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.

CYK4 activity as a GTPase-activating protein is required during anaphase to inhibit Rac1-dependent effector pathways associated with control of cell spreading and adhesion.

Immunohistochemistry was used to investigate the leukocyte populations in the endometrium of women suffering recurrent miscarriage. Mid-luteal phase endometrial biopsies were taken from 22 patients with idiopathic recurrent miscarriage and from nine women with normal obstetric histories. The samples were dated histologically and stained with a panel of monoclonal antibodies to identify leukocytes. The outcome of any pregnancy in subsequent cycles following the biopsy was determined. Similar numbers of cluster designation (CD)3(+) and CD8(+) cells were seen in both groups. However, CD4(+), CD14(+), CD16(+), CD56(+) and MHC class II(+) cells were significantly higher in the recurrent miscarriage group than in the controls. Two patients had B cells (CD22(+)) in their endometrium. No CD57(+) cells were seen in the controls; however, eight of the patients had a few CD57(+) cells present. Only two patients, both from the recurrent miscarriage group, had CD69(+) leukocytes in their endometrium. Patients who had miscarriages following endometrial biopsy had significantly more CD4(+), CD8(+), CD14(+), CD16(+), and CD56(+) leukocytes in their endometrium than either those who had live births or women with proven fertility. A different population of leukocytes was found in the pre-implantation endometrium from recurrent miscarriage patients as compared to those from fertile controls. These differences were accentuated in women who had a miscarriage subsequent to the biopsy compared with those who subsequently had a live birth.

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