COVID-19 Mortality Prediction From Deep Learning in a Large Multistate Electronic Health Record and Laboratory Information System Data Set: Algorithm Development and Validation
Background: COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests perfor...
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| Published in | Journal of medical Internet research Vol. 23; no. 9; p. e30157 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Toronto
Gunther Eysenbach MD MPH, Associate Professor
28.09.2021
JMIR Publications |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1438-8871 1439-4456 1438-8871 |
| DOI | 10.2196/30157 |
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| Abstract | Background: COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. Objective: Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. Methods: We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient’s first positive COVID-19 nucleic acid test result. Results: The GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106). Conclusions: Our deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19–positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result. |
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| AbstractList | Background: COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. Objective: Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. Methods: We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient’s first positive COVID-19 nucleic acid test result. Results: The GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106). Conclusions: Our deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19–positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result. BackgroundCOVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. ObjectiveHere, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. MethodsWe retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient’s first positive COVID-19 nucleic acid test result. ResultsThe GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106). ConclusionsOur deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19–positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result. COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment.BACKGROUNDCOVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment.Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population.OBJECTIVEHere, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population.We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient's first positive COVID-19 nucleic acid test result.METHODSWe retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient's first positive COVID-19 nucleic acid test result.The GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106).RESULTSThe GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106).Our deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19-positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result.CONCLUSIONSOur deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19-positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result. |
| Author | Klee, Eric W Jenkinson, Garrett Bates, Kathy L Sankaranarayanan, Saranya Minnich, Sara Lesko, Jessica Kreuter, Justin Kipp, Benjamin Block, Darci R Oliver, Gavin R O’Horo, John C Piazza, Amy DiGuardo, Margaret Balan, Jagadheshwar Walsh, Jesse R Wu, Yanhong Khezeli, Kia Osborne, Collin Salama, Mohamed E Kalantari, John Morice, William G |
| AuthorAffiliation | 1 Mayo Clinic Rochester, MN United States |
| AuthorAffiliation_xml | – name: 1 Mayo Clinic Rochester, MN United States |
| Author_xml | – sequence: 1 givenname: Saranya orcidid: 0000-0002-7656-4094 surname: Sankaranarayanan fullname: Sankaranarayanan, Saranya – sequence: 2 givenname: Jagadheshwar orcidid: 0000-0002-8291-4054 surname: Balan fullname: Balan, Jagadheshwar – sequence: 3 givenname: Jesse R orcidid: 0000-0001-6048-1166 surname: Walsh fullname: Walsh, Jesse R – sequence: 4 givenname: Yanhong orcidid: 0000-0001-7930-2201 surname: Wu fullname: Wu, Yanhong – sequence: 5 givenname: Sara orcidid: 0000-0003-2971-0113 surname: Minnich fullname: Minnich, Sara – sequence: 6 givenname: Amy orcidid: 0000-0002-1100-0255 surname: Piazza fullname: Piazza, Amy – sequence: 7 givenname: Collin orcidid: 0000-0001-5165-6729 surname: Osborne fullname: Osborne, Collin – sequence: 8 givenname: Gavin R orcidid: 0000-0002-9948-3799 surname: Oliver fullname: Oliver, Gavin R – sequence: 9 givenname: Jessica orcidid: 0000-0001-5999-989X surname: Lesko fullname: Lesko, Jessica – sequence: 10 givenname: Kathy L orcidid: 0000-0002-8646-2120 surname: Bates fullname: Bates, Kathy L – sequence: 11 givenname: Kia orcidid: 0000-0002-1982-9391 surname: Khezeli fullname: Khezeli, Kia – sequence: 12 givenname: Darci R orcidid: 0000-0002-2130-3372 surname: Block fullname: Block, Darci R – sequence: 13 givenname: Margaret orcidid: 0000-0003-0900-377X surname: DiGuardo fullname: DiGuardo, Margaret – sequence: 14 givenname: Justin orcidid: 0000-0001-7842-8208 surname: Kreuter fullname: Kreuter, Justin – sequence: 15 givenname: John C orcidid: 0000-0002-0880-4498 surname: O’Horo fullname: O’Horo, John C – sequence: 16 givenname: John orcidid: 0000-0003-4229-162X surname: Kalantari fullname: Kalantari, John – sequence: 17 givenname: Eric W orcidid: 0000-0003-2946-5795 surname: Klee fullname: Klee, Eric W – sequence: 18 givenname: Mohamed E orcidid: 0000-0001-6696-0061 surname: Salama fullname: Salama, Mohamed E – sequence: 19 givenname: Benjamin orcidid: 0000-0001-9477-0118 surname: Kipp fullname: Kipp, Benjamin – sequence: 20 givenname: William G orcidid: 0000-0002-5801-2501 surname: Morice fullname: Morice, William G – sequence: 21 givenname: Garrett orcidid: 0000-0003-2548-098X surname: Jenkinson fullname: Jenkinson, Garrett |
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| ContentType | Journal Article |
| Copyright | 2021. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Saranya Sankaranarayanan, Jagadheshwar Balan, Jesse R Walsh, Yanhong Wu, Sara Minnich, Amy Piazza, Collin Osborne, Gavin R Oliver, Jessica Lesko, Kathy L Bates, Kia Khezeli, Darci R Block, Margaret DiGuardo, Justin Kreuter, John C O’Horo, John Kalantari, Eric W Klee, Mohamed E Salama, Benjamin Kipp, William G Morice, Garrett Jenkinson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.09.2021. Saranya Sankaranarayanan, Jagadheshwar Balan, Jesse R Walsh, Yanhong Wu, Sara Minnich, Amy Piazza, Collin Osborne, Gavin R Oliver, Jessica Lesko, Kathy L Bates, Kia Khezeli, Darci R Block, Margaret DiGuardo, Justin Kreuter, John C O’Horo, John Kalantari, Eric W Klee, Mohamed E Salama, Benjamin Kipp, William G Morice, Garrett Jenkinson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.09.2021. 2021 |
| Copyright_xml | – notice: 2021. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Saranya Sankaranarayanan, Jagadheshwar Balan, Jesse R Walsh, Yanhong Wu, Sara Minnich, Amy Piazza, Collin Osborne, Gavin R Oliver, Jessica Lesko, Kathy L Bates, Kia Khezeli, Darci R Block, Margaret DiGuardo, Justin Kreuter, John C O’Horo, John Kalantari, Eric W Klee, Mohamed E Salama, Benjamin Kipp, William G Morice, Garrett Jenkinson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.09.2021. – notice: Saranya Sankaranarayanan, Jagadheshwar Balan, Jesse R Walsh, Yanhong Wu, Sara Minnich, Amy Piazza, Collin Osborne, Gavin R Oliver, Jessica Lesko, Kathy L Bates, Kia Khezeli, Darci R Block, Margaret DiGuardo, Justin Kreuter, John C O’Horo, John Kalantari, Eric W Klee, Mohamed E Salama, Benjamin Kipp, William G Morice, Garrett Jenkinson. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.09.2021. 2021 |
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| Snippet | Background: COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease... COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a... BackgroundCOVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease... |
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| SubjectTerms | Acids Age Algorithms Blood pressure Cognitive style Comorbidity Coronaviruses COVID-19 Data collection Datasets Deep learning Diabetes Electronic health records Fibrinogen Information systems Iron Kidney diseases Laboratories Medical treatment Missing data Mortality Multimedia Neural networks Original Paper Oxygen Pandemics Patients Polymerase chain reaction Recurrent Saturation Serum Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Stratification Time series Variables |
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| Title | COVID-19 Mortality Prediction From Deep Learning in a Large Multistate Electronic Health Record and Laboratory Information System Data Set: Algorithm Development and Validation |
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