Thus, a multi-hit model of MPO and its multifaceted reactions that lead to production of ROS such as HOCl, O2•-, H2O2 and •OH, which then mediate decrease O2 diffusion, carriage, and delivery through interaction with heme proteins and other players could explain the rapid evolution of respiratory failure and subsequent mortality in patients in critical stages of COVID-19. The gene discussed is MPO; the disease is COVID-19.