EBioMedicine (Sep 2022)

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

  • Al Ozonoff,
  • Joanna Schaenman,
  • Naresh Doni Jayavelu,
  • Carly E. Milliren,
  • Carolyn S. Calfee,
  • Charles B. Cairns,
  • Monica Kraft,
  • Lindsey R. Baden,
  • Albert C. Shaw,
  • Florian Krammer,
  • Harm van Bakel,
  • Denise A. Esserman,
  • Shanshan Liu,
  • Ana Fernandez Sesma,
  • Viviana Simon,
  • David A. Hafler,
  • Ruth R. Montgomery,
  • Steven H. Kleinstein,
  • Ofer Levy,
  • Christian Bime,
  • Elias K. Haddad,
  • David J. Erle,
  • Bali Pulendran,
  • Kari C. Nadeau,
  • Mark M. Davis,
  • Catherine L. Hough,
  • William B. Messer,
  • Nelson I. Agudelo Higuita,
  • Jordan P. Metcalf,
  • Mark A. Atkinson,
  • Scott C. Brakenridge,
  • David Corry,
  • Farrah Kheradmand,
  • Lauren I.R. Ehrlich,
  • Esther Melamed,
  • Grace A. McComsey,
  • Rafick Sekaly,
  • Joann Diray-Arce,
  • Bjoern Peters,
  • Alison D. Augustine,
  • Elaine F. Reed,
  • Matthew C. Altman,
  • Patrice M. Becker,
  • Nadine Rouphael,
  • Al Ozonoff,
  • Joanna Schaenman,
  • Naresh Doni Jayavelu,
  • Carly E. Milliren,
  • Carolyn S. Calfee,
  • Charles B. Cairns,
  • Monica Kraft,
  • Lindsey R. Baden,
  • Albert C. Shaw,
  • Florian Krammer,
  • Harm van Bakel,
  • Denise A. Esserman,
  • Shanshan Liu,
  • Ana Fernandez Sesma,
  • Viviana Simon,
  • David A. Hafler,
  • Ruth R. Montgomery,
  • Steven H. Kleinstein,
  • Ofer Levy,
  • Chris Bime,
  • Elias K. Haddad,
  • David J. Erle,
  • Bali Pulendran,
  • Kari C. Nadeau,
  • Mark M Davis,
  • Catherine L. Hough,
  • William B. Messer,
  • Nelson I. Agudelo Higuita,
  • Jordan P. Metcalf,
  • Mark A. Atkinson,
  • Scott C. Brakenridge,
  • David Corry,
  • Farrah Kheradmand,
  • Lauren I.R. Ehrlich,
  • Esther Melamed,
  • Grace A. McComsey,
  • Rafick Sekaly,
  • Joann Diray-Arce,
  • Bjoern Peters,
  • Alison D. Augustine,
  • Elaine F. Reed,
  • Kerry McEnaney,
  • Brenda Barton,
  • Claudia Lentucci,
  • Mehmet Saluvan,
  • Ana C. Chang,
  • Annmarie Hoch,
  • Marisa Albert,
  • Tanzia Shaheen,
  • Alvin T. Kho,
  • Sanya Thomas,
  • Jing Chen,
  • Maimouna D. Murphy,
  • Mitchell Cooney,
  • Scott Presnell,
  • Gabriela K. Fragiadakis,
  • Ravi Patel,
  • Leying Guan,
  • Jeremy Gygi,
  • Shrikant Pawar,
  • Anderson Brito,
  • Zain Khalil,
  • Cole Maguire,
  • Slim Fourati,
  • James A. Overton,
  • Randi Vita,
  • Kerstin Westendorf,
  • Ramin Salehi-Rad,
  • Aleksandra Leligdowicz,
  • Michael A. Matthay,
  • Jonathan P. Singer,
  • Kirsten N. Kangelaris,
  • Carolyn M. Hendrickson,
  • Matthew F. Krummel,
  • Charles R. Langelier,
  • Prescott G. Woodruff,
  • Debra L. Powell,
  • James N. Kim,
  • Brent Simmons,
  • I. Michael Goonewardene,
  • Cecilia M. Smith,
  • Mark Martens,
  • Jarrod Mosier,
  • Hiroki Kimura,
  • Amy C. Sherman,
  • Stephen R. Walsh,
  • Nicolas C. Issa,
  • Charles Dela Cruz,
  • Shelli Farhadian,
  • Akiko Iwasaki,
  • Albert I. Ko,
  • Sharon Chinthrajah,
  • Neera Ahuja,
  • Angela J. Rogers,
  • Maja Artandi,
  • Sarah A.R. Siegel,
  • Zhengchun Lu,
  • Douglas A. Drevets,
  • Brent R. Brown,
  • Matthew L. Anderson,
  • Faheem W. Guirgis,
  • Rama V. Thyagarajan,
  • Justin F. Rousseau,
  • Dennis Wylie,
  • Johanna Busch,
  • Saurin Gandhi,
  • Todd A. Triplett,
  • George Yendewa,
  • Olivia Giddings,
  • Evan J. Anderson,
  • Aneesh K. Mehta,
  • Jonathan E. Sevransky,
  • Bernard Khor,
  • Adeeb Rahman,
  • Daniel Stadlbauer,
  • Jayeeta Dutta,
  • Hui Xie,
  • Seunghee Kim-Schulze,
  • Ana Silvia Gonzalez-Reiche,
  • Adriana van de Guchte,
  • Keith Farrugia,
  • Zenab Khan,
  • Holden T. Maecker,
  • David Elashoff,
  • Jenny Brook,
  • Estefania Ramires-Sanchez,
  • Megan Llamas,
  • Adreanne Rivera,
  • Claudia Perdomo,
  • Dawn C. Ward,
  • Clara E. Magyar,
  • Jennifer A. Fulcher,
  • Yumiko Abe-Jones,
  • Saurabh Asthana,
  • Alexander Beagle,
  • Sharvari Bhide,
  • Sidney A. Carrillo,
  • Suzanna Chak,
  • Gabriela K. Fragiadakis,
  • Rajani Ghale,
  • Ana Gonzalez,
  • Alejandra Jauregui,
  • Norman Jones,
  • Tasha Lea,
  • Deanna Lee,
  • Raphael Lota,
  • Jeff Milush,
  • Viet Nguyen,
  • Logan Pierce,
  • Priya A. Prasad,
  • Arjun Rao,
  • Bushra Samad,
  • Cole Shaw,
  • Austin Sigman,
  • Pratik Sinha,
  • Alyssa Ward,
  • Andrew Willmore,
  • Jenny Zhan,
  • Sadeed Rashid,
  • Nicklaus Rodriguez,
  • Kevin Tang,
  • Luz Torres Altamirano,
  • Legna Betancourt,
  • Cindy Curiel,
  • Nicole Sutter,
  • Maria Tercero Paz,
  • Gayelan Tietje-Ulrich,
  • Carolyn Leroux,
  • Jennifer Connors,
  • Mariana Bernui,
  • Michel A. Kutzler,
  • Carolyn Edwards,
  • Edward Lee,
  • Edward Lin,
  • Brett Croen,
  • Nicholas C. Semenza,
  • Brandon Rogowski,
  • Nataliya Melnyk,
  • Kyra Woloszczuk,
  • Gina Cusimano,
  • Mathew R. Bell,
  • Sara Furukawa,
  • Renee McLin,
  • Pamela Marrero,
  • Julie Sheidy,
  • George P. Tegos,
  • Crystal Nagle,
  • Nathan Mege,
  • Kristen Ulring,
  • Vicki Seyfert-Margolis,
  • Michelle Conway,
  • Dave Francisco,
  • Allyson Molzahn,
  • Heidi Erickson,
  • Connie Cathleen Wilson,
  • Ron Schunk,
  • Bianca Sierra,
  • Trina Hughes,
  • Kinga Smolen,
  • Michael Desjardins,
  • Simon van Haren,
  • Xhoi Mitre,
  • Jessica Cauley,
  • Xiaofang Li,
  • Alexandra Tong,
  • Bethany Evans,
  • Christina Montesano,
  • Jose Humberto Licona,
  • Jonathan Krauss,
  • Jun Bai Park Chang,
  • Natalie Izaguirre,
  • Omkar Chaudhary,
  • Andreas Coppi,
  • John Fournier,
  • Subhasis Mohanty,
  • M. Catherine Muenker,
  • Allison Nelson,
  • Khadir Raddassi,
  • Michael Rainone,
  • William E. Ruff,
  • Syim Salahuddin,
  • Wade L. Schulz,
  • Pavithra Vijayakumar,
  • Haowei Wang,
  • Elsio Wunder Jr.,
  • H. Patrick Young,
  • Yujiao Zhao,
  • Miti Saksena,
  • Deena Altman,
  • Erna Kojic,
  • Komal Srivastava,
  • Lily Q. Eaker,
  • Maria C. Bermúdez-González,
  • Katherine F. Beach,
  • Levy A. Sominsky,
  • Arman R. Azad,
  • Juan Manuel Carreño,
  • Gagandeep Singh,
  • Ariel Raskin,
  • Johnstone Tcheou,
  • Dominika Bielak,
  • Hisaaki Kawabata,
  • Lubbertus CF Mulder,
  • Giulio Kleiner,
  • Alexandra S. Lee,
  • Evan Do Do,
  • Andrea Fernandes,
  • Monali Manohar,
  • Thomas Hagan,
  • Catherine A. Blish,
  • Hena Naz Din,
  • Jonasel Roque,
  • Samuel Yang,
  • Amanda Brunton,
  • Peter E. Sullivan,
  • Matthew Strnad,
  • Zoe L. Lyski,
  • Felicity J. Coulter,
  • J. Leland Booth,
  • Lauren A. Sinko,
  • Lyle L. Moldawer,
  • Brittany Borresen,
  • Brittney Roth-Manning,
  • Li-Zhen Song,
  • Ebony Nelson,
  • Megan Lewis-Smith,
  • Jacob Smith,
  • Pablo Guaman Tipan,
  • Nadia Siles,
  • Sam Bazzi,
  • Janelle Geltman,
  • Kerin Hurley,
  • Gio Gabriele,
  • Scott Sieg,
  • Tatyana Vaysman,
  • Laurel Bristow,
  • Laila Hussaini,
  • Kieffer Hellmeister,
  • Hady Samaha,
  • Andrew Cheng,
  • Christine Spainhour,
  • Erin M. Scherer,
  • Brandi Johnson,
  • Amer Bechnak,
  • Caroline R. Ciric,
  • Lauren Hewitt,
  • Erin Carter,
  • Nina Mcnair,
  • Bernadine Panganiban,
  • Christopher Huerta,
  • Jacob Usher,
  • Susan Pereira Ribeiro,
  • Matthew C. Altman,
  • Patrice M. Becker,
  • Nadine Rouphael

Journal volume & issue
Vol. 83
p. 104208

Abstract

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Summary: Background: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28–3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13–2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63– 4.80) or troponin (OR 1.89; 95% 1.03–3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61–2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96–5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17–2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH.

Keywords