In conclusion, we used poly(I:C) + SP to establish a robust, non-infectious, highly safe, time-saving murine model that mimics the pathologic changes of SARS-CoV-2–induced CSS and ARDS, and we identified that TNF-α and IL-6 in BALF, were induced by poly (I:C) and recombinant SP of SARS-CoV-2 in both virus-assisted human ACE2 expression or wild type BALB/c mice. Here, ACE2 is linked to acute respiratory distress syndrome.