Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.
Identifieur interne : 000287 ( Main/Corpus ); précédent : 000286; suivant : 000288Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.
Auteurs : Stephen R. Knight ; Antonia Ho ; Riinu Pius ; Iain Buchan ; Gail Carson ; Thomas M. Drake ; Jake Dunning ; Cameron J. Fairfield ; Carrol Gamble ; Christopher A. Green ; Rishi Gupta ; Sophie Halpin ; Hayley E. Hardwick ; Karl A. Holden ; Peter W. Horby ; Clare Jackson ; Kenneth A. Mclean ; Laura Merson ; Jonathan S. Nguyen-Van-Tam ; Lisa Norman ; Mahdad Noursadeghi ; Piero L. Olliaro ; Mark G. Pritchard ; Clark D. Russell ; Catherine A. Shaw ; Aziz Sheikh ; Tom Solomon ; Cathie Sudlow ; Olivia V. Swann ; Lance Cw Turtle ; Peter Jm Openshaw ; J Kenneth Baillie ; Malcolm G. Semple ; Annemarie B. Docherty ; Ewen M. HarrisonSource :
- BMJ (Clinical research ed.) [ 1756-1833 ] ; 2020.
English descriptors
- KwdEn :
- Aged (MeSH), Aged, 80 and over (MeSH), Betacoronavirus (MeSH), Clinical Protocols (MeSH), Cohort Studies (MeSH), Coronavirus Infections (diagnosis), Coronavirus Infections (mortality), Female (MeSH), Hospital Mortality (MeSH), Hospitalization (MeSH), Humans (MeSH), Male (MeSH), Middle Aged (MeSH), Pandemics (MeSH), Pneumonia, Viral (diagnosis), Pneumonia, Viral (mortality), Predictive Value of Tests (MeSH), ROC Curve (MeSH), Risk Assessment (MeSH), Survival Rate (MeSH), United Kingdom (MeSH).
- MESH :
- geographic : United Kingdom.
- diagnosis : Coronavirus Infections, Pneumonia, Viral.
- mortality : Coronavirus Infections, Pneumonia, Viral.
- Aged, Aged, 80 and over, Betacoronavirus, Clinical Protocols, Cohort Studies, Female, Hospital Mortality, Hospitalization, Humans, Male, Middle Aged, Pandemics, Predictive Value of Tests, ROC Curve, Risk Assessment, Survival Rate.
Abstract
OBJECTIVE
To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).
DESIGN
Prospective observational cohort study.
SETTING
International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020
MAIN OUTCOME MEASURE
In-hospital mortality.
RESULTS
35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).
CONCLUSIONS
An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.
STUDY REGISTRATION
ISRCTN66726260.
DOI: 10.1136/bmj.m3339
PubMed: 32907855
Links to Exploration step
pubmed:32907855Le document en format XML
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Knight</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Ho, Antonia" sort="Ho, Antonia" uniqKey="Ho A" first="Antonia" last="Ho">Antonia Ho</name><affiliation><nlm:affiliation>Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Pius, Riinu" sort="Pius, Riinu" uniqKey="Pius R" first="Riinu" last="Pius">Riinu Pius</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Buchan, Iain" sort="Buchan, Iain" uniqKey="Buchan I" first="Iain" last="Buchan">Iain Buchan</name><affiliation><nlm:affiliation>Institute of Population Health Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Carson, Gail" sort="Carson, Gail" uniqKey="Carson G" first="Gail" last="Carson">Gail Carson</name><affiliation><nlm:affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Drake, Thomas M" sort="Drake, Thomas M" uniqKey="Drake T" first="Thomas M" last="Drake">Thomas M. Drake</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Dunning, Jake" sort="Dunning, Jake" uniqKey="Dunning J" first="Jake" last="Dunning">Jake Dunning</name><affiliation><nlm:affiliation>National Infection Service, Public Health England, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Fairfield, Cameron J" sort="Fairfield, Cameron J" uniqKey="Fairfield C" first="Cameron J" last="Fairfield">Cameron J. Fairfield</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Gamble, Carrol" sort="Gamble, Carrol" uniqKey="Gamble C" first="Carrol" last="Gamble">Carrol Gamble</name><affiliation><nlm:affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Green, Christopher A" sort="Green, Christopher A" uniqKey="Green C" first="Christopher A" last="Green">Christopher A. Green</name><affiliation><nlm:affiliation>Institute of Microbiology & Infection, University of Birmingham, Birmingham, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Gupta, Rishi" sort="Gupta, Rishi" uniqKey="Gupta R" first="Rishi" last="Gupta">Rishi Gupta</name><affiliation><nlm:affiliation>Institute of Global Health, University College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Halpin, Sophie" sort="Halpin, Sophie" uniqKey="Halpin S" first="Sophie" last="Halpin">Sophie Halpin</name><affiliation><nlm:affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hardwick, Hayley E" sort="Hardwick, Hayley E" uniqKey="Hardwick H" first="Hayley E" last="Hardwick">Hayley E. Hardwick</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Holden, Karl A" sort="Holden, Karl A" uniqKey="Holden K" first="Karl A" last="Holden">Karl A. Holden</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Horby, Peter W" sort="Horby, Peter W" uniqKey="Horby P" first="Peter W" last="Horby">Peter W. Horby</name><affiliation><nlm:affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Jackson, Clare" sort="Jackson, Clare" uniqKey="Jackson C" first="Clare" last="Jackson">Clare Jackson</name><affiliation><nlm:affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mclean, Kenneth A" sort="Mclean, Kenneth A" uniqKey="Mclean K" first="Kenneth A" last="Mclean">Kenneth A. Mclean</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Merson, Laura" sort="Merson, Laura" uniqKey="Merson L" first="Laura" last="Merson">Laura Merson</name><affiliation><nlm:affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Nguyen Van Tam, Jonathan S" sort="Nguyen Van Tam, Jonathan S" uniqKey="Nguyen Van Tam J" first="Jonathan S" last="Nguyen-Van-Tam">Jonathan S. Nguyen-Van-Tam</name><affiliation><nlm:affiliation>Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Norman, Lisa" sort="Norman, Lisa" uniqKey="Norman L" first="Lisa" last="Norman">Lisa Norman</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Noursadeghi, Mahdad" sort="Noursadeghi, Mahdad" uniqKey="Noursadeghi M" first="Mahdad" last="Noursadeghi">Mahdad Noursadeghi</name><affiliation><nlm:affiliation>Division of Infection and Immunity, University College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Olliaro, Piero L" sort="Olliaro, Piero L" uniqKey="Olliaro P" first="Piero L" last="Olliaro">Piero L. Olliaro</name><affiliation><nlm:affiliation>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Pritchard, Mark G" sort="Pritchard, Mark G" uniqKey="Pritchard M" first="Mark G" last="Pritchard">Mark G. Pritchard</name><affiliation><nlm:affiliation>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Russell, Clark D" sort="Russell, Clark D" uniqKey="Russell C" first="Clark D" last="Russell">Clark D. Russell</name><affiliation><nlm:affiliation>Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Shaw, Catherine A" sort="Shaw, Catherine A" uniqKey="Shaw C" first="Catherine A" last="Shaw">Catherine A. Shaw</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Sheikh, Aziz" sort="Sheikh, Aziz" uniqKey="Sheikh A" first="Aziz" last="Sheikh">Aziz Sheikh</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Solomon, Tom" sort="Solomon, Tom" uniqKey="Solomon T" first="Tom" last="Solomon">Tom Solomon</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Walton Centre NHS Foundation Trust, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Sudlow, Cathie" sort="Sudlow, Cathie" uniqKey="Sudlow C" first="Cathie" last="Sudlow">Cathie Sudlow</name><affiliation><nlm:affiliation>Health Data Research UK, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Swann, Olivia V" sort="Swann, Olivia V" uniqKey="Swann O" first="Olivia V" last="Swann">Olivia V. Swann</name><affiliation><nlm:affiliation>Department of Child Life and Health, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Turtle, Lance Cw" sort="Turtle, Lance Cw" uniqKey="Turtle L" first="Lance Cw" last="Turtle">Lance Cw Turtle</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Tropical & Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Openshaw, Peter Jm" sort="Openshaw, Peter Jm" uniqKey="Openshaw P" first="Peter Jm" last="Openshaw">Peter Jm Openshaw</name><affiliation><nlm:affiliation>National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Baillie, J Kenneth" sort="Baillie, J Kenneth" uniqKey="Baillie J" first="J Kenneth" last="Baillie">J Kenneth Baillie</name><affiliation><nlm:affiliation>Roslin Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Semple, Malcolm G" sort="Semple, Malcolm G" uniqKey="Semple M" first="Malcolm G" last="Semple">Malcolm G. Semple</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK m.g.semple@liverpool.ac.uk.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Respiratory Medicine, Alder Hey Children's Hospital, Institute in The Park, University of Liverpool, Alder Hey Children's Hospital, Liverpool L12 2AP, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Docherty, Annemarie B" sort="Docherty, Annemarie B" uniqKey="Docherty A" first="Annemarie B" last="Docherty">Annemarie B. Docherty</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Harrison, Ewen M" sort="Harrison, Ewen M" uniqKey="Harrison E" first="Ewen M" last="Harrison">Ewen M. Harrison</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32907855</idno><idno type="pmid">32907855</idno><idno type="doi">10.1136/bmj.m3339</idno><idno type="wicri:Area/Main/Corpus">000287</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000287</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.</title><author><name sortKey="Knight, Stephen R" sort="Knight, Stephen R" uniqKey="Knight S" first="Stephen R" last="Knight">Stephen R. Knight</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Ho, Antonia" sort="Ho, Antonia" uniqKey="Ho A" first="Antonia" last="Ho">Antonia Ho</name><affiliation><nlm:affiliation>Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Pius, Riinu" sort="Pius, Riinu" uniqKey="Pius R" first="Riinu" last="Pius">Riinu Pius</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Buchan, Iain" sort="Buchan, Iain" uniqKey="Buchan I" first="Iain" last="Buchan">Iain Buchan</name><affiliation><nlm:affiliation>Institute of Population Health Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Carson, Gail" sort="Carson, Gail" uniqKey="Carson G" first="Gail" last="Carson">Gail Carson</name><affiliation><nlm:affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Drake, Thomas M" sort="Drake, Thomas M" uniqKey="Drake T" first="Thomas M" last="Drake">Thomas M. Drake</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Dunning, Jake" sort="Dunning, Jake" uniqKey="Dunning J" first="Jake" last="Dunning">Jake Dunning</name><affiliation><nlm:affiliation>National Infection Service, Public Health England, London, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Fairfield, Cameron J" sort="Fairfield, Cameron J" uniqKey="Fairfield C" first="Cameron J" last="Fairfield">Cameron J. Fairfield</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Gamble, Carrol" sort="Gamble, Carrol" uniqKey="Gamble C" first="Carrol" last="Gamble">Carrol Gamble</name><affiliation><nlm:affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Green, Christopher A" sort="Green, Christopher A" uniqKey="Green C" first="Christopher A" last="Green">Christopher A. Green</name><affiliation><nlm:affiliation>Institute of Microbiology & Infection, University of Birmingham, Birmingham, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Gupta, Rishi" sort="Gupta, Rishi" uniqKey="Gupta R" first="Rishi" last="Gupta">Rishi Gupta</name><affiliation><nlm:affiliation>Institute of Global Health, University College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Halpin, Sophie" sort="Halpin, Sophie" uniqKey="Halpin S" first="Sophie" last="Halpin">Sophie Halpin</name><affiliation><nlm:affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hardwick, Hayley E" sort="Hardwick, Hayley E" uniqKey="Hardwick H" first="Hayley E" last="Hardwick">Hayley E. Hardwick</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Holden, Karl A" sort="Holden, Karl A" uniqKey="Holden K" first="Karl A" last="Holden">Karl A. Holden</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Horby, Peter W" sort="Horby, Peter W" uniqKey="Horby P" first="Peter W" last="Horby">Peter W. Horby</name><affiliation><nlm:affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Jackson, Clare" sort="Jackson, Clare" uniqKey="Jackson C" first="Clare" last="Jackson">Clare Jackson</name><affiliation><nlm:affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Mclean, Kenneth A" sort="Mclean, Kenneth A" uniqKey="Mclean K" first="Kenneth A" last="Mclean">Kenneth A. Mclean</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Merson, Laura" sort="Merson, Laura" uniqKey="Merson L" first="Laura" last="Merson">Laura Merson</name><affiliation><nlm:affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Nguyen Van Tam, Jonathan S" sort="Nguyen Van Tam, Jonathan S" uniqKey="Nguyen Van Tam J" first="Jonathan S" last="Nguyen-Van-Tam">Jonathan S. Nguyen-Van-Tam</name><affiliation><nlm:affiliation>Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Norman, Lisa" sort="Norman, Lisa" uniqKey="Norman L" first="Lisa" last="Norman">Lisa Norman</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Noursadeghi, Mahdad" sort="Noursadeghi, Mahdad" uniqKey="Noursadeghi M" first="Mahdad" last="Noursadeghi">Mahdad Noursadeghi</name><affiliation><nlm:affiliation>Division of Infection and Immunity, University College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Olliaro, Piero L" sort="Olliaro, Piero L" uniqKey="Olliaro P" first="Piero L" last="Olliaro">Piero L. Olliaro</name><affiliation><nlm:affiliation>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Pritchard, Mark G" sort="Pritchard, Mark G" uniqKey="Pritchard M" first="Mark G" last="Pritchard">Mark G. Pritchard</name><affiliation><nlm:affiliation>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Russell, Clark D" sort="Russell, Clark D" uniqKey="Russell C" first="Clark D" last="Russell">Clark D. Russell</name><affiliation><nlm:affiliation>Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Shaw, Catherine A" sort="Shaw, Catherine A" uniqKey="Shaw C" first="Catherine A" last="Shaw">Catherine A. Shaw</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Sheikh, Aziz" sort="Sheikh, Aziz" uniqKey="Sheikh A" first="Aziz" last="Sheikh">Aziz Sheikh</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Solomon, Tom" sort="Solomon, Tom" uniqKey="Solomon T" first="Tom" last="Solomon">Tom Solomon</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Walton Centre NHS Foundation Trust, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Sudlow, Cathie" sort="Sudlow, Cathie" uniqKey="Sudlow C" first="Cathie" last="Sudlow">Cathie Sudlow</name><affiliation><nlm:affiliation>Health Data Research UK, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Swann, Olivia V" sort="Swann, Olivia V" uniqKey="Swann O" first="Olivia V" last="Swann">Olivia V. Swann</name><affiliation><nlm:affiliation>Department of Child Life and Health, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Turtle, Lance Cw" sort="Turtle, Lance Cw" uniqKey="Turtle L" first="Lance Cw" last="Turtle">Lance Cw Turtle</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Tropical & Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Openshaw, Peter Jm" sort="Openshaw, Peter Jm" uniqKey="Openshaw P" first="Peter Jm" last="Openshaw">Peter Jm Openshaw</name><affiliation><nlm:affiliation>National Heart and Lung Institute, Imperial College London, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Baillie, J Kenneth" sort="Baillie, J Kenneth" uniqKey="Baillie J" first="J Kenneth" last="Baillie">J Kenneth Baillie</name><affiliation><nlm:affiliation>Roslin Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Semple, Malcolm G" sort="Semple, Malcolm G" uniqKey="Semple M" first="Malcolm G" last="Semple">Malcolm G. Semple</name><affiliation><nlm:affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK m.g.semple@liverpool.ac.uk.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Respiratory Medicine, Alder Hey Children's Hospital, Institute in The Park, University of Liverpool, Alder Hey Children's Hospital, Liverpool L12 2AP, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Docherty, Annemarie B" sort="Docherty, Annemarie B" uniqKey="Docherty A" first="Annemarie B" last="Docherty">Annemarie B. Docherty</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Harrison, Ewen M" sort="Harrison, Ewen M" uniqKey="Harrison E" first="Ewen M" last="Harrison">Ewen M. Harrison</name><affiliation><nlm:affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK.</nlm:affiliation></affiliation></author></analytic><series><title level="j">BMJ (Clinical research ed.)</title><idno type="eISSN">1756-1833</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged (MeSH)</term><term>Aged, 80 and over (MeSH)</term><term>Betacoronavirus (MeSH)</term><term>Clinical Protocols (MeSH)</term><term>Cohort Studies (MeSH)</term><term>Coronavirus Infections (diagnosis)</term><term>Coronavirus Infections (mortality)</term><term>Female (MeSH)</term><term>Hospital Mortality (MeSH)</term><term>Hospitalization (MeSH)</term><term>Humans (MeSH)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (diagnosis)</term><term>Pneumonia, Viral (mortality)</term><term>Predictive Value of Tests (MeSH)</term><term>ROC Curve (MeSH)</term><term>Risk Assessment (MeSH)</term><term>Survival Rate (MeSH)</term><term>United Kingdom (MeSH)</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>United Kingdom</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Betacoronavirus</term><term>Clinical Protocols</term><term>Cohort Studies</term><term>Female</term><term>Hospital Mortality</term><term>Hospitalization</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Pandemics</term><term>Predictive Value of Tests</term><term>ROC Curve</term><term>Risk Assessment</term><term>Survival Rate</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>OBJECTIVE</b></p><p>To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).</p></div><div type="abstract" xml:lang="en"><p><b>DESIGN</b></p><p>Prospective observational cohort study.</p></div><div type="abstract" xml:lang="en"><p><b>SETTING</b></p><p>International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020</p></div><div type="abstract" xml:lang="en"><p><b>MAIN OUTCOME MEASURE</b></p><p>In-hospital mortality.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.</p></div><div type="abstract" xml:lang="en"><p><b>STUDY REGISTRATION</b></p><p>ISRCTN66726260.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32907855</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>16</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>16</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1756-1833</ISSN><JournalIssue CitedMedium="Internet"><Volume>370</Volume><PubDate><Year>2020</Year><Month>09</Month><Day>09</Day></PubDate></JournalIssue><Title>BMJ (Clinical research ed.)</Title><ISOAbbreviation>BMJ</ISOAbbreviation></Journal><ArticleTitle>Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score.</ArticleTitle><Pagination><MedlinePgn>m3339</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1136/bmj.m3339</ELocationID><Abstract><AbstractText Label="OBJECTIVE">To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).</AbstractText><AbstractText Label="DESIGN">Prospective observational cohort study.</AbstractText><AbstractText Label="SETTING">International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium-ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020<i>.</i> PARTICIPANTS: Adults (age ≥18 years) admitted to hospital with covid-19 at least four weeks before final data extraction.</AbstractText><AbstractText Label="MAIN OUTCOME MEASURE">In-hospital mortality.</AbstractText><AbstractText Label="RESULTS">35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73).</AbstractText><AbstractText Label="CONCLUSIONS">An easy-to-use risk stratification score has been developed and validated based on commonly available parameters at hospital presentation. The 4C Mortality Score outperformed existing scores, showed utility to directly inform clinical decision making, and can be used to stratify patients admitted to hospital with covid-19 into different management groups. The score should be further validated to determine its applicability in other populations.</AbstractText><AbstractText Label="STUDY REGISTRATION">ISRCTN66726260.</AbstractText><CopyrightInformation>© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Knight</LastName><ForeName>Stephen R</ForeName><Initials>SR</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ho</LastName><ForeName>Antonia</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Medical Research Council, University of Glasgow Centre for Virus Research, Glasgow, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pius</LastName><ForeName>Riinu</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Buchan</LastName><ForeName>Iain</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Institute of Population Health Sciences, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carson</LastName><ForeName>Gail</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Drake</LastName><ForeName>Thomas M</ForeName><Initials>TM</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dunning</LastName><ForeName>Jake</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>National Infection Service, Public Health England, London, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>National Heart and Lung Institute, Imperial College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fairfield</LastName><ForeName>Cameron J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gamble</LastName><ForeName>Carrol</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Green</LastName><ForeName>Christopher A</ForeName><Initials>CA</Initials><AffiliationInfo><Affiliation>Institute of Microbiology & Infection, University of Birmingham, Birmingham, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gupta</LastName><ForeName>Rishi</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institute of Global Health, University College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Halpin</LastName><ForeName>Sophie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hardwick</LastName><ForeName>Hayley E</ForeName><Initials>HE</Initials><AffiliationInfo><Affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holden</LastName><ForeName>Karl A</ForeName><Initials>KA</Initials><AffiliationInfo><Affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Horby</LastName><ForeName>Peter W</ForeName><Initials>PW</Initials><AffiliationInfo><Affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jackson</LastName><ForeName>Clare</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mclean</LastName><ForeName>Kenneth A</ForeName><Initials>KA</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Merson</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>ISARIC Global Support Centre, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nguyen-Van-Tam</LastName><ForeName>Jonathan S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Norman</LastName><ForeName>Lisa</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Noursadeghi</LastName><ForeName>Mahdad</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Infection and Immunity, University College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Olliaro</LastName><ForeName>Piero L</ForeName><Initials>PL</Initials><AffiliationInfo><Affiliation>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pritchard</LastName><ForeName>Mark G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Russell</LastName><ForeName>Clark D</ForeName><Initials>CD</Initials><AffiliationInfo><Affiliation>Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shaw</LastName><ForeName>Catherine A</ForeName><Initials>CA</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sheikh</LastName><ForeName>Aziz</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Solomon</LastName><ForeName>Tom</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Walton Centre NHS Foundation Trust, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sudlow</LastName><ForeName>Cathie</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Health Data Research UK, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Swann</LastName><ForeName>Olivia V</ForeName><Initials>OV</Initials><AffiliationInfo><Affiliation>Department of Child Life and Health, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Turtle</LastName><ForeName>Lance Cw</ForeName><Initials>LC</Initials><AffiliationInfo><Affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Tropical & Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Openshaw</LastName><ForeName>Peter Jm</ForeName><Initials>PJ</Initials><AffiliationInfo><Affiliation>National Heart and Lung Institute, Imperial College London, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baillie</LastName><ForeName>J Kenneth</ForeName><Initials>JK</Initials><AffiliationInfo><Affiliation>Roslin Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Semple</LastName><ForeName>Malcolm G</ForeName><Initials>MG</Initials><Identifier Source="ORCID">0000-0001-9700-0418</Identifier><AffiliationInfo><Affiliation>NIHR Health Protection Research Unit, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK m.g.semple@liverpool.ac.uk.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Respiratory Medicine, Alder Hey Children's Hospital, Institute in The Park, University of Liverpool, Alder Hey Children's Hospital, Liverpool L12 2AP, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Docherty</LastName><ForeName>Annemarie B</ForeName><Initials>AB</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harrison</LastName><ForeName>Ewen M</ForeName><Initials>EM</Initials><AffiliationInfo><Affiliation>Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>ISARIC4C investigators</CollectiveName></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ISRCTN</DataBankName><AccessionNumberList><AccessionNumber>ISRCTN66726260</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><Acronym>WT_</Acronym><Agency>Wellcome Trust</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D064888">Observational Study</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>BMJ</MedlineTA><NlmUniqueID>8900488</NlmUniqueID><ISSNLinking>0959-8138</ISSNLinking></MedlineJournalInfo><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName><SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName></SupplMeshList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="Y">Betacoronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002985" MajorTopicYN="N">Clinical Protocols</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015331" MajorTopicYN="N">Cohort Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000401" MajorTopicYN="Y">mortality</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017052" MajorTopicYN="N">Hospital Mortality</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006760" MajorTopicYN="Y">Hospitalization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000401" MajorTopicYN="Y">mortality</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011237" MajorTopicYN="N">Predictive Value of Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012372" MajorTopicYN="N">ROC Curve</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018570" MajorTopicYN="N">Risk Assessment</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015996" MajorTopicYN="N">Survival Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006113" MajorTopicYN="N" Type="Geographic">United Kingdom</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement>Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the National Institute for Health Research (NIHR), the Medical Research Council (MRC), the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, Public Health England (PHE), Liverpool School of Tropical Medicine, University of Oxford, NIHR HPRU in Respiratory Infections at Imperial College London, Wellcome Trust, Department for International Development, the Bill and Melinda Gates Foundation, Liverpool Experimental Cancer Medicine Centre, NIHR Biomedical Research Centre at Imperial College London, EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE), and NIHR Clinical Research Network for the submitted work; ABD reports grants from Department of Health and Social Care (DHSC), during the conduct of the study, grants from Wellcome Trust, outside the submitted work; CAG reports grants from DHSC National Institute of Health Research (NIHR) UK, during the conduct of the study; PWH reports grants from Wellcome Trust, Department for International Development, Bill and Melinda Gates Foundation, NIHR, during the conduct of the study; JSN-V-T reports grants from DHSC, England, during the conduct of the study, and is seconded to DHSC, England; MN is supported by a Wellcome Trust investigator award and the NIHR University College London Hospitals Biomedical Research Centre (BRC); PJMO reports personal fees from consultancies and from European Respiratory Society, grants from MRC, MRC Global Challenge Research Fund, EU, NIHR BRC, MRC/GSK, Wellcome Trust, NIHR (Health Protection Research Unit (HPRU) in Respiratory Infection), and is NIHR senior investigator outside the submitted work; his role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the Society; JKB reports grants from MRC UK; MGS reports grants from DHSC NIHR UK, grants from MRC UK, grants from HPRU in Emerging and Zoonotic Infections, University of Liverpool, during the conduct of the study, other from Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work; LCWT reports grants from HPRU in Emerging and Zoonotic Infections, University of Liverpool, during the conduct of the study, and grants from Wellcome Trust outside the submitted work; EMH, HEH, JD, RG, RP, LN, KAH, GC, LM, SH, CJ, and CG, all declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.</CoiStatement><InvestigatorList><Investigator ValidYN="Y"><LastName>Baillie</LastName><ForeName>J Kenneth</ForeName><Initials>JK</Initials></Investigator><Investigator ValidYN="Y"><LastName>Semple</LastName><ForeName>Malcolm G</ForeName><Initials>MG</Initials></Investigator><Investigator ValidYN="Y"><LastName>Openshaw</LastName><ForeName>Peter Jm</ForeName><Initials>PJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Carson</LastName><ForeName>Gail</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Alex</LastName><ForeName>Beatrice</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bach</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Barclay</LastName><ForeName>Wendy S</ForeName><Initials>WS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bogaert</LastName><ForeName>Debby</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Chand</LastName><ForeName>Meera</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cooke</LastName><ForeName>Graham S</ForeName><Initials>GS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Docherty</LastName><ForeName>Annemarie B</ForeName><Initials>AB</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dunning</LastName><ForeName>Jake</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>da Silva Filipe</LastName><ForeName>Ana</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fletcher</LastName><ForeName>Tom</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Green</LastName><ForeName>Christopher A</ForeName><Initials>CA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Harrison</LastName><ForeName>Ewen M</ForeName><Initials>EM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hiscox</LastName><ForeName>Julian A</ForeName><Initials>JA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ho</LastName><ForeName>Antonia Ying Wai</ForeName><Initials>AYW</Initials></Investigator><Investigator ValidYN="Y"><LastName>Horby</LastName><ForeName>Peter W</ForeName><Initials>PW</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ijaz</LastName><ForeName>Samreen</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Khoo</LastName><ForeName>Saye</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Klenerman</LastName><ForeName>Paul</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Law</LastName><ForeName>Andrew</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lim</LastName><ForeName>Wei Shen</ForeName><Initials>WS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Mentzer</LastName><ForeName>Alexander J</ForeName><Initials>AJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Merson</LastName><ForeName>Laura</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Meynert</LastName><ForeName>Alison M</ForeName><Initials>AM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Noursadeghi</LastName><ForeName>Mahdad</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Moore</LastName><ForeName>Shona C</ForeName><Initials>SC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Palmarini</LastName><ForeName>Massimo</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Paxton</LastName><ForeName>William A</ForeName><Initials>WA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Pollakis</LastName><ForeName>Georgios</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Price</LastName><ForeName>Nicholas</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Rambaut</LastName><ForeName>Andrew</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Robertson</LastName><ForeName>David L</ForeName><Initials>DL</Initials></Investigator><Investigator ValidYN="Y"><LastName>Russell</LastName><ForeName>Clark D</ForeName><Initials>CD</Initials></Investigator><Investigator ValidYN="Y"><LastName>Sancho-Shimizu</LastName><ForeName>Vanessa</ForeName><Initials>V</Initials></Investigator><Investigator ValidYN="Y"><LastName>Scott</LastName><ForeName>Janet T</ForeName><Initials>JT</Initials></Investigator><Investigator ValidYN="Y"><LastName>Sigfrid</LastName><ForeName>Louise</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Solomon</LastName><ForeName>Tom</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Sriskandan</LastName><ForeName>Shiranee</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Stuart</LastName><ForeName>David</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Summers</LastName><ForeName>Charlotte</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Tedder</LastName><ForeName>Richard S</ForeName><Initials>RS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Thomson</LastName><ForeName>Emma C</ForeName><Initials>EC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Thwaites</LastName><ForeName>Ryan S</ForeName><Initials>RS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Turtle</LastName><ForeName>Lance Cw</ForeName><Initials>LC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Zambon</LastName><ForeName>Maria</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hardwick</LastName><ForeName>Hayley</ForeName><Initials>H</Initials></Investigator><Investigator ValidYN="Y"><LastName>Donohue</LastName><ForeName>Chloe</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ewins</LastName><ForeName>Jane</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Oosthuyzen</LastName><ForeName>Wilna</ForeName><Initials>W</Initials></Investigator><Investigator ValidYN="Y"><LastName>Griffiths</LastName><ForeName>Fiona</ForeName><Initials>F</Initials></Investigator><Investigator ValidYN="Y"><LastName>Norman</LastName><ForeName>Lisa</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Pius</LastName><ForeName>Riinu</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Drake</LastName><ForeName>Tom M</ForeName><Initials>TM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fairfield</LastName><ForeName>Cameron J</ForeName><Initials>CJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Knight</LastName><ForeName>Stephen</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Mclean</LastName><ForeName>Kenneth A</ForeName><Initials>KA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Murphy</LastName><ForeName>Derek</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Shaw</LastName><ForeName>Catherine A</ForeName><Initials>CA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dalton</LastName><ForeName>Jo</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Girvan</LastName><ForeName>Michelle</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Saviciute</LastName><ForeName>Egle</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Roberts</LastName><ForeName>Stephanie</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Harrison</LastName><ForeName>Janet</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Marsh</LastName><ForeName>Laura</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Connor</LastName><ForeName>Marie</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Halpin</LastName><ForeName>Sophie</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jackson</LastName><ForeName>Clare</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Gamble</LastName><ForeName>Carrol</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Leeming</LastName><ForeName>Gary</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Law</LastName><ForeName>Andrew</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hendry</LastName><ForeName>Ross</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Scott-Brown</LastName><ForeName>James</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Greenhalf</LastName><ForeName>William</ForeName><Initials>W</Initials></Investigator><Investigator ValidYN="Y"><LastName>Shaw</LastName><ForeName>Victoria</ForeName><Initials>V</Initials></Investigator><Investigator ValidYN="Y"><LastName>McDonald</LastName><ForeName>Sarah</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ahmed</LastName><ForeName>Katie A</ForeName><Initials>KA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Armstrong</LastName><ForeName>Jane A</ForeName><Initials>JA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ashworth</LastName><ForeName>Milton</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Asiimwe</LastName><ForeName>Innocent G</ForeName><Initials>IG</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bakshi</LastName><ForeName>Siddharth</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Barlow</LastName><ForeName>Samantha L</ForeName><Initials>SL</Initials></Investigator><Investigator ValidYN="Y"><LastName>Booth</LastName><ForeName>Laura</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Brennan</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bullock</LastName><ForeName>Katie</ForeName><Initials>K</Initials></Investigator><Investigator ValidYN="Y"><LastName>Catterall</LastName><ForeName>Benjamin Wa</ForeName><Initials>BW</Initials></Investigator><Investigator ValidYN="Y"><LastName>Clark</LastName><ForeName>Jordan J</ForeName><Initials>JJ</Initials></Investigator><Investigator ValidYN="Y"><LastName>Clarke</LastName><ForeName>Emily A</ForeName><Initials>EA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cole</LastName><ForeName>Sarah</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cooper</LastName><ForeName>Louise</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cox</LastName><ForeName>Helen</ForeName><Initials>H</Initials></Investigator><Investigator ValidYN="Y"><LastName>Davis</LastName><ForeName>Christopher</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dincarslan</LastName><ForeName>Oslem</ForeName><Initials>O</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dunn</LastName><ForeName>Chris</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dyer</LastName><ForeName>Philip</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Elliott</LastName><ForeName>Angela</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Evans</LastName><ForeName>Anthony</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fisher</LastName><ForeName>Lewis Ws</ForeName><Initials>LW</Initials></Investigator><Investigator ValidYN="Y"><LastName>Foster</LastName><ForeName>Terry</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Garcia-Dorival</LastName><ForeName>Isabel</ForeName><Initials>I</Initials></Investigator><Investigator ValidYN="Y"><LastName>Greenhalf</LastName><ForeName>Willliam</ForeName><Initials>W</Initials></Investigator><Investigator ValidYN="Y"><LastName>Gunning</LastName><ForeName>Philip</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hartley</LastName><ForeName>Catherine</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ho</LastName><ForeName>Antonia</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jensen</LastName><ForeName>Rebecca L</ForeName><Initials>RL</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jones</LastName><ForeName>Christopher B</ForeName><Initials>CB</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jones</LastName><ForeName>Trevor R</ForeName><Initials>TR</Initials></Investigator><Investigator ValidYN="Y"><LastName>Khandaker</LastName><ForeName>Shadia</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>King</LastName><ForeName>Katharine</ForeName><Initials>K</Initials></Investigator><Investigator ValidYN="Y"><LastName>Kiy</LastName><ForeName>Robyn T</ForeName><Initials>RT</Initials></Investigator><Investigator ValidYN="Y"><LastName>Koukorava</LastName><ForeName>Chrysa</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lake</LastName><ForeName>Annette</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lant</LastName><ForeName>Suzannah</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Latawiec</LastName><ForeName>Diane</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lavelle-Langham</LastName><ForeName>L</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lefteri</LastName><ForeName>Daniella</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Lett</LastName><ForeName>Lauren</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Livoti</LastName><ForeName>Lucia A</ForeName><Initials>LA</Initials></Investigator><Investigator ValidYN="Y"><LastName>Mancini</LastName><ForeName>Maria</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>McDonald</LastName><ForeName>Sarah</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>McEvoy</LastName><ForeName>Laurence</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>McLauchlan</LastName><ForeName>John</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Metelmann</LastName><ForeName>Soeren</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Miah</LastName><ForeName>Nahida S</ForeName><Initials>NS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Middleton</LastName><ForeName>Joanna</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Mitchell</LastName><ForeName>Joyce</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Moore</LastName><ForeName>Shona C</ForeName><Initials>SC</Initials></Investigator><Investigator ValidYN="Y"><LastName>Murphy</LastName><ForeName>Ellen G</ForeName><Initials>EG</Initials></Investigator><Investigator ValidYN="Y"><LastName>Penrice-Randal</LastName><ForeName>Rebekah</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Pilgrim</LastName><ForeName>Jack</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Prince</LastName><ForeName>Tessa</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Reynolds</LastName><ForeName>Will</ForeName><Initials>W</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ridley</LastName><ForeName>P Matthew</ForeName><Initials>PM</Initials></Investigator><Investigator ValidYN="Y"><LastName>Sales</LastName><ForeName>Debby</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Shaw</LastName><ForeName>Victoria E</ForeName><Initials>VE</Initials></Investigator><Investigator ValidYN="Y"><LastName>Shears</LastName><ForeName>Rebecca K</ForeName><Initials>RK</Initials></Investigator><Investigator ValidYN="Y"><LastName>Small</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Subramaniam</LastName><ForeName>Krishanthi S</ForeName><Initials>KS</Initials></Investigator><Investigator ValidYN="Y"><LastName>Szemiel</LastName><ForeName>Agnieska</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Taggart</LastName><ForeName>Aislynn</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Tanianis-Hughes</LastName><ForeName>Jolanta</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Thomas</LastName><ForeName>Jordan</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Trochu</LastName><ForeName>Erwan</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>van Tonder</LastName><ForeName>Libby</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Wilcock</LastName><ForeName>Eve</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Zhang</LastName><ForeName>J Eunice</ForeName><Initials>JE</Initials></Investigator><Investigator ValidYN="Y"><LastName>Adeniji</LastName><ForeName>Kayode</ForeName><Initials>K</Initials></Investigator><Investigator ValidYN="Y"><LastName>Agranoff</LastName><ForeName>Daniel</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Agwuh</LastName><ForeName>Ken</ForeName><Initials>K</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ail</LastName><ForeName>Dhiraj</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Alegria</LastName><ForeName>Ana</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Angus</LastName><ForeName>Brian</ForeName><Initials>B</Initials></Investigator><Investigator ValidYN="Y"><LastName>Ashish</LastName><ForeName>Abdul</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Atkinson</LastName><ForeName>Dougal</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bari</LastName><ForeName>Shahedal</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Barlow</LastName><ForeName>Gavin</ForeName><Initials>G</Initials></Investigator><Investigator ValidYN="Y"><LastName>Barnass</LastName><ForeName>Stella</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Barrett</LastName><ForeName>Nicholas</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bassford</LastName><ForeName>Christopher</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Baxter</LastName><ForeName>David</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Beadsworth</LastName><ForeName>Michael</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bernatoniene</LastName><ForeName>Jolanta</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Berridge</LastName><ForeName>John</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Best</LastName><ForeName>Nicola</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bothma</LastName><ForeName>Pieter</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Brealey</LastName><ForeName>David</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Brittain-Long</LastName><ForeName>Robin</ForeName><Initials>R</Initials></Investigator><Investigator ValidYN="Y"><LastName>Bulteel</LastName><ForeName>Naomi</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Burden</LastName><ForeName>Tom</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Burtenshaw</LastName><ForeName>Andrew</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Caruth</LastName><ForeName>Vikki</ForeName><Initials>V</Initials></Investigator><Investigator ValidYN="Y"><LastName>Chadwick</LastName><ForeName>David</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Chambler</LastName><ForeName>Duncan</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Chee</LastName><ForeName>Nigel</ForeName><Initials>N</Initials></Investigator><Investigator ValidYN="Y"><LastName>Child</LastName><ForeName>Jenny</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Chukkambotla</LastName><ForeName>Srikanth</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Clark</LastName><ForeName>Tom</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Collini</LastName><ForeName>Paul</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cosgrove</LastName><ForeName>Catherine</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cupitt</LastName><ForeName>Jason</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Cutino-Moguel</LastName><ForeName>Maria-Teresa</ForeName><Initials>MT</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dark</LastName><ForeName>Paul</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dawson</LastName><ForeName>Chris</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dervisevic</LastName><ForeName>Samir</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Donnison</LastName><ForeName>Phil</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Douthwaite</LastName><ForeName>Sam</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>DuRand</LastName><ForeName>Ingrid</ForeName><Initials>I</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dushianthan</LastName><ForeName>Ahilanadan</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Dyer</LastName><ForeName>Tristan</ForeName><Initials>T</Initials></Investigator><Investigator ValidYN="Y"><LastName>Evans</LastName><ForeName>Cariad</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Eziefula</LastName><ForeName>Chi</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fegan</LastName><ForeName>Chrisopher</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Finn</LastName><ForeName>Adam</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Fullerton</LastName><ForeName>Duncan</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Garg</LastName><ForeName>Sanjeev</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Garg</LastName><ForeName>Sanjeev</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Garg</LastName><ForeName>Atul</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Godden</LastName><ForeName>Jo</ForeName><Initials>J</Initials></Investigator><Investigator ValidYN="Y"><LastName>Goldsmith</LastName><ForeName>Arthur</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Graham</LastName><ForeName>Clive</ForeName><Initials>C</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hardy</LastName><ForeName>Elaine</ForeName><Initials>E</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hartshorn</LastName><ForeName>Stuart</ForeName><Initials>S</Initials></Investigator><Investigator ValidYN="Y"><LastName>Harvey</LastName><ForeName>Daniel</ForeName><Initials>D</Initials></Investigator><Investigator ValidYN="Y"><LastName>Havalda</LastName><ForeName>Peter</ForeName><Initials>P</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hawcutt</LastName><ForeName>Daniel B</ForeName><Initials>DB</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hobrok</LastName><ForeName>Maria</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hodgson</LastName><ForeName>Luke</ForeName><Initials>L</Initials></Investigator><Investigator ValidYN="Y"><LastName>Holme</LastName><ForeName>Anita</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Hormis</LastName><ForeName>Anil</ForeName><Initials>A</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jacobs</LastName><ForeName>Michael</ForeName><Initials>M</Initials></Investigator><Investigator ValidYN="Y"><LastName>Jain</LastName><ForeName>Susan</ForeName><Initials>S</Initials></Investigator><Investigator 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