Global, regional, and national sepsis incidence and mortality, 1990–2021: a systematic analysis

Usha Adiga Samah W. Al-Jabi Meriem Abdoun Quique Bassat Zulfiqar A. Bhutta Hany Aly Ashish Bhargava Hasan Yaser Alniss Razique Anwer Abdul Monim Batiha Asrat Agalu Abejew Samar Abd ElHafeez Mahwish Arooj Matteo Bauckneht Mohammad R. Alqudimat Alok Atreya Abdelazeem M. Algammal Saeid Anvari Auwal Abdullahi Tahira Ashraf Shereen M. Aleidi Mohammad R. Alosta Senthilkumar Balakrishnan Zarrin Basharat Montaha Al-Iede Nasir Abbas Syed Shujait Ali Williams Agyemang-Duah Sahel Majed Alrousan Lucien R. Swetschinski Sonu Bhaskar Anayochukwu Edward Anyasodor Lisa C. Adams Ahmad Naoras Bitar Madineh Abbasi Habib Benzian Intima Alrimawi Nicole Davis Weaver Mohammed Albashtawy Meshack Achore Domenico Azzolino Eve E. Wool Kamoru Ademola Adedokun Fahad A. Alhumaydhi Ahmad Alrawashdeh Aqeel Ahmad Simachew Animen Bante Nelson Alvis-Guzman Umar Muhammad Bello Rafat Ali Kevin S. Ikuta Qorinah Estiningtyas Sakilah Adnani Rajon Banik Amadou Barrow Mina Borran Wondu Feyisa Balcha Chieh Han Gasha Salih Ahmed Aanuoluwapo Adeyimika Afolabi Alaa Aboelnour Badran Anna Gershberg Hayoon Hamed Borhany Nikha Bhardwaj Ahmad Rajeh Al-Qudimat Najim Z. Alshahrani Fentahun Alemnew Mesfin Abebe Md Akib Al-Zubayer Ema Akter Ridwan Olamilekan Adesola Ali Azargoonjahromi Authia P. Gray Mahsa Ahadi Mohammed Usman Ali Zelalem Asmare Hana J. Abukhadijah Alemwork Abie Amani Alansari Asnake Gashaw Belayneh Yaser Mohammed Al-Worafi Filippos Anagnostakis Daniel T. Araki Hassan Abolhassani Sabah Al-Marwani Gokce Belge Bilgin Mohammad Mahdi Bastan Meqdad Saleh Ahmed Rebecca L. Hsu Abiye Assefa Berihun Erin Chung Hiba Jawdat Barqawi Julie Alaere Atta Nurila Aryntayeva Wakgari Mosisa Abdisa Redeat Libanos Assefa Syed Anees Ahmed Haroon Ahmed Sadat Abdulla Aziz Avinash Aujayeb Tomislav Mestrovic

Publication Name: Lancet Global Health

Publication Date: 2025-12-01

Volume: 13

Issue: 12

Page Range: e2013-e2026

Description:

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.

Open Access: Yes

DOI: 10.1016/S2214-109X(25)00356-0

Authors - 100

Usha Adiga

14057674100

Samah W. Al-Jabi

16302963700

Meriem Abdoun

20336514800

Quique Bassat

23024176000

Zulfiqar A. Bhutta

24342648300

Hany Aly

35571391500

Ashish Bhargava

35788617400

Hasan Yaser Alniss

36024914100

Razique Anwer

54416938700

Abdul Monim Batiha

54940645200

Asrat Agalu Abejew

55204820500

Samar Abd ElHafeez

55551273300

Mahwish Arooj

55599732000

Matteo Bauckneht

55617887700

Mohammad R. Alqudimat

55676796600

Alok Atreya

55856196800

Abdelazeem M. Algammal

55953589200

Saeid Anvari

55967502900

Auwal Abdullahi

56102934500

Tahira Ashraf

56366752600

Shereen M. Aleidi

56459017600

Mohammad R. Alosta

56610262200

Senthilkumar Balakrishnan

56640778400

Zarrin Basharat

56641793600

Montaha Al-Iede

56823547000

Nasir Abbas

56940204900

Syed Shujait Ali

57188688612

Williams Agyemang-Duah

57190228903

Sahel Majed Alrousan

57190412987

Lucien R. Swetschinski

57191617721

Sonu Bhaskar

57192268582

Anayochukwu Edward Anyasodor

57192947419

Lisa C. Adams

57192991712

Ahmad Naoras Bitar

57193844216

Madineh Abbasi

57193923353

Habib Benzian

57195256480

Intima Alrimawi

57197726332

Nicole Davis Weaver

57203300193

Mohammed Albashtawy

57203680806

Meshack Achore

57204045088

Domenico Azzolino

57204596055

Eve E. Wool

57207302408

Kamoru Ademola Adedokun

57207983240

Fahad A. Alhumaydhi

57208327474

Ahmad Alrawashdeh

57209326108

Aqeel Ahmad

57210400531

Simachew Animen Bante

57210601612

Nelson Alvis-Guzman

57210741239

Umar Muhammad Bello

57211456920

Rafat Ali

57211501723

Kevin S. Ikuta

57211541916

Qorinah Estiningtyas Sakilah Adnani

57211604149

Rajon Banik

57212134381

Amadou Barrow

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Mina Borran

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Wondu Feyisa Balcha

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Chieh Han

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Gasha Salih Ahmed

57219224652

Aanuoluwapo Adeyimika Afolabi

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Alaa Aboelnour Badran

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Anna Gershberg Hayoon

57219861225

Hamed Borhany

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Nikha Bhardwaj

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Ahmad Rajeh Al-Qudimat

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Najim Z. Alshahrani

57222248550

Fentahun Alemnew

57222401328

Mesfin Abebe

57223854886

Md Akib Al-Zubayer

57226083282

Ema Akter

57251034300

Ridwan Olamilekan Adesola

57255844500

Ali Azargoonjahromi

57328028900

Authia P. Gray

57442982500

Mahsa Ahadi

57719216200

Mohammed Usman Ali

57726370200

Zelalem Asmare

57753879900

Hana J. Abukhadijah

57865346000

Alemwork Abie

58020591000

Amani Alansari

58044807900

Asnake Gashaw Belayneh

58134325700

Yaser Mohammed Al-Worafi

58143034700

Filippos Anagnostakis

58156665900

Daniel T. Araki

58565193000

Hassan Abolhassani

58597704600

Sabah Al-Marwani

58665514600

Gokce Belge Bilgin

58686449000

Mohammad Mahdi Bastan

58798063200

Meqdad Saleh Ahmed

59039407300

Rebecca L. Hsu

59282633000

Abiye Assefa Berihun

59321953500

Erin Chung

59617590200

Hiba Jawdat Barqawi

59730836600

Julie Alaere Atta

59893190200

Nurila Aryntayeva

59998436200

Wakgari Mosisa Abdisa

59998578600

Redeat Libanos Assefa

60126004500

Syed Anees Ahmed

60262936500

Haroon Ahmed

60271518200

Sadat Abdulla Aziz

60277166300

Avinash Aujayeb

6504403791

Tomislav Mestrovic

6507240107