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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Respiratory viral infection is associated with exacerbations of COPD. Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected. Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD. Viruses were more commonly detected in those with more severe airways disease.

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Recent studies indicate that the proinflammatory enzyme cyclooxygenase (COX)-2, an enzyme involved in inflammatory cascades but also normal neuronal activities, is elevated in the brain and spinal cord of amyotrophic lateral sclerosis (ALS) patients and ALS mouse model systems. On the basis of this evidence, we explored the impact of COX-2 inhibition on the onset and progression of ALS-like disease in the G93A human superoxide dismutase (SOD)1 mouse model of ALS. We found that prophylactic administration of nimesulide, a preferential COX-2 inhibitor, in the feed resulted in a significant delay in the onset of ALS type motor impairment. This delay of ALS symptomatology temporally overlapped with the inhibition of prostaglandin E2 elevation in the spinal cord of SOD1-G93A transgenic mice relative to untreated SOD1-G93A controls. This study strongly supports a role for COX-2 in the pathophysiology of ALS and provides the first experimental evidence that prophylactic treatment with COX-2 inhibitors can significantly delay the onset of motor dysfunction in the SOD1-G93A transgenic mouse model of ALS.