Pathogenicity Difference Between Male and Female mice by Recent SARS-CoV-2/2025

Covid-19 pandemic was caused by a novel coronavirus, SARS-CoV-2 and caused a tremendous burden to humans including thousands of deaths. SARS-CoV-2 still causes the respiratory diseases to humans annually. It is known that the pathological outcomes may be different from sexes of humans infected with viral diseases. Here, we studied the pathological difference between females and males infected with the recent SARS-CoV-2 in 6-week-old hACE2-trangenic mouse models. When female and male mice were intranasally infected with the recent SARS-CoV-2/2025, no mortality was observed in both infected female and male mice. However, the infected female mice suffered from more body-weight loss than the infected male mice with higher viral titers in the lungs. The infected male mice produced higher amount of the immune-stimulatory cytokines such as TNF-α and IFN-γ, and anti-apoptotic genes such as BCL2 and Bcl-XL in the lungs than those of the infected female mice. Taken together, it seems that the infected male mice with the recent SARS-CoV-2/2025 could suffer from milder clinical signs than the infected female mice because of the increased expression of immune-enhancing cytokines and anti-apoptotic genes.