Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients
Joann Diray‐Arce(Boston Children's Hospital), Slim Fourati(Emory University), Naresh Doni Jayavelu(University of Washington), Ravi K. Patel(University of California, San Francisco), Cole Maguire(The University of Texas at Austin), Ana C. Chang(Boston Children's Hospital), Ravi Dandekar(University of California, San Francisco), Jingjing Qi(Icahn School of Medicine at Mount Sinai), Brian Lee(Icahn School of Medicine at Mount Sinai), Patrick van Zalm(Boston Children's Hospital), Andrew Schroeder(University of California, San Francisco), Ernie Chen(Yale University), Anna Konstorum(Yale University), Anderson F. Brito(Yale University), Jeremy P. Gygi(Yale University), Alvin T. Kho(Boston Children's Hospital), Jing Chen(Boston Children's Hospital), Shrikant Pawar(Yale University), Ana S. Gonzalez‐Reiche(Icahn School of Medicine at Mount Sinai), Annmarie Hoch(Boston Children's Hospital), Carly E. Milliren(Boston Children's Hospital), James A. Overton, Kerstin Westendorf(La Jolla Institute for Immunology), James Abraham(Drexel University), Michael Adkisson(Emory University), Albert Marisa(Emory University), Luz Torres Altamirano(Icahn School of Medicine at Mount Sinai), Bonny D. Alvarenga(Icahn School of Medicine at Mount Sinai), Matthew L. Anderson(National Institute of Allergy and Infectious Diseases), Evan J. Anderson(Yale University), Azlann Arnett(Icahn School of Medicine at Mount Sinai), Hiromitsu Asashima(University of California, San Francisco), Mark A. Atkinson(University of California, San Francisco), Lindsey R. Baden(Boston Children's Hospital), Brenda Barton(University of California, San Francisco), Katherine F. Beach(Broad Institute), Elizabeth Beagle(University of California, San Francisco), Patrice M. Becker(Broad Institute), Matthew R. Bell(University of Washington), Mariana Bernui(Palo Alto University), Christian Bime(Yale University), Arun K. Boddapati(Drexel University), J. Leland Booth(Emory University), Brittney Borresen(Yale University), Scott C. Brakenridge(Broad Institute), Laurel Bristow(National Institute of Allergy and Infectious Diseases), Robert W. Bryant(National Institute of Allergy and Infectious Diseases), Carolyn S. Calfee(Yale University), Juan Manuel Carreño(La Jolla Institute for Immunology), Sidney Carrillo(Yale University), Suzanna Chak, Iris Chang(University of California, San Francisco), Jennifer Connors, Michelle Conway, David B. Corry, David Cowan(Yale University), Brett Croen(Yale University), Charles S. Dela Cruz, Gina Cusimano, Lily Eaker, Carolyn Pope Edwards(National Institute of Allergy and Infectious Diseases), Lauren I. R. Ehrlich, David Elashoff, Heidi L. Erickson, David J. Erle(National Institute of Allergy and Infectious Diseases), Shelli Farhadian, Keith Farrugia, Benoit Fatou, Andrea Fernandes, Ana Fernández-Sesma, Gabriela K. Fragiadakis, Sara Furukawa, Janelle N. Geltman, Rajani Ghale, María González, I. Michael Goonewardene, Estella Sanchez Guerrero, Faheem W. Guirgis, David A. Hafler(Boston Children's Hospital), Sydney Hamilton, Paul G. Harris, Arash Nemati Hayati, Carolyn M. Hendrickson, Nelson Iván Agudelo Higuita, Thomas Hodder, Steven M. Holland, Catherine L. Hough, Christopher Huerta, Kerin Hurley, Scott R. Hutton, Akiko Iwasaki, Alejandra Jáuregui(Broad Institute), Meenakshi Jha, Brandi Johnson, David Joyner, Kirsten N. Kangelaris, Geoffrey Kelly(Icahn School of Medicine at Mount Sinai), Zain Khalil, Zenab Khan, Farrah Kheradmand, James N. Kim, Hiroki Kimura, Albert I. Ko, Bernard Kohr, Monica Kraft, Matthew F. Krummel, Michele A. Kutzler, Jessica Lasky‐Su, Serena Lee, Deanna Lee, Michael D. Leipold, Claudia Lentucci, Carolyn Leroux, Edward Lin, Shanshan Liu, Christina Love, Zhengchun Lu, Lenka Maliskova, Brittany Roth Manning, Monali Manohar, Mark G. Martens, Grace A. McComsey, Kerry McEnaney, Renee McLin, Esther Melamed, Nataliya Melnyk, Kevin Mendez, William B. Messer(Icahn School of Medicine at Mount Sinai), Jordan P. Metcalf, Gregory Michelotti(Yale University), Eran Mick, Subhasis Mohanty, Jarrod Mosier(University of Washington), Lubbertus C. F. Mulder, Maimouna D. Murphy, Kari R.C. Nadeau(Icahn School of Medicine at Mount Sinai), Ebony Nelson(Icahn School of Medicine at Mount Sinai), Allison Nelson(University of California, San Francisco), Viet Thanh Nguyen, Jordan Oberhaus, Bernadine Panganiban(National Institute of Allergy and Infectious Diseases), Kathryn L. Pellegrini, Harry Pickering, Debra Powell(University of Washington), Scott Presnell, Bali Pulendran, Adeeb Rahman, Ahmad Sadeed Rashid, Ariel Raskin, Elaine F. Reed, Susan Pereira Ribeiro, Adreanne M. Rivera, Jacob E. Rogers, Angela J. Rogers, Brandon Rogowski, Rebecca Rooks, Yael Rosenberg‐Hasson, Jessica E. Rothman, Justin F. Rousseau, Ramin Salehi‐Rad, Mehmet Saluvan, Hady Samaha, Joanna Schaenman, Ron Schunk, Nicholas C. Semenza, Subha Sen, Jonathan Sevransky, Vicki Seyfert‐Margolis, Tanzia Shaheen, Albert C. Shaw, Scott F. Sieg, Sarah Siegel, Natalia Sigal, Nadia Siles, Brent Simmons, Viviana Simon, Gagandeep Singh, Lauren A. Sinko, Cecilia M. Smith, Kinga K. Smolen, Li-Zhen Song, Komal Srivastava, Peter Sullivan, Caitlin Syphurs, Johnstone Tcheou, George P. Tegos, Greg K. Tharp, Alexandra Tong, Alexandra Tsitsiklis, Ricardo Ungaro, Tatyana Vaysman, Arthur Viodé, Randi Vita(National Institute of Allergy and Infectious Diseases), Xiaomei Wang, Alyssa Ward, Dawn C. Ward, Andrew Willmore, Kyra Woloszczuk, Kari E. Wong, Prescott G. Woodruff, Leqi Xu, Simon van Haren, Adriana van de Guchte, Yujiao Zhao, Charles B. Cairns(Drexel University), Nadine Rouphael(Emory University), Steven E. Bosinger(Emory University), Seunghee Kim‐Schulze(Icahn School of Medicine at Mount Sinai), Florian Krammer(Icahn School of Medicine at Mount Sinai), Lindsey B. Rosen(La Jolla Institute for Immunology), Nathan D. Grubaugh(Yale University), Harm van Bakel(Icahn School of Medicine at Mount Sinai), Michael R. Wilson(University of California, San Francisco), Jayant V. Rajan(University of California, San Francisco), Hanno Steen(Boston Children's Hospital), Walter L. Eckalbar(University of California, San Francisco), Chris Cotsapas(Broad Institute), Charles Langelier(University of California, San Francisco), Ofer Levy(Broad Institute), Matthew C. Altman(University of Washington), Holden T. Maecker(Palo Alto University), Ruth R. Montgomery(Yale University), Elias K. Haddad(Drexel University), Rafick‐Pierre Sékaly(Emory University), Denise Esserman(Yale University), Al Ozonoff(Boston Children's Hospital), Patrice M. Becker(National Institute of Allergy and Infectious Diseases), Alison D. Augustine(National Institute of Allergy and Infectious Diseases), Leying Guan(Yale University), Bjoern Peters(La Jolla Institute for Immunology), Steven H. Kleinstein(Yale University)
Cited by 53Open Access
Abstract
The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.
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