Bacterial pathogens exacerbate viral infections, especially influenza, to cause significant morbidity and mortality. Understanding how different mechanisms contribute to susceptibility and pathogenicity is challenging, and knowledge about how bacteria impact SARS-CoV-2 infections is relatively unknown. I’ll discuss an integrative model-experiment exchange that we used to disentangle viral- and bacterial-mediated effects on host immunity, pathogen dissemination within the lung, lung pathology, and disease severity during influenza-bacterial coinfections and whether the same is true for SARS-CoV-2-bacterial coinfection.