To investigate the potential roles of NEIL2 in CoV-2 pathogenesis, we infectedNeil2-null (Neil2−/−) mice with a mouse-adapted CoV-2 strain and found thatNeil2−/−mice suffered more severe viral infection concomitant with increased expression of proinflammatory genes, which resulted in an enhanced mortality rate of 80%, up from 20% for the age matchedNeil2+/+cohorts. The gene discussed is NEIL2; the disease is viral infectious disease.