The impact of vaccination and SARS-CoV-2 variants on the virological response to SARS-CoV-2 infections during the Alpha, Delta, and Omicron waves in England.

Vaccination status and the SARS-CoV-2 variant individuals are infected with are known to independently impact viral dynamics; however, little is known about the interaction of these two factors and how this impacts viral dynamics. Here we investigated how monovalent vaccination modified the time course and viral load of infections from different variants. Regression analyses were used to investigate the impact of vaccination on cycle threshold values and disease severity, and interval-censored survival analyses were used to investigate the impact of vaccination on duration of positivity. A range of covariates were adjusted for as potential confounders and investigated for their own effects in exploratory analyses. All analyses were done combining all variants and stratified by variant. For those infected with Alpha or Delta, vaccinated individuals were more likely to report mild disease than moderate/severe disease and had significantly shorter duration of positivity and lower viral loads compared to unvaccinated individuals. Vaccination had no impact on self-reported disease severity, viral load, or duration if positivity for those infected with Omicron. Overall, individuals who were immunosuppressed and clinically extremely vulnerable had longer duration of positivity and higher viral loads. This study adds to the evidence base on disease dynamics following COVID-19, demonstrating that vaccination mitigates severity of disease, the amount of detectable virus within infected individuals and reduces the time individuals are positive for. However, these effects have been significantly attenuated since the emergence of Omicron. Therefore, our findings strengthen the argument for using modified or multivalent vaccines that target emerging variants.

A protocol paper for the MOTION Study-A longitudinal study in a cohort aged 60 years and older to obtain mechanistic knowledge of the role of the gut microbiome during normal healthy ageing in order to develop strategies that will improve lifelong health and wellbeing.

BACKGROUND: Advances in medicine and public health mean that people are living longer; however, a significant proportion of that increased lifespan is spent in a prolonged state of declining health and wellbeing which places increasing pressure on medical, health and social services. There is a social and economic need to develop strategies to prevent or delay age-related disease and maintain lifelong health. Several studies have suggested links between the gut microbiome and age-related disease, which if confirmed would present a modifiable target for intervention development. The MOTION study aims to determine whether and how changes in the gut microbiome are associated with physical and mental capacity. A comprehensive longitudinal multiparameter study such as this has not been previously undertaken. METHODS: MOTION is a longitudinal prospective cohort study with a focus on gut health and cognitive function. 360 healthy individuals aged 60 years and older, living in East Anglia, UK will be recruited to the study, stratified into one of three risk groups (cohorts) for developing dementia based on their cognitive function. Participants will attend study appointments every six months over four years, providing stool and blood samples and a health questionnaire. Participants will also undergo physical measurements and cognitive tests at alternating appointments, and undergo Optical Coherence Tomography scans at 3 timepoints. Two subgroups of participants in the study will provide colonic tissue biopsies (n = ≥30 from each cohort), and brain imaging (n = 30) at two timepoints. DISCUSSION: This study will provide new insights into the gut-(microbiota)-brain axis and the relationship between age-associated changes in gut microbe populations and cognitive health. Such insights could help develop new microbe-based strategies to improve lifelong health and wellbeing. TRIAL REGISTRATION: This study is registered in the ClinicalTrials.gov Database with ID: NCT04199195 Registered: May 14, 2019.