Table 1 Current and potential anti-rheumatic drugs in pediatric COVID-19 and MIS-C
From: Severe COVID-19 in pediatric age: an update on the role of the anti-rheumatic agents
Drug | Mechanism of action | Therapeutic rationale | Experience in pediatric age |
|---|---|---|---|
Corticosteroids | Broad-spectrum anti-inflammatory effect, at a transcriptional and post-transcriptional level. Modulation of the expression of cytokines and adhesion molecules | Anti-inflammatory activity useful in patients with severe and progressive ARDS and MIS-C. | Retrospective cohort studies, case reports, and series RCTs (ongoing) |
Hydroxychloroquine | Altered glycosylation of the ACE2 receptor, alkalization of the endosomal pH. | Direct antiviral effect through inhibition of viral entry and maturation and immune modulation secondary to the interference with TLR signaling. | Retrospective cohort studies RCTs (ongoing) |
Colchicine | Inhibition of cytokine synthesis and neutrophil chemotaxis | Reduction of the SARS-CoV-2 related hyperinflammation and prevention of disease worsening | Case reports, and series RCTs (ongoing) |
IVIG | Reduction of antibody-mediated damage. Immune modulation on multiple antibody-independent pathways, including cytokine modulation and complement downregulation. | Reduction of the antibody-dependent enhancement of cytokine production. Potential utility in case of early seroconversion and in MIS-C. | Case reports, and series RCTs (ongoing) |
Tocilizumab, sarilumab | Monoclonal anti-IL-6 antibodies | Action on the main mediator of the cytokine storm | Retrospective cohort studies, case reports, and series RCTs (ongoing) |
Anakinra | IL-1 receptor antagonist | Action on the cytokine initiating the cytokine storm, demonstrated efficacy in patients with sepsis | Case reports, and series RCTs (ongoing) |
Canakinumab | Monoclonal anti-IL-1 antibody | Action on the cytokine initiating the cytokine storm | No experience RCTs (ongoing) |
Baricitinib, ruxolitinib | JAK/STAT blockers | Inhibition of viral entry, modulation of the immune response and IFN-dependent signaling | No experience RCTs on ruxolitinib (ongoing) |
Emapalumab | Monoclonal anti-IFN-γ antibody | Action on the cytokine storm | No experience |
Infliximab | Monoclonal anti-TNF-α antibody | Action on the cytokine storm, proposed for refractory MIS-C | Case reports and series |
Adalimumab | Monoclonal anti-TNF-α antibody | Action on the cytokine storm | No experience |