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.

Summary Objectives Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID‐19) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID‐19; to assess the prevalence of VDD among COVID‐19 inpatients, and examine potential associations with disease severity and fatality. Design and Participants We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID‐19. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID‐19 severity and fatality were analysed. Results 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years ± 11.8 vs. 76.4 years ± 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score‐2 and C‐Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non‐ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. Conclusions Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.

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