This project will spatially resolve the host and viral transcriptome of patients who died of influenza during the pandemics of the 20th century in order to identify the molecular mechanisms behind severe disease and death. This project will compare lung tissue taken from patients of different ages to determine why children and young adults are uniquely susceptible to pandemic influenza. The results will inform future pandemic preparedness as the paradigm of which ages are most at-risk during influenza pandemics is shifting. It will also inform on targeted therapies for immune modulation and regulation in children and young adults in the event of a future influenza pandemic.