Evolution of Influenza A(H3N2) Viruses in 2 Consecutive Seasons of Genomic Surveillance, 2021-2023

Amary Fall; Lijie Han; Madeline Yunker; Yu-Nong Gong; Tai-Jung Li; Julie M Norton; Omar Abdullah; Richard E Rothman; Katherine Z J Fenstermacher; C Paul Morris; Andrew Pekosz; Eili Klein; Heba H Mostafa

doi:10.1093/ofid/ofad577

Evolution of Influenza A(H3N2) Viruses in 2 Consecutive Seasons of Genomic Surveillance, 2021-2023

Open Forum Infect Dis. 2023 Nov 16;10(12):ofad577. doi: 10.1093/ofid/ofad577. eCollection 2023 Dec.

Authors

Amary Fall¹, Lijie Han¹, Madeline Yunker¹, Yu-Nong Gong^{2

3

4

5}, Tai-Jung Li^{2

3}, Julie M Norton¹, Omar Abdullah¹, Richard E Rothman⁶, Katherine Z J Fenstermacher⁶, C Paul Morris^{1

7}, Andrew Pekosz^{6

8}, Eili Klein^{6

9}, Heba H Mostafa¹

Affiliations

¹ Division of Medical Microbiology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
² Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ International Master Degree Program for Molecular Medicine in Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁴ Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁵ National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.
⁶ Department of Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
⁷ Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
⁸ W.Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁹ Center for Disease Dynamics, Economics, and Policy, Washington, District of Columbia, USA.

Abstract

Background: The circulation and the genomic evolution of influenza A(H3N2) viruses during the 2021/2022 and 2022/2023 seasons were studied and associated with infection outcomes.

Methods: Remnant influenza A-positive samples following standard-of-care testing from patients across the Johns Hopkins Health System (JHHS) were used for the study. Samples were randomly selected for whole viral genome sequencing. The sequence-based pEpitope model was used to estimate the predicted vaccine efficacy (pVE) for circulating H3N2 viruses. Clinical data were collected and associated with viral genomic data.

Results: A total of 121 683 respiratory specimens were tested for influenza at JHHS between 1 September 2021 and 31 December 2022. Among them, 6071 (4.99%) tested positive for influenza A. Of these, 805 samples were randomly selected for sequencing, with hemagglutinin (HA) segments characterized for 610 samples. Among the characterized samples, 581 were H3N2 (95.2%). Phylogenetic analysis of HA segments revealed the exclusive circulation of H3N2 viruses with HA segments of the 3C.2a1b.2a.2 clade. Analysis of a total of 445 complete H3N2 genomes revealed reassortments; 200 of 227 of the 2022/2023 season genomes (88.1%) were found to have reassorted with clade 3C.2a1b.1a. The pVE was estimated to be -42.53% for the 2021/2022 season and 30.27% for the 2022/2023 season. No differences in clinical presentations or admissions were observed between the 2 seasons.

Conclusions: The increased numbers of cases and genomic diversity of influenza A(H3N2) during the 2022/2023 season were not associated with a change in disease severity compared to the previous influenza season.

Keywords: H3N2; influenza; reassortment; vaccine.

Abstract

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