Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). INTERPRETATION: In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. FUNDING: UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust

Evaluation of antioxidant and antibacterial activities of the stems of Flammulina velutipes and Hypsizygus tessellatus (white and brown var.) extracted with different solvents

Mushrooms are rich in pharmacologically-important phytochemicals with reported medicinal values. In this study, the antibacterial activity of Flammulina velutipes (Enoki), Hypsizygus tessellatus (brown (Buna shimeji) and white (Bunapi shimeji) variants) stem extracts prepared with different solvents (water, methanol, acetone, and ethyl acetate) was investigated against Escherichia coli (E. coli ATCC 25922), Serratia marscenscens (S. marscenscens ATCC14756), Bacillus subtilis (B. subtilis ATCC 23857), and Staphylococcus aureus (S. aureus ATCC 25923). Their antioxidant activities were evaluated using radical scavenging assays of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and ferric reducing power (FRP). The water extracts of Enoki, Buna shimeji, and Bunapi shimeji showed bacterial growth inhibition in a concentration-dependent manner. From the obtained results, all the Enoki extracts showed a significant inhibition of the gram positive bacterial species (E. coli and S. marcescens > 68%) and a reduced inhibition of the gram negative bacterial species (B. subtilis and S. aureus < 45%, p < 0.05) after 24 h of incubation, while water extracts of Buna shimeji showed a significantly lower bacterial growth inhibition (< 60%) against all the studied bacteria. Bunapi shimeji extract inhibited S. marscenscens, E. coli, B. subtilis, and S. aureus by 54, 67, 46, and 44%, respectively. Methanol, acetone and ethyl acetate extracts showed significantly lower antibacterial activities (p < 0.05) compared to water extracts. Similarly, water extracts of Enoki, Bunapi shimeji and Buna shimeji showed significant antioxidant activities using DPPH (67.37 ± 0.01, 66.30 ± 0.18 and 42.44 ± 0.18%, respectively), hydrogen peroxide (67.87 ± 0.000, 45.52 ± 0.160 and 52.08 ± 0.000% respectively), and FRP (0.891 ± 0.001, 0.413 ± 0.001 and 0.491 ± 0.001, respectively) at the concentration of 1 mg/mL, compared to their respective methanol, acetone and ethyl acetate fractions. Upon LC-MS analysis of the most potent fraction (Enoki water extract), several phenolic compounds were identified, of which chromogenic acid, Methyl-5-O-caffeoylquinate, Kukoamine A, Kushenol K, Methyl Kushenol C, Glabrol, Sanggenon J, Corylin, and Moracenin C were confirmed. The antioxidant activities of the water extracts of Enoki, Buna shimeji and Bunapi shimeji correlated with their total phenolic and flavonoid contents, which were (166.56 ± 1.50, 108.13 ± 0.32 and 116.71 ± 0.01 µg gallic acid equivalent (GAE)/mg, respectively) and (96.33 ± 0.03, 82.18 ± 0.20 and 91.37 ± 0.15 µg quercetin equivalent (QE)/mg, respectively). Collectively, the study results have shown the studied mushrooms as potential natural sources of pharmacological agent