Exposure to CS or nicotine upregulated many genes within AGE-RAGE signalling with high confidence, including CCND1, CXCL8, HRAS, IL6, KRAS and TNF [18, 22, 32, 64–76, 78–81, 83, 89, 90, 117–121], suggesting that smokers have a hyperactive AGE-RAGE and are therefore more at risk of severe COVID-19. The gene discussed is TNF; the disease is COVID-19.