PROJECT SUMMARY/ABSTRACT Despite the extensive epidemiologic research conducted during the COVID-19 pandemic, there remain gaps in our knowledge about the epidemiology and transmission of priority respiratory viruses. For example, current surveillance networks in the United States are primarily limited to people who present for medical care and tend to enroll readily accessible populations like health care workers. The result is that policy makers have had limited insight into the epidemiology of respiratory viruses at the community-level, outside of medical settings and in fully representative populations. There is thus a great need for studies that can obtain data on young adults, children and pregnant women, as well as from diverse populations and socially vulnerable neighborhoods. This data would include information on the incidence and clinical burden of respiratory illnesses, attitudes towards preventive interventions, effectiveness of vaccines and antivirals, and duration of immunity following vaccination. In addition, changing viral characteristics with emerging SARS-CoV-2 variants has made it challenging to remain up to date with transmission characteristics, such as duration of infectiousness, attack rates, and determinants of household transmission. There is arguably even less known about these characteristics for influenza and respiratory syncytial virus (RSV), which are also major causes of morbidity. Such data are essential to advise on both protective public health and clinical guidelines to reduce respiratory virus-associated morbidity and mortality. To fill these knowledge gaps, we propose to conduct a prospective, longitudinal observational study of respiratory virus epidemiology in the Greater Boston Area, serving as a Pandemic Preparedness Cohort for the CDC. There are four components to our project, including an observational study with weekly symptom screening and symptomatic swabbing, an in-depth serologic sub-study, a case-ascertained household transmission study, and a data hub/analytic support initiative to coordinate the collective CDC Pandemic Preparedness Cohorts across the country. The overarching goal of our project is to support the US Health and Human Service Strategic Plan in safeguarding and improving national and global health conditions and outcomes.