Functional myeloid-derived suppressor cells expand in blood but not airways of COVID-19 patients and predict disease severity

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 

1. 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 

2. M-MDSC are increased in NPA of influenza patients but not NPA or ETA of COVID-19 patients 

3. 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 

4. Plasma but not NPA levels of IL-6 are increased in influenza and COVID-19, increasing with disease severity in COVID-19 

5. 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 

6. M-MDSC numbers are associated with age and male gender 

• In vitro 

• Key Techniques: flow cytometry of PBMCs and cells from nasopharyngeal aspirates (NPA) and endothracheal aspirates (ETA), T cell suppression assay, ELISA 

Limitations: 

• The MDSC terminology is controversial, according to flow cytometry gating these cells could also be monocytes 

• 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