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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The Rht-B1b and Rht-D1b alleles, which occur at homoeologous loci on chromosomes 4B and 4D, respec-Reduced height alleles at the Rht-B1 and Rht-D1 loci have been tively, reduce sensitivity to gibberellic acid (GA), which widely incorporated into wheat (Triticum aestivum L.) cultivars with the intent of improving partitioning of assimilates to grain. Although is necessary for stem elongation (Flintham et al., 1997). generally effective at increasing yield in high yield environments, In favorable environments, the reduced demand for astheir effects under heat and drought stress have been variable. We similates by a shorter stem results in improved assimilate undertook this study to evaluate the effects of the Rht-B1b and Rhtpartitioning to the developing head, leading to higher D1b dwarfing alleles in a recombinant inbred line (RIL) spring wheat spikelet fertility and more but smaller grain per head. population under a range of soil moisture conditions. Rht-B1 and Semidwarf wheats have smaller leaves, but compensate Rht-D1 genotypes of 140 RILs derived from a cross between 'Kauz' with increased photosynthetic rates resulting in a bioand MTRWA116 were determined by polymerase chain reactions mass similar to that of tall lines (LeCain et al., 1989;(PCR). The population was evaluated for yield and agronomic traits Morgan et al., 1990;Flintham et al., 1997). in four Colorado environments under fully irrigated, partially irri-The relative yield advantage of dwarf and semidwarf gated, and rainfed conditions in 2001 and 2002. Lines with both dwarfing alleles were significantly (P Ͻ 0.01) shorter, lower yielding, and cultivars varies with spring or winter habit, genetic backlater heading in all environments compared with lines with one or no ground, and environmental conditions. The benefits of dwarfing allele. Lines with both tall alleles performed equal to or the dwarfing alleles are more pronounced in high yieldbetter (P Ͻ 0.05) than all other classes for grain yield, test weight, ing winter wheat environments (Flintham et al., 1997) and kernel weight in all environments. Among lines with a single and in high yielding spring wheat locations at latitudes dwarfing allele, those with Rht-B1b on average outyielded those with less than 40Њ (Fischer and Quail, 1990). However, under Rht-D1b in the fully irrigated environment (5432 versus 4993 kg heat and drought stress, there may be no benefit of the ha Ϫ1 , P Ͻ 0.05), but elsewhere their yields did not differ (P Ͼ 0.05).dwarfing alleles in spring wheat (Flintham et al., 1997; Desirable values for most traits occurred across a relatively wide range Nizam Uddin and Marshall, 1989; Richards, 1992a,b). of plant heights, with the best performing lines either shorter lines inRichards (1992a) concluded that grain yield does not the tall class or taller lines in the semidwarf classes. edu).Published in Crop Sci. 45:939-947 (2005).

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