Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China

Abstract

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.

Keywords: SARS-CoV-2; chemokine; cytokine; disease severity.

Figure 1.

Serum cytokine and chemokine levels of SARS-CoV-2–infected symptomatic (mild, moderate, and severe) patients and healthy controls. Data are expressed as median with 25th and 75th percentiles. *P < .05, **P < .01. Abbreviations: CSF, colony-stimulating factor; FGF, fibroblast growth factor; GRO-α, growth related oncogene-α; HGF, hepatocyte growth factor; IFN, interferon; IL, interleukin; IP-10, IFN-γ inducible protein-10; MCP, monocyte chemoattractant protein; MIG, monokine induced by interferon-γ; MIP, macrophage-inflammatory protein; PDGF, platelet-derived growth factor; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor; TRAIL, TNF-related apoptosis inducing ligand; VEGF, vascular endothelial growth factor.

Figure 2.

Serum cytokine and chemokine levels in SARS-CoV-2–infected symptomatic male and female patients. Data are expressed as median with 25th and 75th percentiles. *P < .05, **P < .01. Abbreviations: CSF, colony-stimulating factor; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; IFN, interferon; IL, interleukin; LIF, leukemia inhibitory factor; MCP, monocyte chemoattractant protein; MIP, macrophage-inflammatory protein; NGF-β, nerve growth factor-β; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VEGF, vascular endothelial growth factor.

Figure 3.

Correlations between serum cytokine and chemokine levels and viral load in SARS-CoV-2–infected symptomatic patients. A, Heatmap showing the Spearman rank correlation coefficients between the levels of serum cytokines and the viral loads. The magnitude of correlation coefficients is shown on a color scale of red (strong) to black (intermediate) to green (weak) signal. B, Correlations between MCP-1, G-CSF, and VEGF levels and viral load. Abbreviations: CTACK, cutaneous T cell-attracting chemokine; FGF, fibroblast growth factor; G-CSF, granulocyte-colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor, GRO-α, growth related oncogene α; HGF, hepatocyte growth factor; IFN, interferon; IL, interleukin; IP-10, IFN-γ inducible protein-10; LIF, leukemia inhibitory factor; MCP-1, monocyte chemoattractant protein-1; MIF, migration inhibitory factor; MIG, monokine induced by interferon-γ; MIP, macrophage-inflammatory protein; NGF-β, nerve growth factor-β; PDGF, platelet-derived growth factor; r, correlation coefficient; RANTES, regulated upon activation normal T cell expressed and secreted; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SCF, stem cell factor; SCGF-β, stem cell growth factor-β; SDF-1α, stromal cell-derived factor-1α; TNF, tumor necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand; VEGF, vascular endothelial growth factor.