Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

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669The results on the overnight urine specimens in all the subjects are shown in the figure. The mean overnight 1 1-hydroxycorticosteroid levels and the standard deviations in the control, obese, and hirsute groups were similar, being 119 +47 nmol (43 + 17 [g), 121 ± 50 nmol (44 ± 18 Lg), and 138 +55 nmol (50 +20 :'g) respectively. The highest value of 271 nmol (98 ug) occurred in an obese patient. By contrast, only one of the patients with Cushing's syndrome had a urinary 11-hydroxycorticosteroid excretion of less than 276 nmol (100 ug) during the night. On the night in question her midnight plasma 11-hydroxycorticosteroid was normal at 189 nmol/l (6-8 ,ug/100 ml), and her overnight urine contained 254 nmol (92 ,tg); on a subsequent occasion a repeat overnight collection gave a raised value of 389 nmol (141 ILg). The diagnosis of bilateral hyperplasia was confirmed at operation. The overnight specimens from all the other patients with Cushing's syndrome contained more than 276 nmol (100 bLg) of 1 1-hydroxycorticosteroids, the highest containing 2663 nmol (965 ,ug). DiscussionOur results confirm that there is a circadian rhythm in the urinary excretion of adrenal steroids in normal people, the lowest levels occurring during the night. In patients with Cushing's syndrome this rhythm is not so apparent, and the nocturnal excretion is much higher.2 3 We therefore thought that patients with adrenocortical overactivity might be identified by their higher overnight urinary excretion of 1 1-hydroxycorticosteroids, and this was found to be so.Our data were obtained solely from women because only one man with Cushing's syndrome was admitted during the study. The overnight 11-hydroxycorticosteroid level in this man with an adrenal carcinoma was grossly raised at 5382 nmol (1950 [Lg).Thus this test is probably applicable to both men and women.Clinical suspicion of Cushing's syndrome is often aroused by obesity and hirsutism in women, particularly if it is associated with hypertension or diabetes mellitus, but it is not practicable to investigate all such patients in hospital. This simple screening test, requiring only the collection of an overnight urine specimen for 1 1-hydroxycorticosteroid estimation, has proved useful in selecting those outpatients who require more extensive investigation. Our data indicate that levels over 276 nmol (100 ,ug) that were examined by electron microscopy aggregates of HBsAg and HBsAb were seen. In contrast, HBsAb was never detected by RIA in those with non-fulminant hepatitis, and in only one serum specimen (5%) were aggregates seen on electron microscopy. A significant sex difference between fulminant and non-fulminant hepatitis was observed, 65%' of patients with fulminant hepatitis but only 15% of patients with non-fulminant hepatitis being women (P <0 01).