A study protocol of external validation of eight COVID-19 prognostic models for predicting mortality risk in older populations in a hospital, primary care, and nursing home setting
Authors: Zahra Anum , Luijken Kim , Abbink Evertine J. , van den Berg Jesse M. , Blom Marieke T. , Elders Petra , Festen Jan , Gussekloo Jacobijn , Joling Karlijn J. , Melis René , Mooijaart Simon , Peters Jeannette B. , Polinder-Bos Harmke A. , van Raaij Bas F. M. , Smorenberg Annemieke , la Roi-Teeuw Hannah M. , Moons Karel G. M. , van Smeden Maarten ,   on behalf of the COOP Consortium, Achterberg Wilco P. , van de Beek Sifra H. , Beekman Marian , Beenen Ludo F. M. , van den Borst Bram , Bredie Sebastiaan J. H. , van den Bos Frederiek , Dalm Virgil A. S. H. , Drewes Yvonne M. , van den Dries Carline J. , Elders Petra J. M. , Faes Miriam C. , Geersing Geert-Jan , Haaksma Miriam L. , Harris Vanessa C. , Herings Ron M. C. , Hertogh Cees M. P. M. , Hoogerwerf Jacobien J. , Jacobs-Peters Jeannette , Jansen Steffy , G.Julien Anneke , van der Klei Veerle M. G. T. H. , Kuranova Anna , van der Kuy P. Hugo M. , van der Linden Carolien M. J. , van Loon Anouk M. , van de Maat Josephine S. , Raso Francesco U. S. Mattace , Melis René J. F. , Minnema Julia , Mooijaart Simon P. , Mook-Kanamori Dennis O. , Netea Mihai G. , Peeters Geeske , Polinder-Bos Harmke A. , Sablerolles Roos S. G. , Slagboom P. Eline , Smits Rosalinde A. L. , Tap Lisanne , van Tol Lisa S. , Willems Hanna C. 
Published: April 2023

Abstract
Background
The COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥ 70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting.

Methods
Based on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2 + model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch older population (three hospital cohorts, two primary care cohorts, and a nursing home cohort). All prognostic models will be validated in a hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥ 70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated.

Discussion
Insight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older population. Such insight will be important for possible future waves of the COVID-19 pandemic or future pandemics.