Remarks

• Corticosteroids have previously been strongly recommended in patients with severe and critical COVID-19, and we recommend patients meeting these severity criteria should receive both corticosteroids and IL-6 receptor blockers.
• The JAK inhibitor baricitinib is now recommended for the treatment of patients with severe and critical COVID-19. IL-6 receptor blockers and baricitinib may be given together.

Practical info Route: IL-6 receptor blockers are administered intravenously for the treatment of patients with severe or critical COVID-19; subcutaneous administration is not used in this case. IL-6 receptor blocker therapy should be administered in combination with systemic corticosteroids, which may be administered both orally and intravenously, with due consideration to their high bioavailability but possible malabsorption in the case of intestinal dysfunction with critical illness. Duration: Tocilizumab and sarilumab are administered as single intravenous doses, typically over 1 hour. A second dose may be administered 12 to 48 hours after the first dose; this was offered variably in major clinical trials at the discretion of treating clinicians if a clinical response was felt to be inadequate. Duration of concurrent systemic corticosteroids is typically up to 10 days, though may vary between 5 and 14 days. Dose: Tocilizumab is dosed at 8 mg per kilogram of actual body weight, up to a maximum of 800 mg. Sarilumab is most commonly dosed at 400 mg, consistent with what was used in REMAP-CAP. Renal dose adjustment is not currently warranted for either drug. Monitoring: Routine bloodwork including neutrophil count, platelets, transaminases and total bilirubin should be checked prior to initiation of therapy. All patients should be monitored for signs and symptoms of infection, given the increased risk with immunosuppression in addition to systemic corticosteroids. Patients on longer term IL-6 receptor blocker therapy are at risk of active tuberculosis, invasive fungal infections and opportunistic pathogens. Risks and benefits of therapy should be considered carefully in patients with any active, severe infection other than COVID-19; caution is advised when considering the use of tocilizumab in patients with a history of recurring or chronic infections or with underlying conditions which may predispose them to infections. Timing: IL-6 receptor blockers should be initiated with systemic corticosteroids; specific timing during hospitalization or the course of illness is not specified. That being said, IL-6 receptor blockers have been administered early in the course of hospitalization in the included trials and clinicians may consider this approach if possible. See section on resource implications, equity and human rights.