Short-Form-36 Mental Component Score, 4-m gait speed and Metabolic Syndrome Severity-Z score. Serious adverse events, the incidence of eating disorders and bone mineral density will be evaluated as safety outcomes. We will also examine the cost-effectiveness of the intervention, within the trial and in the longer term through modelling. We will conduct a process evaluation to inform any future implementation.

Ethical approval was granted in Denmark (December 2023, H-23051332) and the UK (August 2024, 24/SC/0210). Findings from the trial will be disseminated through peer-reviewed journals and scientific conferences.

NCT06321432.