Amongst the top genes we see altered in COVID-19 is the interferon response protein ISG15, which is also known to be a direct target of the SARS-CoV-2 NSP3 protease for the removal of ISGylation from target proteins such as the MDA5 sensor that can regulate the intracellular IFN response by viruses (61–63). The gene discussed is IFIH1; the disease is COVID-19.