Coinfection of Influenza A and B and Human OC43 Coronavirus in Normal Human Bronchial Epithelial Cells

Abstract

BackgroundInfluenza 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.

The impacts of viral interaction on household transmission of respiratory viruses

“…As for the current study, one hypothesis is that the observed protective effect of exposure to coinfected index cases may be driven by this antagonistic relationship between rhinovirus and RSV/IAV, which could inhibit the transmission of these viruses of interest. Kim et al (2024) examined coinfections between influenza viruses and human OC43 coronavirus in normal human bronchial epithelial cells and found that while coinfection with OC43 did not affect replication of IAV or IBV, select cytokine/chemokine expression was increased in coinfected cells compared to singly infected cells. 26 A hypothesis for our other main finding is that coinfection among secondary cases with IAV or RSV plus another virus led to more symptomatic illness than infection with either of the viruses alone; because the HIVE study requires a standard ARI case definition for testing, these virus combinations would be detected more frequently if they more often resulted in illnesses that met the ARI definition.…”

“…Kim et al (2024) examined coinfections between influenza viruses and human OC43 coronavirus in normal human bronchial epithelial cells and found that while coinfection with OC43 did not affect replication of IAV or IBV, select cytokine/chemokine expression was increased in coinfected cells compared to singly infected cells. 26 A hypothesis for our other main finding is that coinfection among secondary cases with IAV or RSV plus another virus led to more symptomatic illness than infection with either of the viruses alone; because the HIVE study requires a standard ARI case definition for testing, these virus combinations would be detected more frequently if they more often resulted in illnesses that met the ARI definition. Studies comparing disease severity between coinfections and single virus infections have had mixed results.…”