Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19
Authors: Xie Jianfeng , Hungerford Daniel , Chen Hui , Abrams Simon T , Li Shusheng , Wang Guozheng , Wang Yishan , Kang Hanyujie , Bonnett Laura , Zheng Ruiqiang , Li Xuyan , Tong Zhaohui , Du Bin , Qiu Haibo , Toh Cheng-Hock 
Published: March 2020

Background

COVID-19 pandemic has developed rapidly and the ability to stratify the most vulnerable patients is vital. However, routinely used severity scoring systems are often low on diagnosis, even in non-survivors. Therefore, clinical prediction models for mortality are urgently required.

Methods

We developed and internally validated a multivariable logistic regression model to predict inpatient mortality in COVID-19 positive patients using data collected retrospectively from Tongji Hospital, Wuhan (299 patients). External validation was conducted using a retrospective cohort from Jinyintan Hospital, Wuhan (145 patients). Nine variables commonly measured in these acute settings were considered for model development, including age, biomarkers and comorbidities. Backwards stepwise selection and bootstrap resampling were used for model development and internal validation. We assessed discrimination via the C statistic, and calibration using calibration-in-the-large, calibration slopes and plots.

Findings

The final model included age, lymphocyte count, lactate dehydrogenase and SpO2as independent predictors of mortality. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Internal calibration was excellent (calibration slope=1). External validation showed some over-prediction of risk in low-risk individuals and under-prediction of risk in high-risk individuals prior to recalibration. Recalibration of the intercept and slope led to excellent performance of the model in independent data.

Interpretation

COVID-19 is a new disease and behaves differently from common critical illnesses. This study provides a new prediction model to identify patients with lethal COVID-19. Its practical reliance on commonly available parameters should improve usage of limited healthcare resources and patient survival rate.

Funding

This study was supported by following funding: Key Research and Development Plan of Jiangsu Province (BE2018743 and BE2019749), National Institute for Health Research (NIHR) (PDF-2018-11-ST2-006), British Heart Foundation (BHF) (PG/16/65/32313) and Liverpool University Hospitals NHS Foundation Trust in UK.

Research in context

Evidence before this study

Since the outbreak of COVID-19, there has been a pressing need for development of a prognostic tool that is easy for clinicians to use. Recently, a Lancet publication showed that in a cohort of 191 patients with COVID-19, age, SOFA score and D-dimer measurements were associated with mortality. No other publication involving prognostic factors or models has been identified to date.

Added value of this study

In our cohorts of 444 patients from two hospitals, SOFA scores were low in the majority of patients on admission. The relevance of D-dimer could not be verified, as it is not included in routine laboratory tests. In this study, we have established a multivariable clinical prediction model using a development cohort of 299 patients from one hospital. After backwards selection, four variables, including age, lymphocyte count, lactate dehydrogenase and SpO2remained in the model to predict mortality. This has been validated internally and externally with a cohort of 145 patients from a different hospital. Discrimination of the model was excellent in both internal (c=0·89) and external (c=0·98) validation. Calibration plots showed excellent agreement between predicted and observed probabilities of mortality after recalibration of the model to account for underlying differences in the risk profile of the datasets. This demonstrated that the model is able to make reliable predictions in patients from different hospitals. In addition, these variables agree with pathological mechanisms and the model is easy to use in all types of clinical settings.

Implication of all the available evidence

After further external validation in different countries the model will enable better risk stratification and more targeted management of patients with COVID-19. With the nomogram, this model that is based on readily available parameters can help clinicians to stratify COVID-19 patients on diagnosis to use limited healthcare resources effectively and improve patient outcome.