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

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 f...

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Published in:eLife
Main Authors: Alex R Schuurman, Tom DY 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
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-08-01
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Online Access:https://elifesciences.org/articles/69661
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author Alex R Schuurman
Tom DY 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
author_facet Alex R Schuurman
Tom DY 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
author_sort Alex R Schuurman
collection DOAJ
container_title eLife
description 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.
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spelling doaj-art-86b1440bbe734205ab4a4e76ebe22bbb2025-08-19T21:43:19ZengeLife Sciences Publications LtdeLife2050-084X2021-08-011010.7554/eLife.69661Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumoniaAlex R Schuurman0https://orcid.org/0000-0001-9322-1117Tom DY Reijnders1https://orcid.org/0000-0002-1764-0114Anno Saris2Ivan Ramirez Moral3Michiel Schinkel4Justin de Brabander5Christine van Linge6Louis Vermeulen7Brendon P Scicluna8https://orcid.org/0000-0003-2826-0341W Joost Wiersinga9Felipe A Vieira Braga10Tom van der Poll11Center for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Division of Infectious Diseases, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsLaboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Amsterdam, Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsThe 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.https://elifesciences.org/articles/69661PBMCCOVID-19Pneumonia
spellingShingle Alex R Schuurman
Tom DY 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
Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia
PBMC
COVID-19
Pneumonia
title Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia
title_full Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia
title_fullStr Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia
title_full_unstemmed Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia
title_short Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia
title_sort integrated single cell analysis unveils diverging immune features of covid 19 influenza and other community acquired pneumonia
topic PBMC
COVID-19
Pneumonia
url https://elifesciences.org/articles/69661
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