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

Stephen Knight, Rishi Gupta, Antonia Ho, Riinu Pius, Iain Buchan, Gail Carson, Thomas Drake, Jake Dunning, Cameron Fairfield, Carrol Gamble, Christopher A. Green, Sophie Halpin, Hayley E Hardwick, Karl A. Holden, Peter Horby, Clare Jackson, Kenneth Mclean, Laura Merson, Jonathan S. Nguyen-Van-Tam, Lisa NormanPiero L Olliaro, Mark G Pritchard, Clark D. Russell, Katie Shaw, Aziz Sheikh, Tom Solomon, Cathie L M Sudlow, Olivia Swann, Lance CW Turtle, Peter Openshaw, J Kenneth Baillie, Annemarie B Docherty, Malcolm G Semple, Mahdad Noursadeghi, Ewen M Harrison

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Purpose To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with coronavirus disease 2019 (covid-19).
Methods Prospective observational cohort study of adults (age ≥18 years) admitted or first assessed for covid-19 in hospital and recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland, and Wales. Patients were recruited between 27th August 2020 and 17th February 2021, with at least four 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 18 211 (25.1%) 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 NHS regions, with similar performance metrics to the original validation cohorts. Calibration remained good and was demonstrated to be stable (4C Mortality: slope 1.09, calibration-in-the-large 0.12; 4C Deterioration: 1.00, -0.04), with no need for temporal recalibration during the second wave of hospital admissions.
Conclusion Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective 2nd 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.
Study registration number ISRCTN66726260
Original languageEnglish
Publication statusPublished - 21 Nov 2021


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