BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

Arabian Gulf University Manama Bahrain

Brotman Baty Institute University of Washington Seattle Washington USA

Canadian Center for Vaccinology IWK Health Centre and Nova Scotia Health Dalhousie University Halifax Nova Scotia Canada

Center for Infectious Diseases Research American University of Beirut Beirut Lebanon

Clínica Internacional Instituto de Medicina Tropical Universidad Nacional Mayor de San Marcos Lima Peru

Department of Epidemiology and Biostatistics 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Infectious Diseases and Clinical Microbiology Hacettepe University School of Medicine Ankara Turkey

Department of Infectious Diseases Epidemiology National Institute of Public Health Prague Czech Republic

Department of Internal Medicine Hacettepe University School of Medicine Ankara Turkey

Department of Medical Education Icahn School of Medicine at Mount Sinai New York New York USA

Department of Science and Technology National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

Division of International Epidemiology and Population Studies Fogarty International Center National Institutes of Health Bethesda Maryland USA

Faculty of Medicine University of Novi Sad Novi Sad Serbia

Foundation for Influenza Epidemiology Fondation de France Paris France

Fundación Para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana Valencia Spain

Gamaleya Federal Research Center for Epidemiology and Microbiology Ministry of Health of Russian Federation Moscow Russia

Grupo de Investigación UNIMOL Facultad de Medicina Universidad de Cartagena Cartagena de Indias Colombia

Hôpital Edouard Herriot Lyon France

Institut Pasteur de Tunis Tunis Tunisia

Institute for Public Health of Vojvodina Novi Sad Serbia

Kenya Medical Research Institute Nairobi Kenya

National Institute for Infectious Diseases Prof Dr Matei Bals Bucharest Romania

National Institute of Public Hygiene Abidjan Côte d'Ivoire

PandemiX Center Department of Science and Environment Roskilde University Denmark

Ready2Respond p o The Task Force for Global Health Decatur Georgia USA

Respiratory Virus Laboratory Virology Department INEI ANLIS Buenos Aires Argentina

School of Public Health Fudan University Shanghai China

Sheri Kashmir Institute of Medical Sciences Srinagar India

Smorodintsev Research Institute of Influenza St Petersburg Russia

South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

Turkish Society of Internal Medicine Ankara Turkey

Virology Laboratory Infectious Diseases Division Universidade Federal do Paraná Hospital Pequeno Principe Curitiba Paraná Brazil

Zobrazit více v PubMed

Iuliano  AD, Roguski  KM, Chang  HH, et al.  Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet  2018; 391:1285–300. PubMed PMC

World Health Organization.  Influenza (seasonal). https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal). Accessed 13 June 2022.

Neuzil  KM, Wright  PF, Jr ME, Griffin  MR. The burden of influenza illness in children with asthma and other chronic medical conditions. J Pediatr  2000; 137:856–64. PubMed

Chow  EJ, Rolfes  MA, O’Halloran  A, et al.  Respiratory and nonrespiratory diagnoses associated with influenza in hospitalized adults. JAMA Netw Open  2020; 3:e201323. PubMed PMC

Derqui  N, Nealon  J, Mira-Iglesias  A, Díez-Domingo  J, Mahé  C, Chaves  SS. Predictors of influenza severity among hospitalized adults with laboratory confirmed influenza: analysis of nine influenza seasons from the Valencia region, Spain. Influenza Other Respi Viruses  2022; 16:862–72. PubMed PMC

Sellers  SA, Hagan  RS, Hayden  FG, Fischer  WA  2nd. The hidden burden of influenza: a review of the extra-pulmonary complications of influenza infection. Influenza Other Respi Viruses  2017; 11:372–93. PubMed PMC

Paget  J, Spreeuwenberg  P, Charu  V, et al.  Global mortality associated with seasonal influenza epidemics: new burden estimates and predictors from the GLaMOR project. J Glob Health  2019; 9:020421. PubMed PMC

Roguski  KM, Rolfes  MA, Reich  JS, et al.  Variability in published rates of influenza-associated hospitalizations: a systematic review, 2007–2018. J Glob Health  2020; 10:020430. PubMed PMC

Lina  B, Georges  A, Burtseva  E, et al.  Complicated hospitalization due to influenza: results from the Global Hospital Influenza Network for the 2017–2018 season. BMC Infect Dis  2020; 20:465. PubMed PMC

Puig-Barberà  J, Burtseva  E, Yu  H, et al.  Influenza epidemiology and influenza vaccine effectiveness during the 2014–2015 season: annual report from the Global Influenza Hospital Surveillance Network. BMC Public Health  2016; 16(suppl 1):757. PubMed PMC

Puig-Barberà  J, Tormos  A, Trushakova  S, et al.  The Global Influenza Hospital Surveillance Network (GIHSN): a new platform to describe the epidemiology of severe influenza. Influenza Other Respi Viruses  2015; 9:277–86. PubMed PMC

World Bank.  Data catalog. https://datacatalog.worldbank.org/home. Accessed 13 June 2022.

Chen  C, Jiang  D, Yan  D, et al.  The global region-specific epidemiologic characteristics of influenza: WHO FluNet data from 1996 to 2021. Int J Infect Dis  2023; 129:118–24. PubMed

Saha  S, Chadha  M, Al Mamun  A, et al.  Influenza seasonality and vaccination timing in tropical and subtropical areas of southern and south-eastern Asia. Bull World Health Organ  2014; 92:318–30. PubMed PMC

Chaves  SS, Aragon  D, Bennett  N, et al.  Patients hospitalized with laboratory-confirmed influenza during the 2010–2011 influenza season: exploring disease severity by virus type and subtype. J Infect Dis  2013; 208:1305–14. PubMed

Xing  Z, Cardona  CJ. Preexisting immunity to pandemic (H1N1) 2009. Emerg Infect Dis  2009; 15:1847–9. PubMed PMC

Coleman  BL, Fadel  SA, Fitzpatrick  T, Thomas  S-M. Risk factors for serious outcomes associated with influenza illness in high- versus low- and middle-income countries: systematic literature review and meta-analysis. Influenza Other Respi Viruses  2018; 12:22–9. PubMed PMC

Zbinden  D, Manuel  O. Influenza vaccination in immunocompromised patients: efficacy and safety. Immunotherapy  2014; 6:131–9. PubMed

Ortiz  JR, Neuzil  KM. Influenza immunization in low- and middle-income countries: preparing for next-generation influenza vaccines. J Infect Dis  2019; 219:S97–106. PubMed

Bhan  MK, Sinha  B. Immunisation against influenza in low-income and middle-income countries. Lancet Glob Health  2019; 7:e827-8. PubMed

Bresee  JS, Lafond  KE, McCarron  M, et al.  The Partnership for Influenza Vaccine Introduction (PIVI): supporting influenza vaccine program development in low and middle-income countries through public-private partnerships. Vaccine  2019; 37:5089–95. PubMed PMC

Salluh  JIF, Burghi  G, Haniffa  R. Intensive care for COVID-19 in low- and middle-income countries: research opportunities and challenges. Intensive Care Med  2021; 47:226–9. PubMed PMC

Turner  HC, Van Hao  N, Yacoub  S, et al.  Achieving affordable critical care in low-income and middle-income countries. BMJ Glob Health  2019; 4:e001675. PubMed PMC

Skrip  L, Derra  K, Kaboré  M, et al.  Clinical management and mortality among COVID-19 cases in sub-Saharan Africa: a retrospective study from Burkina Faso and simulated case analysis. Int J Infect Dis  2020; 101:194–200. PubMed PMC

Malinczak  CA, Fonseca  W, Rasky  AJ, et al.  Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease. Mucosal Immunol  2019; 12:969–79. PubMed PMC

Bwire  GM. Coronavirus: why men are more vulnerable to Covid-19 than women?  SN Compr Clin Med  2020; 2:874–6. PubMed PMC

Garten  R, Blanton  L, Elal  AIA, et al.  Update: influenza activity in the United States during the 2017–18 season and composition of the 2018–19 influenza vaccine. MMWR Morb Mortal Wkly Rep  2018; 67:634–42. PubMed PMC

Global Influenza Programme WEP . Review of the 2017–2018 influenza season in the northern hemisphere. Published 24 August 2018.  https://www.who.int/publications/i/item/who-wer-9334-429-444. Accessed 7 July 2022.

Hansen  CL, Chaves  SS, Demont  C, Viboud  C. Mortality associated with influenza and respiratory syncytial virus in the US, 1999–2018. JAMA Netw Open  2022; 5:e220527. PubMed PMC

Shi  T, McAllister  DA, O’Brien  KL, et al.  Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet  2017; 390:946–58. PubMed PMC

Heikkinen  T, Osterback  R, Peltola  V, Jartti  T, Vainionpää  R. Human metapneumovirus infections in children. Emerg Infect Dis  2008; 14:101–6. PubMed PMC

Morales  KF, Brown  DW, Dumolard  L, et al.  Seasonal influenza vaccination policies in the 194 WHO member states: the evolution of global influenza pandemic preparedness and the challenge of sustaining equitable vaccine access. Vaccine X  2021; 8:100097. PubMed PMC

Olsen  SJ, Azziz-Baumgartner  E, Budd  AP, et al.  Decreased influenza activity during the COVID-19 pandemic—United States, Australia, Chile, and South Africa, 2020. MMWR Morb Mortal Wkly Rep  2020; 69:1305–9. PubMed PMC

Gomez  GB, Mahé  C, Chaves  SS. Uncertain effects of the pandemic on respiratory viruses. Science  2021; 372:1043–4. PubMed

Eden  J-S, Sikazwe  C, Xie  R, et al.  Off-season RSV epidemics in Australia after easing of COVID-19 restrictions. Nat Commun  2022; 13:2884. PubMed PMC

Agha  R, Avner  JR. Delayed seasonal RSV surge observed during the COVID-19 pandemic. Pediatrics  2021; 148:e2021052089. PubMed

Prin  M, Wunsch  H. International comparisons of intensive care: informing outcomes and improving standards. Curr Opin Crit Care  2012; 18:700–6. PubMed PMC

Cohen  C, Walaza  S, Treurnicht  FK, et al.  In- and out-of-hospital mortality associated with seasonal and pandemic influenza and respiratory syncytial virus in South Africa, 2009–2013. Clin Infect Dis  2018; 66:95–103. PubMed PMC

Gill  CJ, Mwananyanda  L, MacLeod  WB, et al.  Infant deaths from respiratory syncytial virus in Lusaka, Zambia from the ZPRIME study: a 3-year, systematic, post-mortem surveillance project. Lancet Glob Health  2022; 10:e269–77. PubMed PMC

Finelli  L, Fiore  A, Dhara  R, et al.  Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics  2008; 122:805–11. PubMed

Barnes  SR, Wansaula  Z, Herrick  K, et al.  Mortality estimates among adult patients with severe acute respiratory infections from two sentinel hospitals in southern Arizona, United States, 2010–2014. BMC Infect Dis  2018; 18:78. PubMed PMC