# Genomic Evolution of Influenza A(H1N1)pdm09 and A/H3N2 Viruses Among Children in Wuhan, China, Spanning the COVID-19 Pandemic (2020–2023)

## TL;DR

This study tracks how influenza A viruses evolved in Wuhan children during the COVID-19 pandemic, showing genetic changes and reduced spread.

## Contribution

The study provides new insights into influenza A virus genomic evolution in China during the pandemic, including antigenic drift and reassortment events.

## Key findings

- Influenza A virus positivity was low (3.43%) in Wuhan children during 2020–2023, likely due to pandemic NPIs.
- H1N1pdm09 was the dominant strain, with mutations like R240Q linked to antigenic drift and S247N possibly conferring antiviral resistance.
- H3N2 strains showed mutations like E78G and R158G, and evidence of reassortment was detected despite low prevalence.

## Abstract

Despite the persistent global threat of seasonal influenza viruses such as A(H1N1)pdm09 and A/H3N2, their epidemiological and genetic characteristics in China following the implementation of COVID-19 non-pharmaceutical interventions (NPIs) remain poorly characterized. Between September 2020 and December 2023, we conducted an integrated epidemiological and genomic analysis of influenza A viruses in children in Wuhan. The overall positivity rate for influenza A virus was markedly low at 3.43% (109/3171), reflecting a profound suppression of circulation during the pandemic. Among genotyped positives, H1N1pdm09 was predominant (52.3%), followed by H3N2 (16.5%) and untypeable strains (32.1%). Preschool children showed the highest susceptibility. Phylogenetic analysis revealed that the circulating H1N1 strains (90%) belonged to clade 6B.1A.5a.2, clustering with viruses from Hong Kong and Pakistan. In contrast, H3N2 strains (76.92%) primarily fell into clade 3C.2a1b.2a.2b, closely related to contemporary strains from Europe and North America. Notably, we identified key hemagglutinin mutations associated with antigenic drift (e.g., R240Q in H1N1; E78G, R158G in H3N2) and neuraminidase mutations potentially conferring antiviral resistance (e.g., S247N in H1N1; S245N, a putative novel glycosylation site, in H3N2). Evidence of reassortment events was also detected, underscoring the continued genomic evolution of these viruses despite their low prevalence. Our findings demonstrate that genetically diverse and antigenically drifted influenza A viruses continued to circulate and evolve in Wuhan during the COVID-19 pandemic, albeit at dramatically reduced levels. This highlights the critical need for sustained genomic surveillance and timely updates of vaccine compositions to pre-empt the resurgence of influenza in the post-pandemic era.