Association Between Methylprednisolone and the Increase of Respiratory Infections in COVID-19 Patients in the Intensive Care Unit

Background: This study aimed to assess whether methylprednisolone treatment, while effective in reducing COVID-19 mortality, increases the risk of intensive-care-unit-acquired respiratory tract infections (RTI-ICU) in critically ill patients. Methods: This was a multicenter prospective cohort study conducted in ten countries across Latin America and Europe. It included patients over 18 years of age with confirmed SARS-CoV-2 infection who required ICU admission. A multivariable logistic regression analysis and propensity score matching (PSM) were performed to determine the association between methylprednisolone treatment and RTI-ICU. Results: A total of 3239 patients were included, of whom 1527 patients (47.1%) were treated with methylprednisolone. Methylprednisolone treatment was associated with a higher risk of developing RTI-ICU (OR = 1.59; 95% CI: 1.33–1.91). Patients with RTI-ICU had a significantly higher average number of days on invasive mechanical ventilation (IMV) (24.6, SD: 15.9 vs. 9.5, SD: 11.7; p < 0.001), longer hospital stays (40 days, SD: 24.9 vs. 24.4 days, SD: 18.7; p < 0.001), and higher ICU mortality (39.2%, 259/660 vs. 29.2%, 754/2579; p < 0.001). Conclusions: Methylprednisolone treatment is associated with an increased risk of RTI-ICU in critically ill patients with COVID-19. RTI-ICU was linked to higher mortality, a greater need for invasive mechanical ventilation, prolonged ICU stay, elevated leukocyte and C-reactive protein levels, and a higher comorbidity burden. However, methylprednisolone may not be the sole factor explaining these differences, as residual confounding related to baseline disease severity and comorbidities could have influenced the outcomes.