Table 1.
Drug Class | Drug/Monoclonal antibody | Mechanism of Action | Conventional Use | Dose in COVID-19 | Inclusion criteria for administration | Effects observed – % of patients | Limitations | Reference |
---|---|---|---|---|---|---|---|---|
IL-6 inhibitors | Tocilizumab | Binds to both trans-membrane receptor (mIL-6 R) and soluble bound receptor (sIL-6 R) and blocks both classic and trans-signaling pathways of IL-6 | Rheumatoid arthritis Juvenile idiopathic arthritis Crohn’s disease |
400/800 mg once or twice (Intravenous infusion) |
High level of IL-6 (> 40 pg/mL) Increased D-dimer and ferritin Progressively increased fibrinogen |
Temperature returned to normal Improved oxygenation – 75% Normalized % of peripheral lymphocytes – 52.6% Improved respiratory function Absorption of primary lesions, decreased lung opacity – 90.5% Decreased IL-6 levels |
Contraindicated in patients with tuberculosis Hepatotoxicity, hypertriglyceridemia, diverticulitis Inhibition of both protective and inflammatory pathways of IL-6 |
[89–95] |
Siltuximab | Binds to both mIL-6 R and sIL-6 R Inhibits IL-6 dimerization with gp130, causing inactivation of downstream signaling Forms high-affinity complexes with soluble human IL-6 |
Castleman’s disease | 700–1200 mg Single dose (intravenous infusion) |
Patients with diagnosed ARDS Patients requiring ventilation High levels of IL-6 |
Reduction of serum CRP to normal range – 76.2% Reduction in need for ventilation – 33% Stabilized condition – 43% |
Worsened condition (related to mortality or cerebrovascular events) and intubation required Side effects – hypertension, fatigue, nausea, neutropenia, infection Contraindicated in patients having diminished cytochrome P450 activity |
[96–98] | |
JAK/STAT inhibitors | Baricitinib | Selective inhibition of JAK1 and JAK2 kinase activity Inhibits adaptor associated protein kinase 1 (AAK1) Binds to cyclin G-associated kinase (GAK) |
Rheumatoid arthritis Psoriatic arthritis |
2–4 mg Once daily for 10 days – 2 weeks (oral) |
Moderate to severe COVID-19 Hospitalized patient SpO2 ≤ 94% on room air Required mechanical ventilation Temperature ≥ 36.6°C armpit |
Improved respiratory function Decreased cytokine storm Reduction of SARS-CoV-2 particle entry in host lung cells Decreased IL-6 and GM-CSF levels |
Inhibition of IFN-γ Ongoing clinical trials |
[99–101] |
IL-1 inhibitors | Anakinra | Prevents binding of IL-1α and IL-1β, thus reducing availability of ligand for endogenous IL-1 receptor | Rheumatoid arthritis Macrophage activation syndrome Hemophagocytic lymphohistiocytosis Still’s disease Cryopyrin associated periodic syndrome |
5 mg/kg twice a day (intravenous – high dose) 100–200 mg twice a day (subcutaneous – low dose) |
Moderate to severe ARDS and COVID-19 Hyperinflammation (CRP ≥ 100 mg/L, Ferritin ≥ 900 ng/mL) Noninvasive ventilation required Presence of severe sepsis |
Decreased CRP and improved respiratory function (72%) Reduced mortality Reduced need for mechanical ventilation |
Associated with injection site reactions Majorly well tolerated No beneficial effects observed in patients having thromboembolism |
[102–108] |