Single-cell analysis identifies shared and distinct immune features of COVID-19, Influenza and other community-acquired pneumonia

The exact immunopathophysiology of COVID-19 remains clouded by methodological heterogeneity and a lack of relevant disease controls. The absence of single-cell investigations into the broader population of patients with community-acquired pneumonia (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 strictly matched cohort of eight patients with COVID-19, eight patients with CAP, and four non-infectious control subjects. With this balanced, multi-omic approach we describe diverging transcriptional and phenotypic patterns in T cell, NK cell and monocyte populations between patients with CAP caused by either SARS-CoV-2, Influenza A or other pathogens, and thereby expand our understanding of the peripheral immune response in different forms of CAP. Single-cell transcriptomic and proteomic analysis of PBMCs from eight COVID-19 patients, 8 CAP patients (3 CAP-Flu) and 4 matched controls. Comparisons: COVID-19 vs controls, CAP vs controls, COVID-19 vs CAP.