Critical Care Explorations (Sep 2022)

Modulation of the Association Between Age and Death by Risk Factor Burden in Critically Ill Patients With COVID-19

  • Ashwin Sunderraj, BS,
  • Chloe Cho,
  • Xuan Cai, MS,
  • Shruti Gupta, MD, MPH,
  • Rupal Mehta, MD, MSCI,
  • Tamara Isakova, MD, MMSc,
  • David E. Leaf, MD, MMSc,
  • Anand Srivastava, MD, MPH,
  • STOP-COVID Investigators,
  • Carl P. Walther,
  • Samaya J. Anumudu,
  • Justin Arunthamakun,
  • Kathleen F. Kopecky,
  • Gregory P. Milligan,
  • Peter A. McCullough,
  • Thuy-Duyen Nguyen,
  • Shahzad Shaefi,
  • Megan L. Krajewski,
  • Sidharth Shankar,
  • Ameeka Pannu,
  • Juan D. Valencia,
  • Sushrut S. Waikar,
  • Zoe A. Kibbelaar,
  • Ambarish M. Athavale,
  • Peter Hart,
  • Shristi Upadhyay,
  • Ishaan Vohra,
  • Ajiboye Oyintayo,
  • Adam Green,
  • Jean-Sebastien Rachoin,
  • Christa A. Schorr,
  • Lisa Shea,
  • Daniel L. Edmonston,
  • Christopher L. Mosher,
  • Alexandre M. Shehata,
  • Zaza Cohen,
  • Valerie Allusson,
  • Gabriela Bambrick-Santoyo,
  • Noor ul aain Bhatti,
  • Bijal Mehta,
  • Aquino Williams,
  • Samantha K. Brenner,
  • Patricia Walters,
  • Ronaldo C. Go,
  • Keith M. Rose,
  • Miguel A. Hernán,
  • Amy M. Zhou,
  • Ethan C. Kim,
  • Rebecca Lisk,
  • Lili Chan,
  • Kusum S. Mathews,
  • 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,
  • Pattharawin Pattharanitima,
  • Emily J. Gallagher,
  • Allon N. Friedman,
  • John Guirguis,
  • Rajat Kapoor,
  • Christopher Meshberger,
  • Katherine J. Kelly,
  • Chirag R. Parikh,
  • Brian T. Garibaldi,
  • Celia P. Corona-Villalobos,
  • Yumeng Wen,
  • Steven Menez,
  • Rubab F. Malik,
  • Carmen Elena Cervantes,
  • Samir C. Gautam,
  • Mary C. Mallappallil,
  • Jie Ouyang,
  • Sabu John,
  • Ernie Yap,
  • Yohannes Melaku,
  • Ibrahim Mohamed,
  • Siddhartha Bajracharya,
  • Isha Puri,
  • Mariah Thaxton,
  • Jyotsna Bhattacharya,
  • John Wagner,
  • Leon Boudourakis,
  • H. Bryant Nguyen,
  • Afshin Ahoubim,
  • Leslie F. Thomas,
  • Dheeraj Reddy Sirganagari,
  • Pramod K. Guru,
  • Kianoush Kashani,
  • Shahrzad Tehranian,
  • Yan Zhou,
  • Paul A. Bergl,
  • Jesus Rodriguez,
  • Jatan A. Shah,
  • Mrigank S. Gupta,
  • Princy N. Kumar,
  • Deepa G. Lazarous,
  • Seble G. Kassaye,
  • Michal L. Melamed,
  • Tanya S. Johns,
  • Ryan Mocerino,
  • Kalyan Prudhvi,
  • Denzel Zhu,
  • Rebecca V. Levy,
  • Yorg Azzi,
  • Molly Fisher,
  • Milagros Yunes,
  • Kaltrina Sedaliu,
  • Ladan Golestaneh,
  • Maureen Brogan,
  • Neelja Kumar,
  • Michael Chang,
  • Jyotsana Thakkar,
  • Ritesh Raichoudhury,
  • Akshay Athreya,
  • Mohamed Farag,
  • Edward J. Schenck,
  • 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,
  • Sobaata Chaudhry,
  • Benjamin Wu,
  • Frank Modersitzki,
  • Anand Srivastava,
  • Alexander S. Leidner,
  • Carlos Martinez,
  • Jacqueline M. Kruser,
  • Richard G. Wunderink,
  • Alexander J. Hodakowski,
  • Juan Carlos Q. Velez,
  • Eboni G. Price-Haywood,
  • Luis A. Matute-Trochez,
  • Anna E. Hasty,
  • Muner MB. Mohamed,
  • Rupali S. Avasare,
  • David Zonies,
  • David E. Leaf,
  • Shruti Gupta,
  • Meghan E. Sise,
  • Erik T. Newman,
  • Samah Abu Omar,
  • Kapil K. Pokharel,
  • Shreyak Sharma,
  • Harkarandeep Singh,
  • Simon Correa,
  • Tanveer Shaukat,
  • Omer Kamal,
  • Wei Wang,
  • Heather Yang,
  • Jeffery O. Boateng,
  • Meghan Lee,
  • Ian A. Strohbehn,
  • Jiahua Li,
  • Ariel L. Mueller,
  • Roberta E. Redfern,
  • Nicholas S. Cairl,
  • Gabriel Naimy,
  • Abeer Abu-Saif,
  • Danyell Hall,
  • Laura Bickley,
  • Chris Rowan,
  • Farah Madhani-Lovely,
  • Vivian S. Cruz,
  • Kristen M. Hess,
  • Alanna L. Jacobs,
  • Vasil Peev,
  • Jochen Reiser,
  • John J. Byun,
  • Andrew Vissing,
  • Esha M. Kapania,
  • Zoe Post,
  • Nilam P. Patel,
  • Joy-Marie Hermes,
  • Anne K. Sutherland,
  • Amee Patrawalla,
  • Diana G. Finkel,
  • Barbara A. Danek,
  • Sowminya Arikapudi,
  • Jeffrey M. Paer,
  • Peter Cangialosi,
  • Mark Liotta,
  • Jared Radbel,
  • Sonika Puri,
  • Jag Sunderram,
  • Matthew T. Scharf,
  • Ayesha Ahmed,
  • Ilya Berim,
  • Jayanth S. Vatson,
  • Shuchi Anand,
  • Joseph E. Levitt,
  • Pablo Garcia,
  • Suzanne M. Boyle,
  • Rui Song,
  • Jingjing Zhang,
  • Sang Hoon Woo,
  • Xiaoying Deng,
  • Goni Katz-Greenberg,
  • Katharine Senter,
  • Moh’d A. Sharshir,
  • Vadym V. Rusnak,
  • Muhammad Imran Ali,
  • Anip Bansal,
  • Amber S. Podoll,
  • Michel Chonchol,
  • Sunita Sharma,
  • Ellen L. Burnham,
  • David J. Douin,
  • Arash Rashidi,
  • Rana Hejal,
  • Eric 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,
  • Madona Elias,
  • Yahya Ahmad,
  • Alfredo Iardino,
  • Elizabeth H. Au,
  • Jill H. Sharma,
  • Marie Anne Sosa,
  • Sabrina Taldone,
  • Gabriel Contreras,
  • David De La Zerda,
  • Hayley B. Gershengorn,
  • Bhavarth Shukla,
  • Alessia Fornoni,
  • Tanira Ferreira,
  • Salim S. Hayek,
  • Pennelope Blakely,
  • Hanna Berlin,
  • Tariq U. Azam,
  • Husam Shadid,
  • Michael Pan,
  • Patrick O’ Hayer,
  • Chelsea Meloche,
  • Rafey Feroze,
  • Rayan Kaakati,
  • Danny Perry,
  • Abbas Bitar,
  • Elizabeth Anderson,
  • Kishan J. Padalia,
  • John P. Donnelly,
  • Andrew J. Admon,
  • Jennifer E. Flythe,
  • Matthew J. Tugman,
  • Emily H. Chang,
  • Brent R. Brown,
  • Amanda K. Leonberg-Yoo,
  • Ryan C. Spiardi,
  • Todd A. Miano,
  • Meaghan S. Roche,
  • Charles R. Vasquez,
  • Amar D. Bansal,
  • Natalie C. Ernecoff,
  • Sanjana Kapoor,
  • Siddharth Verma,
  • Huiwen Chen,
  • Csaba P. Kovesdy,
  • Miklos Z. Molnar,
  • Ambreen Azhar,
  • S. Susan Hedayati,
  • Mridula V. Nadamuni,
  • Shani Shastri,
  • Duwayne L. Willett,
  • Samuel A.P. Short,
  • Amanda D. Renaghan,
  • Kyle B. Enfield,
  • Pavan K. Bhatraju,
  • A. Bilal Malik,
  • Matthew W. Semler,
  • Anitha Vijayan,
  • Christina Mariyam Joy,
  • Tingting Li,
  • Seth Goldberg,
  • Patricia F. Kao,
  • Greg L. Schumaker,
  • Nitender Goyal,
  • Anthony J. Faugno,
  • Greg L. Schumaker,
  • Caroline M. Hsu,
  • Asma Tariq,
  • Leah Meyer,
  • Ravi K. Kshirsagar,
  • Daniel E. Weiner,
  • Aju Jose,
  • Marta Christov,
  • Jennifer Griffiths,
  • Sanjeev Gupta,
  • Aromma Kapoor,
  • Perry Wilson,
  • Tanima Arora,
  • Ugochukwu Ugwuowo

DOI
https://doi.org/10.1097/CCE.0000000000000755
Journal volume & issue
Vol. 4, no. 9
p. e0755

Abstract

Read online

OBJECTIVES:. Older age is a key risk factor for adverse outcomes in critically ill patients with COVID-19. However, few studies have investigated whether preexisting comorbidities and acute physiologic ICU factors modify the association between age and death. DESIGN:. Multicenter cohort study. SETTING:. ICUs at 68 hospitals across the United States. PATIENTS:. A total of 5,037 critically ill adults with COVID-19 admitted to ICUs between March 1, 2020, and July 1, 2020. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary exposure was age, modeled as a continuous variable. The primary outcome was 28-day inhospital mortality. Multivariable logistic regression tested the association between age and death. Effect modification by the number of risk factors was assessed through a multiplicative interaction term in the logistic regression model. Among the 5,037 patients included (mean age, 60.9 yr [± 14.7], 3,179 [63.1%] male), 1,786 (35.4%) died within 28 days. Age had a nonlinear association with 28-day mortality (p for nonlinearity <0.001) after adjustment for covariates that included demographics, preexisting comorbidities, acute physiologic ICU factors, number of ICU beds, and treatments for COVID-19. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and 28-day mortality (p for interaction <0.001), but this effect modification was modest as age still had an exponential relationship with death in subgroups stratified by the number of risk factors. CONCLUSIONS:. In a large population of critically ill patients with COVID-19, age had an independent exponential association with death. The number of preexisting comorbidities and acute physiologic ICU factors modified the association between age and death, but age still had an exponential association with death in subgroups according to the number of risk factors present. Additional studies are needed to identify the mechanisms underpinning why older age confers an increased risk of death in critically ill patients with COVID-19.