Abstract
BACKGROUND AND OBJECTIVES: Co-infection with Clostridioides difficile (C. difficile) in COVID-19 patients has emerged as a clinical challenge associated with increased morbidity and mortality. While both infections elicit systemic inflammation, the interplay between inflammatory markers, disease severity, and outcomes in patients with COVID-19 and concurrent C. difficile infection remains poorly characterized. This study aimed to evaluate the inflammatory status and clinical outcomes of patients hospitalized with COVID-19, with and without C. difficile co-infection, and to identify the inflammatory markers most predictive of severe disease. METHODS: We conducted a retrospective cohort study of 200 hospitalized adults with confirmed COVID-19, of whom 92 had laboratory-confirmed C. difficile infection. Baseline demographic data, comorbidities, inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], ferritin, neutrophil-to-lymphocyte ratio [NLR], platelet count, albumin, and derived indices such as the CRP-to-Albumin Ratio [CAR] and Prognostic Nutritional Index [PNI]) were recorded. Clinical outcomes included ICU admission, need for mechanical ventilation, length of stay, and in-hospital mortality. RESULTS: Patients with COVID-19 and C. difficile co-infection had significantly elevated inflammatory markers (CRP, IL-6, NLR) and higher CAR, alongside lower PNI, compared to those with COVID-19 alone (p < 0.001). Inflammatory indices correlated strongly with disease severity: elevated CAR and low PNI were associated with higher odds of ICU admission and mortality (p < 0.001). Multivariate analysis identified co-infection status, increased IL-6, and elevated CAR as independent predictors of severe outcomes. CONCLUSIONS: C. difficile co-infection in COVID-19 patients is associated with an intensified inflammatory response and worse clinical outcomes. Among the evaluated markers, CAR and PNI emerged as robust predictors of severe disease. Timely recognition of C. difficile co-infection and use of targeted anti-inflammatory and supportive therapies may improve patient management. Future studies should expand on these findings to optimize care and guide therapeutic strategies.