Superinfections MESHD of bacterial/fungal origin are known to affect the course and severity of respiratory viral infections MESHD. An increasing number of evidence indicate a relatively high prevalence SERO of superinfections MESHD associated with COVID-19, including invasive aspergillosis MESHD, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection MESHD we sought to determine and compare the host transcriptional response to SARS-CoV-2 versus Aspergillus superinfection MESHD, using a model of reconstituted humain airway epithelium. Our analyses reveal that both simple infection MESHD and superinfection MESHD induce a strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection MESHD in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection MESHD, such as an imbalanced type I/type III IFN, and an induction of several monocyte- and neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and but also management of severe forms of aspergillosis MESHD in this specific context.