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Clinical MedicineIn-Press PreviewInfectious diseasePulmonology Open Access | 10.1172/JCI170682

Machine learning links unresolving secondary pneumonia to mortality in patients with severe pneumonia, including COVID-19

Catherine A. Gao,1 Nikolay S. Markov,1 Thomas Stoeger,2 Anna E. Pawlowski,3 Mengjia Kang,1 Prasanth Nannapaneni,3 Rogan A. Grant,1 Chiagozie Pickens,1 James M. Walter,1 Jacqueline M. Kruser,4 Luke V. Rasmussen,5 Daniel Schneider,3 Justin Starren,5 Helen K. Donnelly,1 Alvaro Donayre,1 Yuan Luo,5 G.R. Scott Budinger,1 Richard G. Wunderink,1 Alexander V. Misharin,1 and Benjamin D. Singer1

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Gao, C. in: JCI | PubMed | Google Scholar |

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Kang, M. in: JCI | PubMed | Google Scholar |

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Starren, J. in: JCI | PubMed | Google Scholar |

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

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1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Luo, Y. in: JCI | PubMed | Google Scholar |

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Budinger, G. in: JCI | PubMed | Google Scholar |

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Wunderink, R. in: JCI | PubMed | Google Scholar

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Misharin, A. in: JCI | PubMed | Google Scholar |

1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America

2Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, United States of America

3Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, United States of America

4Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, United States of America

5Division of Health and Biomedical Informatics, Department of Preventive Med, Northwestern University Feinberg School of Medicine, Chicago, United States of America

Find articles by Singer, B. in: JCI | PubMed | Google Scholar |

Published April 27, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI170682.
Copyright © 2023, Gao et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 27, 2023 - Version history
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Abstract

BACKGROUND. Despite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear.  We aimed to determine the contribution of unsuccessful treatment of VAP to mortality in patients with severe pneumonia.

METHODS. We performed a single-center prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least one bronchoalveolar lavage. A panel of ICU physicians adjudicated pneumonia episodes and endpoints based on clinical and microbiologic data. Given the relatively long ICU length of stay among patients with COVID-19, we developed a machine learning approach called CarpeDiem, which groups similar ICU patient-days into clinical states based on electronic health record data.

RESULTS.CarpeDiem revealed that the long ICU length of stay among patients with COVID-19 is attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, mortality was higher in patients with one episode of unsuccessfully treated VAP compared with successfully treated VAP (76.4% versus 17.6%, P < 0.001). In all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with transitions to clinical states associated with higher mortality.

CONCLUSIONS. Unsuccessful treatment of VAP is associated with greater mortality. The relatively long length of stay among patients with COVID-19 is primarily due to prolonged respiratory failure, placing them at higher risk of VAP.

FUNDING. U19AI135964

Graphical Abstract
graphical abstract
Supplemental material

View Supplemental File 1. Standardized score sheet used by physician reviewers to adjudicate pneumonia episodes.

View Supplemental File 2. The NU SCRIPT Study Investigators.

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Version history
  • Version 1 (April 27, 2023): In-Press Preview
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