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BMJ Open
. 2026 Jan 8;16(1):e111643.
doi: 10.1136/bmjopen-2025-111643. Association of influenza viral genetic information with severity markers in patients hospitalised with influenza: multicentre retrospective cohort study
Aung Pone Myint 1 2 , George Shirreff 2 , Vicky Baillie 3 , Antonin Bal 4 , Celina F Boutros 5 , Elena Burtseva 6 , Daouda Coulibaly 7 , Daria Danilenko 8 , Ghassan Dbaibo 9 , Gregory Destras 4 , Ndongo Dia 10 , Anca Cristina Drăgănescu 11 , Heloisa I G Giamberardino 12 , Andrey B Komissarov 8 , Parvaiz A Koul 13 , Victor Alberto Laguna-Torres 14 , Jason J LeBlanc 15 , Ainara Mira-Iglesias 16 17 , Alla Mironenko 18 , Alejandro Orrico-Sánchez 16 17 , Nancy A Otieno 19 , Oana Săndulescu 20 , Viviana Simon 21 , Anna Sominina 8 , Emilia Sordillo 21 , Mine Durusu Tanriover 22 , Nataliia Teteriuk 18 , Serhat Unal 23 , Harm Van Bakel 21 , Melissa K Andrew 15 , Joseph Bresee 24 , Bruno Lina 4 , F Xavier López-Labrador 16 25 , Justin R Ortiz 26 , Sonia M Raboni 27 , Wenqing Zhang 28 , Sandra S Chaves 29 , Giacomo Cacciapaglia 30 , Laurence Josset 4 , Cécile Chauvel 2 , Marta C Nunes 31 3
Affiliations
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.
Keywords: EPIDEMIOLOGY; Epidemics; Epidemiology; INFECTIOUS DISEASES; Respiratory infections.
. 2026 Jan 8;16(1):e111643.
doi: 10.1136/bmjopen-2025-111643. Association of influenza viral genetic information with severity markers in patients hospitalised with influenza: multicentre retrospective cohort study
Aung Pone Myint 1 2 , George Shirreff 2 , Vicky Baillie 3 , Antonin Bal 4 , Celina F Boutros 5 , Elena Burtseva 6 , Daouda Coulibaly 7 , Daria Danilenko 8 , Ghassan Dbaibo 9 , Gregory Destras 4 , Ndongo Dia 10 , Anca Cristina Drăgănescu 11 , Heloisa I G Giamberardino 12 , Andrey B Komissarov 8 , Parvaiz A Koul 13 , Victor Alberto Laguna-Torres 14 , Jason J LeBlanc 15 , Ainara Mira-Iglesias 16 17 , Alla Mironenko 18 , Alejandro Orrico-Sánchez 16 17 , Nancy A Otieno 19 , Oana Săndulescu 20 , Viviana Simon 21 , Anna Sominina 8 , Emilia Sordillo 21 , Mine Durusu Tanriover 22 , Nataliia Teteriuk 18 , Serhat Unal 23 , Harm Van Bakel 21 , Melissa K Andrew 15 , Joseph Bresee 24 , Bruno Lina 4 , F Xavier López-Labrador 16 25 , Justin R Ortiz 26 , Sonia M Raboni 27 , Wenqing Zhang 28 , Sandra S Chaves 29 , Giacomo Cacciapaglia 30 , Laurence Josset 4 , Cécile Chauvel 2 , Marta C Nunes 31 3
Affiliations
- PMID: 41506775
- DOI: 10.1136/bmjopen-2025-111643
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.
Keywords: EPIDEMIOLOGY; Epidemics; Epidemiology; INFECTIOUS DISEASES; Respiratory infections.