H3N2 influenza virus characteristics in China (2019–2022): Genetic, antigenic, and infection dynamics during the COVID-19 pandemic
Jiaming Li, Huan Yu, Qianfeng Xia, Yan Li, Rahat Ullah Khan, Qingzhi Liu, Chuanran Dou, Marina Gulyaeva, А. М. Шестопалов, Ning Zhang, Xuefeng Duan, Jing Yang, Hongchun Zhang, Yuhai Bi
Abstract
Seasonal influenza activity significantly decreased in China during the coronavirus disease 2019 (COVID-19) pandemic, yet the H3N2 virus led to three epidemic waves. Understanding the characteristics of H3N2 epidemic viruses is essential for recognizing influenza during COVID-19 and for updating vaccines. In this study, we analyzed 579 respiratory samples from patients exhibiting influenza-like symptoms, collected between late 2019 and summer 2022, leading to the successful sequencing of 36 complete H3N2 genomes. Genomic analysis indicated that the epidemic strains from these periods belonged to different hemagglutinin ( HA ) clades and exhibited phylogenetic divergence from the concurrently used vaccine strains. Significant antigenic differences were identified through cross-hemagglutination inhibition (HI) and microneutralization (MN) assays. Further pathogenicity studies showed that representative strains replicated in MDCK cells, with varying abilities, and all replicated more effectively at 37 °C than 33 °C. These strains also replicated well in the respiratory tracts of mice and guinea pigs. The findings indicate a mismatch between circulating H3N2 viruses and recommended vaccine strains, highlighting the need for improved international cooperation and epidemiological surveillance of influenza viruses post-COVID-19. Prioritizing effective vaccine strain updates and developing a universal influenza vaccine are crucial for future preparedness. • The H3N2 influenza viruses caused three known outbreaks in China during the spread of COVID-19, underscoring the associated public health risks. • The epidemic strains replicated well in vitro and in vivo without prior adaptation, and replicated better at 37 °C compared to 33°C, which may explain the H3N2 outbreak in summer. • The mismatches between the recommended vaccine strains and the epidemic H3N2 viruses were identified before and after the implementation of strict strategies against COVID-19. • A personalized and precise vaccination update program needs to be added to the agenda after the COVID-19 pandemic.