We found an increased incidence of re-infection in aged mice compared to young mice, in particular, a similar level of SARS-CoV-2 replication in the NT upon re-infection compared to that of the primary infection [primary infection vs. re-infection in NT at 2dpi: 1.31955 vs. 1.26542 RdRp copy/β-actin (log10)], which suggested lower protective effects to the upper respiratory tissue were conferred by the primary infection. This evidence concerns the gene ACTB and infection.