Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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

Toxicidade do pericarpo da Jatropha curcas em ovinos

O pinhão manso (Jatropha curcas) é uma planta cultivada para a produção de biocombustível. O pericarpo é um coproduto com potencial para alimentação animal, e a presença de componentes tóxicos, principalmente ésteres de forbol, pode limitar sua utilização. Assim, objetivou-se avaliar a toxicidade do pericarpo. Vinte ovinos foram distribuídos em quatro grupos - um grupo-controle, que não recebeu a planta, e três experimentais, que receberam o pericarpo nas concentrações de 15% (G15), 30% (G30) e 45% (G45), durante 23 dias. Após o 10º dia, a ingestão do pericarpo promoveu redução do consumo de alimento, diarreia, desidratação e caquexia. Todos os grupos tratados apresentaram redução na concentração de fosfatase alcalina. Animais do G30 apresentaram redução na concentração de ureia e proteínas totais e elevação de potássio e sódio. No G45, houve aumento de aspartato aminotransferase, albumina, creatinina bilirrubina indireta e total. A avaliação anatomo-histopatológica revelou ascite, hidropericárdio, congestão no trato gastrintestinal e nos pulmões, edema pulmonar, aderências à parede torácica, degeneração hepática centrolobular e das células tubulares renais, pneumonia linfo-histiocitica e enterite linfoplasmocitária e histiocítica. À análise fitoquímica, constatou-se 0,3845mg de ésteres de forbol/g de pericarpo. Conclui-se que o pericarpo de J. curcas é tóxico, não sendo recomendado para alimentação de ovinos