Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal

Laure Wynants* (Corresponding Author), Ben Van Calster, Gary S Collins, Richard D Riley, Georg Heinze, Ewoud Schuit, Marc M J Bonten, Darren L Dahly, Johanna A Damen, Thomas P A Debray, Valentijn M T de Jong, Maarten De Vos, Paula Dhiman, Maria C Haller, Michael O Harhay, Liesbet Henckaerts, Pauline Heus, Michael Kammer, Nina Kreuzberger, Anna LohmannKim Luijken, Jie Ma, Glen P Martin, David J McLernon, Constanza L Andaur Navarro, Johannes B Reitsma, Jamie C Sergeant, Chunhu Shi, Nicole Skoetz, Luc J M Smits, Kym I E Snell, Matthew Sperrin, René Spijker, Ewout W Steyerberg, Toshihiko Takada, Ioanna Tzoulaki, Sander M J van Kuijk, Bas C T van Bussel, Iwan C C van der Horst, Florien S van Royen, Jan Y Verbakel, Christine Wallisch, Jack Wilkinson, Robert Wolff, Lotty Hooft, Karel G M Moons, Maarten van Smeden

*Corresponding author for this work

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Abstract

Objective
To review and appraise the validity and usefulness of published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at increased risk of covid-19 infection or being admitted to hospital with the disease.
Design
Living systematic review and critical appraisal by the COVID-PRECISE (Precise Risk Estimation to optimise covid-19 Care for Infected or Suspected patients in diverse sEttings) group. Data sources PubMed and Embase through Ovid, up to 1 July 2020, supplemented with arXiv, medRxiv, and bioRxiv up to 5 May 2020.Study selection Studies that developed or validated a multivariable covid-19 related prediction model.
Data extraction
At least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool).Results 37 421 titles were screened, and 169 studies describing 232 prediction models were included. The review identified seven models for identifying people at risk in the general population; 118 diagnostic models for detecting covid-19 (75 were based on medical imaging, 10 to diagnose disease severity); and 107 prognostic models for predicting mortality risk, progression to severe disease, intensive care unit admission, ventilation, intubation, or length of hospital stay. The most frequent types of predictors included in the covid-19 prediction models are vital signs, age, comorbidities, and image features. Flu-like symptoms are frequently predictive in diagnostic models, while sex, C reactive protein, and lymphocyte counts are frequent prognostic factors. Reported C index estimates from the strongest form of validation available per model ranged from 0.71 to 0.99 in prediction models for the general population, from 0.65 to more than 0.99 in diagnostic models, and from 0.54 to 0.99 in prognostic models. All models were rated at high or unclear risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, high risk of model overfitting, and unclear reporting. Many models did not include a description of the target population (n=27, 12%) or care setting (n=75, 32%), and only 11 (5%) were externally validated by a calibration plot. The Jehi diagnostic model and the 4C mortality score were identified as promising models.
Conclusion Prediction models for covid-19 are quickly entering the academic literature to support medical decision making at a time when they are urgently needed. This review indicates that almost all published prediction models are poorly reported, and at high risk of bias such that their reported predictive performance is probably optimistic. However, we have identified two (one diagnostic and one prognostic) promising models that should soon be validated in multiple cohorts, preferably through collaborative efforts and data sharing to also allow an investigation of the stability and heterogeneity in their performance across populations and settings. Details on all reviewed models are publicly available at https://www.covprecise.org/. Methodological guidance as provided in this paper should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, prediction model authors should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline.
Original languageEnglish
Article numberm1328
Number of pages16
JournalBMJ
Volume369
DOIs
Publication statusPublished - 7 Apr 2020

Bibliographical note

Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 3 of the original article published on 7 April 2020 (BMJ 2020;369:m1328). Previous updates can be found as data supplements (https://www.bmj.com/content/369/bmj.m1328/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.
Funding: LW, BVC, LH, and MDV acknowledge specific funding for this work from Internal Funds KU Leuven, KOOR, and the COVID-19 Fund. LW is a postdoctoral fellow of Research Foundation-Flanders (FWO) and receives support from ZonMw (grant 10430012010001). BVC received support from FWO (grant G0B4716N) and Internal Funds KU Leuven (grant C24/15/037). TPAD acknowledges financial support from the Netherlands Organisation for Health Research and Development (grant 91617050). VMTdJ was supported by the European Union Horizon 2020 Research and Innovation Programme under ReCoDID
grant agreement 825746. KGMM and JAAD acknowledge financial support from Cochrane Collaboration (SMF 2018). KIES is funded by the National Institute for Health Research (NIHR) School for Primary Care Research. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. GSC was supported by the NIHR Biomedical Research Centre, Oxford, and Cancer Research UK (programme grant C49297/A27294). JM was supported by the Cancer Research UK (programme grant C49297/A27294). PD was supported by the NIHR Biomedical Research Centre, Oxford. MOH is supported by the National Heart, Lung, and Blood Institute of the United States National Institutes of Health (grant R00 HL141678). ICCvDH and BCTvB received funding from Euregio Meuse-Rhine (grant Covid Data Platform (coDaP) interref EMR187). The funders played no role in study design, data collection, data analysis, data interpretation, or reporting.

Keywords

  • COVID-19
  • Coronavirus
  • Coronavirus Infections/diagnosis
  • Disease Progression
  • Hospitalization/statistics & numerical data
  • Humans
  • Models, Theoretical
  • Multivariate Analysis
  • Pandemics
  • Pneumonia, Viral/diagnosis
  • Prognosis
  • RISK
  • EXPLANATION

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