SARS-CoV-2 is the known coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). It was first identified in late December 2019 and causes severe respiratory syndrome in humans1, 2. The disease caused by SARS-CoV-2 has been recently named COVID-19 by the World Health Organization (WHO). Globally, as of August 2020, there have been 24,854,140 confirmed cases of COVID-19, including 838,924 deaths. According to the epidemiological statistics, most of the COVID-19 patients (about 80%) belong to the mild patients3, 4. The city of Shiyan is located in Hubei Province, and most of the COVID-19 patients there had mild cases. For this reason, it is necessary to study the immunological characteristics of mild COVID-19 patients and find a suitable therapeutic strategy to prevent the transformation of mild to severe patients.
Inflammation is the body’s first line of defense against viral infection. It involves activating both the innate and adaptive immune responses. However, excessive immune responses after infection, also called a cytokine storms, have been found to be associated with extreme levels of pro-inflammatory cytokines and widespread tissue damage.
Preliminary studies have shown that SARS-CoV-2 infection triggers a cytokine storm, and results in the increase of a variety of cytokines, including chemokine5–7. Chemokines are low-molecular-weight proteins with powerful chemoattractant activity. They play a role in the immune cell recruitment during inflammation. Chemokines are classified according to their chemical structure, the C, CC CXC and CX3C families8. The binding of chemokines to their receptors is responsible for their chemoattractant ability. The chemokine receptors are seven-transmembrane-spanning, G-protein-coupled receptors. They are expressed on leukocytes and endothelial cells, etc.9. Serum chemokine levels were found to be elevated in patients with COVID-19, and they were even higher in those who required ICU admission, suggesting a relationship with lung damage and disease severity10. However, it is not clear whether the concentration of chemokines is higher in mild COVID-19 patients, and the highly expressed chemokines can be used as a marker of the diagnosis and prognosis of mild COVID-19 patients.
Type I interferons have broad-spectrum antiviral activities against RNA viruses, which act by inducing an antiviral response and mediating adaptive immune response. Type I interferons include IFN-α and IFN-β11. Infection of cells with virus causes the activation of several cellular transcription factors, such as interferon regulatory factor 3/7 (IRF3/7) and NF-kB, which activate the expression of a number of interferon-stimulated genes (ISGs) and exert antiviral effect12,13. The downstream signaling pathway of the transcription factors can recruit and coordinate specific subsets of leukocytes, which is orchestrated primarily by chemokine secretion14,15. This means that the secretion of chemokines may be related to the release of interferon, but the specific relationship between them in the process of SARS-CoV-2 infection has not been clearly established.
Clinically, Type I IFNs have already been approved for use in the treatment of certain cancers, autoimmune disorders, and viral infections16. Type I IFNs are currently in clinical trials to evaluate their ability to treat MERS-CoV and therefore have been proposed for the treatment of COVID-19, but there is currently no evidence from laboratory testing against SARS-CoV-217.
In this study, we first demonstrated that COVID-19 patients are characterized by higher levels of chemokine. In particular, MCP-1 has shown higher expression in patients with mild cases of COVID-19 in Shiyan City. The receptor of MCP-1, CCR2 was then found higher expression in the Peripheral blood mononuclear cells (PBMCs) from same mild COVID-19 patients. Finally, mild COVID-19 patients are found to have lower levels of IFN-β in the serum. The higher expression of MCP-1 in mild COVID-19 patients is correlated with the inhibition of IRF3. Our results suggested that MCP-1 may be an effective indicator in mild patients, and interferon was a good antiviral therapeutic agent for mild COVID-19 diseases.