Evaluation of Myeloid-derived Suppressor Cells in the Blood  of Iranian COVID-19 Patients

Esmaeil Mortaz; Mehrnaz Movassaghi; Ali Bassir; Neda K. Dezfuli; Neda Dalil Roofchayee; Hamidreza Jamaati; Johan Garssen; Ian M. Adcock

doi:10.18502/ijaai.v21i4.10294

Esmaeil Mortaz Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mehrnaz Movassaghi Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, USA
Ali Bassir Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Neda K. Dezfuli Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Neda Dalil Roofchayee Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hamidreza Jamaati Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
Johan Garssen Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
Ian M. Adcock National Heart and Lung Institute, Imperial College London, London, United Kingdom

DOI: https://doi.org/10.18502/ijaai.v21i4.10294

Keywords: Blood; COVID-19; Interleukin-8; Myeloid-derived suppressor cells; Serum

Abstract

The cytokine storm and lymphopenia are reported in coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs), that both suppress T-cell function. In COVID-19, the role of chemokines such as interleukin (IL)-8 in recruiting MDSCs is unclear. A recent report has correlated IL-8 and MDSCs with poor clinical outcomes in melanoma patients. In the current study, we evaluated the frequency of MDSCs and their correlation with serum IL-8 levels in severe COVID-19 patients from Iran.

Thirty-seven severe patients (8 on ventilation, 29 without ventilation), thirteen moderate COVID-19 patients, and eight healthy subjects participated in this study between 10^th April 2020 and 9th March 2021. Clinical and biochemical features, serum, and whole blood were obtained. CD14, CD15, CD11b, and HLA-DR expression on MDSCs was measured by flow cytometry.

COVID-19 patients compared to healthy subjects had a greater frequency of M-MDSCs (12.7±13.3% vs 0.19±0.20%,), G-MDSCs (15.8±12.6% vs 0.35±0.40%,) and total-MDSCs (27.5±17.3% vs 0.55±0.41%,). M-MDSC (16.8±15.8% vs 5.4±4.8%,) and total-MDSC (33.3±18.5% vs 17.3±13.3%) frequency was higher in non- ventilated compared to moderate COVID-19 subjects. Serum IL-8 levels were higher in patients with COVID-19 than in
normal healthy subjects (6.4±7.8 vs. 0.10±00 pg/mL). Ventilated patients (15.7±6.7 pg/mL), non-ventilated patients (5.7±2.7 pg/mL) and moderate patients (2.8±3.0 pg/mL) had significantly different levels of IL-8. A negative correlation was found between the frequency of G-MDSCs and the international normalized ratio (INR) test (r=-0.39), and between the frequency of total-MDSCs and oxygen saturation (%) (r=-0.39).

COVID-19 patients with severe non-ventilated disease had the highest levels of M-MDSCs. In addition to systemic MDSCs, lung, serum IL-8, and other inflammatory biomarkers should be measured.