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.

In recognition memory tests, feelings of familiarity for stimuli vary in strength. Increasing levels of felt familiarity should modulate activity in brain structures that mediate familiarity memory. We used this expectation to identify the neural system that underlies scene familiarity memory. Normal subjects studied pictures of scenes and 2 days later while undergoing event-related functional magnetic resonance imaging (fMRI) rated old and new pictures as novel, slightly familiar, moderately familiar, very familiar, or recollected, although they were specifically instructed not to try and recollect. Familiarity strength was, therefore, judged as absent (misses) or present at three levels of increasing strength. A parametric analysis showed that, as perceived strength of familiarity increased activity in the perirhinal cortex, insula and left superior temporal cortex declined linearly whereas activity in the left dorsomedial thalamus, left ventrolateral and anteromedial frontal cortex, posterior cingulate cortex, and left parietal neocortex increased linearly. Hippocampal activity was not modulated linearly or quadratically by changes in familiarity strength. Recollection activated the hippocampus, and left anterior and inferolateral frontal and parietal cortices more than strong familiarity. In contrast, no brain region that was unaffected by recollection (relative to misses and correct rejections) was modulated by variations in familiarity strength. The implications of these findings for the functional and neural bases of familiarity and recollection are considered.

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