Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19.

Carlos Jiménez-Cortegana,Antonio León-Justel,Luis De La Cruz-Merino,José Garnacho-Montero,Nerissa Álvarez,Luisa Cantón-Bulnes,Marta Jiménez,Flora Sánchez-Jiménez,Teresa Vilariño-García,Sandra Fuentes,Alberto Sousa,Antonio Pérez-Pérez,Víctor Sánchez-Margalet,Salomón Martín

doi:10.3389/fimmu.2021.801410

Carlos Jiménez-Cortegana, Antonio León-Justel + Show 12 more

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https://doi.org/10.3389/fimmu.2021.801410

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Abstract

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may produce a systemic disease termed COVID-19, with high morbidity and mortality
It has been observed that lymphocyte subsets such as CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, especially in severe cases
In line with this notion, myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that mainly inhibit T-cell immune responses and NK cell proliferation using different mechanisms. They consist of monocytic (M-MDSCs) and granulocytic (G-MDSCs) subsets, which have been recently defined as pathologically activated neutrophils and monocytes with potent immunosuppressive activity [4]

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may produce a systemic disease termed COVID-19 (coronavirus disease 2019), with high morbidity and mortality. Understanding of the pathophysiology of this viral infection is a major challenge and is absolutely necessary to improve the somber prognosis of COVID-19 patients with severe disease who require admission to the intensive care unit (ICU) [1] Impairment of both innate and adaptive immunity has been described in patients with SARS-CoV-2 infection, and it has been associated with poor outcomes [2]. The underlying mechanisms responsible for lymphopenia in COVID-19 patients still need to be investigated since these could be responsible for the delayed virus clearance and the increased mortality rate among patients In line with this notion, myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that mainly inhibit T-cell immune responses and NK cell proliferation using different mechanisms. They consist of monocytic (M-MDSCs) and granulocytic (G-MDSCs) subsets, which have been recently defined as pathologically activated neutrophils and monocytes with potent immunosuppressive activity [4]

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