Question 5. should steroids be administered?
So far, no RCT has been performed on corticosteroids administration in patients with COVID-19, and there are controversial opinions regarding the extrapolation of inference from previous studies in SARS-CoV-1 and MERS-CoV patients [15,54,55].
In an observational study conducted in 84 COVID-19 patients with acute respiratory distress syndrome (ARDS) in China, administration of methylprednisolone was associated with reduced progression to death (hazard ratio 0.38, 95% confidence interval 0.20–0.72, p 0.003), although the unadjusted analysis and the relatively small sample size preclude firm generalization and call for further investigation [47]. Indirect data on the possible efficacy (RCT) or effectiveness (observational comparative studies) of corticosteroid therapy come from studies performed in patients with MERS-CoV, SARS-CoV-1 or other viral infections.
With regard to patients with mild clinical presentation, a RCT including 16 not critically ill patients with SARS-CoV-1 did not report a beneficial effect of hydrocortisone administration. Of note, higher viraemia was observed in the second and third weeks after infection in the hydrocortisone group compared to the control group [56]. Moreover, as reported in a systematic review and meta-analysis of observational studies on corticosteroids provided to patients with SARS-CoV-1, only four studies provided conclusive data, reporting no survival benefit and possible harms including avascular necrosis, psychosis, diabetes and delayed virus clearance [57].
In critically ill patients, corticosteroids may be provided to decrease the inflammation–coagulation–fibroproliferation observed during acute respiratory distress syndrome (ARDS) [[58], [59], [60], [61]]. A meta-analysis on corticosteroid use in ARDS including eight controlled studies reported a significant reduction in markers of systemic inflammation, pulmonary and extrapulmonary organ dysfunction scores, duration of mechanical ventilation and ICU length of stay [62]. A recent multicentre RCT included 277 patients with ARDS to assess the effects of dexamethasone treatment. Patients in the study arm received dexamethasone 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. This study reported a significant reduction in duration of mechanical ventilation in the dexamethasone group than in the control group (between-group difference 4.8 days, p < 0.0001) and a significant reduction in mortality at 60 days (between-group difference −15.3%, p 0.0047). The proportion of adverse events did not differ significantly between the dexamethasone group and the control group [63].
Data on the use of corticosteroids in critically ill patients with SARS-CoV-1 and MERS-CoV infection are available, albeit with conflicting results. In a retrospective observational study of 152 SARS-CoV-1–infected, critically ill patients, corticosteroid therapy was found to reduce mortality and shorten the length of hospital stay (odds ratio 0.08, 95% confidence intervals 0.01–0.97, p 0.046). The study did not report increased secondary infections or other complications with corticosteroid administration [64]. Conversely, in a retrospective observational study on 309 critically ill patients with MERS-CoV, the administration of a median hydrocortisone equivalent dose of 300 mg per day was not associated with a difference in 90-day mortality. In addition, corticosteroid administration was associated with delayed clearance of MERS-CoV RNA from the patients' respiratory tract [65].
With regard to other viral infections, it is worth noting that a recent meta-analysis on patients with influenza pneumonia (including ten observational studies with a total of 6548 included patients) reported increased mortality (risk ratio: 1.75, 95% CI 1.3–2.4; p 0.0002), increased length of ICU stay (mean difference: 2.1, 95% CI 1.2–3.1; p < 0.0001) and increased rate of secondary bacterial or fungal infection (risk ratio: 2.0, 95% CI 1.0–3.8; p 0.04) in patients who received corticosteroids [66].

Question 5 statement
So far, no definitive efficacy or effectiveness data are available on the benefit of corticosteroid administration in patients with SARS-CoV-2 infection. As the World Health Organization underlines, there is an important need for efficacy data from RCT for supporting corticosteroids therapy in patients with SARS-CoV-2. However, considering that overwhelming inflammation and cytokine-related lung injury might be responsible for the rapidly progressive pneumonia and clinical deterioration in COVID-19 patients [44,58,67], we suggest (expert opinion only) to consider administration of corticosteroids in critically ill COVID-19 patients with ARDS or with worsening of non-ARDS respiratory failure in the absence of bacterial/fungal superinfections (independent of ICU admission). However, in the absence of convincing evidence, the following cannot currently be supported: steroid administration stratified according to inflammatory markers and steroid administration in non–critically ill COVID-19 patients.