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.

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

eLife ◽

10.7554/elife.69661 ◽

2021 ◽

Vol 10 ◽

Author(s):

Alex R Schuurman ◽

Tom DY Reijnders ◽

Anno Saris ◽

Ivan Ramirez Moral ◽

Michiel Schinkel ◽

...

Keyword(s):

Single Cell ◽

Influenza A ◽

Mononuclear Cells ◽

Single Cell Analysis ◽

Community Acquired Pneumonia ◽

Type I ◽

Cell Analysis ◽

Peripheral Blood Mononuclear ◽

The Common ◽

Peripheral Immune Response

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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SINGLE CELL ANALYSIS REVEALS A FATAL TYPE I INTERFERON RESPONSE AFTER MYOCARDIAL INFARCTION

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(18)33203-0 ◽

2018 ◽

Vol 71 (11) ◽

pp. A2662

Author(s):

Kevin R. King ◽

Aaron Aguirre ◽

Richard P. Ng ◽

Ralph Weissleder

Keyword(s):

Myocardial Infarction ◽

Single Cell ◽

Single Cell Analysis ◽

Type I Interferon ◽

Interferon Response ◽

Type I ◽

Cell Analysis

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Faculty Opinions recommendation of Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1366959.838057 ◽

2010 ◽

Author(s):

Avinash Bhandoola

Keyword(s):

Single Cell ◽

Single Cell Analysis ◽

Molecular Heterogeneity ◽

Cell Analysis ◽

The Common ◽

Progenitor Compartment

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Single-Cell and Bulk RNA-Sequencing Reveal Differences in Monocyte Susceptibility to Influenza A Virus Infection Between Africans and Europeans

Frontiers in Immunology ◽

10.3389/fimmu.2021.768189 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mary B. O’Neill ◽

Hélène Quach ◽

Julien Pothlichet ◽

Yann Aquino ◽

Aurélie Bisiaux ◽

...

Keyword(s):

Mrna Expression ◽

Single Cell ◽

Rna Sequencing ◽

Influenza A Virus ◽

Influenza A ◽

Type I Interferon ◽

African Ancestry ◽

Cellular Heterogeneity ◽

European Ancestry ◽

Type I

There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use single-cell RNA-sequencing to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. We show widespread inter-individual variability in the percentage of IAV-infected monocytes. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3, MX1 and OAS3. Upon IAV challenge, we find that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. We also uncover a stronger resistance of CD16+ monocytes to IAV infection, together with CD16+-specific mRNA expression of IL6 and TNF in response to IAV. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16+ monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Based on these data, we hypothesize that higher basal monocyte activation, driven by environmental factors and/or weak-effect genetic variants, underlies the lower cellular susceptibility to IAV infection of individuals of African ancestry relative to those of European ancestry. Further studies are now required to investigate how such cellular differences in IAV susceptibility translate into population differences in clinical outcomes and susceptibility to severe influenza.

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