Abstract
Two main mechanisms contribute to the continuous evolution of influenza viruses: accumulation of mutations in the hemagglutinin and neuraminidase genes (antigenic drift) and genetic re-assortments (antigenic shift). Epidemiological surveillance is important in identifying new genetic variants of influenza viruses with potentially increased pathogenicity and transmissibility. In order to characterize the 2019/20 influenza epidemic in Romania, 1042 respiratory samples were collected from consecutive patients hospitalized with acute respiratory infections in the National Institute for Infectious Diseases "Prof. Dr. Matei Balș", Bucharest Romania and tested for influenza A virus, influenza B virus and respiratory syncytial virus (RSV) by real-time PCR. Out of them, 516 cases were positive for influenza, with relatively equal distribution of influenza A and B. Two patients had influenza A and B co-infection and 8 patients had influenza-RSV co-infection. The most severe cases, requiring supplemental oxygen administration or intensive care, and the most deaths were reported in patients aged 65 years and over. Subtyping showed the predominance of A(H3N2) compared to A(H1N1)pdm09 pdm09 (60.4% and 39.6% of all subtyped influenza A isolates, respectively), and the circulation of Victoria B lineage only. Influenza B started to circulate first (week 47/2019), with influenza A appearing slightly later (week 50/2019), followed by continued co-circulation of A and B viruses throughout the season. Sixty-eight samples, selected to cover the entire influenza season and all circulating viral types, were analysed by next generation sequencing (NGS). All A(H1N1)pdm09 sequences identified during this season in Romania were clustered in the 6b1.A clade (sub-clades: 6b1.A.183P -5a and 6b1.A.187A). For most A(H1N1)pdm09 sequences, the dominant epitope was Sb (pepitope = 0.25), reducing the vaccine efficacy by approximately 60%. According to phylogenetic analysis, influenza A(H3N2) strains circulating in this season belonged predominantly to clade 3C.3A, with only few sequences in clade 3C.2A1b. These 3C.2A1b sequences, two of which belonged to vaccinated patients, harbored mutations in antigenic sites leading to potential reduction of vaccine efficacy. Phylogenetic analysis of influenza B, lineage Victoria, sequences showed that the circulating strains belonged to clade V1A3. As compared to the other viral types, fewer mutations were observed in B/Victoria strains, with limited impact on vaccine efficiency based on estimations.
Highlights
Due to constant viral evolution, influenza strains included in the vaccines are revised yearly based on WHO’s recommendations [1]
Romania participates in international respiratory infection surveillance networks with annual prospective data collection
The 2019/20 influenza season started and finished earlier than in previous years, potentially due to travel restrictions and sanitary protection measures in the context of the COVID-19 pandemic.In the studied season, the first influenza cases in Romania were identified in week 47/2019, initially as sporadic circulation of influenza B; influenza A cases appeared slightly later, starting with week 50/2019 [15]
Summary
Due to constant viral evolution, influenza strains included in the vaccines are revised yearly based on WHO’s recommendations [1]. Epidemiological surveillance and, in particular, molecular characterization of the circulating viral strains, are essential for making informed predictions on the upcoming influenza circulation and for defining the vaccine composition. All known pandemics were generated by influenza A through genetic re-assortments of different viral strains followed by human transmission. Random viral mutations can increase the viral pathogenicity. In contrast with type A viruses, influenza B strains were reported almost exclusively in humans. Two distinct lineages (Victoria and Yamagata) circulated continuously starting with the 1980s [2]. In human populations, A (H1N1)pdm and A(H3N2) subtypes co-circulated with B type viruses, one or both lineages being present at a given moment
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