Systemic corticosteroids for severe community-acquired pneumonia: a narrative review of mechanisms and critical appraisal of recent trials in ICU

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Clinical trials investigating the effect of systemic corticosteroids as an adjunctive therapy for severe community-acquired pneumonia (sCAP) requiring admission to the intensive care unit have produced heterogeneous results over recent decades. The most recent trials, despite being significantly larger than their predecessors, have displayed similarly heterogeneous results. This narrative review aims to explore the possible underlying reasons for this heterogeneity of treatment effect, providing detail for each of the proposed immune- and nonimmune-mediated mechanisms through which corticosteroids might offer therapeutic benefit for patients with severe pneumonia and providing an in-depth critical appraisal of the most recent large-scale multicentre randomised controlled trials, namely ESCAPe (2022), CAPE COD (2023) and REMAP-CAP (2025). We discuss the importance of recognising sCAP as a heterogeneous disease, in which local processes in the lung are not always reflected in systemic features, and the need for further characterisation of endotypes of the disease. Shareable abstract The heterogeneity of treatment effect observed in trials of systemic corticosteroids in sCAP is likely due to a multitude of immune- and nonimmune-mediated mechanisms which vary between underexplored disease endotypes. https://bit.ly/4dqrRWE short abstract-1