Effects of Vaccination on Acute and Post-Acute Respiratory Viral Infection Outcomes in Solid Organ Transplant Recipients

Project Summary/Abstract Respiratory viral infections (RVI) including SARS-CoV-2, RSV, and influenza, are major threats to the health of solid organ transplant recipients (SOTRs), who live at the intersection of chronic comorbidity, frailty, and heavy immunosuppression. These factors contribute to high rates of clinically observed severe RVI and pose risks for poorly understood post-acute syndromes including organ dysfunction and protracted infections associated with immune evasive mutations of public/health/relevance. Furthermore, as starkly outlined during the COVID-19 pandemic, RVI vaccine immunogenicity and effectiveness are suboptimal in SOTRs, connoting ongoing risk for adverse outcomes despite vaccination. Due to a lack of clinical trials of novel platforms in SOTRs, such as variant-updated SARS-CoV-2 and RSV vaccines, robust prospective observational data are urgently needed. In this proposal, we will leverage and expand the first national-scale prospective cohort of US SOTRs designed to measure acute and post-acute RVI outcomes in the COVID-19-endemic era and assess real-world immunoprotective effects of vaccination. Goals of this proposal include ascertainment of acute RVI events in a large national cohort of SOTRs through asymptomatic and symptom-driven screening protocols to calculate effectiveness of clinically-available vaccinations (Aim 1). Clinical and immunological associations with breakthrough RVI in SOTRs post vaccination will then be assessed, including the role of longitudinal pathogenspecific plasma and mucosal immune responses (Aim 2). Additionally, the prevalence and phenotypes of postacute RVI sequela including "Long COVID" in SOTRs will be determined, including evaluation of potential associations with persistent RVI shedding and evolution as well as vaccine-associated immune responses (Aim 3). Taken together, this proposal will generate critical data on the contemporary burden of RVI among US SOTRs, with particular focus on vaccine-preventable infections, to inform personalized risk calculations incorporating clinical and mechanistic data. These findings will provide evidence base for further optimization of immunoprophylactic interventions against acute and post-acute RVI complications among vulnerable SOTRs in the COVID-19-endemic era.