Objective:

To describe trends in sepsis incidence, in-hospital mortality, clinical characteristics, infection sources, and healthcare burden in Spain from 2017 through 2022 while assessing the impact of COVID-19.

Approach:

• Study Design: A nationwide, population-based retrospective study of hospitalized patients with sepsis in Spanish public and private hospitals from January 1, 2017, through December 31, 2022.
• Data Source: Data were obtained from the Spanish Minimum Basic Data Set, an administrative clinical database covering 99.5% of hospital discharges.
• Study Variables: Sepsis was identified by the concurrent presence of infection and organ dysfunction using an algorithm adapted to ICD-10-CM. Primary outcomes included population-adjusted incidence, in-hospital mortality, and average cost. A non-COVID-19 sepsis cohort was analyzed separately to assess the pandemic’s impact.
• Statistical Analysis: Multivariable logistic regression was used to identify independent predictors of in-hospital mortality, while Poisson regression assessed temporal changes in incidence.

Key Findings:

• The study identified 1,187,393 sepsis hospitalizations, with annual cases increasing from 183,971 in 2017 to 226,884 in 2022. Age-adjusted incidence reached 4.65 per 1,000 inhabitants in 2022.
• In-hospital mortality increased from 19.4% in 2017 to a peak of 23.7% in 2020 before declining to 20.8% in 2022. Mortality in the non-COVID-19 sepsis cohort remained relatively stable.
• Patients had a mean age of 74.3 years and a substantial comorbidity burden. Respiratory and genitourinary infections were the leading infection sources, accounting for 40.7% and 40.4% of cases, respectively.
• Total national expenditure increased from €6.6 billion in 2017 to €9.6 billion in 2021 before declining to €7.9 billion in 2022.
• The number of organ failures, Charlson Comorbidity Index, intensive care unit admission, and invasive mechanical ventilation were independently associated with increased in-hospital mortality.

Interpretation:

Sepsis epidemiology in Spain was strongly influenced by the COVID-19 pandemic, particularly the increases in overall incidence and mortality during the pandemic period. The relatively stable mortality pattern among patients without COVID-19 and the concentration of disease among older, multimorbid patients indicate a persistent underlying healthcare burden.

Limitations:

• The retrospective analysis relied on administrative data, which may be affected by undercoding, unavailable analytic variables, and the inability to identify multiple admissions by the same patient.
• The non-COVID-19 analysis excluded patients directly diagnosed with COVID-19 but could not eliminate indirect pandemic effects, including healthcare-system strain, staffing shortages, altered clinical practices, and delayed presentations.
• Community-acquired and hospital-acquired sepsis could not be distinguished.
• Direct laboratory microbiology results and detailed antimicrobial susceptibility testing were not available.
• In-hospital mortality was assessed because post-discharge mortality data were unavailable.

Conclusion:

Sepsis remains a substantial burden on the Spanish National Health System. Age-adjusted incidence rebounded to 4.65 per 1,000 inhabitants in 2022, while hospital mortality stabilized at 20.8%. The findings underscore the need for adequate healthcare resource allocation and clinical management tailored to an increasingly older and more medically complex patient population.