Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production (111–113), viral RNA, and sustained interferon (IFN) response all of which are recapitulated and required for pathology in the SARS-CoV-2 infected MISTRG6-hACE2 humanized mouse model (based on the Rag2-/- IL2rg-/-129xBalb/c background supplemented with genes for human M-CSF, IL-3, SIRPα, TPO, GM-CSF, and IL-6 knocked into their respective mouse loci) of COVID-19 with a human immune system (108). Here, RAG2 is linked to COVID-19.