ABSTRACTBackgroundInfluenza viruses and seasonal coronaviruses are pathogens transmitted via an airborne route that can cause respiratory diseases in humans that have similar symptoms such as fever, cough, and pneumonia. These two viruses can infect similar human tissues, such as the respiratory tract and nasal, bronchial, and alveolar epithelial cells. Influenza virus and seasonal coronavirus coinfections are poorly understood.MethodsHere, we coinfected normal human bronchial epithelial (NHBE) cells with influenza A/California/04/09 (IAV) or B/Victoria/504/2000 (IBV) strains and the seasonal human beta‐coronavirus OC43 and evaluated viral replication capacities. We also examined changes in the expression of various cytokines/chemokines by qPCR and Luminex assay.ResultsWe observed that the replication of IAV and IBV was not affected by coinfection with OC43. However, coinfection reduced OC43 titers (~3‐fold) compared with infection with OC43 alone. Select cytokine/chemokine expression was increased in coinfected cells compared with all single infections with greater differences seen between coinfected cells and cells infected with OC43 alone compared with IAV‐ or IBV‐infected cells. In addition, IL‐8 and IL‐1RA showed the highest expression among a panel of 22 cytokines by Luminex.ConclusionsAs the rate of influenza and seasonal coronavirus coinfection continue to increase, our findings may help set guidelines for the treatments of the individuals coinfected with both viruses.