article · The Lancet Global Health
Quantifying the global impact of sepsis has long been difficult due to complex diagnostic and reporting challenges. An extensive analysis combining mortality registries, hospital records, and tissue sampling covering 149 million deaths evaluated sepsis incidence and mortality from 1990 to 2021 across global locations. In 2021, an estimated 166 million sepsis cases occurred, causing 21.4 million deaths, which accounted for almost a third of all global deaths. Although sepsis deaths steadily declined between 1990 and 2019, this progress reversed with a major surge in 2020 and 2021. Adults aged 15 and older experienced substantial rises in incidence and mortality over the study period, with the heaviest burden falling on individuals aged 70 and older. Sepsis is also increasingly emerging as a lethal complication of non-infectious conditions, particularly stroke, chronic obstructive pulmonary disease, and cirrhosis, frequently mediated by lower respiratory and bloodstream infections.
Sepsis accounts for nearly one in three deaths worldwide and presents an escalating threat to ageing populations and patients with chronic illnesses. By demonstrating how pandemic shocks and chronic non-infectious diseases exacerbate fatal infections, these findings provide essential evidence for public health agencies, hospital networks, and policymakers seeking to allocate intensive care resources and improve infection management protocols.
The abstract does not indicate an application pathway, as it focuses entirely on epidemiological modelling and burden estimation without assessing specific clinical products or commercial technologies.
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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.
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DOI: 10.1016/s2214-109x(25)00356-0
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