Plasma cytokines in patients with COVID-19 during acute phase of the disease and following complete recovery
N. A. Аrsentieva, N. E. Liubimova, O. K. Batsunov, Zoia R. Korobova, Oksana V. Stanevich, А. А. Лебедева, Evgeny A. Vorobyov, Snejana V. Vorobyova, А. Н. Куликов, Dmitry Lioznov, Maria A. Sharapova, D. E. Pevtcov, Арег А. Тотолян
Abstract
COVID-19, an infection caused by the new coronavirus SARS-CoV-2, is associated with a number of pathophysiological mechanisms, mobilizing a wide spectrum of biomolecules, mainly, cytokines. The purpose of this study was to evaluate levels of multiple cytokines in blood plasma from the patients with COVID-19 during acute phase of the disease, and upon complete recovery. Samples of peripheral blood plasma of 56 patients with COVID-19, 69 convalescents and 10 healthy individuals were examined. Concentrations of 46 molecules, such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNα2, IFNγ, TNFα, TNFβ/ Lymphotoxin-α (LTA), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine, IL-1ra, IL-10, EGF, FGF-2/FGF-basic, Flt3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGF-AB/ BB, TGF-α, VEGF-A were measured via xMAP multiplexing technology. Significantly increased levels of 18 cytokines were found in blood plasma from COVID-19 patients during acute phase of the disease (as compared to control group), i.e., IL-6, IL-7, IL-15, IL-27, TNFα, TNFβ/Lymphotoxin-α (LTA), CCL2/MCP-1, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, CXCL9/MIG, IL-1rа, IL-10, M-CSF, GM-CSF, VEGF-A. We found a significant decrease of nearly all the mentioned cytokines in recovered patients, in comparison with those who had moderate, severe/extremely severe disease. Moreover, we revealed a significantly decreased level of 8 cytokines in plasma from convalescents, as compared with control group, i.e., IL-1α, IL-2, IL-9, IL-12 p40, IL-18, CCL22/MDC, Flt3 Ligand, TGF-α. Immune response caused by SARS-CoV-2 infection involves multiple cytokines, mostly, with pro-inflammatory effects. We have shown for the first time that the convalescence phase is characterized by significantly lower levels of cytokines which regulate cellular differentiation and hematopoiesis (in particular, lymphocytes, T-cells and NK-cells). Over acute phase of the disease, the levels of these cytokines did not change. We revealed a significant decrease of most plasma cytokines upon recovery as compared to acute phase. On the contrary, acute phase of the disease is accompanied by significant increase of both pro- and antiinflammatory cytokines in blood plasma.