Table 3.

Immunomodulatory and Anti-Inflammatory Agents Under Investigation for COVID-19

Drug/Mechanism	Proposed Concept	Published Reports/Clinical Observations
Tocilizumab: A recombinant humanized monoclonal antibody against both soluble and membrane-bound IL-6 receptor	Inhibits IL-6–mediated proinflammatory responses. No established IL-6 cutoff values to predict disease severity or clinical outcomes.	Multiple reports showed improved oxygen requirement, normalization in CRP, and resolution of fever, and increased the lymphocyte count to normal 77, 78, 79, 80.
	The optimal timing and dosing schedule of tocilizumab are not established.	Others showed tocilizumab failed to prevent ICU admission or impact disease progression and mortality 81, 82, 83.
	Monitor for hepatic function abnormalities, local injection site reactions, and possible inducible effects on drugs metabolized by CYP450 given the drug's long half-life. FDA black box warnings for the risk of severe infections that can lead to hospitalization and death [84].	IL-6 levels normally increase after tocilizumab administration from inhibited cytokine/receptor catabolism. Post-tocilizumab IL-6 levels should not be used as a surrogate marker for clinical response [85,86].
Baricitinib: Janus kinas inhibitor, approved for rheumatoid arthritis [88]	Interference with viral endocytosis.Concerns for impairment of IFN-mediated antiviral response	In a pilot study of 12 patients with moderate COVID-19 disease, the baricitinib group showed improved respiratory function parameters and CRP values compared with the standard of care. No adverse events were noted. and no cancer patients were included [87].
Anakinra A recombinant human IL-1 receptor antagonist. Approved for rheumatoid arthritis. Off label use for familial Mediterranean fever and hemophagocytic lymphohistiocytosis syndrome [92,93]	Counteract SARS-CoV-2–induced severe inflammatory response with macrophage activation syndrome–like picture or cytokine release syndrome [89].	Clinical trials are currently conducted outside the United States.
		A small Italian retrospective study of 29 patients showed a better mortality rates in patients with acute respiratory distress syndrome who received high-dose i.v. anakinra. Patient also received hydroxychloroquine and lopinavir/ritonavir [90].
		A French study compared outcomes of 52 patients with COVID-19 with 44 historical patients. The anakinra group had lower rates of mechanical ventilation or death (25% versus 73%; P < .0001) with similar results for death only (P = .0063) [91].