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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Eradication and suppression of Pseudomonas aeruginosa is a key priority in national guidelines for bronchiectasis, and is a major focus of drug development and clinical trials. An accurate estimation of the clinical impact of P. aeruginosa in bronchiectasis is, therefore, essential. Methods Data from 21 observational cohort studies comparing patients with P. aeruginosa colonisation to those without were pooled by random effects meta-analysis with data collected for key longitudinal clinical outcomes of mortality, hospital admissions, exacerbations and lung function decline along with cross sectional outcomes such as quality of life. Measurements and main results: Studies included 3683 patients. P. aeruginosa was associated with a highly significant and consistent increase in all markers of disease severity including mortality (odds ratio (OR) 2.95, 95% CI 1.98-4.40; p<0.0001), hospital admissions (OR 6.57, 95% CI 3.19-13.51; p<0.0001) and exacerbations (mean difference 0.97 per year, 95% CI 0.64-1.30; p<0.0001). Patients with P. aeruginosa also had worse quality of life using the St Georges Respiratory Questionnaire (mean difference 18.2 points, 95% CI 14.7-21.8; p<0.0001). There were also large differences in lung function and radiological severity. Definitions of colonisation were inconsistent but findings were robust irrespective of the definition used. Conclusion: P. aeruginosa is associated with an approximate 3-fold increased risk of death and an increase in hospital admissions and exacerbations in adult bronchiectasis.

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