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). This evidence concerns the gene SH2D3C and COVID-19.