However, this pathway is directly antagonized by SARS-CoV-2 to evade host innate immunity via the overexpression of PLpro, a gene with redundant functionality of ISG-deconjugating enzyme USP18 (a negative regulator of type I and III interferons) (27), as several studies (27, 28) show upregulation of USP18 upon SARS-CoV-2 infection. This evidence concerns the gene USP18 and COVID-19.