ABSTRACT
BackgroundLow-dose corticosteroids have been shown to reduce mortality for hypoxic COVID-19 patients requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation or extra-corporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. MethodsThis 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 (i.e. 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 once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality. On 11 May 2022, the independent Data Monitoring Committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only to this comparison due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support continues. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). FindingsBetween 25 May 2021 and 12 May 2022, 1272 COVID-19 patients with hypoxia and receiving no oxygen (1%) or simple oxygen only (99%) were randomly allocated to receive usual care plus higher dose corticosteroids versus usual care alone (of whom 87% received low dose corticosteroids during the follow-up period). Of those randomised, 745 (59%) were in Asia, 512 (40%) in the UK and 15 (1%) in Africa. 248 (19%) had diabetes mellitus. Overall, 121 (18%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio [RR] 1{middle dot}56; 95% CI 1{middle dot}18-2{middle dot}06; p=0{middle dot}0020). There was also an excess of pneumonia reported to be due to non-COVID infection (10% vs. 6%; absolute difference 3.7%; 95% CI 0.7-6.6) and an increase in hyperglycaemia requiring increased insulin dose (22% vs. 14%; absolute difference 7.4%; 95% CI 3.2-11.5). InterpretationIn patients hospitalised for COVID-19 with clinical hypoxia but requiring either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared to 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 extra-corporeal membrane oxygenation. FundingUK Research and Innovation (Medical Research Council) and National Institute of Health and Care Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).
ABSTRACT
ObjectiveWe aimed to determine the prevalence of the severity of COVID-19 illness and its associated predisposing factors in Nepal. DesignCross-sectional, observational study SettingSingle-centered hospital-based study, conducted at Nepal armed police force (APF) hospital, Kathmandu, Nepal. ParticipantsAll individuals aged [≥]18 years with laboratory-confirmed SARS-Cov-2 (the SARS-CoV-2 specific real-time-RT-PCR result positive), regardless the severity of their disease. MeasurementsDisease severity was evaluated as a primary outcome and age, sex, BMI, smoking history, alcohol history, Hypertension, diabetes mellitus were evaluated as predictors in the analysis. ResultsMean ages of the patients were 40.79{+/-}16.04 years, and about two-thirds of the patients were male 146 (73.7%). More than half 57.1% (95%CI: 52.42-61.51) of the population had a mild infection, whereas 16.7% (95%CI: 7.4-24.6%) had severe/critical illness. In univariate analysis, each 1-year increase in age (OR: 1.05; 95% CI:1.030-1.081; P<0.001), each 1 unit increase in BMI (OR:1.12; 95% CI:1.02-1.25; P=0.033), comorbid illness (OR: 5.79; 95%CI: 2.51-13.33; P<0.001), hypertension (OR:5.95; 95%CI:2.66-13.30: P<0.001), diabetes mellitus (OR:3.26; 95%CI:1.30-8.15: P<0.005), and fever (OR:34.64; 95% CI:7.98-150.38; P<0.001) were independently associated with severity of the disease, whereas age (OR: 1.049; 95% CI: 1.019-1.080; P=0.02), hypertension (OR: 4.77; 95%CI: 1.62-14.04; P=0.004), and fever (OR: 51.02; 95%CI: 9.56-272.51; P<0.001) remained a significant predictive factors in multivariate analysis. ConclusionThe majority of the patients with COVID-19 had a mild illness, with 16.7% severe illness. Age, BMI, hypertension, diabetes mellitus, comorbidity, and temperature were associated the severity of the illness. Age, hypertension, and fever emerged as an independent predictive factors in multivariate analysis, and thus, these vulnerable groups should be given special protection to the infection and proactive intervention should be initiated at an early stage of the infection to diminish the severity of the illness and improve the clinical outcome of the disease. Strengths and limitations of the studyO_LIMuch of the studies on COVID-19 in Nepal focus on the describing epidemiology and clinical profile of the disease, however, risk factors that contribute to the severity of the illness are overlooked. C_LIO_LIThis study may help estimate the burden of the disease and identify the vulnerable group with poor prognosis, which is vital for clinicians and the public health approach to deal with the disease. C_LIO_LIAlthough limiting the study to a single-center with a relatively small sample size, it, however, allows evaluation of the importance of the demographic and geographical variation. C_LIO_LISocio-economic factors, lifestyle, and availability of quality medical care may have contributed to the severity of the COVID-19, which needs to be addressed in a further large-scale study. C_LI
