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. 2023 Dec 19;13(1):1.
doi: 10.3390/pathogens13010001.

An Investigation of Severe Influenza Cases in Russia during the 2022-2023 Epidemic Season and an Analysis of HA-D222G/N Polymorphism in Newly Emerged and Dominant Clade 6B.1A.5a.2a A(H1N1)pdm09 Viruses

Natalia P Kolosova  1 , Nikita D Boldyrev  1 , Svetlana V Svyatchenko  1 , Alexey V Danilenko  1 , Natalia I Goncharova  1 , Kyunnei N Shadrinova  1 , Elena I Danilenko  1 , Galina S Onkhonova  1 , Maksim N Kosenko  1 , Maria E Antonets  1 , Ivan M Susloparov  1 , Tatiana N Ilyicheva  1 , Vasily Y Marchenko  1 , Alexander B Ryzhikov  1
Affiliations

An Investigation of Severe Influenza Cases in Russia during the 2022-2023 Epidemic Season and an Analysis of HA-D222G/N Polymorphism in Newly Emerged and Dominant Clade 6B.1A.5a.2a A(H1N1)pdm09 Viruses

Natalia P Kolosova et al. Pathogens. .

Abstract

In Russia, during the COVID-19 pandemic, a decrease in influenza circulation was initially observed. Influenza circulation re-emerged with the dominance of new clades of A(H3N2) viruses in 2021-2022 and A(H1N1)pdm09 viruses in 2022-2023. In this study, we aimed to characterize influenza viruses during the 2022-2023 season in Russia, as well as investigate A(H1N1)pdm09 HA-D222G/N polymorphism associated with increased disease severity. PCR testing of 780 clinical specimens showed 72.2% of them to be positive for A(H1N1)pdm09, 2.8% for A(H3N2), and 25% for influenza B viruses. The majority of A(H1N1)pdm09 viruses analyzed belonged to the newly emerged 6B.1A.5a.2a clade. The intra-sample predominance of HA-D222G/N virus variants was observed in 29% of the specimens from A(H1N1)pdm09 fatal cases. The D222N polymorphic variant was registered more frequently than D222G. All the B/Victoria viruses analyzed belonged to the V1A.3a.2 clade. Several identified A(H3N2) viruses belonged to one of the four subclades (2a.1b, 2a.3a.1, 2a.3b, 2b) within the 3C.2a1b.2a.2 group. The majority of antigenically characterized viruses bore similarities to the corresponding 2022-2023 NH vaccine strains. Only one influenza A(H1N1)pdm09 virus showed reduced inhibition by neuraminidase inhibitors. None of the influenza viruses analyzed had genetic markers of reduced susceptibility to baloxavir.

Keywords: A(H1N1)pdm09; D222G/N polymorphism; influenza; monitoring; severe cases.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A maximum likelihood phylogenetic tree of the HA gene of influenza A(H1N1)pdm09 viruses analyzed in this study. Viruses isolated in Russia during the 2022–2023 epidemic season are indicated in blue. Vaccine strains are indicated in red. Amino acid substitutions in HA are in purple.
Figure 2
Figure 2
Pie charts representing the proportions of influenza A(H1N1)pdm09 virus samples with different intra-sample content of viral subpopulations bearing polymorphisms at the 222 codon. (A). Influenza cases with recovery (N = 70). (B). Fatal influenza cases (N = 90).
Figure 3
Figure 3
A normalized stacked bar chart representing profiles of the intra-sample genetic diversity of 40 individual influenza A(H1N1)pdm09 virus specimens originating from fatal influenza cases and containing at least 1% of HA-D222G and/or 1% of HA-D222N polymorphic variants.
Figure 4
Figure 4
Comparison of the HA-D222N polymorphic virus variant content in the original clinical sample and the corresponding MDCK isolate for seven different influenza A(H1N1)pdm09 cases.
Figure 5
Figure 5
Box-and-whisker plot analysis of log-transformed IC50 fold changes of individual strains compared to the median IC50 determined for all viruses of the same subtype analyzed during the 2022–2023 influenza season (90 A(H1N1)pdm09 and 17 B/Victoria viruses). Red and blue horizontal lines represent threshold levels of log-transformed IC50 fold changes above which neuraminidase inhibition is considered to be reduced for influenza A and B viruses, respectively.
See this image and copyright information in PMC

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