Although the subject of intensive preclinical and clinical research, controversy on the protective versus deleterious effects of endogenous and therapeutic IFN on COVID-19 remains. Some apparently conflicting results are most likely due to the intricacy of IFN subtypes (ie, type I interferon alfa and interferon beta, type III interferon lambda), timing and mode of administration (ie, nebulised or subcutaneous), and clinical groups that are targeted (ie, patients with asymptomatic, mild, moderate, or severe or critical COVID-19).