• The panel ackno wledged that giv en that the clinic al trials were not representative of the global population and that the risk - benefit may be less adv antageous, particularly in ar eas where certain infectious diseases such as HIV in fections, tuber culosis and certain fungal infections are endemic or in patien ts with an incr eased risk o f opportunistic in fections.
• The panel an ticipated that ther e would be situations wher e clinicians may op t for less aggr essive immunosuppressive therapy and/ or to combine medic ations in a st epwise fashion in patien ts who ar e deteriorating.
• None of the included R CTs enrolled children, and ther efore the applic ability of this recommendation t o children remains uncertain.

Practical Info Additional considerations are available in a summary of practical issues. Useful information can also be f ound in the U nited States Food and D rug Administration (FDA) fact sheet for health care providers, based on the emer gency use authorization (EUA) of baricitinib (38). Here follows a brief summary o f key points: Route, dosage and duration:

• The recommended dose is 4 mg daily or ally in adults with e GFR ≥ 60 m L/min/1.73 m 2 .
• A duration of 14 da ys of total treatment or until hospital discharge, whichever is first. The optimal duration of treatment is unknown, and the pr oposed duration reflects what was used in the trials pr oviding evidence on treatment effects of baricitinib. Dose regimen adjustment:
• Patients with leukopenia, renal impairment or hepatic impairment (note: these parameters should be monitored during treatment);
• Patients taking strong organic anion transporter 3 (OAT3) inhibitors (e.g. probenecid), there are drug interactions which warrant dose reductions. Timing: Baricitinib (like IL-6 receptor blockers) should be initiated at the same time as s ystemic corticosteroids; specific timing during hospitalization or the c ourse of illness is no t specified.

Resources and other considerations Resource implications, equity and human rights Compared with some o ther candidate treatments for COVID-19, baricitinib is expensive. The recommendation does no t take account of cost-effectiveness. Access to these drugs is challenging in man y 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 could exacerbate health inequity. The GDG w as also sensitive to the fact tha t allowing the c ombined use o f the J AK inhibitor baricitinib and IL-6 receptor blockers would likely further reduce the a vailability of these medica tions. The GDG strongly reinforces the need to impr ove drug availability, particularly in resource-constrained areas. On the o ther 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. On 17 D ecember 2021, WHO published the 7th I nvitation to Manufacturers of therapeutics against COVID-19 to submit an Expression of Interest (EOI) for Product Evaluation to the WHO Prequalification Unit, which includes baricitinib. At a time o f drug shortage, it may be nec essary to prioritize use o f baricitinib through clinical triage (6) such as prioritizing patients with the highest baseline risk f or mortality (e.g. those with critical disease o ver those with se vere disease), in whom the absolute benefit of treatment is therefore greatest. Other suggestions for prioritization, which lack dir ect evidence, include focusing on pa tients with an activ ely deteriorating clinical course, and avoiding baricitinib in those with established multiorgan failure (in whom the bene fit is likely to be smaller). Acceptability and feasibility As baricitinib is administered orally once daily, hospitalized patients should find it eas y to ac cept this treatment. In patients who canno t swallow tablets, baricitinib can be crushed, dispersed in w ater, and giv en via a nasogastric tube (see Practical info).