Global, regional, and national sepsis incidence and mortality, 1990-2021: a systematic analysis
- PMID: 41135560
- DOI: 10.1016/S2214-109X(25)00356-0
Global, regional, and national sepsis incidence and mortality, 1990-2021: a systematic analysis
Abstract
Background: The global burden of sepsis, a life-threatening dysregulated host response to infection leading to organ dysfunction, remains challenging to quantify. We aimed to comprehensively estimate the global, regional, and national burden of sepsis, including the impact of the COVID-19 pandemic and underlying causes of sepsis-related deaths with co-occurring infectious syndromes.
Methods: We used multiple cause-of-death, hospital, minimally invasive tissue sampling, and linked death certificate and hospital record data representing 149 million deaths, covering 4290 location-years with mortality estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to capture explicit and implicit sepsis cases and deaths. We estimated age-location-sex-specific fractions of sepsis-related deaths from 195 underlying causes of death and 22 infectious syndromes from 1990 to 2021 using binomial logistic regression models, and estimated sepsis-related deaths using GBD cause-specific mortality estimates. Using 250 million hospital admissions and 7·82 million deaths from hospital data, representing 1310 location-years, we modelled case fatality rates by use of binomial logistic regression, applied to sepsis death estimates to estimate sepsis incidence by age, location, and year.
Findings: In 2021, we estimated 166 million (95% uncertainty interval 135-201) sepsis cases and 21·4 million (20·3-22·5) all-cause sepsis-related deaths globally, representing 31·5% of total global deaths. Sepsis-related deaths decreased between 1990 and 2019, followed by a surge in 2020 and 2021. As of 2021, individuals aged 15 years and older experienced increases across incidence (230%) and mortality (26·3%) since 1990. Those aged 70 years and older had the highest sepsis-related mortality in 2021 (9·28 million [8·74-9·86] deaths). Sepsis-related deaths from infectious underlying causes decreased from 11·8 million (11·1-12·5) in 1990 to 8·34 million (7·72-9·01) in 2019, then increased by 86·4% to 15·5 million (14·7-16·4) in 2021. Sepsis-related mortality due to non-infectious underlying causes of death increased from 4·69 million (4·35-5·05) in 1990 to 5·81 million (5·40-6·25) in 2021; the leading non-infectious underlying causes of death with sepsis were stroke, chronic obstructive pulmonary disease, and cirrhosis. In 2021, bloodstream infections inclusive of HIV and malaria (3·08 million [2·83-3·35]) and lower respiratory infections inclusive of COVID-19 (11·33 million [1·20-1·47]) were the most prominent infectious syndromes complicating sepsis-related deaths from non-infectious underlying causes, representing a consistent trend since 1990.
Interpretation: The global burden of sepsis increased in 2020 and 2021, reversing progress from 1990. Sepsis incidence and mortality increased in people aged 15 years and older, especially those aged 70 years and older, and as a complication of non-infectious underlying causes of death such as stroke, primarily through bloodstream infections and lower respiratory infections. The global burden of sepsis is substantial, and sepsis is increasingly a complication of non-infectious causes of death.
Funding: Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of interests Q E S Adnani reports grants or contracts from the Scientific Excellence Research Grant from Universitas Padjadjaran, Bandung, Indonesia, with contract number 908/UN6.3.1/PT.00/2025, outside the submitted work. S Bhaskar reports grants or contracts from the Japan Society for the Promotion of Science (JSPS), Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), Grant-in-Aid for Scientific Research (KAKENHI; Grant ID 23KF0126), JSPS and the Australian Academy of Science, JSPS International Fellowship (Grant ID P23712); leadership or fiduciary roles in other board, society, committee, or advocacy groups, paid or unpaid as District Chair, Diversity, Equity, Inclusion & Belonging of Rotary District 9675 (Sydney, Australia), as Chair, Founding Member and Manager of the Global Health & Migration Hub Community, Global Health Hub Germany (Berlin, Germany), as Editorial Board Member of PLOS One, BMC Neurology, Frontiers in Neurology, Frontiers in Stroke, Frontiers in Public Health, Journal of Aging Research, Neurology International, Diagnostics, and BMC Medical Research Methodology; as a member of the College of Reviewers, Canadian Institutes of Health Research (CIHR), Government of Canada; as the Director of Research of World Headache Society (Bengaluru, India); as Expert Adviser/Reviewer of Cariplo Foundation (Milan, Italy); as Visiting Director of National Cerebral and Cardiovascular Center, Department of Neurology, Division of Cerebrovascular Medicine and Neurology, Suita (Osaka, Japan); as Member, Scientific Review Committee of Cardiff University Biobank (Cardiff, UK); as Chair of Rotary Reconciliation Action Plan; and Healthcare and Medical Adviser at Japan Connect (Osaka, Japan); outside the submitted work. E Chung reports support for the present manuscript from the US National Institutes of Health (Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] T32HD007233). Z B Harboe reports grants or contracts from Independent Research Fund Denmark (Inge Lehmanns grant number 3162-00031B), Helen Rudes Foundation, the Danish Cancer Society (grant number KBVU-MS R327-A19137), Novo Nordisk Foundation (grant number NNF24SA0090556), and the Danish National Research Foundation (grant number DNRF170); is affiliated as medical advisor to the Pneumococcal laboratory at Statens Serum Institut, Copenhagen, Denmark; is a member of the Danish Vaccination Council, outside of this work; and reports leadership or fiduciary roles in other board, society, committee, or advocacy groups, paid or unpaid with the Vaccine Study Group (EVASG) and European Society of Microbiology and Infectious Diseases (ESCMID), outside this work. I Ilic reports support for the present manuscript from the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (number 451-03-137/2025-03/200110). M Ilic reports support for the present manuscript from the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (number 451-03-47/2023-01/200111). N Kissoon reports leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid as President of the Global Sepsis Alliance, outside the submitted work. L Monasta reports support for the present manuscript from the Italian Ministry of Health (Ricerca Corrente 34/2017), and payments made to the Institute for Maternal and Child Health Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo. B Oancea reports support for the present manuscript from the Ministry of Research, Innovation and Digitalization through the Core Program of the National Research, Development and Innovation Plan 2022–27, project number PN 23-02-0101-Contract Number 7N/2023 PNRR/2022/C9/MCID/I8 project 760096. S Panda reports support for the present manuscript from Siksha ‘O’ Anusandhan Deemed to be University for payment of salary; and grants or contracts from file number 17-59/2023-24/CCRH/Tech./Coll./ICMR-Diabetes/960 as Co-Investigator, outside the submitted work. R Passera reports participation on a data safety monitoring board or advisory board as a member of the data safety monitoring board dello studio “Consolidation with ADCT-402 (loncastuximab tesirine) after immunochemotherapy: a phase II study in BTKi-treated/ineligible Relapse/Refractory Mantle Cell Lymphoma (MCL) patients”—Fondazione Italiana Linfomi (FIL), Alessandria; leadership or fiduciary roles in other board, society, committee, or advocacy groups, unpaid as member of the EBMT Statistical Committee, European Society for Blood and Marrow Transplantation, Paris (F) and as past member 2020–23 (biostatistician) of the IRB/IEC Comitato Etico AO SS Antonio e Biagio Alessandria-ASL AL-VC, outside the submitted work. I-R Petcu reports grants or contracts from the project “Societal and economic resilience within multi-hazards environment in Romania” funded by the European Union – NextgenerationEU and Romanian Government, under the National Recovery and Resilience Plan for Romania, contract number 760050/23.05.2023, code PNRR-C9-I8-CF 267/29.11.2022, through the Romanian Ministry of Research, Innovation and Digitalization, within Component 9, Investment I8, outside the submitted work. A Randolph reports grants or contracts from the Centers for Disease Control and Prevention, and the US National Institutes of Health; royalties or licences from UpToDate; consulting fees from Inotrem; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ThermoFisher; support for attending meetings or travel, or both, from the International Sepsis Forum; participation on a data safety monitoring board or advisory board with ReMAP CAP and Prevent VILI, US National Institutes of Health; leadership or fiduciary roles in other board, society, committee, or advocacy group, unpaid with the International Sepsis Forum Council; outside the submitted work. L F Reyes reports grants or contracts from GSK and MSD; consulting fees from GSK, MSK, and Pfizer; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK; support for attending meetings or travel, or both, from GSK and Pfizer; outside the submitted work. Y L Samodra reports grants or contracts from the Institute of Epidemiology and Preventive Medicine and NSTC Taiwan and from Taipei Medical University; leadership or fiduciary roles in other board, society, committee, or advocacy groups, paid or unpaid as the co-founder of Benang Merah Research Center (Indonesia); other financial or non-financial support from Jago Beasiswa (idebeasiswa.com) as a mentor; outside the submitted work. V Sharma reports financial or non-financial support from the Directorate of Forensic Sciences Services (DFSS) Ministry of Home Affairs (MHA's) research project (DFSS28(1)2019/EMR/6) at the Institute of Forensic Science & Criminology, Panjab University, Chandigarh, India, outside the submitted work. V Shivarov reports one patent from the Bulgarian patent office (#BG113116A); and other financial support from ICON (salary); outside the submitted work. C Simpson reports grants or contracts from the Health Research Council (NZ), Ministry of Health (NZ), Ministry of Business, Innovation and Employment (NZ), Chief Scientist Office (UK), Medical Research Council (UK); and leadership or fiduciary roles in other board, society, committee, or advocacy groups, paid or unpaid as the NZ Government Data Ethics Advisory Group Chair; outside the submitted work. J H V Ticoalu reports leadership or fiduciary roles in other board, society, committee, or advocacy groups, paid or unpaid as the co-founder of Benang Merah Research Center (Indonesia), outside the submitted work. E Upadhyay reports the following patents planned, issued, or pending with The Office of the Controller General of Patents, Designs & Trade Marks (CGPDTM; https://iprsearch.ipindia.gov.in/PublicSearch/PublicationSearch/ApplicationStatus): “Eco-friendly bio-shoe polish from banana and turmeric” (filed 202511021382), “Honey-based polyherbal syrup composition to treat air pollution-induced inflammation and preparation method thereof” (filed 202511035171), “Process for preparing a caffeine free, antioxidant and nutrient rich beverage” (filed 202511042794), “A system and method of reusable filters for anti-pollution mask” (published 202011003559), “A system and method for electricity generation through crop stubble by using microbial fuel cells” (published 202011008531), “A system for disposed personal protection equipment (PPE) into biofuel through pyrolysis and method” (published 202111005659), “A novel herbal pharmaceutical aid for formulation of gel and method thereof” (published 202111023333), “Herbal drug formulation for treating lung tissue degenerated by particulate matter exposure” (published 202311035276), “A method to transform cow dung into the wall paint by using natural materials and composition thereof” (filed 202311085452), “Biodegradable packaging composition and method of preparation thereof” (filed 202511017848); leadership or fiduciary roles in other board, society, committee, or advocacy groups as an Executive Council Member for the Indian Meteorological Society, Jaipur Chapter (India) and a Member Secretary for the DSTPURSE Program; outside the submitted work. B Venkatesh reports grants or contracts from the Investigator Grant from the National Health and Medical Research Council of Australia and research grants from Baxter, all payments made to the George Institute for Global Health, outside the submitted work. Y Yasufuku reports grants or contracts from Shionogi & Co. Ltd (employment expenses are paid from the joint research fund provided by this pharmaceutical company to The University of Osaka. The joint research with this pharmaceutical company is unrelated to the content of this GBD study). G Zamagni reports support for the present manuscript from the Italian Ministry of Health (Ricerca Corrente 34/2017) and payments made to the Institute for Maternal and Child Health IRCCS Burlo Garofolo. All other authors declare no competing interests.