Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients
Joann Diray‐Arce, Slim Fourati, Naresh Doni Jayavelu, Ravi K. Patel, Cole Maguire, Ana C. Chang, Ravi Dandekar, Jingjing Qi, Brian Lee, Patrick van Zalm, Andrew Schroeder, Ernie Chen, Anna Konstorum, Anderson F. Brito, Jeremy P. Gygi, Alvin T. Kho, Jing Chen, Shrikant Pawar, Ana S. Gonzalez‐Reiche, Annmarie Hoch, Carly E. Milliren, James A. Overton, Kerstin Westendorf, James Abraham, Michael Adkisson, Albert Marisa, Luz Torres Altamirano, Bonny D. Alvarenga, Matthew L. Anderson, Evan J. Anderson, Azlann Arnett, Hiromitsu Asashima, Mark A. Atkinson, Lindsey R. Baden, Brenda Barton, Katherine F. Beach, Elizabeth Beagle, Patrice M. Becker, Matthew R. Bell, Mariana Bernui, Christian Bime, Arun K. Boddapati, J. Leland Booth, Brittney Borresen, Scott C. Brakenridge, Laurel Bristow, Robert W. Bryant, Carolyn S. Calfee, Juan Manuel Carreño, Sidney Carrillo, Suzanna Chak, Iris Chang, Jennifer Connors, Michelle Conway, David B. Corry, David Cowan, Brett Croen, Charles S. Dela Cruz, Gina Cusimano, Lily Eaker, Carolyn Pope Edwards, Lauren I. R. Ehrlich, David Elashoff, Heidi L. Erickson, David J. Erle, 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, 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, Meenakshi Jha, Brandi Johnson, David Joyner, Kirsten N. Kangelaris, Geoffrey Kelly, Zain Khalil, Zenab Khan, Farrah Kheradmand
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.