Background Influenza disease data remain scarce in middle and lower-income countries. We used data from the Global Influenza Hospital Surveillance Network (GIHSN), a prospective multi-country surveillance system from 2012-2019, to assess differences in the epidemiology and severity of influenza hospitalizations by country income level. Methods We compiled individual-level data on acute respiratory hospitalizations, with standardized clinical reporting and testing for influenza. Adjusted odds ratios (aORs) for influenza-associated intensive care unit (ICU) admission and in-hospital death were estimated with multivariable logistic regression that included country income group (World Bank designation: high-income countries: HIC; upper middle-income countries: UMIC; lower middle-income countries: LMIC), age, sex, number of comorbidities, influenza subtype and lineage, and season as covariates. Findings From 73,121 patients hospitalized with respiratory illness in 22 countries, 15,660 were laboratory-confirmed for influenza. After adjustment for patient-level covariates, there was a two-fold increased risk of ICU admission for patients in UMIC (aOR 2.31; 95% confidence interval (CI) 1.85-2.88, p < 0.001), and a 5-fold increase in LMIC (aOR 5.35; 95% CI 3.98-7.17, p < 0.001), compared to HIC. The risk of in-hospital death in HIC and UMIC was comparable (UMIC: aOR 1.14; 95% 0.87-1.50; p > 0.05), though substantially lower than that in LMIC (aOR 5.05; 95% 3.61-7.03; p < 0.001 relative to HIC). A similar severity increase linked to country income was found in influenza-negative patients. Interpretation We found significant disparities in influenza severity among hospitalized patients in countries with limited resources, supporting global efforts to implement public health interventions. Funding The GIHSN is partially funded by the Foundation for Influenza Epidemiology (France). This analysis was funded by Ready2Respond under Wellcome Trust grant 224690/Z/21/Z.

The authors have declared no competing interest.

The GIHSN is partially funded by the Foundation for Influenza Epidemiology (France). This analysis was funded by Ready2Respond under Wellcome Trust grant 224690/Z/21/Z.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The following ethics committees gave ethical approval for the GIHSN surveillance work: the Research Ethics Board of Nova Scotia Health and of each participating site in Canada; le Comité de Protection des Personnes (CPP) Ile de France IV, Hôpital Saint-Louis, France, as part of the FLUVAC study; the Ethical Committee of the Hospital Na Bulovce, Czech Republic; CEIC Direccion General de Salud Publica/Centro Superior de Investigación en Salud Pública of FISABIO, Spain; the Fudan University School of Public Health Institution Review Board, China; the Institutional Review Board, American University of Beirut, Lebanon; Comité Institucional de Ética en Investigación: Instituto de Medicina Tropical DAC Universidad Nacional de San Marcos, Perú; the Bioethics Committee of the National Institute for Infectious Diseases Prof. Dr. Matei Bals, Bucharest, Romania; Comité de Bioética del Hospital Dr. Alejandro Posadas, Argentina; the Research Ethics Committee (Medical) of the University of the Cartagena, the Ethical Committee of the Hospital Universitario del Caribe, the Ethics Committee Hospital children Napoleon Franco Pareja in Cartagena, Colombia; Comitê de Ética em Pesquisa - CEP 0097 - Hospital Pequeno Príncipe, Brazil; the Human Research Ethics Committee (Medical) of the University of the Witwatersrand, South Africa; the local Ethic Committee of Hospital 1 for Infectious Diseases of Moscow Health Department of the Federal State Budgetary Healthcare Institution, Moscow, Russia; the Local Ethics Committee at the Federal State Budget Institution Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation; the Ethical committee of the Institute of Public Health Vojvodina, Serbia; the National Institute of Public Hygiene (INPH), Côte d'Ivoire, as part of the national epidemiological surveillance of influenza; the medical ethics committee of Dr. Abderrahmane Mami, Ariana, Tunisia; KEMRI Scientific and Ethics Review Unit of the Kenya Medical Research Institute, Kenya; the Institute Ethics Committee of the Sher-i Kashmir Institute of Medical Sciences, Srinagar, India; and Hacettepe University Noninterventional Clinical Research Ethics Board, Türkiye.

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Anonymized data used for this analysis, along with a data dictionary, are available upon request made to contact@gihsn.org. The use of data depends on the approval of an analytical proposal by the Independent Scientific Committee. Investigators from participant sites are informed up front for any planned data analysis and they have the possibility to opt-out.