General Objective: To determine what viral and human host factors are responsible for inducing severe respiratory distress or fatal outcomes. To constrain our analytical models and validate predictive sensitivity using human patient samples. Here, we chose to focus on severe acute respiratory syndrome coronavirus two (SARS-CoV2), influenza, respiratory syncytial virus (RSV), and Hantavirus for their clear relevance to public health but also to leverage our existing investigations that include extensive inventories of clinical samples and diagnostics for these viral agents. We will combine data from different immunological, virological, biochemical, and molecular tactics with known clinical information to define signatures related to disease severity. This integrated approach is critical for identifying parameters associated with protective or harmful immune responses.