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.

Objective To estimate the incidence and predictors of severe obstetric morbidity. Design Development of definitions of severe obstetric morbidity by literature review. Case-control study from a defined delivery population with four randomly selected pregnant women as controls for every case. Setting All 19 maternity units within the South East Thames region and six neighbouring hospitals caring for pregnant women from the region between 1 March 1997 and 28 February 1998. Participants 48 865 women who delivered during the time frame. Results There were 588 cases of severe obstetric morbidity giving an incidence of 12.0/1000 deliveries (95% confidence interval 11.2 to 13.2). During the study there were five maternal deaths attributed to conditions studied. Disease specific morbidities per 1000 deliveries were 6.7 (6.0 to 7.5) for severe haemorrhage, 3.9 (3.3 to 4.5) for severe pre-eclampsia, 0.2 (0.1 to 0.4) for eclampsia, 0.5 (0.3 to 0.8) for HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, 0.4 (0.2 to 0.6) for severe sepsis, and 0.2 (0.1 to 0.4) for uterine rupture. Age over 34 years, non-white ethnic group, past or current hypertension, previous postpartum haemorrhage, delivery by emergency caesarean section, antenatal admission to hospital, multiple pregnancy, social exclusion, and taking iron or anti-depressants at antenatal booking were all independently associated with morbidity after adjustment. Conclusion Severe obstetric morbidity and its relation to mortality may be more sensitive measures of pregnancy outcome than mortality alone. Most events are related to obstetric haemorrhage and severe pre-eclampsia. Caesarean section quadruples the risk of morbidity. Development and evaluation of ways of predicting and reducing risk are required with particular emphasis paid on the management of haemorrhage and pre-eclampsia.

Objective To estimate the incidence and predictors of severe obstetric morbidity. Design Development of definitions of severe obstetric morbidity by literature review. Case-control study from a defined delivery population with four randomly selected pregnant women as controls for every case. Setting All 19 maternity units within the South East Thames region and six neighbouring hospitals caring for pregnant women from the region between 1 March 1997 and 28 February 1998. Participants 48 865 women who delivered during the time frame. Results There were 588 cases of severe obstetric morbidity giving an incidence of 12.0/1000 deliveries (95% confidence interval 11.2 to 13.2). During the study there were five maternal deaths attributed to conditions studied. Disease specific morbidities per 1000 deliveries were 6.7 (6.0 to 7.5) for severe haemorrhage, 3.9 (3.3 to 4.5) for severe pre-eclampsia, 0.2 (0.1 to 0.4) for eclampsia, 0.5 (0.3 to 0.8) for HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, 0.4 (0.2 to 0.6) for severe sepsis, and 0.2 (0.1 to 0.4) for uterine rupture. Age over 34 years, non-white ethnic group, past or current hypertension, previous postpartum haemorrhage, delivery by emergency caesarean section, antenatal admission to hospital, multiple pregnancy, social exclusion, and taking iron or anti-depressants at antenatal booking were all independently associated with morbidity after adjustment. Conclusion Severe obstetric morbidity and its relation to mortality may be more sensitive measures of pregnancy outcome than mortality alone. Most events are related to obstetric haemorrhage and severe pre-eclampsia. Caesarean section quadruples the risk of morbidity. Development and evaluation of ways of predicting and reducing risk are required with particular emphasis paid on the management of haemorrhage and pre-eclampsia.