Corticosteroids in Influenza-Related ARDS: Real-World 6-Month Outcomes From a Global Federated Study

Introduction: The role of systemic corticosteroids in influenza-associated acute respiratory distress syndrome (ARDS) remains debated, with limited real-world data available. This study evaluated short- and intermediate-term outcomes following corticosteroid therapy in patients with influenza-related ARDS.


Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network, encompassing electronic health records from 146 healthcare organizations. Adult patients with concurrent diagnoses of ARDS and influenza were identified and divided into two groups: those treated with systemic corticosteroids (n = 7,146) and those not treated (n = 19,300). Propensity score matching was used to balance baseline characteristics. Outcomes were assessed at 1, 3, and 6 months. The primary outcome was in-hospital mortality. Secondary outcomes included myocardial infarction (MI), stroke, respiratory failure, mechanical ventilation, heart failure exacerbation, acute kidney injury (AKI), dialysis, and readmission. Odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated.


Results: Corticosteroid use was associated with significantly higher odds of in-hospital mortality at 1 month (OR 1.71, 95% CI 1.55–1.88), 3 months (OR 1.70, 95% CI 1.56–1.86), and 6 months (OR 1.69, 95% CI 1.55–1.85; all p < 0.001). Increased risks were also observed across all timepoints for respiratory failure (ORs 1.37–1.57), mechanical ventilation (ORs 2.03–2.10), heart failure exacerbation (ORs 2.49–2.58), dialysis (ORs 1.81–2.18), and hospital readmission (ORs 4.27–5.64). At 6 months, hazard ratios confirmed elevated risks for heart failure exacerbation (HR 2.13, p < 0.001) and dialysis (HR 1.778, p < 0.001). No significant differences were found for MI, stroke, or AKI.


Conclusions: In this large multicenter analysis, systemic corticosteroid use in influenza-related ARDS was associated with increased mortality and higher rates of several complications up to 6 months. These findings suggest potential harm and underscore the need for caution when prescribing corticosteroids in this setting. Further randomized trials are needed to better define their role.