Elevated frequencies of CD14+HLA-DRlo/neg MDSCs in COVID-19 patients

Abstract

Background: The immune responses, hyper-inflammation or immunosuppression, may be closely related to COVID-19 progression. We aimed to evaluate the changes of frequency of CD14 + HLA-DR lo/neg MDSCs, a population of cells with potent immunosuppressive capacity, in COVID-19 patients. Methods: The levels of CD14 + HLA-DR lo/neg MDSCs were determined by flow cytometry in 27 COVID-19 patients, and their association with clinical characteristics and laboratory data were analyzed. Results: The frequency of CD14 + HLA-DR lo/neg MDSCs was elevated in COVID-19 patients, particularly severe patients. A follow-up comparison revealed a decline of CD14 + HLA-DR lo/neg MDSCs percentages in most patients 1 day after testing negative for SARS-CoV-2 nucleic acid, but the levels of CD14 + HLA-DR lo/neg MDSCs were still greater than 50.0% in 3 ICU patients 4-10 days after negative SARS-CoV-2 results. Elevated frequency of CD14 + HLA-DR lo/neg MDSCs was positively correlated with oropharyngeal viral loads and length of hospital stay, while negatively correlated with lymphocyte counts and serum albumin. Moreover, strong correlations were observed between the frequency of CD14 + HLA-DR lo/neg MDSCs and T cell subsets, NK cell counts, and B cell percentages. The frequency of CD14 + HLA-DR lo/neg MDSCs could be used as a predictor of COVID-19 severity. Conclusions: A high frequency of CD14 + HLA-DR lo/neg MDSCs, especially in severe patients, may indicate an immunoparalysis status and could be a predictor of disease severity and prognosis.

The Expansion of Myeloid-Derived Suppressor Cells Correlates With the Severity of Pneumonia in Kidney Transplant Patients

“…The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic can cause severe pneumonia, which manifests hyperinflammation and immunosuppression ( 29 ). MDSCs were found to expand in the patients infected with SARS-CoV-2, and the frequency of MDSCs was correlated with COVID-19 disease severity ( 18 , 19 ). Therefore, the frequency of MDSCs was suggested as a predictor of COVID-19 severity.…”

“…Two major subsets of MDSCs in humans have been identified: CD11b + CD14 − CD15 + granulocytic-MDSCs (G-MDSCs) or polymorphonuclear-MDSCs (PMN-MDSCs) with a low density, and CD11b + CD14 + HLA-DR low/− CD15 − monocytic-MDSCs (M-MDSCs) (16). Previously, the expansion of MDSCs has been reported in patients with sepsis or coronavirus disease 2019 (COVID-19), and it was correlated with the severity of the diseases (17)(18)(19). Our previous work also found a lower expression of HLA-DR on monocytes in KTRs with pneumonia, indicating the possibility of MDSC expansion in these patients (9).…”

Myeloid-derived suppressor cells in COVID-19: A review

“…The literature is inconclusive regarding the correlation between the number of MDSCs and immunological parameters in COVID-19 patients. Several studies reported negative correlations between the frequencies of MDSCs and the absolute counts of T cells in COVID-19 patients [ 68 , 75 , 85 , 86 ]. There was also a negative correlation between the number of M-MDSCs and activated CD8 + T cells [ 73 ].…”

“…Some studies reported a negative correlation between MDSC frequencies and NK cells in COVID-19 patients, suggesting that MDSCs may be involved in the inhibition of this innate immune cell population in COVID-19 [ 85 , 86 ]. Two studies investigated correlations between MDSCs and inflammatory markers in patients with COVID-19.…”

“…Emsen et al reported a positive correlation between MDSCs and C-reactive protein, ferritin, and lactate dehydrogenase levels [ 70 ]. Xue et al found that the MDSCs frequency was positively correlated with C-reactive protein and D-dimer [ 86 ].…”