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.

No abstract

No abstract

induced oxidative stress is instrumental in achieving the health benefits from regular exercise. Therefore, inappropriate use of fruit-derived products (commonly applied as prophalytic antioxidants) may counteract the positive effects of exercise. Using human exercise and cellular models we found that 1) blackcurrant supplementation suppressed exercise-induced oxidative stress, e.g., plasma carbonyls (0.9 Ϯ 0.1 vs. 0.6 Ϯ 0.1 nmol/mg protein, placebo vs. blackcurrant), and 2) preincubation of THP-1 cells with an anthocyanin-rich blackcurrant extract inhibited LPS-stimulated cytokine secretion 453 Ϯ 322 vs. 10,941 Ϯ 82 pg/ml, control vs. extract, P Ͻ 0.05) and IL-6 (476 Ϯ 14 vs. 326 Ϯ 32 pg/ml, control vs. extract, P Ͻ 0.05)] and NF-B activation. In addition to its antioxidant and anti-inflammatory properties, we found that postexercise plasma collected after blackcurrant supplementation enhanced the differential temporal LPS-stimulated inflammatory response in THP-1 cells, resulting in an early suppression of TNF-␣ (1,741 Ϯ 32 vs. 1,312 Ϯ 42 pg/ml, placebo vs. blackcurrant, P Ͻ 0.05) and IL-6 (44 Ϯ 5 vs. 36 Ϯ 3 pg/ml, placebo vs. blackcurrant, P Ͻ 0.05) secretion after 24 h. Furthermore, by using an oxidative stress cell model, we found that preincubation of THP-1 cells with hydrogen peroxide (H 2O2) prior to extract exposure caused a greater suppression of LPS-stimulated cytokine secretion after 24 h, which was not evident when cells were simultaneously incubated with H 2O2 and the extract. In summary, our findings support the concept that consumption of blackcurrant anthocyanins alleviate oxidative stress, and may, if given at the appropriate amount and time, complement the ability of exercise to enhance immune responsiveness to potential pathogens. acute inflammation; fruit anthocyanins; moderate exercise PARTICIPATING IN REGULAR PHYSICAL exercise has a number of health benefits (14). Exercise-induced oxidative stress (11,48,50), either via reactive oxygen species (ROS)-dependent (2, 14) or -independent (23) mechanisms, appears to be an important modulator in a number of adaptive responses to exercise: upregulation of endogenous antioxidant systems (42, 18), modulation of muscle function (17), improved efficacy of influenza immunization (15), and enhanced immune surveillance (14). Characterization of how exercise modulates the immune system in untrained individuals as well as athletes shows how the type, intensity, and duration of exercise affects the immune responses to pathogenic agents, such as bacterial endotoxin LPS (9,12,16). In addition to regular exercise, the ingestion of antioxidant supplements or foods high in antioxidants and vitamins, such as C and E, have become commonplace in efforts to maintain health and prevent chronic oxidative stressassociated aliments (5). While antioxidant supplementation has been shown to alleviate exercise-induced oxidative stress and benefit athletes undergoing long-term strenuous training by reducing oxidative stress-related injuries and illnesses (48, 51), exercise ...

No abstract