Table 2.

Potential Therapeutic Agents for Mitigating and Managing COVID-19 Cytokine Storms

Class	Therapeutic Agent	Mechanism of Action	Stage of Development	References
Micronutrients	Zinc	Decreased gene expression of pro-inflammatory cytokines, Regulates several enzymes within the apoptotic cascade, Recruitment of Lck to the TCR complex	Nutraceutical	[138,139]
Fatty acids	Omega-3 Fatty acid (PUFA)	Induce apoptosis in leucocytes	Nutraceutical	[140]
	Butyrate	Suppress IL-12 expression, Enhance IL-10 expression	Nutraceutical	[141]
Vitamins	Vit. C	Inhibit mRNA expression of pro-inflammatory cytokines, increased production of type 1 interferons	Nutraceutical	[142]
	Vit. D	Suppress IL-17 production	Nutraceutical	[143]
Phytochemicals	Resveratrol	Increased expression of IL-10	Nutraceutical	[144]
	Kaempferol	Decreased expression of IL-6 and TNF-alpha	Nutraceutical	[144]
	Apigenin	Decreased expression of IL-6 and TNF-alpha	Nutraceutical	[144]
	Quercetin	Decreased expression of IL-6 and TNF-alpha	Nutraceutical	[144]
Plant Extracts	Echinacea purpurea	Inhibit the release of TNF-α	Nutraceutical	[145]
	Camellia sinensis	Promote γδ T lymphocyte functions	Nutraceutical	[146]
	Echium amoenum	Decrease expression of IL-1β, IL-6, TNF-α, iNOS and COX2	Herbal Tea	[147]
	Abelmoschus esculentus	Activation of NK cells	Nutraceutical	[148]
	Andrographis paniculata	Activation of NK cells	Nutraceutical	[44]
Interferons	IFN-λ	Suppression of neutrophil infiltration and IL-1β production.	Clinical trial	[149,150]
Monoclonal Antibodies	Tocilizumab	Blocks IL-6 receptors	Approved	[151,152]
	Anakinra	Interleukin-1 receptor antagonist	Approved	[153,154]
S1PR modulators	Fingolimod	Agonist of S1P1R, S1P3R, S1P4R, and S1P5R receptors.	Approved	[155,156]
JAK inhibitors	Baricitinib	JAK1, JAK2, JAK 3, and Tyrosine Kinase 2 inhibition	Approved	[157,158]
	Pacritinib	JAK2 and IRAK1 inhibition	Under investigation	[159]
Antimalarials	Hydroxychloroquine	Inhibits antigen processing	Approved	[160,161]
Macrolides (Antibiotics)	Azithromycin	Inhibits bacterial protein synthesis and neutrophil activity	Approved	[162]
	Clarithromycin	Inhibits bacterial protein synthesis and neutrophil activity	Approved	[163]
Immune Supplements	Transfer Factor	Activate NK cells, Reduce IL-6, and Increase IL-10	Nutraceutical	[164,165]
Corticosteroids	Dexamethasone	Promote anti-inflammatory activities	Approved	[166]
	Methylprednisolone	Promote anti-inflammatory activities	Approved	[167]
Others	Ulinastatin	Increases IL-10 level, reduces the levels of TNF-α, IL-6, and IFN-γ	Approved	[168]
	Eritoran	TLR4 antagonist		[167]