IFNA1 and COVID-19: Our study adds further knowledge to why IFN-I responses are defective in severe COVID-19 through two major findings: first, we show that a combination of decreased circulating pDC numbers and dysregulated monocytes in critical disease is a major cause of ineffective IFNα secretion and second, IFN-I stimulation of leukocytes from severe COVID-19 patients promotes an inflammatory response that was not observed in moderate patients.