Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol

Knight, S. R. et al. (2022) Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. Thorax, 77(6), pp. 606-615. (doi: 10.1136/thoraxjnl-2021-217629) (PMID:34810237) (PMCID:PMC8610617)

[img] Text
257554.pdf - Published Version
Available under License Creative Commons Attribution.



Purpose: To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19. Methods: Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups. Results: 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, –0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions. Conclusion: Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making.

Item Type:Articles
Additional Information:Funding: This work is supported by grants from: the National Institute for Health Research (NIHR) (award CO-CIN-01), the Medical Research Council (grant MC_ PC_19059) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200 907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200 927), Wellcome Trust and Department for International Development (215091/Z/18/Z), and the Bill and Melinda Gates Foundation (OPP1209135), and Liverpool Experimental Cancer Medicine Centre (Grant Reference: C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (IS-BRC-1215-20013), EU Platform foR European Preparedness Against (Re-) emerging Epidemics (PREPARE) (FP7 project 602 525) and NIHR Clinical Research Network for providing infrastructure support for this research. PJO is supported by an NIHR Senior Investigator Award (award 201 385). LT is supported by the Wellcome Trust (award 205228/Z/16/Z). MN is funded by a WT investigator award (207511/Z/17/Z) and the NIHR University College London Hospitals Biomedical Research Centre. Christopher Davis is a member of the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC4C) InvestigatorsConsortium.
Glasgow Author(s) Enlighten ID:Scott, Dr Janet and Davis, Dr Chris and Ho, Dr Antonia
Authors: Knight, S. R., Gupta, R. K., Ho, A., Pius, R., Buchan, I., Carson, G., Drake, T. M., Dunning, J., Fairfield, C. J., Gamble, C., Green, C. A., Halpin, S., Hardwick, H. E., Holden, K. A., Horby, P. W., Jackson, C., Mclean, K., Merson, L., Nguyen-Van-Tam, J. S., Norman, L., Olliaro, P. L., Pritchard, M. G., Russell, C. D., Shaw, C. A., Sheikh, A., Solomon, T., Sudlow, C., Swann, O. V., Turtle, L. C. W., Openshaw, P. J. M., Baillie, J. K., Docherty, A., Semple, M. G., Noursadeghi, M., Harrison, E. M., Scott, J. T., and Davis, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Thorax
Publisher:BMJ Publishing Group
ISSN (Online):1468-3296
Published Online:22 November 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Thorax 77(6): 606-615
Publisher Policy:Reproduced under a Creative Commons licence

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
310665ISARIC - Coronavirus Clinical Characterisation ConsortiumAntonia HoMedical Research Council (MRC)MC_PC_19059 - 9815274III - Centre for Virus Research