Correlation of myeloid‐derived suppressor cells with C‐reactive protein, ferritin and lactate dehydrogenase levels in patients with severe COVID‐19

Abstract

The novel coronavirus disease 2019 (COVID‐19) remains a global health emergency, and understanding the interactions between the virus and host immune responses is crucial to preventing its lethal effects. The expansion of myeloid‐derived suppressor cells (MDSCs) in COVID‐19, thereby suppressing immune responses, has been described as responsible for the severity of the disease, but the correlation between MDSC subsets and COVID‐19 severity remains elusive. Therefore, we classified patients according to clinical and laboratory findings—aiming to investigate the relationship between MDSC subsets and laboratory findings such as high C‐reactive protein, ferritin and lactate dehydrogenase levels, which indicate the severity of the disease. Forty‐one patients with COVID‐19 (26 mild and 15 severe; mean age of 49.7 ± 15 years) and 26 healthy controls were included in this study. MDSCs were grouped into two major subsets—polymorphonuclear MDSCs (PMN‐MDSCs) and monocytic MDSCs—by flow cytometric immunophenotyping, and PMN‐MDSCs were defined as mature and immature, according to CD16 expressions, for the first time in COVID‐19. Total MDSCs, PMN‐MDSCs, mature PMN‐MDSCs and monocytic MDSCs were significantly higher in patients with COVID‐19 compared with the healthy controls ( P < .05). Only PMN‐MDSCs and their immature PMN‐MDSC subsets were higher in the severe subgroup than in the mild subgroup. In addition, a significant correlation was found between C‐reactive protein, ferritin and lactate dehydrogenase levels and MDSCs in patients with COVID‐19. These findings suggest that MDSCs play a role in the pathogenesis of COVID‐19, while PMN‐MDSCs, especially immature PMN‐MDSCs, are associated with the severity of the disease.

New Discovery of Myeloid-Derived Suppressor Cell’s Tale on Viral Infection and COVID-19

“…A recent study reported a significant correlation between C-reactive protein, ferritin, and lactate dehydrogenase levels and MDSC in patients with COVID-19. This indicates that immature PMN-MDSCs are associated with disease severity (102). Expansion of PMN-MDSCs and immature neutrophils in severe COVID-19 conditions indicates Th1 cell suppression and an increase in the frequency of Th17 cells due to strong polar migration to Th17 cells (103).…”

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

“… No change in e-MDSC (proportion) No [ 2 ] 14 N = 58 (COVID-19: 13 moderate, 37 severe; HD: 8) PB No Fresh M-MDSC: HLA-DR -/dim CD11b + CD14 + CD15 − PMN-MDSC: HLA-DR -/dim CD11b + CD14 − CD15 + Increase in M-MDSC and PMN-MDSC (proportion, in patients as compared to HD) No [ 84 ] 15 N = 26 (COVID-19: 13 convalescent; HD: 13) PB Yes Fresh M-MDSC: Lin − HLA-DR -/dim CD11b + CD14 + CD15 − PMN-MDSC: Lin − HLA-DR -/dim CD11b + CD14 − CD15 + e-MDSC: Lin − HLA-DR − CD11b + CD14 − CD15 − Increase in PMN-MDSC (proportion, in convalescent patients as compared to HD). No change in M-MDSC and e-MDSC (proportion) Inhibition of antigen-nonspecific T cell proliferation [ 68 ] 16 N = 67 (COVID-19: 26 mild, 15 severe; HD: 26) PB Yes Fresh M-MDSC: HLA-DR − CD11b + CD66b − CD14 + CD15 − PMN-MDSC: HLA-DR − CD11b + CD66b + CD14 − CD15 + Increase in M-MDSC and PMN-MDSC (proportion, in patients as compared to HD; increase in PMN-MDSC in mild patients as compared to severe patients) No [ 70 ] 17 N = 120 (COVID-19: 27 mild, 47 severe, 46 deceased) PB No Fresh M-MDSC: HLA-DR − CD14 + Increase in M-MDSC (proportion, in deceased patients as compared to mild and severe patients) No [ 3 ] 18 N = 80 (COVID-19: 40 ICU discharged, 40 ICU deceased) PB No Fresh <...>…”

“…Intriguingly, while some studies reported a substantial increase in both circulating M-MDSC and PMN-MDSC subpopulations [ 2 , 63 , 64 , 70 ], other studies failed to identify M-MDSCs in either mild, moderate, or severe COVID-19 patients at different observation time points [ 67 , 71 ]. Takano et al found an elevated frequency of PMN-MDSCs but no M-MDSCs in severe COVID-19 [ 72 ].…”

“…Similarly, COVID-19 patients who developed ARDS showed a significant increase in PMN-MDSC values during hospitalization, whereas PMN-MDSCs did not rise in patients without ARDS [ 66 ]. Frequencies of PMN-MDSCs were significantly associated with disease severity in a study of 26 mild and 15 severe patients [ 70 ]. Falck-Jones et al demonstrated that an early increase in M-MDSC frequency was associated with later disease severity [ 63 ].…”

“…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 ].…”