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Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US

Educational Objective
To understand the factors associated with death in critically ill patients with COVID-19
1 Credit CME
Key Points

Question  What are the characteristics, outcomes, and factors associated with death among critically ill patients with coronavirus disease 2019 (COVID-19) in the US?

Findings  In a cohort of 2215 adults with COVID-19 who were admitted to intensive care units at 65 sites, 784 (35.4%) died within 28 days, with wide variation among hospitals. Factors associated with death included older age, male sex, morbid obesity, coronary artery disease, cancer, acute organ dysfunction, and admission to a hospital with fewer intensive care unit beds.

Meaning  This study identified demographic, clinical, and hospital-level factors associated with death in critically ill patients with COVID-19 that may be used to facilitate the identification of medications and supportive therapies that can improve outcomes.

Abstract

Importance  The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19.

Objectives  To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19.

Design, Setting, and Participants  This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020.

Exposures  Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds.

Main Outcomes and Measures  The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes.

Results  A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30–5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46–4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies.

Conclusions and Relevance  This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

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Article Information

Accepted for Publication: June 19, 2020.

Published Online: July 15, 2020. doi:10.1001/jamainternmed.2020.3596

Correction: This article was corrected on August 6, 2020, to correct an error in the Key Points and to list the STOP-COVID Investigators in the Article Information. The article was also corrected on September 10, 2020, to remove the incorrect expansion of the BREATHE trial in the conflict of interest disclosures.

Corresponding Author: David E. Leaf, MD, MMSc, Division of Renal Medicine, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115 (deleaf@bwh.harvard.edu).

Author Contributions: Drs Gupta and Leaf had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Gupta, Hayek, Melamed, Radbel, Green, Shaefi, Parikh, Arunthamakun, Kibbelaar, Gershengorn, Leaf.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Gupta, Hayek, Wang, Mathews, Radbel, Reiser, Green, Vijayan, Abu Omar, Admon, Semler, Leaf.

Critical revision of the manuscript for important intellectual content: Gupta, Hayek, Wang, Chan, Mathews, Melamed, Brenner, Leonberg-Yoo, Schenck, Radbel, Bansal, Srivastava, Zhou, Sutherland, Green, Shehata, Goyal, Velez, Shaefi, Parikh, Arunthamakun, Athavale, Friedman, Short, Kibbelaar, Admon, Donnelly, Gershengorn, Hernán, Semler, Leaf.

Statistical analysis: Gupta, Wang, Mathews, Admon, Donnelly, Hernán, Semler, Leaf.

Administrative, technical, or material support: Gupta, Hayek, Chan, Schenck, Radbel, Reiser, Bansal, Zhou, Goyal, Velez, Shaefi, Parikh, Arunthamakun, Athavale, Short, Kibbelaar, Abu Omar, Leaf.

Supervision: Hayek, Mathews, Leonberg-Yoo, Zhou, Sutherland, Shaefi, Arunthamakun, Athavale, Hernán, Semler, Leaf.

Conflict of Interest Disclosures: Dr Gupta reported receiving grants from the National Institutes of Health (NIH) and is a scientific coordinator for GlaxoSmithKline’s ASCEND (Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat) trial. Dr Chan reported receiving grants from the Renal Research Institute outside the submitted work. Dr Mathews reported receiving grants from the NIH/National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study and serves on the steering committee for the BREATHE trial, funded by Roivant/Kinevant Sciences. Dr Melamed reported receiving honoraria from the American Board of Internal Medicine and Icon Medical Consulting. Dr Reiser reported receiving personal fees from Biomarin, TRISAQ, Thermo BCT, Astellas, Massachusetts General Hospital, Genentech, UptoDate, Merck, Inceptionsci, GLG, and Clearview and grants from the NIH and Nephcure outside the submitted work. Dr Srivastava reported receiving personal fees from Horizon Pharma PLC, AstraZeneca, and CVS Caremark outside the submitted work. Dr Vijayan reported receiving personal fees from NxStage, Boeringer Ingelheim, and Sanofi outside the submitted work. Dr Velez reported receiving personal fees from Mallinckrodt Pharmaceuticals, Retrophin, and Otsuka Pharmaceuticals outside the submitted work. Dr Shaefi reported receiving grants from the NIH/National Institute on Aging and NIH/National Institute of General Medical Sciences outside the submitted work. Dr Admon reported receiving grants from the NIH/NHLBI during the conduct of the study. Dr Donnelly reported receiving grants from the NIH/NHLBI during the conduct of the study and personal fees from the American College of Emergency Physicians/Annals of Emergency Medicine outside the submitted work. Dr Hernán reported receiving grants from the NIH during the conduct of the study. Dr Semler reported receiving grants from the NIH/NHLBI during the conduct of the study. No other disclosures were reported.

The STOP-COVID Investigators: Carl P. Walther, Samaya J. Anumudu, Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, Thuy-Duyen Nguyen, Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Peter Hart, Oyintayo Ajiboye, Matthew Itteera, Jean-Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Christopher L. Mosher, Aaron Karp, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Patricia Walters, Ronaldo C. Go, Keith M. Rose, Amy M. Zhou, Ethan C. Kim, Rebecca Lisk, Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni, John Guirguis, Rajat Kapoor, Christopher Meshberger, Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, Samir C. Gautam, H. Bryant Nguyen, Afshin Ahoubim, Leslie F. Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G. Lazarous, Seble G. Kassaye, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Ritesh Raichoudhury, Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, William Whalen, David Charytan, Ashley Macina, Daniel W. Ross, Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alexander J. Hodakowski, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, Muner MB. Mohamed, Rupali S. Avasare, David Zonies, Rebecca M. Baron, Meghan E. Sise, Erik T. Newman, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, Saif A. Muhsin, Ernest I. Mandel, Ariel L. Mueller, Nicholas S. Cairl, Chris Rowan, Farah Madhai-Lovely, Vasil Peev, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, Joy-Marie Hermes, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Sabiha Hussain, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui Song, Jingjing Zhang, Moh’d A. Sharshir, Vadym V. Rusnak, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen L. Burnham, Arash Rashidi, Rana Hejal, Erik T. Judd, Laura Latta, Ashita Tolwani, Timothy E. Albertson, Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Carl E. Schulze, Etienne Macedo, Harin Rhee, Kathleen D. Liu, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikaransingh, Stephanie M. Toth-Manikowski, Min J. Joo, James P. Lash, Javier A. Neyra, Nourhan Chaaban, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma, Marie Anne Sosa, Sabrina Taldone, Gabriel Contreras, David De La Zerda, Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’ Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Abbas Bitar, Jennifer E. Flythe, Matthew J. Tugman, Brent R. Brown, Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, Charles R. Vasquez, Amar D. Bansal, Natalie C. Ernecoff, Csaba P. Kovesdy, Miklos Z. Molnar, Ambreen Azhar, Susan S. Hedayati, Mridula V. Nadamuni, Sadaf S. Khan, Duwayne L. Willett, Amanda D. Renaghan, Pavan K. Bhatraju, Bilal A. Malik, Christina Mariyam Joy, Tingting Li, Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Anthony J. Faugno, Caroline M. Hsu, Asma Tariq, Leah Meyer, Daniel E. Weiner, Marta Christov, Francis P. Wilson, Tanima Arora, Ugochukwu Ugwuowo, Erik T. Newman.

Additional Contributions: Dino Mazzarelli, JD, Partners Healthcare Research Management, Boston, Massachusetts, and Patricia Reaser, Division of Renal Medicine at Brigham and Women’s Hospital, Boston, Massachusetts, provided assistance coordinating the data use agreements with each institution. No compensation was provided to these individuals. We thank the clinical and research staff from each of the participating sites.

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