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

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

Abstract

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 Cstatistic 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.

Citation

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. A., Merson, L., Nguyen-Van-Tam, J. S., Norman, L., …Harrison, E. M. (2022). Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. Thorax, 77(6), 606-615. https://doi.org/10.1136/thoraxjnl-2021-217629

• Journal Article Type: Article
• Acceptance Date: Oct 11, 2021
• Online Publication Date: Nov 22, 2021
• Publication Date: 2022-06
• Deposit Date: Nov 1, 2021
• Publicly Available Date: Nov 22, 2021
• Journal: Thorax
• Print ISSN: 0040-6376
• Electronic ISSN: 1468-3296
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 77
• Issue: 6
• Pages: 606-615
• DOI: https://doi.org/10.1136/thoraxjnl-2021-217629
• Keywords: Covid-19; deterioration; mortality; prognostic score; revalidation
• Public URL: https://nottingham-repository.worktribe.com/output/6606197
• Publisher URL: https://thorax.bmj.com/content/early/2021/11/21/thoraxjnl-2021-217629