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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Modern large-scale scientific simulations running on HPC systems generate data in the order of terabytes during a single run. To lessen the I/O load during a simulation run, scientists are forced to capture data infrequently, thereby making data collection an inherently lossy process. Yet, lossless compression techniques are hardly suitable for scientific data due to its inherently random nature; for the applications used here, they offer less than 10% compression rate. They also impose significant overhead during decompression, making them unsuitable for data analysis and visualization that require repeated data access.To address this problem, we propose an effective method for In-situ Sort-And-B-spline Error-bounded Lossy Abatement (ISABELA) of scientific data that is widely regarded as effectively incompressible. With IS-ABELA, we apply a preconditioner to seemingly random and noisy data along spatial resolution to achieve an accurate fitting model that guarantees a ≥ 0.99 correlation with the original data. We further take advantage of temporal patterns in scientific data to compress data by ≈ 85%, while introducing only a negligible overhead on simulations in terms of runtime. ISABELA significantly outperforms existing lossy compression methods, such as Wavelet compression. Moreover, besides being a communication-free and scalable compression technique, ISABELA is an inherently local decompression method, namely it does not decode the entire data, making it attractive for random access.

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