The immunomodulation of SARS-COV-2 infection on the production of cytokines by peripheral blood mononuclear cells and neutrophils in COVID-19 ICU patients.

COVID-19 pandemic is spreading globally with a worrying mortality rate. Unique medical features of severe COVID-19 include neutrophilia, cytokine storm, acute respiratory distress syndrome, and severe inflammatory syndrome. Here, we propose investigating the influence of SARS-CoV-2 infection on the cytokines profile of peripheral blood mononuclear cells (PBMC) and neutrophils in COVID-19 patients. This study examines PBMC and neutrophils as a potential source of immunopathologic complications for severely ill COVID-19 patients or as an immunomodulation target for SARS-CoV-2 infection. Neutrophils and PBMC were separated by density gradient sedimentation and stimulated with mitogen. Culture supernatants from 89 COVID-19 patients and 89 sex and age-matched healthy control (HC) were stimulated evaluated for levels of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), interferon (IFN)- α, IFN-γ, interleukin (IL)-2, -4, -5, -6, -9, -10, -12, -17A, and tumor necrosis factor (TNF)-α using anticytokine antibody MACSPlex capture beads. The PBMC cytokine profiles showed significantly lower mean values of GM-CSF, IFN-γ, IL-6, IL-9, IL-10, IL-17A, and TNF-α (p < 0.0001) for COVID-19 patients compared to HC. In contrast, COVID-19 patients showed higher mean levels of PBMC cytokine values for IL-2 (p <0.001) and IL-5 (p <0.01). As for neutrophils, COVID-19 patients showed significantly lower mean values in the levels of GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-17A, IL-12, TNF-α (p < 0.0001), and IFN-α (p < 0.01). The Th1:Th2 cytokine ratios revealed a lower inflammatory cytokine for 12 out of 24 combinations in COVID-19 ICU patients, suggesting downregulation of the cellmediated immunity by SARS-CoV-2 infection for both the PBMC and neutrophils. Our finding may also indicate the source of raised serum cytokine levels (GM-CSF, IFN-α, IFN-γ, IL-4, IL-6, IL-9, IL-10, IL-17A, IL-12, and TNF-α) documented by previous studies in COVID-19 patients are not from PBMC or neutrophils but maybe from another cell type. We also detected a significant increase in the cytokine levels of IL-2 and IL-5 by PBMC, which may indicate that PBMC do play a part in the elevated IL-2 and IL-5 serum levels in COVID-19 patients. In conclusion, data collected for the cytokine profiles and Th1:Th2 cytokine ratios suggest that SARS-CoV-2 infection brings about an immunomodulatory effect on PBMC and neutrophils.

Author(s): Sahar Essa

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