Effect of human H3N2 influenza virus reassortment on influenza incidence and severity during the 2017-18 influenza season in the USA: a retrospective observational genomic analysis.

Journal

The Lancet. Microbe
ISSN: 2666-5247
Titre abrégé: Lancet Microbe
Pays: England
ID NLM: 101769019

Informations de publication

Date de publication:
07 May 2024
Historique:
received: 31 03 2023
revised: 15 02 2024
accepted: 29 02 2024
medline: 12 5 2024
pubmed: 12 5 2024
entrez: 11 5 2024
Statut: aheadofprint

Résumé

During the 2017-18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017-18 influenza season. Samples included were collected from patients with influenza who were prospectively recruited during the 2016-17 and 2017-18 influenza seasons at the Johns Hopkins Hospital Emergency Departments in Baltimore, MD, USA, as well as from archived samples from Johns Hopkins Health System sites. Among 647 recruited patients with influenza A virus infection, 411 patients with whole-genome sequences were available in the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016-17 and 2017-18 seasons. Phylogenetic trees were constructed based on viral whole-genome sequences. Representative viral isolates of the two seasons were characterised in immortalised cell lines and human nasal epithelial cell cultures, and patients' demographic data and clinical outcomes were analysed. Unique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017-18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titre compared with the parental 3C.2a2 and 3C.2a1 viruses (48 h vs 72 h). Furthermore, patients infected with reassortant 3C.2a2 viruses had higher Influenza Severity Scores than patients infected with the parental 3C.2a2 viruses (median 3·00 [IQR 1·00-4·00] vs 1·50 [1·00-2·00]; p=0·018). Our findings suggest that the increased severity of the 2017-18 influenza season was due in part to two intrasubtypes, cocirculating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information could help inform future vaccine development and public health policies. The Center of Excellence for Influenza Research and Response in the US, National Science and Technology Council, and Chang Gung Memorial Hospital in Taiwan.

Sections du résumé

BACKGROUND BACKGROUND
During the 2017-18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017-18 influenza season.
METHODS METHODS
Samples included were collected from patients with influenza who were prospectively recruited during the 2016-17 and 2017-18 influenza seasons at the Johns Hopkins Hospital Emergency Departments in Baltimore, MD, USA, as well as from archived samples from Johns Hopkins Health System sites. Among 647 recruited patients with influenza A virus infection, 411 patients with whole-genome sequences were available in the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016-17 and 2017-18 seasons. Phylogenetic trees were constructed based on viral whole-genome sequences. Representative viral isolates of the two seasons were characterised in immortalised cell lines and human nasal epithelial cell cultures, and patients' demographic data and clinical outcomes were analysed.
FINDINGS RESULTS
Unique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017-18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titre compared with the parental 3C.2a2 and 3C.2a1 viruses (48 h vs 72 h). Furthermore, patients infected with reassortant 3C.2a2 viruses had higher Influenza Severity Scores than patients infected with the parental 3C.2a2 viruses (median 3·00 [IQR 1·00-4·00] vs 1·50 [1·00-2·00]; p=0·018).
INTERPRETATION CONCLUSIONS
Our findings suggest that the increased severity of the 2017-18 influenza season was due in part to two intrasubtypes, cocirculating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information could help inform future vaccine development and public health policies.
FUNDING BACKGROUND
The Center of Excellence for Influenza Research and Response in the US, National Science and Technology Council, and Chang Gung Memorial Hospital in Taiwan.

Identifiants

DOI: 10.1016/S2666-5247(24)00067-3 PMID: 38734029
pubmed: 38734029
pii: S2666-5247(24)00067-3
doi: 10.1016/S2666-5247(24)00067-3
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests SV owns stock in VIR Biotechnology as an employee of the company, unrelated to the submitted work. The other authors declare no competing interests.

Auteurs

Hsuan Liu (H)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Kathryn Shaw-Saliba (K)

Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Jason Westerbeck (J)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

David Jacobs (D)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Katherine Fenstermacher (K)

Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Chia-Yu Chao (CY)

Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan.

Yu-Nong Gong (YN)

Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.

Harrison Powell (H)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Zexu Ma (Z)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Thomas Mehoke (T)

Research and Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA.

Amanda W Ernlund (AW)

Research and Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA.

Amanda Dziedzic (A)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Siddhant Vyas (S)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Jared Evans (J)

Research and Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA.

Lauren M Sauer (LM)

Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Chin-Chieh Wu (CC)

Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Artificial Intelligence, College of Intelligent Computing, Chang Gung University, Taoyuan, Taiwan.

Shu-Hui Chen (SH)

Department of Emergency Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.

Richard E Rothman (RE)

Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Peter Thielen (P)

Research and Exploratory Development Department, Johns Hopkins Applied Physics Laboratory, Laurel, MD, USA.

Kuan-Fu Chen (KF)

Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Artificial Intelligence, College of Intelligent Computing, Chang Gung University, Taoyuan, Taiwan; Department of Emergency Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan. Electronic address: kfchen@mail.cgu.edu.tw.

Andrew Pekosz (A)

W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: apekosz1@jhu.edu.

Classifications MeSH