Rates, determinants, and transmissibility of respiratory virus re-infections (360G-Wellcome-226002_Z_22_Z)

Multiple reinfections are characteristic of many respiratory viruses and a critical determinant of endemicity in human populations. However, there is a paucity of data on the rates and determinants of reinfections, and the importance of reinfections in chains of transmission. This project will investigate reinfection for three common respiratory viruses - SARS-CoV-2, influenza, and respiratory syncytial virus - within the household setting. I will determine the frequency and timing of reinfections independent of clinical presentation; identify viral genomic and host immunological characteristics of reinfections; and determine the factors that influence the transmission potential of reinfections. My proposal includes a three-year household cohort study in coastal Kenya, with intensive respiratory sampling for RT-PCR and genomic sequencing, and bimonthly blood samples to assess immune status and serological responses relating to reinfection. I will estimate the rate of immunity loss and reinfection infectiousness in relation to age, virus load, symptoms, and host immunity, and use mathematical models to explore the transmission dynamics and intervention impact building on the new understanding from this research.