Interferons are potent natural antivirals, rallying other parts of the immune system to defend against viruses. Some clinical trials have tested interferons as a treatment for COVID-19, but results have been mixed, and the science has been unclear about whether interferons are helpful or harmful. New research in Cell, led by Ivan Zanoni, Ph.D. at Boston Children’s Hospital, provides a more complete picture of interferons’ role in mild versus severe COVID-19, informing future research, and potentially, treatment.