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

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Abstract

The COVID-19 pandemic is spreading globally with a worrying mortality rate. There is a crucial necessity for effective therapeutic approaches to fight potentially deadly complications. Unique medical features of severe COVID-19 include neutrophilia, and cytokine storm, besides 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 target for the immunopathologic complications of severely ill COVID-19 patients. Neutrophils and PBMC were separated by density gradient sedimentation and stimulated with a mitogen. Culture supernatants from 100 COVID-19 patients and 100 sex and age- matched healthy control (HC) were evaluated for levels of GMCSF, interferon (IFN)- α, IFN-γ, Interleukin (IL)-2, -4, -5, -6, -9, -10, -12, -17A, and tumor necrosis factor (TNF)-α by using the MACSPlex cytokine kit. The PBMC cytokine profiles showed significantly lower mean values for IL-6 and IL-10 (p < 0.0001) of COVID-19 patients compared to HC. In contrast, COVID-19 patients showed higher mean levels of PBMC cytokine values for IL-5 (p < 0.05), and IL-17A (p < 0.0001). As for neutrophils, COVID-19 patients showed significantly lower mean values in the levels of GMCSF, IFN-γ, IL-4, IL-6, IL-9, IL-10, IL-12, IL-17A, and TNF-α (p < 0.0001). Our results suggest that SARS-CoV-2 infection brings about an immunomodulatory effect not only PBMC but also to a greater extent on neutrophils. Such studies may aid in finding novel targets for therapeutic interventions.

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