ISG15 and coinfection: H1N1, H3N2 (OK/483), or H5N1 co-infection with SARS-CoV-2 elevated the expression of IFN-β, IFN-λ1, IFN-λ2/3, and ISG15, which has been shown to be associated with pathology in severe COVID-19 [27,28,29] and pro-inflammatory cytokines and chemokines upon H5N1 co-infection.