Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape.
Front Immunol
; 12: 738073, 2021.
Article
in English
| MEDLINE | ID: covidwho-1497076
ABSTRACT
The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
T-Lymphocytes
/
Systemic Inflammatory Response Syndrome
/
Mucosal-Associated Invariant T Cells
/
SARS-CoV-2
/
COVID-19
/
Neutrophils
Type of study:
Cohort study
/
Diagnostic study
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Front Immunol
Year:
2021
Document Type:
Article
Affiliation country:
Fimmu.2021.738073
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