In this preprint, Hadjadj et al. analyse the late-stage immune responses in 50 patients with COVID-19 spanning a range of disease severity but controlled for age, duration from symptom onset and comorbidities. Compared with mild or moderate cases, severe and critically ill patients have a profoundly impaired type I interferon response, despite comparable viral loads as measured by nasal swab. In addition, clinical severity correlated with increased IL-6, TNF and chemokine signatures. These findings suggest that type I interferon may hold promise for prognostic and therapeutic strategies. Further studies of these cytokines earlier in disease and with more precise quantification of viral load in the respiratory tract will be crucial to validate the result.