Practical Info With the c onditional recommendation against the use o f corticosteroids in pa tients with non-se vere COVID-19 the f ollowing practical information apply in situa tions where such treatment is to be c onsidered: Route: Systemic corticosteroids may be administered both orally and intravenously. Of note, while the bioa vailability of dexamethasone is very high (i.e. similar c oncentrations 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 (i.e. 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 (e.g. 50 mg e very 8 hours), or 40 mg o f prednisone, or 32 mg o f methylprednisolone (e.g. 8 mg e very 6 hours or 16 mg e very 12 hours). 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 treatment 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 frequently appear late (i.e. 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). Other endemic infections that may worsen with corticosteroids should be c onsidered. For example, for Strongyloides st ercoralis hyperinfection associated with c orticosteroid therapy, diagnosis or empiric tr eatment may be c onsidered in endemic ar eas if steroids are used.

Resources and other considerations Resource implications, feasibility, equity and human rights The panel also c onsidered that in order to help guar antee access to s ystemic corticosteroids for patients with severe and critical COVID-19, it is r easonable to avoid administering this intervention to pa tients who, giv en the current evidence, would not appear to derive any benefit from this intervention.