Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. 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. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Transverse distortion of a relativistic composite system in impact parameter space

We investigate the Generalized Parton Distributions (GPDs) in impact parameter space using the explicit light front wave functions (LFWFs) for the two-particle Fock state of the electron in QED. The Fourier transform (FT) of the GPDs gives the distribution of quarks in the transverse plane for zero longitudinal momentum transfer ($\xi=0$). We study the relationship of the spin flip GPD $E(x,0,-\vec{\Delta}_\perp^2)$ with the distortion of unpolarized quark distribution in the transverse plane when the target nucleon is transversely polarized and also determine the sign of distortion from the sign of anomalous magnetic moment. To verify the sign of distortion, we also compute it directly from the LFWFs by performing a FT in position space coordinate $\vec{f}_\perp$. The explicit relation between the deformation in the two spaces can also be obtained using the convolution integrals. To show the relation of the model LFWFs to a realistic model of nucleon physics, we have designed a specific weight function of our model LFWFs and integrated it over the mass parameter. Also we have simulated the form factor of the nucleon in the AdS/QCD holographic LFWFs model and studied the power-law behaviour at short distances.Comment: 17 pages, 6 figures. To appear in Eur. Phys. J. A. arXiv admin note: text overlap with arXiv:1410.322

Efeitos do manganês sobre o desenvolvimento e a composição mineral de quatro leguminosas forrageiras tropicais

Quatro leguminosas forrageiras tropicais (Galactia striata (Jacq) Urb; Glycine wightii cv. Tinaroo, Macroptilium atropurpureum cv. Siratro e Stylosanthes guianensis cv. IRI 1022) foram cultivadas em solução nutritiva recebendo doses de manganês de 0, 5, 10 e 20 ppm, com o objetivo de se verificarem os efeitos das doses crescentes do elemento sobre as diferentes espécies. Submetendo-se os dados de produção de matéria seca e de concentrações de macro e micronutrientes à análise estatística, observou-se o seguinte: a) O estilosantes foi o que se mostrou mais tolerante, não apresentando variação significativa na produção de matéria seca com o aumento dos teores de manganês. Não se observaram sintomas severos nas folhas ou nas raízes. A galactia também mostrou-se tolerante, apresentando queda significativa de produção em presença de 100 ppm de manganês e sentomas mais severos de toxidez que os apresentados pelo estilosantes. b) O Siratro e a soja mostraram-se sensíveis ao excesso de manganês. A soja mostrou a mínima produção em presença de 25 ppm do elemento não havendo modificação significativa nas concentrações mais elevadas. O siratro apresentou a mínima produção de matéria seca total em presença de 50 ppm de manganês. Os sintomas de toxidez apresentados pela soja foram mais severos que os apresentados pelas plantas de siratro. c) A adição de manganês provocou uma diminuição nas concentrações de cálcio, potássio e magnésio nas partes aéreas ou raízes das plantas estudadas; elevação dos teores de zinco e cobre nas aéreas ou raízes e de manganês na planta toda.Four tropical forage legumes (Galactia striata. Glycine wightii, Macroptilium atropurpureum and Stylosanthes guianensis), were grown in nutrient solution under varying levels of manganese (0., 25, 50 e 100 ppm). With respect to the differential tolerance between the species, the following was observed: a) Stylosanthes was not affected neither in therms of growth nor in terms of symptons of toxicity. Galactia was realtively less tolerant: its growth was significantly reduced by 100 ppm of Mn in the substrate which also caused severe toxicity symptons. b) Glycine and Macroptilium were sensitive to high Mn. Growth of the former was decreased by 25 ppm, being not further reduced by higher concentrations. The Mn concentration of 50 ppm caused the highest reduction of the growth of Macroptilium. Toxicity symptoms were more acute in the case of Glycine. c) The addition of Mn induced a decrease in the content of K, Ca and Mg. The levels of Cu and Zn in the tops decreased whereas the Mn concentration increased in the whole plant