Table 1.

Summary of the common cytokine and chemokine profile of patients infected with SARS-CoV, MERS-CoV, and SARS-CoV-2.

Common Chemokine Profile	Common Cytokine Profile	Important Chemokine/Cytokine Involved in Disease Pathogenesis (Particularly in Severely Infected Cases)	Role of the Most Prominent Chemokine/Cytokine in Disease Pathogenesis	Drugs Targeting Chemokines and Cytokines
SARS-CoV
CCL2, CCL3, CCL5, CCL10, CXCL-8 (IL-8), CXCL9, and CXCL10	IL-1β, IL-2, IL-6, IL-10, IL-12, TNF-α, IFN-α/α2, IFN-β1, IFN2, IFN-γ, and TGFβ	Dysregulation of IFN (α and γ)	Induces excessive cytokine and chemokine levels [109].	IFN alfacon-1 and steroids at early stage infection [169,170,171,172,173].
		Elevation in CXCL10	Recruits monocytes, macrophages, dendritic cells, NK cells, and T-lymphocytes toward interstitial lung tissue [112].
MERS-CoV
CCL-2, CCL-3, CCL-5, CXCL-8 (IL-8), and CXCL-10	IL-1β, IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, IL-23, TNF-α, IFN-γ, IFN- α2, and TGFβ	Dysregulation of IFN (α, β γ)	Develops early antiviral Th-1 [121].	Recombinant IFNα/β and IFN agonists (e.g., poly(I:C)) and mycophenolic acid [66,174,175,176,177,178,179,180].
		Elevation in IL-10	Inhibits IFN-γ production [121,125]. Reduces CD8+ T-cells proliferation. [121,125] Increases viral replication [121,125].
		Elevation in IL-6
		Elevation in CXCL10
		Elevation in IL-17	Recruits neutrophils and monocytes [33,123]. Contributes to the release of IL-1β, IL-6, TNF-α, TGF-β, IL-8, and CCL2 [33,123].
SARS-CoV-2
CCL2, CCL3, CCL4, CCL7, CCL8, CXCL1, CXCL2, CXCL-8 (IL-8), CXCL6, CCL20, CXCL-10, and CXCL17	IL-1β, IL-2, IL-6, IL-7, IL-10, IL-17, IL-33, IFN-ɣ, TNF-α, and TGFβ	Elevation in IL-6	Contributes to the release of VEGF, CCL2, IL-8 and additional IL-6 [138]. Decreases E-cadherin expression on endothelial cells, leading, together with VEGF, to an increase in vascular permeability and leakage, hypotension, and pulmonary dysfunction [138]. Inhibits HLA-DR expression on CD14 monocytes, leading to defective lymphoid function [141]. Impairs the cytotoxic function of NK cells [143,144]. Increases CRP, serum amyloid A, fibrinogen, and hepcidin and inhibits albumin synthesis [138].	IL-6 and IL-6R inhibitors: tocilizumab, sarilumab, siltuximab, and myo-inositol [142,181,182,183]. JAK Inhibitors [158].
		Upregulation of IFN signaling pathway, but downregulation of IFN levels	Increases ISGs and IFITMs, which inhibit the cellular entry of the virus [131,149,150].	PEGylated IFN-λ1(PEG-IFN-λ1) [184].
		Elevation in IL-17	Induces the release of G-CSF responsible for granulopoiesis and neutrophils recruitment [158]. Contributes to pulmonary edema by inducing the release of metalloproteinases responsible for tissue damage and remodeling [158]. Induces IL-1β, IL-6, and TNFα, which collectively cause systemic inflammatory response [158]. Induces the release of CXCL1, CXCL2, IL-8, CXCL10, and CCL20, which recruit more immune cells to injured lung [158].	Anti-IL-17, anti-IL-17R and anti-IL-12/23p40 [158]. Anti-ROR-γt and ROR-α [158]. JAK Inhibitors: Fedratinib [158].
		Elevation in TNF-α	Amplifies inflammation by enhancing oxidative stress and leukocyte adhesion to the epithelium, modulating blood coagulation and inducing fever indirectly [162].	Anti-TNF-α drugs: Adalimumab and infliximab [185,186].
		Elevation in TGF-β	Recruits neutrophils and remodel the airways by regulating processes used by the virus to develop pulmonary fibrosis through promoting myelofibroblast differentiation and proliferation [157,159,160,161].	Anti-active TGF-β antibodies and/or TGF-β inhibitors [159].