Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza and other community-acquired pneumonia.

Abstract The exact immunopathophysiology of community-acquired pneumonia (CAP) caused by SARS-CoV-2 (COVID-19) remains clouded by methodological heterogeneity and a lack of relevant disease controls. The absence of single-cell investigations in the broader population of patients with CAP renders it difficult to distinguish immune features unique to COVID-19 from the common characteristics of a dysregulated host response to pneumonia. We performed integrated single-cell transcriptomic and proteomic analyses in PBMCs from a matched cohort of eight patients with COVID-19, eight patients with CAP caused by Influenza A or other pathogens, and four non-infectious control subjects. Using this balanced, multi-omics approach we describe shared and diverging transcriptional and phenotypic patterns – including increased levels of type I interferon stimulated NK cells in COVID-19, cytotoxic CD8 T EMRA cells in both COVID-19 and influenza, and distinctive monocyte compositions between all groups – and thereby expand our understanding of the peripheral immune response in different etiologies of pneumonia.