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.

Historic approaches to radiation protection are founded on the conjecture that measures to safeguard humans are adequate to protect non-human organisms. This view is disparate with other toxicants wherein well-developed frameworks exist to minimise exposure of biota. Significant data gaps for many organisms, coupled with high profile nuclear incidents such as Chernobyl and Fukushima, have prompted the re-evaluation of our approach toward environmental radioprotection. Elucidating the impacts of radiation on biota has been identified as priority area for future research within both scientific and regulatory communities. The crustaceans are ubiquitous in aquatic ecosystems, comprising greater than 66,000 species of ecological and commercial importance. This paper aims to assess the available literature of radiation-induced effects within this subphylum and identify knowledge gaps. A literature search was conducted pertaining to radiation effects on four endpoints as stipulated by a number of regulatory bodies: mortality, morbidity, reproduction and mutation. A major finding of this review was the paucity of data regarding the effects of environmentally relevant radiation doses on crustacean biology. Extremely few studies utilising chronic exposure durations or wild populations were found across all four endpoints. The dose levels at which effects occur was found to vary by orders of magnitude thus presenting difficulties in developing phyla-specific benchmark values and reference levels for radioprotection. Based on the limited data, mutation was found to be the most sensitive endpoint of radiation exposure, with mortality the least sensitive. Current phyla-specific dose levels and limits proposed by major regulatory bodies were found to be inadequate to protect species across a range of endpoints including morbidity, mutation and reproduction and examples are discussed within. These findings serve to prioritise areas for future research that will significantly advance understanding of radiation-induced effects in aquatic invertebrates and consequently enhance ability to predict the impacts of radioactive releases on the environment.

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Analysis of genetic diversity represents a fundamental component of ecological risk assessments in contaminated environments. Many studies have assessed the genetic implications of chronic radiation exposure at Chernobyl, generally recording an elevated genetic diversity and mutation rate in rodents, plants, and birds inhabiting contaminated areas. Only limited studies have considered genetic diversity in aquatic biota at Chernobyl, despite the large number of freshwater systems where elevated dose rates will persist for many years. Consequently, the present study aimed to assess the effects of chronic radiation exposure on genetic diversity in the freshwater crustacean, Asellus aquaticus, using a genome‐wide SNP approach (Genotyping‐by‐sequencing). It was hypothesized that genetic diversity in A. aquaticus would be positively correlated with dose rate. A. aquaticus was collected from six lakes in Belarus and the Ukraine ranging in dose rate from 0.064 to 27.1 µGy/hr. Genotyping‐by‐sequencing analysis was performed on 74 individuals. A significant relationship between geographical distance and genetic differentiation confirmed the Isolation‐by‐Distance model. Conversely, no significant relationship between dose rate and genetic differentiation suggested no effect of the contamination gradient on genetic differentiation between populations. No significant relationship between five measures of genetic diversity and dose rate was recorded, suggesting that radiation exposure has not significantly influenced genetic diversity in A. aquaticus at Chernobyl. This is the first study to adopt a genome‐wide SNP approach to assess the impacts of environmental radiation exposure on biota. These findings are fundamental to understanding the long‐term success of aquatic populations in contaminated environments at Chernobyl and Fukushima.

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