#Pathogens #analysis and modeling of #mortality #risk in #sepsis patients with #COVID19 and without COVID-19

 

Abstract

This study compared isolate-level pathogen profiles, antimicrobial susceptibility, clinical characteristics, and mortality predictors between sepsis patients with and without coronavirus disease 2019 (COVID-19), and developed cohort-specific nomograms for in-hospital mortality. This retrospective intensive care unit (ICU) cohort included 608 adults with sepsis: 158 in group COVID-19 and 450 in group non–COVID-19. All patients were assessed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection status. Patient-level comparisons and mortality modeling used the full cohort, whereas microbiological analyses were restricted to 235 eligible bacterial or fungal isolates from baseline cultures after exclusion of colonizers, contaminants, clinically non-causative organisms, and duplicates. Candidate predictors were selected by least absolute shrinkage and selection operator (LASSO) regression and entered into multivariable logistic regression; coefficients were pooled using Rubin’s rules when multiple imputation was performed. External validation used MIMIC-IV with fixed internal coefficients. Gram-negative organisms predominated, mainly Acinetobacter baumannii and Klebsiella pneumoniae, with substantial antimicrobial resistance. The COVID-19 and non–COVID-19 models showed apparent internal area under the curve values of 0.938 and 0.871, conservative optimism-corrected values of 0.913 and 0.871, and external validation AUC values of 0.841 and 0.859, respectively. Cohort-specific nomograms may provide supplementary risk-stratification information in critically ill patients with sepsis.

Source: 

Link: https://www.nature.com/articles/s41598-026-58450-w

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#Global burden of lower respiratory #infections and aetiologies, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023

 

Summary

Background

Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years.

Methods

Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years.

Findings

In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24–2·81) deaths and 98·7 million (87·7–112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4–47·4) since 2010, with a global mortality rate of 94·8 (75·6–116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000–721 000] deaths or 25·3% [24·5–26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000–298 000] deaths or 10·9% [10·3–11·3]), and Klebsiella pneumoniae (228 000 [204 000–261 000] deaths or 9·1% [8·8–9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000–201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900–75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths.

Interpretation

This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies—including newer interventions such as respiratory syncytial virus monoclonal antibodies—and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies.

Funding

Gates Foundation.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00689-9/abstract?rss=yes

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