Coronavirus disease (COVID-19) induces an alteration of Interferon (IFN) genes expression potentially responsible for the observed low HLA-DR expression in circulating monocytes (mHLA-DR).<h4>Methods</h4>We report a case of one-time INFy injection (100 mcg s.c.)in a superinfected 61-year-old man with COVID-19-associated acute respiratory distress syndrome (ARDS), with monitoring of mHLA-DR expression and clinical tolerance.<h4>Observations</h4>Low mHLA-DR pretreatment expression (26.7%) was observed. The gene discussed is IFNA1; the disease is acute respiratory distress syndrome.