Functional myeloid-derived suppressor cells expand in blood but not airways of COVID-19 patients and predict disease severity
Cardiff University review respiratory
First Author: Sara Falck-Jones
Journal/preprint name: medRxiv
DOI: 10.1101/2020.09.08.20190272
Tags: MDSC, respiratory immunology
Summary
The authors compare blood and respiratory samples from patients with different severities of COVID-19 to influenza A and healthy controls to investigate changes in M-MDSC. They report alterations in COVID-19 patients similar to those suffering from influenza including increased plasma frequencies of M-MDSC, decreased T cells and alterations in cytokine levels.
Importantly, the authors suggest that an expansion of M-MDSC early in SARS-CoV-2 infection is indicative of increased disease severity and could be used to identify patients with high risk of developing severe disease.
Research Highlights
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M-MDSC are increased in blood of influenza and moderate and severe COVID-19 patients compared to healthy controls, with numbers increasing with disease severity
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M-MDSC are increased in NPA of influenza patients but not NPA or ETA of COVID-19 patients
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Purified M-MDSC from COVID-19 patients suppress CD4 and CD8 T cell proliferation and IFNg secretion in an Arg-1 dependent manner in vitro
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Plasma but not NPA levels of IL-6 are increased in influenza and COVID-19, increasing with disease severity in COVID-19
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Numbers of CD4 and CD8 T cells are decreased in COVID-19 patients, with lower expression of the CD3ζ chain, but no correlation between blood M-MDSC frequency and T cell count is found
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M-MDSC numbers are associated with age and male gender
Impact for COVID-19 research:
M-MDSC frequency in the first two weeks from onset of symptoms could potentially predict more severe outcomes of COVID-19
Methodologies:
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In vitro
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Key Techniques: flow cytometry of PBMCs and cells from nasopharyngeal aspirates (NPA) and endothracheal aspirates (ETA), T cell suppression assay, ELISA
Limitations:
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The MDSC terminology is controversial, according to flow cytometry gating these cells could also be monocytes
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NPA and ETA do not necessarily reflect what’s happening in the lower airways and it would be interesting to see whether these cells are increased deeper in the lungs