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Background: Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B. Methods: Nasopharyngeal samples from patients found to be influenza B positive in four US and three Taiwanese ED over four consecutive influenza seasons (2014–2018) were tested for coinfections with the ePlex RP RUO panel. Multivariable logistic regressions were fitted to model adjusted odds ratios (aOR) for two severity outcomes separately: hospitalization and pneumonia diagnosis. Adjusting for demographic factors, underlying health conditions, and the National Early Warning Score (NEWS), we estimated the association of upper respiratory coinfections and comorbidity with disease severity (including hospitalization or pneumonia). Results: Amongst all influenza B positive individuals (n = 446), presence of another upper respiratory pathogen was associated with an increased likelihood of hospitalization (aOR = 2.99 [95% confidence interval (95% CI): 1.14–7.85, p = 0.026]) and pneumonia (aOR = 2.27 [95% CI: 1.25–4.09, p = 0.007]). Chronic lung diseases (CLD) were the strongest predictor for hospitalization (aOR = 3.43 [95% CI: 2.98–3.95, p < 0.001]), but not for pneumonia (aOR = 1.73 [95% CI: 0.80–3.78, p = 0.166]). Conclusion: Amongst ED patients infected with influenza B, the presence of other upper respiratory pathogens was independently associated with both hospitalization and pneumonia; presence of CLD was also associated with hospitalization. These findings may be informative for ED clinician's in managing patients infected with influenza B. [ABSTRACT FROM AUTHOR]