Table 2.

Anti-rheumatic and anti-inflammatory drugs for the management of COVID-19 and cytokines they affected.

Class	Drug	Main Class	Main mechanism of action	Predominant mechanism to management of COVID-19	Cytokines	Cytokines study type	References
Anti-rheumatic drugs	Anakinra	Anti-arthritic agent	Recombinant IL-1Ra antagonist	Interleukin-1 receptor antagonist	↓TNF-α ↓IL-1β ↓IL-6	In vivo	[67], [151], [69]
	Baricitinib	Anti-arthritic agent	Potent and selective Janus Kinases (JAK) inhibitor	Interrupts the passage and intracellular assembly of SARS-CoV-2 into the target cells via disruption of AAK1 Block clathrin-mediated endocytosis and thereby inhibit viral infection of cells	↓TNF-α ↓ IL-4 ↓ IL-6	Clinical In vitro	[152], [153], [116], [154], [117]
	Etanercept	Anti-arthritic agent	Inhibitor of TNFα	TNFα inhibitor	↓TNF-α ↓IL-1 β ↓IL-6	In vivo	[155], [156], [157], [158], [63]
	Infliximab	Anti-arthritic agent Crohn's disease	Inhibitor of TNFα	TNFα inhibitor	↓TNF-α ↓IL-1 ↓IL-6 ↓IL-8	Clinical In vivo	[79], [159]
	Tocilizumab	Anti-arthritic agent	IL-6 receptor inhibitors Monoclonal anti-soluble IL-6 receptor antibody	Recombinant humanized monoclonal anti-IL6R antibody. It binds both soluble and membrane‐bound IL6R to inhibit IL6‐mediated signaling	Patients with high IL-6 levels Inhibiting IL-6 signal transduction	Clinical	[160], [75], [161]
Anti-inflammatory drugs	Indomethacin	Nonsteroidal anti-inflammatory drug	Non-selective cyclooxygenase (COX) inhibitor	Inhibition of viral replication and infectious viral particle production Inhibition of viral replication and infectious viral particle production	↓TNF-α ↓IL-1β ↓IL-6 ↓IL-8	In vivo	[93], [92], [90], [162]
	Thalidomide	Phthalimides	Immunomodulatory, anti-inflammatory, and anti-angiogenic agent	Immunomodulatory and anti-inflammatory Immunomodulatory and anti-inflammatory agent	↓TNF-α ↓IL-1β ↓IL-6 ↑IL-10 ↓IL-17 ↓IFN-γ	In vivo	[99], [163], [164]
	Corticosteroids	Steroidal anti-inflammatory drug	Suppression of multiple inflammatory genes by linking glucocorticoid recruitment of histone deacetylase 2 for the activated transcription complex.	Inhibits the NFκB transcription factor.	↓TNF-α ↓IL-1 ↓IL-2 ↓IL-3 ↓IL-5 ↓IL-6 ↓IL-8 ↑IL-10 ↑IL-12 ↓IL-13 ↓IL-15 ↓IFN-β ↓IFN-λ1 ↓IFN-γ	In vitro In vivo	[165], [166], [167]

AAK1: AP2-associated protein kinase; 1IL: Interleukin; IFNs: Interferons; IL6R: IL-6 receptor; SARS-CoV-2: Severe Acute Respiratory Syndrome coronavirus 2.