{
  "abstract": "Objective The objective of this study was to determine the association between viral subtype/clade and disease severity.Design Multicentre retrospective cohort study.Setting This study used data from the Global Influenza Hospital Surveillance Network (GIHSN). The dataset comprised hospitalised influenza patients with viral sequencing data across 14 countries, collected from August 2022 through October 2023.Participants A total of 761 hospitalised patients were enrolled during the study period, and 745 patients were included in the analysis. We excluded patients with missing data on explanatory or outcome variables, those infected with viral clades represented by fewer than 11 sequences, and those enrolled at study sites contributing fewer than 5 patients.Outcome measures Disease severity was defined by admission to intensive care unit (ICU), receipt of non-invasive oxygen supplementation, 3-variable definition (ICU, mechanical ventilation or death) or 4-variable definition (3-variable plus oxygen supplementation).Outcomes were analysed in association with subtype or clade using the mixed-effects logistic regression models, adjusting for age group, sex, underlying medical conditions, influenza vaccination status, antiviral use, country income level and epidemic period, while study site was included as a random effect.Results 745 patients were included: 263 A(H1N1)pdm09, 380 A(H3N2), 102 B/Victoria. A(H1N1)pdm09 infection was associated with increased odds of ICU admission (adjusted ORs (aORs) 2.5, 95% CI 1.1 to 5.8) compared with A(H3N2). 6B.1A.5a.2a.1 clade of A(H1N1)pdm09 was associated with increased severity compared with 6B.1A.5a.2a clade (aOR 3.0, 95% CI 1.0 to 9.5) and (aOR 5.4, 95% CI 1.6 to 18.3) for the 3-variable and 4-variable definitions respectively. Among A(H3N2), the (3C.2a1b.2a.)2b clade showed a trend toward increased severity using the 4-variable definition compared with the 2a.1b clade (aOR 2.9, 95% CI 0.8 to 10.0).Conclusions This analysis highlights the differential impact of influenza subtypes and clades on disease severity in hospitalised patients. Future research should investigate the role of specific viral mutations of these clades in modulating immune evasion or disease severity. These findings reinforce the GIHSN’s critical role in global surveillance. Ongoing genomic surveillance is crucial for understanding the clinical impact of emerging influenza variants and informing public health responses.",
  "authors": [
    {
      "affiliations": [
        "Université Claude Bernard Lyon 1, Villeurbanne, France",
        "Centre of Excellence in Respiratory Pathogens (CERP), Hospices Civils de Lyon (HCL) and Centre International de Recherche en Infectiologie (CIRI), Équipe Santé Publique, Épidémiologie et Écologie Évolutive des Maladies Infectieuses (PHE3ID), Inserm U1111, CNRS UMR5308, ENS de Lyon, Université Claude Bernard Lyon 1 (UCBL Lyon 1), Lyon, France"
      ],
      "name": "Aung Pone Myint"
    },
    {
      "affiliations": [
        "Centre of Excellence in Respiratory Pathogens (CERP), Hospices Civils de Lyon (HCL) and Centre International de Recherche en Infectiologie (CIRI), Équipe Santé Publique, Épidémiologie et Écologie Évolutive des Maladies Infectieuses (PHE3ID), Inserm U1111, CNRS UMR5308, ENS de Lyon, Université Claude Bernard Lyon 1 (UCBL Lyon 1), Lyon, France"
      ],
      "name": "George Shirreff"
    },
    {
      "affiliations": [
        "South African Medical Research Council, Vaccines and Infectious Diseases Analytics (VIDA) Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"
      ],
      "name": "Vicky Baillie"
    },
    {
      "affiliations": [
        "HCL and CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL Lyon 1, Lyon, France"
      ],
      "name": "Antonin Bal"
    },
    {
      "affiliations": [
        "American University of Beirut Centre for Infectious Diseases Research, Beirut, Beirut Governorate, Lebanon"
      ],
      "name": "Celina F Boutros"
    },
    {
      "affiliations": [
        "Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of Russian Federation, Moscow, Russian Federation"
      ],
      "name": "Elena Burtseva"
    },
    {
      "affiliations": [
        "Institut National d’Hygiène Publique, Abidjan, Côte d’Ivoire"
      ],
      "name": "Daouda Coulibaly"
    },
    {
      "affiliations": [
        "Smorodintsev Research Institute of Influenza, Saint Petersburg, Russian Federation"
      ],
      "name": "Daria Danilenko"
    },
    {
      "affiliations": [
        "Centre for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon"
      ],
      "name": "Ghassan Dbaibo"
    },
    {
      "affiliations": [
        "HCL and CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL Lyon 1, Lyon, France"
      ],
      "name": "Gregory Destras"
    },
    {
      "affiliations": [
        "Institut Pasteur of Dakar, Dakar, Senegal"
      ],
      "name": "Ndongo Dia"
    },
    {
      "affiliations": [
        "National Institute of Infectious Diseases Prof Dr Matei Bals, Bucharest, Romania"
      ],
      "name": "Anca Cristina Drăgănescu"
    },
    {
      "affiliations": [
        "Hospital Pequeno Principe, Curitiba, Paraná, Brazil"
      ],
      "name": "Heloisa I G Giamberardino"
    },
    {
      "affiliations": [
        "Smorodintsev Research Institute of Influenza, Saint Petersburg, Russian Federation"
      ],
      "name": "Andrey B Komissarov"
    },
    {
      "affiliations": [
        "Sher-i-Kashmir Institute, Srinagar, Jammu and Kashmir, India"
      ],
      "name": "Parvaiz A Koul"
    },
    {
      "affiliations": [
        "Clínica Internacional, Instituto de Medicina Tropical, Universidad Nacional Mayor de San Marcos, Lima District, Lima Region, Peru"
      ],
      "name": "Victor Alberto Laguna-Torres"
    },
    {
      "affiliations": [
        "Dalhousie University, Halifax, England, Canada"
      ],
      "name": "Jason J LeBlanc"
    },
    {
      "affiliations": [
        "FISABIO, Valencia, Valencian Community, Spain",
        "CIBERESP, Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain"
      ],
      "name": "Ainara Mira-Iglesias"
    },
    {
      "affiliations": [
        "SI Kyiv City Centre for Diseases Control and Prevention of the Ministry of Health of Ukraine, Kyiv, Ukraine"
      ],
      "name": "Alla Mironenko"
    },
    {
      "affiliations": [
        "FISABIO, Valencia, Valencian Community, Spain",
        "CIBERESP, Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain"
      ],
      "name": "Alejandro Orrico-Sánchez"
    },
    {
      "affiliations": [
        "Kenya Medical Research Institute, Kisumu, Kenya"
      ],
      "name": "Nancy A Otieno"
    },
    {
      "affiliations": [
        "Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucuresti, Bucuresti, Romania"
      ],
      "name": "Oana Săndulescu"
    },
    {
      "affiliations": [
        "Icahn School of Medicine at Mount Sinai, New York, New York, USA"
      ],
      "name": "Viviana Simon"
    },
    {
      "affiliations": [
        "Smorodintsev Research Institute of Influenza, Saint Petersburg, Russian Federation"
      ],
      "name": "Anna Sominina"
    },
    {
      "affiliations": [
        "Icahn School of Medicine at Mount Sinai, New York, New York, USA"
      ],
      "name": "Emilia Sordillo"
    },
    {
      "affiliations": [
        "Vaccine Institute, Hacettepe University, Ankara, Ankara, Turkey"
      ],
      "name": "Mine Durusu Tanriover"
    },
    {
      "affiliations": [
        "SI Kyiv City Centre for Diseases Control and Prevention of the Ministry of Health of Ukraine, Kyiv, Ukraine"
      ],
      "name": "Nataliia Teteriuk"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases and Clinical Microbiology, Hacettepe University School of Medicine, Ankara, Turkey"
      ],
      "name": "Serhat Unal"
    },
    {
      "affiliations": [
        "Icahn School of Medicine at Mount Sinai, New York, New York, USA"
      ],
      "name": "Harm Van Bakel"
    },
    {
      "affiliations": [
        "Dalhousie University, Halifax, England, Canada"
      ],
      "name": "Melissa K Andrew"
    },
    {
      "affiliations": [
        "Partnership for International Vaccine Initiatives, The Task Force for Global Health, Decatur, Georgia, USA"
      ],
      "name": "Joseph Bresee"
    },
    {
      "affiliations": [
        "HCL and CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL Lyon 1, Lyon, France"
      ],
      "name": "Bruno Lina"
    },
    {
      "affiliations": [
        "FISABIO, Valencia, Valencian Community, Spain",
        "Department of Microbiology, Medical School, University of Valencia, Valencia, Valencian Community, Spain"
      ],
      "name": "F Xavier López-Labrador"
    },
    {
      "affiliations": [
        "Centre for Vaccine Development and Global Health, University of Maryland Baltimore School of Medicine, Baltimore, Maryland, USA"
      ],
      "name": "Justin R Ortiz"
    },
    {
      "affiliations": [
        "Molecular Biology/Microbiology Research Laboratory, Universidade Federal do Paraná, Curitiba, Paraná, Brazil"
      ],
      "name": "Sonia M Raboni"
    },
    {
      "affiliations": [
        "Global Influenza Program, World Health Organization, Geneve, Switzerland"
      ],
      "name": "Wenqing Zhang"
    },
    {
      "affiliations": [
        "Foundation for Influenza Epidemiology, Fondation de France, Paris, Île-de-France, France"
      ],
      "name": "Sandra S Chaves"
    },
    {
      "affiliations": [
        "Laboratoire de Physique Théorique et Hautes Energies (LPTHE), UMR 7589, Sorbonne Université and CNRS, Paris, France"
      ],
      "name": "Giacomo Cacciapaglia"
    },
    {
      "affiliations": [
        "HCL and CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL Lyon 1, Lyon, France"
      ],
      "name": "Laurence Josset"
    },
    {
      "affiliations": [
        "Centre of Excellence in Respiratory Pathogens (CERP), Hospices Civils de Lyon (HCL) and Centre International de Recherche en Infectiologie (CIRI), Équipe Santé Publique, Épidémiologie et Écologie Évolutive des Maladies Infectieuses (PHE3ID), Inserm U1111, CNRS UMR5308, ENS de Lyon, Université Claude Bernard Lyon 1 (UCBL Lyon 1), Lyon, France"
      ],
      "name": "Cécile Chauvel"
    },
    {
      "affiliations": [
        "Centre of Excellence in Respiratory Pathogens (CERP), Hospices Civils de Lyon (HCL) and Centre International de Recherche en Infectiologie (CIRI), Équipe Santé Publique, Épidémiologie et Écologie Évolutive des Maladies Infectieuses (PHE3ID), Inserm U1111, CNRS UMR5308, ENS de Lyon, Université Claude Bernard Lyon 1 (UCBL Lyon 1), Lyon, France",
        "South African Medical Research Council, Vaccines and Infectious Diseases Analytics (VIDA) Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"
      ],
      "name": "Marta C Nunes"
    }
  ],
  "title": "Association of influenza viral genetic information with severity markers in patients hospitalised with influenza: multicentre retrospective cohort study",
  "uid": "7243aecd-cca9-5ca9-bbee-5a6fb9b4ffd5"
}
