Low concentrations of type‐I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID‐19). However, following the type‐I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU‐admitted patients with severe COVID‐19, and (iii) healthcare workers with mild COVID‐19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN‐α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r‐Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID‐19 pandemic to evaluate the IR in 45‐min with 2 min hand‐on‐time at hospitalization and to monitor the IR in future clinical trials. The type‐I Interferon response impairment increases the risk of severe forms of viral infections (like in COVID‐19 disease). We proposed a new integrated tool allowing the fast assessment of type‐I Interferon response (based on interferon stimulated gene expression measurement) to improve patient management.