Abstract: Objective The aim of this study was to investigate the role and mechanism of SARS-CoV-2 virus on the secretion of inflammatory factors by mononuclear macrophages. Method Fifty-three patients with confirmed COVID-19 hospitalized from January 21 to February 10, 2020 and January 3 to January 7, 2021 were selected from Shijiazhuang Fifth Hospital, fifty-three healthy controls each were included, and the results of medical records and routine blood test were collected. Mononuclear macrophages were stimulated with SARS-CoV-2 virus spiked protein, cell viability was detected by CCK-8 assay. The level of pro-inflammatory cytokines IL-6, IL-1β and CCL2 and the expression of signaling pathway molecules JAK1, STAT1 and NF-κB were detected by quantitative RT-PCR. Result The monocyte ratio and neutrophil ratio were higher, while the lymphocyte ratio, lymphocyte count, eosinophil ratio, and eosinophil count, and hematocrit were lower in COVID-19 patients than those in controls. After stimulation of mononuclear macrophages by SARS-CoV-2 virus spiked protein, cell viability was higher at concentrations of 100ng/ml and 300ng/ml (P=0.046). The highest mRNA expression levels of IL-6, IL-1β and CCL2 at a concentration of 500ng/ml (P<0.01, P=0.036, P<0.001). The expression of JAK1 and STAT1 at a concentration of 100ng/ml (P<0.001), the expression of NF-κB expression was increased at 300 and 500ng/ml stimulation (P<0.001). Conclusion SARS-CoV-2 viral spike protein may promote inflammatory cytokine secretion by mononuclear macrophages through the JAK1/STAT1 signaling pathway, which play a role in the cytokine storm.

Key words: Severe acute respiratory syndrome coronavirus 2, Spike protein, Mononuclear macrophages, Inflammatory cytokine, Cytokine storm, Signal pathway