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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Neural interfaces have great potential to treat disease and disability by modulating the electrical signals within the nervous system. However, whilst neural stimulation is a well-established technique, current neural interfaces are limited by poor recording ability. Low signal amplitudes necessitate the use of highly invasive techniques that divide or penetrate the nerve, and as such are unsuitable for chronic implantation. In this paper, we present the first application of the velocity selective recording technique to the detection of respiration activity in the vagus nerve, which is involved with treatments for epilepsy, depression, and rheumatoid arthritis. Further, we show this using a chronically implantable interface that does not divide the nerve. We also validate our recording setup using electrical stimulation and we present an analysis of the recorded signal amplitudes. The recording interface was formed from a cuff containing ten electrodes implanted around the intact right vagus nerve of a Danish Landrace pig. Nine differential amplifiers were connected to adjacent electrodes, and the resulting signals were processed to discriminate neural activity based on conduction velocity. Despite the average single channel signal-to-noise ratio of-5.8 dB, it was possible to observe distinct action potentials travelling in both directions along the nerve. Further, contrary to expectation given the low signal-to-noise ratio, we have shown that it was possible to identify afferent neural activity that encoded respiration. The significance of this is the demonstration of a chronically implantable method for neural recording, a result that will transform the capabilities of future neuroprostheses.