On the host response to infection, and its clinical implications

A dysregulated host response is a key driver of clinical symptoms and outcomes in patients suffering infectious diseases. This thesis presents research on the host response in patients hospitalized for pneumonia, COVID-19, and sepsis, as reflected by plasma and bronchoalveolar proteins, immune cell phenotypes, and gene expression patterns. The overall aim is to improve our understanding of disease pathophysiology and how this relates to clinical characteristics. Part I describes the host response in different forms of pneumonia – for instance, pneumonia due to different pathogens (including SARS-CoV-2, influenza, and Streptococcus pneumoniae), or pneumonia presenting with lymphopenia – using multiplexed immunoassays, (spectral) flow cytometry, and single-cell RNA sequencing. Part II then examines two types of therapies intended to modulate the dysregulated host response in pneumonia and sepsis, macrolide antibiotics and mesenchymal stem cells, and how they affect clinical outcomes and host response trajectories. This part also contains an investigation of host response trajectories in intensive care unit-acquired pneumonia. The research presented in this thesis provides detailed and wide-ranging snapshots of proteins, cells, and transcriptional pathways that may be involved in the host response, and thereby improves our understanding of the pathophysiological processes affecting patients hospitalized for infections.