Extensive hospital in-ward clustering revealed by molecular characterization of influenza A virus infection.

OBJECTIVE Nosocomial transmission of influenza A virus infection is not fully recognized. The aim of this study was to describe the characteristics of hospitalized patients with influenza A virus (InfA) infection during an entire season and to investigate in-ward transmission at a large acute-care hospital. METHODS During the season 2016-17 all hospitalized patients ≥18 years old with laboratory-verified (real-time PCR) InfA were identified. Cases were characterized according to age, sex, co-morbidity, antiviral therapy, viral load expressed as cycle threshold (Ct) values, length of hospital stay (LOS), 30-day mortality and whether the InfA infection met criteria for a health-care-associated infection (HCAI). Respiratory samples positive for InfA collected at the same wards within 7 days were chosen for whole-genome sequencing (WGS) and phylogenetic analysis was performed to detect clustering. For reference, concurrent InfA strains from patients with community-acquired infection were included. RESULTS We identified a total of 435 InfA cases, of which 114 (26%) met the HCAI-criteria. The overall 30-day mortality rate was higher among patients with HCAI (9.6% vs. 4.6% among non-HCAI), although the difference was not statistically significant in multivariable analysis, where age was the only independent risk factor for death (p<0.05). We identified 8 closely related clusters (involving ≥3 cases) and another 10 pairs of strains supporting in-ward transmission. CONCLUSION We found that in-ward transmission of InfA occurs frequently and that health-care-associated influenza may have a severe outcome. WGS may be used for outbreak investigations as well as for evaluation of the effect of preventive measures.