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

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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 for 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 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data.

RESULTS

CarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality.

CONCLUSIONS

Unsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP.

FUNDING

National Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.

Abstract

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Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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Author and article information

Contributors

Catherine A. Gao:

ORCID: http://orcid.org/0000-0001-5576-3943

Nikolay S. Markov:

ORCID: http://orcid.org/0000-0002-3659-4387

Thomas Stoeger:

ORCID: http://orcid.org/0000-0002-5540-4278

Mengjia Kang:

ORCID: http://orcid.org/0000-0002-1679-9473

Prasanth Nannapaneni:

ORCID: http://orcid.org/0000-0001-8080-3214

Rogan A. Grant:

ORCID: http://orcid.org/0000-0003-0655-0882

Chiagozie Pickens

James M. Walter:

ORCID: http://orcid.org/0000-0001-7428-3101

Jacqueline M. Kruser

Daniel Schneider:

ORCID: http://orcid.org/0000-0002-3523-745X

Justin Starren:

ORCID: http://orcid.org/0000-0002-5403-1115

Helen K. Donnelly:

ORCID: http://orcid.org/0000-0001-8827-8581

Alvaro Donayre:

ORCID: http://orcid.org/0000-0003-1877-0655

Yuan Luo:

ORCID: http://orcid.org/0000-0003-0195-7456

G.R. Scott Budinger:

ORCID: http://orcid.org/0000-0002-3114-5208

Richard G. Wunderink

Alexander V. Misharin:

ORCID: http://orcid.org/0000-0003-2879-3789

Benjamin D. Singer:

ORCID: http://orcid.org/0000-0001-5775-8427

Journal

Journal ID (nlm-ta): J Clin Invest

Journal ID (iso-abbrev): J Clin Invest

Journal ID (publisher-id): J Clin Invest

Title: The Journal of Clinical Investigation

Publisher: American Society for Clinical Investigation

ISSN (Print): 0021-9738

ISSN (Electronic): 1558-8238

Publication date (Electronic, pub): 15 June 2023

Publication date (Electronic, collection): 15 June 2023

Publication date PMC-release: 15 June 2023

Volume: 133

Issue: 12

Electronic Location Identifier: e170682

Affiliations

[1 ]Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

[2 ]Department of Chemical and Biological Engineering, Northwestern University, McCormick School of Engineering, Evanston, Illinois, USA.

[3 ]Northwestern Medicine Enterprise Data Warehouse, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

[4 ]Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

[5 ]Division of Health and Biomedical Informatics, Department of Preventive Medicine and

[6 ]Simpson Querrey Lung Institute for Translational Science (SQLIFTS), Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

[7 ]The Northwestern University (NU) Successful Clinical Response In Pneumonia Therapy (SCRIPT) Study Investigators are listed in Supplemental Table 3.

Author notes

Address correspondence to: GR Scott Budinger, Richard G. Wunderink, Alexander V. Misharin, or Benjamin D. Singer, 303 E. Superior Street, Simpson Querrey, 5th Floor, Chicago, Illinois 60611, USA. Email: s-buding@ 123456northwestern.edu (GRSB); Email: r-wunderink@ 123456northwestern.edu (RGW); Email: a-misharin@ 123456northwestern.edu (AVM); Email: benjamin-singer@ 123456northwestern.edu (BDS).

Authorship note: CAG, NSM, and TS are co–first authors. GRSB, RGW, AVM, and BDS are co–senior authors.

Author information

Catherine A. Gao http://orcid.org/0000-0001-5576-3943

Nikolay S. Markov http://orcid.org/0000-0002-3659-4387

Thomas Stoeger http://orcid.org/0000-0002-5540-4278

Mengjia Kang http://orcid.org/0000-0002-1679-9473

Prasanth Nannapaneni http://orcid.org/0000-0001-8080-3214

Rogan A. Grant http://orcid.org/0000-0003-0655-0882

James M. Walter http://orcid.org/0000-0001-7428-3101

Daniel Schneider http://orcid.org/0000-0002-3523-745X

Justin Starren http://orcid.org/0000-0002-5403-1115

Helen K. Donnelly http://orcid.org/0000-0001-8827-8581

Alvaro Donayre http://orcid.org/0000-0003-1877-0655

Yuan Luo http://orcid.org/0000-0003-0195-7456

G.R. Scott Budinger http://orcid.org/0000-0002-3114-5208

Alexander V. Misharin http://orcid.org/0000-0003-2879-3789

Benjamin D. Singer http://orcid.org/0000-0001-5775-8427

Article

Publisher ID: 170682

DOI: 10.1172/JCI170682

PMC ID: 10266785

PubMed ID: 37104035

SO-VID: 7be3de53-fc16-4824-9dfd-1ab3071f60d9

License:

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/.

History

Date received : 20 March 2023

Date accepted : 25 April 2023

Funding

Funded by: National Institute of Allergy and Infectious Diseases, https://doi.org/10.13039/100000060;

Award ID: U19AI135964

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