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

Analysis of differential expression of protease-activated receptors in patients with allergic fungal rhinosinusitis

Background Ever since its characterization in the 1970s, allergic fungal rhinosinusitis (AFRS) has been the subject of much controversy, especially regarding its pathogenesis. In this study, we analyzed the differential expression of genes that encode protease-activated receptors (PAR) in patients with AFRS and patients with chronic rhinosinusitis, and tried to understand the pathogenic basis of this disease. Objective To analyze the differential expression of PAR genes in patients with AFRS and in patients with chronic rhinosinusitis. Methods Mucosa from ethmoid sinuses of 51 patients (tests and controls) was biopsied and evaluated for messenger RNA expression of PAR genes by using reverse transcriptase–polymerase chain reaction. Each of the four PAR genes, i.e., par1, par2, par3 and par4 was amplified, the final gene products were run on 1.8% agarose gel and analyzed by densitometry to calculate differential expression. The significance level was determined as p ≤ 0.05. Results It was observed that the expressions of all four par genes were higher in the test samples compared with the controls, but statistical significance was achieved only for par1 (p=0.004) and par2 (p=0.05). Comparative expression of the four PAR genes was also performed within the test and control groups, and a statistically significant difference was seen between par1 and par2 (p=0.007), par1 and par3 (p=0.029), par1 and par4 (p=0.0001), par2 and par4 (p=0.002), and par3 and par4 (p=0.009) in the test group. In the control group as well, par1, par2, and par3 exhibited a higher expression compared with par4 but the difference was significant between par3 and par4 genes only. Conclusion Patients with AFRS expressed increased levels of PAR genes in their nasal mucosa, and, of the four PAR genes, a higher expression of par1, par2, and par3 was observed in both the groups compared with par4. This information contributes toward our understanding of pathogenesis and possibly treatment of AFRS

Wind Turbine Performance Losses Due to the Ice Accretion on the Turbine Blades

Ice accretion on wind turbine blades modifies the blade profiles and causes degradation in the aerodynamic characteristic of the blades. In this study ice accretion on turbine blades are simulated under various icing conditions and the resulting power losses are estimated. The Blade Element Momentum method is employed together with an ice accretion prediction methodology based on the Extended Messinger model and 2D flow solvers XFOIL and SU2. The predicted iced profiles are first validated with the experimental and numerical data available in the literature. The power production losses in the presence of iced blades are then investigated. It is shown that the methodology developed successfully predicts ice profiles on blade profiles under various icing conditions and the consequent power losses. It predicts about 20% power loss on the 30kW Aeolos wind turbine exposed to icing conditions for an hour