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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Roux-en-Y gastric bypass (RYGB) surgery has become an accepted treatment for excessive obesity. We conducted a longitudinal study to assess regional body composition, muscle proteolysis, and energy expenditure before RYGB, and 6 and 12 months after RYGB. Whole-body and regional fat mass (FM) and lean mass (LM) were assessed via dual-energy X-ray absorptiometry (DXA), and myofibrillar protein degradation was estimated by urinary 3-methylhistidine (3-MeH) in 29 subjects. Energy expenditure and substrate oxidation were also determined using a whole-room, indirect calorimeter in 12 of these subjects. LM loss constituted 27.8 ± 10.2% of total weight loss achieved 12 months postoperatively, with the majority of LM loss (18 ± 6% of initial LM) occurring in the first 6 months following RYGB. During this period, the trunk region contributed 66% of whole-body LM loss. LM loss occurred in the first 6 months after RYGB despite decreased muscle protein breakdown, as indicated by a decrease in 3-MeH concentrations and muscle fractional breakdown rates. Sleep energy expenditure (SEE) decreased from 2,092 ± 342 kcal/d at baseline to 1,495 ± 190 kcal/day at 6 months after RYGB (P < 0.0001). Changes in both LM and FM had an effect on the reduction in SEE (P < 0.001 and P = 0.005, respectively). These studies suggest that loss of LM after RYGB is significant and strategies to maintain LM after surgery should be explored.