Altogether, these data indicate that S100A12 is involved in COVID-19 lung tissue damage, and that the elevation of AGEs S100B, S100A8/A9, and HMGB1 in the serum of SARS-CoV-2-infected people is associated with worse outcomes and increased mortality, pointing to an overall convergence of RAGE signaling in severe COVID-19. The gene discussed is AGER; the disease is COVID-19.