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

Alex R. Schuurman*, Tom D. Y. Reijnders, Anno Saris, Ivan Ramirez Moral, Michiel Schinkel, Justin de Brabander, Christine van Linge, Louis Vermeulen, Brendon P. Scicluna, W. Joost Wiersinga, Felipe A. Vieira Braga, Tom van der Poll*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The exact immunopathophysiology of community-acquired pneumonia (CAP) caused by SARS-CoV-2 (COVID-19) remains clouded by a general lack of relevant disease controls. The scarcity 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 peripheral blood mononuclear cells 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 natural killer 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.
Original languageEnglish
Article numbere69661
Publication statusPublished - 1 Aug 2021

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