By examining sera collected at two times after infection from mice challenged with SARS-CoV-2, we identified two distinct phases of inflammatory dysregulation and a possible role for C-X-C motif chemokine ligand 5 (CXCL5) as a key modulator of the early stages of inflammatory dysregulation that leads to mortality in COVID-19. The gene discussed is CXCL5; the disease is COVID-19.