• Corticosteroids have previously been str ongly recommended in patien ts with se vere and critic al COVID-19 (see Section 6.15), and we recommend patien ts meeting these se verity criteria should receive both corticosteroids and IL-6 receptor blockers.
• The JAK inhibitor baricitinib is no w recommended f or the tr eatment of patients with se vere and critic al COVID-19 (see S ection

• 6.4). IL-6 receptor blockers and baricitinib may be giv en 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 no t used in this case. IL -6 receptor blocker therapy should be administered in c ombination with systemic corticosteroids, which ma y be administered both orally and intravenously, with due c onsideration to their high bioavailability but possible malabsorption in the case o f intestinal dysfunction with critical illness. Duration: Tocilizumab and sarilumab are administered as single in travenous doses, typically o ver 1 hour. A sec ond dose ma y be administered 12 to 48 hours a fter the first dose; this w as offered variably in major clinical trials at the discretion of treating clinicians if a clinical response w as felt to be inadequa te. Duration of concurrent systemic corticosteroids is typically up to 10 days, though ma y vary between 5 and 14 da ys. Dose: Tocilizumab is dosed a t 8 mg per kilogr am of actual body w eight, up to a maximum o f 800 mg. S arilumab is most commonly dosed a t 400 mg, c onsistent with wha t was used in REMAP -CAP. Renal dose adjustment is no t 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 pa tients should be monitor ed for signs and s ymptoms of infection, given the increased risk with immunosuppression in addition to systemic corticosteroids. Patients on long er term IL-6 receptor blocker therapy are at risk of active tuberculosis, invasive fungal in fections and opportunistic pathogens. Risks and benefits of therapy should be c onsidered carefully in patients with any active, severe infection other than COVID-19; caution is advised when c onsidering the use o f tocilizumab in patients with a history o f recurring or chronic infections or with underlying c onditions which ma y predispose them to infections. Timing: IL-6 receptor blockers should be initiated with s ystemic 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.

Resources and other considerations Resource implications, equity and human rights The GDG no ted that, compared with some o ther candidate treatments for COVID-19, IL-6 receptor blockers are more expensive and the r ecommendation does no t take account of cost-effectiveness. Currently, access to these drugs is challenging in many parts of the w orld, and without c oncerted effort is likely to remain so, especially in r esource-poor areas. It is therefore possible that this strong recommendation for IL-6 receptor blockers could exacerbate health inequity. On the other hand, given the demonstrated benefits for patients, it should also pr ovide a stimulus to engag e all possible mechanisms to improve global access to these tr eatments. Individual countries may formulate their guidelines considering available resources and prioritize treatment options accordingly. At a time o f drug shortage, it may be nec essary to prioritize use o f IL-6 receptor blockade through clinical triage (6). Many jurisdictions have suggested mechanisms f or triaging use of these treatments. These include prioritizing patients with the highest baseline risk for mortality (e.g. those with critical disease o ver those with se vere disease), in whom the absolute benefit of treatment is therefore greatest. For example, despite c onsistent relative effects (OR 0.86 f or mortality) with IL-6 receptor blockers, the absolute risk reduction for mortality in the critically ill would be 31 f ewer deaths per 1000 (95% CI 11 to 47 f ewer deaths) and in the se verely ill would be 13 f ewer deaths per 1000 (95% CI 5 to 19 f ewer deaths). Other suggestions for prioritization, which lack dir ect evidence, include f ocusing on pa tients with an activ ely deteriorating clinical course and avoiding IL-6 receptor blocker therapy in those with established multi-or gan failure (in whom the bene fit is likely to be smaller). Acceptability and feasibility As IL-6 receptor blockers require intravenous administration, this treatment would be primarily indicated for patients with severe and critical COVID-19 who r equire hospitalization. IL-6 receptor blockers are relatively easy to administer, and only require one, or a t most, tw o doses