Fig 1: Prior IAV infection increases SARS-CoV-2 virus replication and mortality in miceC57BL/6 (8-10-week old) mice were intranasally infected with IAV strain PR8 (1 × 104 PFU) in sterile saline. After 5 days, the influenza A virus-infected mice and uninfected mice were intranasally infected with mouse adapted SARS-CoV-2 strain MA10 (1 × 105 PFU).(A–C) Survival of the mice were monitored until day 12 (n = 15 per group) (A), lungs and heart tissues were collected, homogenized, and used to determine the TCID50 virus titer assays on Vero E6 cells using 10-fold serial dilutions assayed in triplicate. The presence of virus replication in each well was assessed by visual examination of cytopathic effect with antibody staining for SARS-CoV-2 N protein antigen (mouse mAb 40143-MM08, Sino Biological) with fluorescent secondary antibody detection. TCID50 titers were calculated using the Reed-Muench method. Viral titers in lung (B) and heart (C) homogenates of IAV_SARS-CoV-2 and SARS-CoV-2 alone mice were measured using TCID titers. A two-tailed Student’s t-test was used to analyze the data (mean ± SEM; ns-nonsignificant; ***p< 0.0005).