As HIF-1α is induced in monocytes by hypoxia, and HMGB1 is released by hypoxic epithelial cells, these findings demonstrate that monocytes adapt to a local hypoxic environment with the remodeling of effector as well as metabolic pathways and that in COVID-19 patients the altered effector pathway is characterized by diminished production of IFNα, which contributes to disease pathogenesis. Here, HIF1A is linked to COVID-19.