Modeling the Complete Dynamics of the SARS-CoV-2 Pandemic of Germany and Its Federal States Using Multiple Levels of Data.

: Epidemiological modeling is a vital tool for managing pandemics, including SARS-CoV-2. Advances in the understanding of epidemiological dynamics and access to new data sources necessitate ongoing adjustments to modeling techniques. In this study, we present a significantly expanded and updated version of our previous SARS-CoV-2 model formulated as input-output non-linear dynamical systems (IO-NLDS). : This updated framework incorporates age-dependent contact patterns, immune waning, and new data sources, including seropositivity studies, hospital dynamics, variant trends, the effects of non-pharmaceutical interventions, and the dynamics of vaccination campaigns. : We analyze the dynamics of various datasets spanning the entire pandemic in Germany and its 16 federal states using this model. This analysis enables us to explore the regional heterogeneity of model parameters across Germany for the first time. We enhance our estimation methodology by introducing constraints on parameter variation among federal states to achieve this. This enables us to reliably estimate thousands of parameters based on hundreds of thousands of data points. : Our approach is adaptable to other epidemic scenarios and even different domains, contributing to broader pandemic preparedness efforts.