Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

• Type of Material: Article
• Authors: Joann Diray-Arce, Children's Hospital Boston; Slim Fourati, Emory University; Naresh Doni Jayavelu, University of Washington; Ravi Patel, University of California San Francisco; Cole Maguire, University of Texas Austin; Evan Anderson, Emory University; Nadine Rouphael, Emory University; Rafick-Pierre Sekaly, Emory University; Jonathan Sevransky, Emory University
• Language: English
• Date: 2023-06-20
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2023.101079
• Title of Journal or Parent Work: Cell Reports Medicine
• Volume: 4
• Issue: 6
• Start Page: 101079
• End Page: 101079
• Grant/Funding Information: The study was funded by the US National Institutes of Health National Institute of Allergy and Infectious Diseases through the following grants: R01AI135803, U19AI118608, U19AI128910, U19AI090023, U19AI090023, P510D11132, U19AI118610, R01AI145835, U19AI062629, U19AI057229, U19AI125357, U19AI128913, U19AI077439, U54AI142766, R01AI104870, U19AI089992, U19AI128913, U19AI1289130, U19AI128913 and R01AI122220.
• Keywords: immunophenotyping; Multiomics; Longitudinal Studies; multi-omics; COVID-19; Disease Progression; SARS-CoV-2; Humans; longitudinal modeling; systems immunology
• Research Categories: Biology, Virology

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.