SIRT2 knockout (KO) mice do not have noticeable defects at a young age but show exacerbated aging-associated conditions at old age.17,29 To determine whether SIRT2 protects aged mice from severe SARS-CoV-2 infection, we infected old (18–24 months old) wild-type (WT) and SIRT2 KO mice with 1,000 plaque-forming units (PFUs) of SARS2-N501YMA30, a mouse-adapted SARS-CoV-2 (Figure S1A).27 Aged SIRT2 KO mice lost more weight upon infection (Figure 1A). This evidence concerns the gene SIRT2 and infection.