Systematic review and critical appraisal of prediction models for diagnosis and prognosis of COVID-19 infection
Authors: Wynants Laure , Van Calster Ben , Bonten Marc MJ , Collins Gary S , Debray Thomas PA , De Vos Maarten , Haller Maria C. , Heinze Georg , Moons Karel GM , Riley Richard D , Schuit Ewoud , Smits Luc JM , Snell Kym IE , Steyerberg Ewout W , Wallisch Christine , van Smeden Maarten 
Published: March 2020

AbstractObjectiveTo review and critically appraise published and preprint reports of models that aim to predict either (i) presence of existing COVID-19 infection, (ii) future complications in individuals already diagnosed with COVID-19, or (iii) models to identify individuals at high risk for COVID-19 in the general population.DesignRapid systematic review and critical appraisal of prediction models for diagnosis or prognosis of COVID-19 infection.Data sourcesPubMed, EMBASE via Ovid, Arxiv, medRxiv and bioRxiv until 24thMarch 2020.Study selectionStudies that developed or validated a multivariable COVID-19 related prediction model. Two authors independently screened titles, abstracts and full text.Data extractionData from included studies were extracted independently by at least two authors based on the CHARMS checklist, and risk of bias was assessed using PROBAST. Data were extracted on various domains including the participants, predictors, outcomes, data analysis, and prediction model performance.Results2696 titles were screened. Of these, 27 studies describing 31 prediction models were included for data extraction and critical appraisal. We identified three models to predict hospital admission from pneumonia and other events (as a proxy for covid-19 pneumonia) in the general population; 18 diagnostic models to detect COVID-19 infection in symptomatic individuals (13 of which were machine learning utilising computed tomography (CT) results); and ten prognostic models for predicting mortality risk, progression to a severe state, or length of hospital stay. Only one of these studies used data on COVID-19 cases outside of China. Most reported predictors of presence of COVID-19 in suspected patients included age, body temperature, and signs and symptoms. Most reported predictors of severe prognosis in infected patients included age, sex, features derived from CT, C-reactive protein, lactic dehydrogenase, and lymphocyte count.Estimated C-index estimates for the prediction models ranged from 0.73 to 0.81 in those for the general population (reported for all 3 general population models), from 0.81 to > 0.99 in those for diagnosis (reported for 13 of the 18 diagnostic models), and from 0.85 to 0.98 in those for prognosis (reported for 6 of the 10 prognostic models). All studies were rated at high 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, and poor statistical analysis, including high risk of model overfitting. Reporting quality varied substantially between studies. A description of the study population and intended use of the models was absent in almost all reports, and calibration of predictions was rarely assessed.ConclusionCOVID-19 related prediction models are quickly entering the academic literature, to support medical decision making at a time where this is urgently needed. Our review indicates proposed models are poorly reported and at high risk of bias. Thus, their reported performance is likely optimistic and using them to support medical decision making is not advised. We call for immediate sharing of the individual participant data from COVID-19 studies to support collaborative efforts in building more rigorously developed prediction models and validating (evaluating) existing models. The aforementioned predictors identified in multiple included studies could be considered as candidate predictors for new models. We also stress the need to follow methodological guidance when developing and validating prediction models, as unreliable predictions may cause more harm than benefit when used to guide clinical decisions. Finally, studies should adhere to the TRIPOD statement to facilitate validating, appraising, advocating and clinically using the reported models.Systematic review registration protocolosf.io/ehc47/,registration: osf.io/wy245Summary boxesWhat is already known on this topic-The sharp recent increase in COVID-19 infections has put a strain on healthcare systems worldwide, necessitating efficient early detection, diagnosis of patients suspected of the infection and prognostication of COVID-19 confirmed cases.-Viral nucleic acid testing and chest CT are standard methods for diagnosing COVID-19, but are time-consuming.-Earlier reports suggest that the elderly, patients with comorbidity (COPD, cardiovascular disease, hypertension), and patients presenting with dyspnoea are vulnerable to more severe morbidity and mortality after COVID-19 infection.What this study adds-We identified three models to predict hospital admission from pneumonia and other events (as a proxy for COVID-19 pneumonia) in the general population.-We identified 18 diagnostic models for COVID-19 detection in symptomatic patients.-13 of these were machine learning models based on CT images.-We identified ten prognostic models for COVID-19 infected patients, of which six aimed to predict mortality risk in confirmed or suspected COVID-19 patients, two aimed to predict progression to a severe or critical state, and two aimed to predict a hospital stay of more than 10 days from admission.-Included studies were poorly reported compromising their subsequent appraisal, and recommendation for use in daily practice. All studies were appraised at high risk of bias, raising concern that the models may be flawed and perform poorly when applied in practice, such that their predictions may be unreliable.