SARS-CoV-2 mouse adaptation generates a gain of function that causes TNF driven age-dependent severe disease with human correlates

To dissect the nature of the immune dysregulation induced by SARS-CoV-2 infection in mouse lungs using mouse-adapted strains of the virus. Comparisons were performed using bulk RNA-seq data from mouse (C57BL/6) lung homogenates taken 3 days post-infection with mouse-adapted SARS-CoV-2, both early and late (virulent) passages, or mock-infected mice. Comparative gene expression profiling analysis of murine lung bulk RNA-seq data. Contrasts were made between mice infected with early and late passage virus strains and mock-infected mice. Comparisons were also made between young and aged mice to determine the associated between age and these transcriptional changes.