Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death.

The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality.

2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14).

In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in late 2019 from a zoonotic source. The majority of COVID-19 infections are either asymptomatic or result in only mild disease. However, a substantial proportion of older infected individuals develop a respiratory illness requiring hospital care, which can progress to critical illness with hypoxemic respiratory failure requiring prolonged ventilatory support. Amongst COVID-19 patients admitted to UK hospitals, the case fatality rate is over 26%, and is over 37% in patients requiring invasive mechanical ventilation. Although remdesivir has been shown to shorten the time to recovery in hospitalized patients, no therapeutic agents have been shown to reduce mortality. The pathophysiology of severe COVID-19 is dominated by an acute pneumonic process with extensive radiological opacity and, on autopsy, diffuse alveolar damage, inflammatory infiltrates and microvascular thromobosis. The host immune response is thought to play a key role in the pathophysiology of organ failure in other severe viral pneumonias such as highly pathogenic avian influenza, severe acute respiratory syndrome (SARS), and pandemic and seasonal influenza.  Inflammatory organ injury may occur in severe COVID-19, with a subset of patients having markedly elevated inflammatory markers such as C-reactive protein, ferritin, and interleukins  and 6.6, Several therapeutic interventions to mitigate inflammatory organ injury have been proposed in viral pneumonia but the value of corticosteroids has been widely debated. In the absence of reliable evidence from large-scale randomized clinical trials, there is great uncertainty about the effectiveness of corticosteroids in COVID-19. Prior to RECOVERY, many COVID-19 treatment guidelines stated that corticosteroids were either ‘contraindicated’ or ‘not recommended’ although in China, corticosteroids are recommended for severe cases.