Given the elevated intracellular and extracellular levels of HMGB-1 and the presence of an immunosuppressive profile, especially in severe COVID-19 patients [57], it is hypothesized that the TIM3/HMGB-1 axis may contribute to dysfunctional immune responses and subsequent tissue manifestations, including skin abnormalities (Fig. 1B). The gene discussed is HAVCR2; the disease is COVID-19.