Influence of SARS-COV-2 Infection on Cytokine Production by Mitogen-Stimulated Peripheral Blood Mononuclear Cells and Neutrophils in COVID-19 Intensive Care Unit Patients

Abstract

We sought to investigate the influence of SARS-CoV-2 infection on the cytokine profiles of peripheral blood mononuclear cells (PBMCs) and neutrophils from coronavirus disease 2019 (COVID-19) intensive care unit (ICU) patients. Neutrophils and PBMCs were separated and stimulated with the mitogen phytohemagglutinin. Culture supernatants of mitogen-stimulated PBMCs and neutrophils from 88 COVID-19 ICU patients and 88 healthy controls were 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 anti-cytokine antibody MACSPlex capture beads. Cytokine profiles of PBMCs showed significantly lower levels of GM-CSF, IFN-γ, IL-6, IL-9, IL-10, IL-17A, and TNF-α (p < 0.0001) in COVID-19 ICU patients. In contrast, COVID-19 ICU patients showed higher median levels of IL-2 (p < 0.001) and IL-5 (p < 0.01) by PBMCs. As for neutrophils, COVID-19 ICU patients showed significantly lower 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). T-helper (Th)1:Th2 cytokine ratios revealed lower inflammatory cytokine for PBMCs and neutrophils in COVID-19 ICU patients. Cytokine production profiles and Th1:Th2 cytokine ratios suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has an immunomodulatory effect on PBMCs and neutrophils. This study also suggests that the increased levels of several cytokines in the serum are not sourced from PBMCs and neutrophils.

Extracorporeal Photopheresis as a Possible Therapeutic Approach for Adults with Severe and Critical COVID-19 Non-Responsive to Standard Treatment: A Pilot Investigational Study

“…On the other hand, dysregulated cytokine responses, most notably fluctuations of serum IL-6 during COVID-19, have also been established in the literature [17]. Among critically ill patients with COVID-19, serum IL-6 and IL-10 levels are usually higher, while serum GM-CSF, TNF-α, IFN-γ, IL-2 and IL-8 serve as ancillary cytokines with clinical prognostic value in contrast to patients without critical disease [14,30,31]. Since tocilizumab is recommended for patients with COVID-19 of critical severity, its effect on cytokine levels should also be mentioned.…”

“…The clearance of apoptotic T-cells also leads to the abatement of systemic inflammation by homeostatic reprogramming of macrophages, normalization of regulatory T-cells counts and type-1/type-2 helper T-cell ratios, and an establishment of anti-inflammatory cytokine milieu in peripheral blood [11]. Based on the published data, COVID-19 with systemic hyperinflammation is also characterized by a pathological decrease of regulatory T-cells and type-2 helper T-cell inhibition, along with an over-activation of tissue macrophages [12][13][14]. Therefore, we hypothesized that ECP may be beneficial for adults hospitalized with severe and critical COVID-19 who do not respond to other pharmacological treatments.…”