Objective:

To assess how the COVID-19 pandemic altered the association between sepsis etiology and in-hospital and 90-day mortality among ICU patients with sepsis in metropolitan France from 2018 through 2022.

Approach:

• Data Sources: Anonymized data were obtained from the French National Hospital Discharge Database and the outpatient healthcare consumption database, both derived from the Système National des Données de Santé (SNDS).
• Study Population: The analysis included 604,517 patients aged 15 years or older admitted to an ICU with sepsis. Sepsis-related hospital stays were identified using explicit and implicit ICD-10 criteria and classified as bacterial, viral, or fungal/parasitic. For patients with multiple sepsis stays, only the last stay was included.
• Statistical Analysis: Hospitalizations were divided into 3 periods: 2018-2019, 2020-2021, and 2022. Logistic regression models assessed associations between sepsis etiology and in-hospital or 90-day mortality separately by period and co-infection status, with adjustment for age, sex, comorbidities, infection sites, and septic shock.

Key Findings:

• Overall, 176,688 patients (29.2%) died during hospitalization, and 205,283 (34.0%) died within 90 days of admission.
• Before the pandemic, viral sepsis was associated with lower in-hospital and 90-day mortality risk than presumed bacterial sepsis in patients with and without co-infections. During the pandemic, mortality risk associated with viral sepsis increased to levels similar to or higher than those associated with bacterial sepsis.
• Among co-infected patients in 2022, viral sepsis was associated with higher in-hospital mortality than bacterial sepsis (adjusted odds ratio [aOR], 1.41; 99% CI, 1.15-1.71) and higher 90-day mortality (aOR, 1.23; 99% CI, 1.01-1.49).
• Fungal or parasitic sepsis generally had mortality risks similar to bacterial sepsis, except among patients without co-infection in 2020-2021, when it was associated with higher in-hospital and 90-day mortality.

Interpretation:

Before the pandemic, viral-related sepsis had an approximately 30% lower mortality risk than bacterial sepsis. During the pandemic, its in-hospital mortality risk increased to levels similar to or higher than bacterial sepsis, particularly among patients with co-infections. Findings for 90-day mortality followed a similar but attenuated pattern.

Limitations:

• The study relied on medical-administrative data without clinical validation of sepsis cases, creating the potential for misclassification, particularly for implicit sepsis.
• Clinical data needed to calculate Sequential Organ Failure Assessment or quick Sequential Organ Failure Assessment scores were unavailable.
• The investigators could not determine which infection occurred first among co-infected patients or distinguish community-acquired from healthcare-associated infections. Data on antibiotics administered during hospitalization and antimicrobial resistance were also unavailable.
• Mortality was assessed using medical-administrative data rather than death certificates.

Conclusion:

Viral-related sepsis was associated with substantial mortality, and the COVID-19 pandemic changed the relationship between sepsis etiology and mortality. Among co-infected patients, viral sepsis emerged as a high-risk condition, with increased in-hospital and 90-day mortality compared with bacterial sepsis. The findings underscore the need for heightened vigilance, more detailed coding strategies for viral sepsis, and targeted management of co-infected sepsis during future pandemics.

Sources:

• Impact of the COVID-19 pandemic on the association between sepsis etiology and mortality among ICU patients in France