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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Cardiac rupture as a complication of acute myocardial infarction (AMI) has been described as occurring infrequently. Because of the recent dramatic decrease in autopsy rates, the authors believe that current studies do not accurately represent the frequency of this catastrophic complication. Autopsy protocols and archived histologic slides of patients with AMI were retrospectively reviewed to determine whether the frequency of cardiac rupture, as a complication of AMI, is altered when a non-hospital-based patient cohort after autopsy is evaluated. This review yielded 153 cases of 41 women and 112 men, whose postmortem examinations revealed gross and histologic evidence of AMI. Cardiac rupture was present in 30.7% of these cases. Of the 47 patients with rupture, 35 had no relevant medical history. The remaining 12 patients had various medical conditions. None of the patients in the rupture group had previously treated symptoms related to coronary artery conditions. Whereas women constituted 26.8% of the total AMI group, they had a cardiac rupture rate of 61%. By contrast, men with AMI had a cardiac rupture rate of 19.6%. All patients in the cardiac rupture group had heart weights over the predicted expected weight as a function of body weight. Age, gender, and heart weight were significant factors associated with cardiac rupture, whereas body mass index was not significantly related. When these factors were evaluated jointly, age was a significant explanatory factor for rupture among both men and women, whereas body mass index and heart weight were significant for men but not for women. When the rupture sites occurred on the left ventricular myocardium, the anterior wall was affected in 21 cases (45%), the posterior wall in 18 (38%), the lateral wall in 4 (9%), and the apex in 3 (6%). The right ventricular myocardium ruptured in 1 case (2%). Most of the patients had severe multivessel coronary artery disease. Histologic study of the specimens showed that the majority of ruptures occurred between 24 and 72 hours after myocardial infarction. This study showed a frequency of cardiac rupture of 30.7% in patients with AMI and sudden death according to medical examiner's records. These findings confirm and reinforce the importance of postmortem examination and autopsy as an adjunct to clinical medical practice.