Publisher Full Text
Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report.N Engl J Med. 2020 Jul 17 [Online ahead of print]NEJM
Abstract
BACKGROUND
Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.
METHODS
In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison.
RESULTS
A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55).
CONCLUSIONS
In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.).
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Authors+Show Affiliations
No affiliation info availableFrom the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.From the Nuffield Department of Medicine (P.H.), Nuffield Department of Population Health (J.R.E., M.M., J.L.B., L.L., N.S., E.J., R.H., M.J.L.), and MRC Population Health Research Unit (J.R.E., N.S., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J.), and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M.), Nottingham, the Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester (C.B.), the Regional Infectious Diseases Unit, North Manchester General Hospital and University of Manchester (A.U.), and the University of Manchester and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (C.G.), the Centre for Clinical Infection, James Cook University Hospital, Middlesbrough (D.C.), the North West Anglia NHS Foundation Trust, Peterborough (K. Rege), the Department of Research and Development, Cardiff and Vale University Health Board, Cardiff (C.F.), the School of Life Course Sciences, King's College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K. Rowan), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.) - all in the United Kingdom.
Pub Type(s)
Journal Article
Language
eng
PubMed ID
32678530
Clinical Trial Links
Citation
RECOVERY Collaborative Group, et al. "Dexamethasone in Hospitalized Patients With Covid-19 - Preliminary Report." The New England Journal of Medicine, 2020.
RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med. 2020.
Horby, P., Lim, W. S., Emberson, J. R., Mafham, M., Bell, J. L., Linsell, L., Staplin, N., Brightling, C., Ustianowski, A., Elmahi, E., Prudon, B., Green, C., Felton, T., Chadwick, D., Rege, K., Fegan, C., Chappell, L. C., Faust, S. N., Jaki, T., ... Landray, M. J. (2020). Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2021436
RECOVERY Collaborative Group, et al. Dexamethasone in Hospitalized Patients With Covid-19 - Preliminary Report. N Engl J Med. 2020 Jul 17; PubMed PMID: 32678530.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR
T1 - Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report.
AU - ,,
AU - Horby,Peter,
AU - Lim,Wei Shen,
AU - Emberson,Jonathan R,
AU - Mafham,Marion,
AU - Bell,Jennifer L,
AU - Linsell,Louise,
AU - Staplin,Natalie,
AU - Brightling,Christopher,
AU - Ustianowski,Andrew,
AU - Elmahi,Einas,
AU - Prudon,Benjamin,
AU - Green,Christopher,
AU - Felton,Timothy,
AU - Chadwick,David,
AU - Rege,Kanchan,
AU - Fegan,Christopher,
AU - Chappell,Lucy C,
AU - Faust,Saul N,
AU - Jaki,Thomas,
AU - Jeffery,Katie,
AU - Montgomery,Alan,
AU - Rowan,Kathryn,
AU - Juszczak,Edmund,
AU - Baillie,J Kenneth,
AU - Haynes,Richard,
AU - Landray,Martin J,
Y1 - 2020/07/17/
PY - 2020/7/18/entrez
PY - 2020/7/18/pubmed
PY - 2020/7/18/medline
JF - The New England journal of medicine
JO - N. Engl. J. Med.
N2 - BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. METHODS: In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. RESULTS: A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). CONCLUSIONS: In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.).
SN - 1533-4406
UR - https://www.unboundmedicine.com/medline/citation/32678530/full_citation
L2 - https://www.nejm.org/doi/10.1056/NEJMoa2021436?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed
DB - PRIME
DP - Unbound Medicine
ER -
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