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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Renewable fuel production, particularly grain-based ethanol, is expanding rapidly in the USA. Although subsidized grain-based ethanol may provide a competitively priced transportation fuel, concerns exist about potential environmental impacts. This contribution focuses on potential water quality implications of expanded grain-based ethanol production and potential impacts of perennial-grass-based cellulosic ethanol. Expanded grain-based ethanol will increase and intensify corn production. Even with recommended fertilizer and land conservation measures, corn acreage can be a major source of N loss to water (20-40 kg ha(-1) yr(-1)). A greater acreage of corn is estimated to increase N and P loss to water by 37% (117 million kg) and 25% (9 million kg), respectively, and measures to encourage adoption of conservation practices are essential to mitigate water quality impairments. Dried distiller's grains remaining after ethanol production from corn grain are used as animal feed and can increase manure P content and may increase N content. Cellulosic fuel-stocks from perennials such as switchgrass and woody materials have the potential to produce ethanol. Although production, storage, and handling of cellulosic materials and conversion technology are limitations, accelerating development of cellulosic ethanol has the potential to reduce dependence on grain fuel-stocks and provide water quality and other environmental benefits. All alternative fuel production technologies could have environmental impacts. There is a need to understand these impacts to help guide policy and help make programmatic and scientific decisions that avoid or mitigate unintended environmental consequences of biofuel production.

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