Practical Info Route: Systemic corticosteroids may be administered both orally and intravenously. Of note, while the bioa vailability of dexamethasone is very high (that is, similar concentrations are achieved in plasma a fter oral and intravenous intake), critically ill patients may be unable to absorb an y nutrients or medications due to in testinal dysfunction. Clinicians therefore may consider administering systemic corticosteroids intravenously rather than orally if intestinal dysfunction is suspected. Duration: While more patients received corticosteroids in the f orm of dexamethasone 6 mg daily f or up to 10 da ys, the to tal duration of regimens evaluated in the se ven trials varied between 5 and 14 da ys, and treatment was generally discontinued at hospital discharge (that is, the dur ation of treatment could be less than the dur ation stipulated in the pr otocols). Dose: The once daily dexamethasone formulation may increase adherence. A dose o f 6 mg o f dexamethasone is equivalent (in terms of glucocorticoid effect) to 150 mg o f hydrocortisone (that is, 50 mg e very 8 hours), 40 mg o f prednisone, or 32 mg o f methylprednisolone (8 mg e very 6 hours or 16 mg e very 12 hours). Monitoring:It would be prudent to monitor gluc ose levels in patients with severe and critical COVID-19, regardless of whe ther the patient is known to ha ve diabetes. Timing: The timing o f therapy from onset of symptoms was discussed b y the panel. T he RECOVERY investigators reported a subgroup analysis suggesting that the initiation of therapy 7 da ys or more after symptom onset may be more beneficial than treatment initiated within 7 da ys of symptom onset. A post hoc subgr oup analysis within the PMA did no t support this hypothesis. While some panel members belie ved that postponing s ystemic corticosteroids until after viral replication is contained by the immune s ystem may be reasonable, many noted that, in practice, it is o ften impossible to asc ertain symptom onset and that signs o f severity often appear late (that is, deno te a c o-linearity between severity and timing). The panel concluded that, given the e vidence, it w as preferable to err on the side o f administering corticosteroids when treating patients with severe or critical COVID-19 (even if within 7 da ys of symptoms onset) and to err on the side o f not giving c orticosteroids when treating patients with non-se vere disease (even if a fter 7 days of symptoms onset).

Resources and other considerations Resource implications, feasibility, equity and human rights In this guideline, the panel took an individual pa tient perspective, but also plac ed a high v alue on resource allocation. In such a perspective, attention is paid to the opportunity c ost associated with the widespr ead provision of therapies for COVID-19. In contrast to o ther candidate treatments for COVID-19 that, generally, are expensive, often unlicensed, difficult to ob tain and require advanced medical infrastructure, systemic corticosteroids are low cost, easy to administer, and readily available globally (159). Dexamethasone and prednisolone are among the most c ommonly listed medicines in na tional essential medicines lists; listed by 95% o f countries. Dexamethasone was first listed by WHO as an essen tial medicine in 1977, while prednisolone was listed 2 y ears later (160). Accordingly, systemic corticosteroids are among a r elatively small number o f interventions for COVID-19 that have the potential to reduce inequities and improve equity in health. T hose considerations influenced the strength of this recommendation. Acceptability The ease o f administration, the relatively short duration of a c ourse of systemic corticosteroid therapy, and the g enerally benign safety profile of systemic corticosteroids for up to 7–10 da ys led the panel to c onclude that the acceptability of this intervention was high.