P1614: MOLECULAR EPIDEMIOLOGY OF INFLUENZA VIRUS IN PATIENTS WITH HEMATOLOGIC DISORDERS

Abstract

Background: Whereas influenza virus infections usually present as self-limiting upper respiratory tract infections, they are also one of the most common causes of viral lower respiratory tract infections. Especially immunocompromised patients, such as ones suffering from malignant diseases, are at a higher risk of severe influenza virus infection, thus leading to increased morbidity and mortality. With influenza viruses possessing the ability of antigenic shift and antigenic drift, consequently altering the viral genome frequently and avoiding long-term immunity of the host, the necessity for regular data collection is clear. Aims: With this study we want to retrospectively assess influenza virus epidemiology in patients with hematological malignancies and investigate clinical and virological risk factors of severe infection to be able to apply information about improvement of hygiene and care. Methods: We included clinical data from 159 influenza positive patients from the Department of Haematology of the University Hospital Heidelberg from the seasons of 2014 to 2019 to analyse occurrence of nosocomial transmission, prolonged viral shedding and associated risk factors for severe infection. Virological data was obtained by nasopharyngeal swabs, which were collected routinely, then Sanger sequencing of the hemagglutinin gene was performed for phylogenetic and mutational analysis. Combination of clinical and virological data was assessed to evaluate specific susceptibility to influenza subtype, subgroup or amino acid mutation. Results: 42 patients (26%) developed LRTI. Associated risk factors with development of lower respiratory tract infection (LRTI) (p<0.05) were nosocomial infection (p=0.008), IgG levels lower than 6g/dl (p=0.046), bacterial (p=0.001), fungal (p<0.001) and bacterial and fungal (p=0.017) coinfection. 9 of 31 (29%) of bacterial copathogens belonged to multi-resistant strains. LRTI associated mortality rate in our study population was noticeably high with 38%. 67% of patients with consecutive testing (n=54) presented with prolonged viral shedding (median 9.5 days). Epidemiological comparison with national surveillance data mostly showed no divergence of our patient group regarding influenza type and subtype. In 115 patients, sequencing of influenza hemagglutinin gene was successful, and 13 virus isolates revealed significant substitutions: In A/H1N1 samples P137S, D187N and D222V; in A/H3N2 samples D7N, T10M, D101E, I140M, Q197K, Q197R and I214T; in B/Yamagata samples Y165H, P171Q and N202R and none in B/Victoria samples. Most of these substitutions could be assigned to an antigenic site or receptor binding site. Summary/Conclusion: While no specific susceptibility to influenza subtypes or subgroups could be observed, high LRTI associated mortality rate and occurrence of nosocomial transmission as well as multi-resistant copathogens illustrate the need for better hospital hygiene and early evaluation of disease severity. To understand detected mutations and their impact on the course of infection as well as virus evolution and vaccination efficiency, further collection of data is needed.