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

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders

Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study

Background No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing. Findings 2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials. Funding UK Research and Innovation and National Institute for Health Research

Apparent nitrogen corrected and true metabolisable energy of processed thevetia oil for broiler finisher birds

Sixty, finishing broilers aged 35 days were used to determine the Apparent, Nitrogen corrected and True metabolisable energy value of thevetia oil. The oil was subjected to heat treatment of 110°C for 25 minutes. Four experimental diets consisting of a basal diet and three other diets in which thevetia oil was substituted for 2.5, 5.0 and 10.0% of the basal diet. The experiment lasted for 10 days, made up of a 7-day adjustment period and a 3-day total collection period. Protein and fibre retention were significantly (P&lt;0.05) influenced by dietary thevetia oil level Three regression equations were derived for estimating the metabolisable energy value of thevetia oil viz: y = 2990 + 61.9x (AME), y = 3076 + 59.8x (TME) and y = 2848 + 57.2x (AMEn). The Apparent metabolisable energy (AME) of thevetia oil was determined to be 9180kcal/kg and 9056kcal/kg respectively.Keywords: Thevetia oil, metabolisable energy, broiler finisher

Dietary supplementation of probiotics and synbiotics on intestinal microbial populations and gut morphology of turkey poults

The effect of dietary supplementation of probiotics and synbiotics on gut microbial population and histomorphological characteristics was examined in a 56-day experiment using 128 seven-day-old turkey poults fed with antibiotic, probiotic and synbiotic supplemented diets. The experimental design was a Randomised Complete Block Design. Poults were brooded for 7 days, after which they were allotted to 4 dietary treatments with 4 replicates of 8 birds per replicate. Treatment 1 was the basal diet with nosupplements while treatments 2, 3, and 4 were supplemented with  antibiotics, probiotics and synbiotics respectively. On day 56, birds were slaughtered and digesta samples from the ileum were collected formicrobial load count and intestinal pH. After flushing out the digesta samples, sections of the ileum (5cm posterior to Meckel’s diverticulum) were removed for ileal morphological measurements. Probiotic andsynbiotic supplementation significantly (P&lt;0.05) reduced the total coliform and total bacteria counts, meanwhile, lactic acid bacteria were significantly increased in birds on the experimental diets. The intestinal pH was slightly acidic across the treatment groups (6.45 – 6.83). However, the probiotic and synbiotic treatment groups had the lowest pH at 6.53 and 6.45 respectively. Probiotic and synbiotic supplementation significantly (P&lt;0.05) improved the villus height and crypt depth of poults which was comparable to those on antibiotic diet. In summary, dietary inclusion of probiotics and synbiotics improved the overall gut integrity of the turkey poults as well as reduction in the populations of coliform and total bacteria, while the population of lactic acid bacteria was significantly increased.Keywords: Antibiotics, Probiotics, Synbiotics, Turkey poult

Fortification of cassava peel meals in balanced diets for rabbits

An eight-week feeding trial was conducted with twenty-four individually caged growing rabbits weighing initially 300 - 380g. Six experimental diets were formulated such that diet 1 was a maize-soyabean based control while in diets 2, 3, 4, 5 and 6, cassava peel meal totally replaced maize. There was also a stepwise reduction in the quantity of soyabean meal utilised in diets 3, 4 and 5 while the quantity of palm kernel cake was increased. Diet 6 was an extruded version of diet 4. The diets were fortified with palm oil for energy and soyabean and palm kernel cake for protein. Each diet was fed to four replicates of rabbits consisting of one rabbit per replicate and water was supplied ad libitum. Feed intake, weight-gain and feed cost/unit weight-gain were significantly affected by dietary treatments (P&lt;0.05) while treatments had no effect on water intake and Feed: Gain ratio (P&gt;0.05). The feed cost was reduced to N13.8/kg in diet 5 compared with N17.8 in the control diet. The extrusion process was not efficient in all indices of measurement as rabbits on the diet showed poor performance. A major finding of the study is that up to 50% of the protein supplied by soyabean meal when fed in conjunction with cassava peel meal can be replaced with palm kernel cake without adverse effects. It is recommended that future studies look into alternatives to palm oil as energy booster in diets containing cassava peel meal so as to further improve the economy of feed utilization.Keywords: Rabbit performance, cassava peel meal, palm kernel cake, soyabeans, extrusion

Haemophilus influenzae type b still remains a leading cause of meningitis among unvaccinated children - A prospective CSF analysis study

A prospective, hospital-based cerebrospinal fluid (CSF) analysis study was undertaken in 65 children who had diagnostic lumbar puncture on admission for suspected central nervous system infections. Twenty-three children were clinically diagnosed to have had sepsis and/or meningitis. CSF bacterial culture grew Haemophilus influenzae type b (Hib) in four cases and Streptococcus pneumonia (SP) was cultured in another child. Bacterial antigen was detected in 13 other CSF specimens and the pathogens were Hib (n = 9), SP (n = 3) and Group B Streptococcus (n = 1). No etiologic cause was identified to explain the abnormal CSP pleocytosis and biochemistry in the remaining five cases. In contrast, the CSF analysis was normal in 42 other children with probable viral and non-infectious neurological condition, mostly febrile convulsions. The overall frequency rate for all types of meningitis and especially for Hib meningitis were 43 and 31 cases per 100 000 children < 5 years of age, respectively. These findings support our earlier observations that Hib meningitis still remains the leading cause of childhood meningitis in our region. Also it reaffirms the observation that bacterial meningitis may often be under-reported if CSF positive culture alone is considered for the diagnosis