Table 1.

Role of immune soluble mediators in COVID-19 infection

Soluble mediator	Biological role in COVID-19 infection	Output effect	References
sPDL-1	Decrease of effector T lymphocytes Increase in lower PaO2/FIO2 ratio and higher CRP concentration	Protective effect	[15–18, 21]
sPD-1	Increase effector T lymphocytes function	Adverse effect	[15, 19, 20]
sTim-3	Activation and exhaustion marker of T lymphocytes in chronic inflammation and viral infection like SARS-CoV-2 Negative and positive correlation with PaO2/FIO2 ratio and NT-ProNBT, respectively	Adverse effect	[19, 24–26]
sTNFRI and sTNFRII	Increase in COVID-19 cases Cleaved by ADAM17 in chronic inflammation Increased mortality risk in cardiovascular diseases Correlate with illness severity iv COVID-19 cases	Adverse effect	[28, 30–34]
sIL-2R	Increase in COVID-19 cases Cause to lymphopenia and reduced cell response to IL-2 Negative regulator of regulatory T lymphocytes, NK cells, and B lymphocytes Negative association with PaO2/FiO2 ratio Positive correlation with morbidity in COVID-19 cases	Adverse effect	[36–40]
sIL-6R	Role in stromal epithelial response to IL-6 Agonist of IL-6 which is cleaved by ADAM17 Increase in HIV, influenza A, and severe COVID-19 cases Cause to increased release of MCP-1 from endothelial cells in COVID-19 cases ( cause to hyper inflammation)	Adverse effect	[43–48]

sPDL-1, soluble programmed cell death ligand 1; sPD-1, soluble programmed cell death 1; sTim3, soluble T-cell immunoglobulin and mucin domain 3; sTNFRI&II, soluble tumor necrosis factor receptor 1&2; sIL6R, soluble interleukin 6 receptor