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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These authors contributed equally. SUMMARYCowpea (Vigna unguiculata L. Walp.) is a legume crop that is resilient to hot and drought-prone climates, and a primary source of protein in sub-Saharan Africa and other parts of the developing world. However, genome resources for cowpea have lagged behind most other major crops. Here we describe foundational genome resources and their application to the analysis of germplasm currently in use in West African breeding programs. Resources developed from the African cultivar IT97K-499-35 include a whole-genome shotgun (WGS) assembly, a bacterial artificial chromosome (BAC) physical map, and assembled sequences from 4355 BACs. These resources and WGS sequences of an additional 36 diverse cowpea accessions supported the development of a genotyping assay for 51 128 SNPs, which was then applied to five bi-parental RIL populations to produce a consensus genetic map containing 37 372 SNPs. This genetic map enabled the anchoring of 100 Mb of WGS and 420 Mb of BAC sequences, an exploration of genetic diversity along each linkage group, and clarification of macrosynteny between cowpea and common bean. The SNP assay enabled a diversity analysis of materials from West African breeding programs. Two major subpopulations exist within those materials, one of which has significant parentage from South and East Africa and more diversity. There are genomic regions of high differentiation between subpopulations, one of which coincides with a cluster of nodulin genes. The new resources and knowledge help to define goals and accelerate the breeding of improved varieties to address food security issues related to limited-input small-holder farming and climate stress.

SummaryCowpea (Vigna unguiculata [L.] Walp.) is a major crop for worldwide food and nutritional security, especially in sub‐Saharan Africa, that is resilient to hot and drought‐prone environments. An assembly of the single‐haplotype inbred genome of cowpea IT97K‐499‐35 was developed by exploiting the synergies between single‐molecule real‐time sequencing, optical and genetic mapping, and an assembly reconciliation algorithm. A total of 519 Mb is included in the assembled sequences. Nearly half of the assembled sequence is composed of repetitive elements, which are enriched within recombination‐poor pericentromeric regions. A comparative analysis of these elements suggests that genome size differences between Vigna species are mainly attributable to changes in the amount of Gypsy retrotransposons. Conversely, genes are more abundant in more distal, high‐recombination regions of the chromosomes; there appears to be more duplication of genes within the NBS‐LRR and the SAUR‐like auxin superfamilies compared with other warm‐season legumes that have been sequenced. A surprising outcome is the identification of an inversion of 4.2 Mb among landraces and cultivars, which includes a gene that has been associated in other plants with interactions with the parasitic weed Striga gesnerioides. The genome sequence facilitated the identification of a putative syntelog for multiple organ gigantism in legumes. A revised numbering system has been adopted for cowpea chromosomes based on synteny with common bean (Phaseolus vulgaris). An estimate of nuclear genome size of 640.6 Mbp based on cytometry is presented.

Cowpea [Vigna unguiculata (L.) Walp.] is a major tropical legume crop grown in warm to hot areas throughout the world and especially important to the people of sub-Saharan Africa where the crop was domesticated. To date, relatively little is understood about its domestication origins and patterns of genetic variation. In this study, a worldwide collection of cowpea landraces and African ancestral wild cowpea was genotyped with more than 1200 single nucleotide polymorphism markers. Bayesian inference revealed the presence of two major gene pools in cultivated cowpea in Africa. Landraces from gene pool 1 are mostly distributed in western Africa while the majority of gene pool 2 are located in eastern Africa. Each gene pool is most closely related to wild cowpea in the same geographic region, indicating divergent domestication processes leading to the formation of two gene pools. The total genetic variation within landraces from countries outside Africa was slightly greater than within African landraces. Accessions from Asia and Europe were more related to those from western Africa while accessions from the Americas appeared more closely related to those from eastern Africa. This delineation of cowpea germplasm into groups of genetic relatedness will be valuable for guiding introgression efforts in breeding programs and for improving the efficiency of germplasm management.

Multi-parent advanced generation inter-cross (MAGIC) populations are an emerging type of resource for dissecting the genetic structure of traits and improving breeding populations. We developed a MAGIC population for cowpea (Vigna unguiculata L. Walp.) from eight founder parents. These founders were genetically diverse and carried many abiotic and biotic stress resistance, seed quality and agronomic traits relevant to cowpea improvement in the United States and sub-Saharan Africa, where cowpea is vitally important in the human diet and local economies. The eight parents were inter-crossed using structured matings to ensure that the population would have balanced representation from each parent, followed by single-seed descent, resulting in 305 F recombinant inbred lines each carrying a mosaic of genome blocks contributed by all founders. This was confirmed by single nucleotide polymorphism genotyping with the Illumina Cowpea Consortium Array. These lines were on average 99.74% homozygous but also diverse in agronomic traits across environments. Quantitative trait loci (QTLs) were identified for several parental traits. Loci with major effects on photoperiod sensitivity and seed size were also verified by biparental genetic mapping. The recombination events were concentrated in telomeric regions. Due to its broad genetic base, this cowpea MAGIC population promises breakthroughs in genetic gain, QTL and gene discovery, enhancement of breeding populations and, for some lines, direct releases as new varieties.

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Linkage mapping is relevant to modern plant biology and provides a framework for downstream analyses including quantitative trait loci identifi cation, map-based cloning, assessment of diversity, association mapping, and molecular breeding. Here, we report a consensus genetic map of cowpea [Vigna unguiculata (L.) Walp.] and synteny to other legumes based on expressed sequence tag (EST)-derived single nucleotide polymorphisms (SNPs). In total, 1293 individuals representing 13 mapping populations were genotyped using an Illumina 1536 GoldenGate Assay. A consensus map containing 1107 ESTderived SNP markers (856 bins) on 11 linkage groups (680 cM) was constructed from 13 population-specifi c maps. This effort combined six new population-specifi c maps and seven revised population-specifi c maps to construct an improved consensus map with 33% more bins, 19% more markers, and improved marker order when compared to the previous cowpea SNP consensus map. Comparative and whole genome visualizations are presented as a framework for discussing map quality and synteny with soybean [Glycine max (L.) Merr.].is a leguminous crop cultivated for fresh and dry grains, leaves, and fodder. Th e crop is a valuable component of rotations and intercrops due to symbiotic N fi xation (Quaye et al., 2009). Important cowpea producing regions span the globe; however, it is an especially valuable component of low-input farming systems in sub-Saharan Africa, South America, and Asia. Cowpea is popular in resource-poor farming because of its consistent production under abiotic stresses (drought, heat, or low soil fertility) and in many regions it is a protein-rich component of an otherwise protein-poor diet (Ehlers and Hall, 1997;Hall, 2004).Research and development of improved crop varieties encompasses advances in genomics and biotechnology. Consensus genetic maps are available for many model and important crop and animal species including soybean [Glycine max (L.) Merr.] (Song et al., 2004), wheat (Triticum aestivum L.) (Somers et al., 2004), barley (Hordeum vulgare L.) (Wenzl et al., 2006), and chicken (Gallus-gallus domesticus L.) (Groenen et al., 2000) and are central to breeding and diversity initiatives. Recently, technological advances that have substantially reduced costs of sequencing and genotyping promoted the development of genome resources for many non-model species (Varshney et al., 2009). Linkage mapping in cowpea has progressed with marker technology to yield informative and increasingly dense genetic maps (Menendez et al., 1997;Ouedraego et al., 2002;Muchero et al., 2009). Abbreviations: AFLP, amplifi ed fragment length polymorphism; EST, expressed sequence tag; LOD, logarithm of the odds; QTL, quantitative trait loci; RAPD, random amplifi ed polymorphic DNA; RIL, recombinant inbred line; RFLP, restriction fragment length polymorphism; SNP, single nucleotide polymorphism; SSR, simple sequence repeat; VuLG, Vigna unguiculata linkage group.