Gene expression regulation of ACE2 and other X-chromosome linked genes, including Toll-like receptors (TLRs), CD40 ligand (CD40L), and Forkhead box P3 (FOXP3)/Scurfin, expressed upon SARS-CoV-2 infection, may play a critical role in COVID-19 pathogenesis and severity. The gene discussed is CD40LG; the disease is COVID-19.