Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality

Journal article

Jeremy P. Gygi, Cole Maguire, Ravi K. Patel, Pramod Shinde, A. Konstorum, Casey P. Shannon, Leqi Xu, Annmarie Hoch, N. Jayavelu, Elias K. Haddad, Elaine F Reed, Monica Kraft, Grace A. McComsey, Jordan Metcalf, Al Ozonoff, D. Esserman, Charles B. Cairns, N. Rouphael, S. Bosinger, S. Kim-Schulze, F. Krammer, Lindsey B. Rosen, H. van Bakel, Michael Wilson, W. Eckalbar, H. Maecker, Charles R. Langelier, Hanno Steen, Matthew C. Altman, R. R. Montgomery, Ofer Levy, Esther Melamed, B. Pulendran, J. Diray-Arce, K. Smolen, G. Fragiadakis, Patrice M. Becker, R. Sekaly, Lauren I. R. Ehrlich, Slim Fourati, Bjoern Peters, S. Kleinstein, Leying Guan
Journal of Clinical Investigation, 2024

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Gygi, J. P., Maguire, C., Patel, R. K., Shinde, P., Konstorum, A., Shannon, C. P., … Guan, L. (2024). Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality. Journal of Clinical Investigation.

Chicago/Turabian Click to copy
Gygi, Jeremy P., Cole Maguire, Ravi K. Patel, Pramod Shinde, A. Konstorum, Casey P. Shannon, Leqi Xu, et al. “Integrated Longitudinal Multiomics Study Identifies Immune Programs Associated with Acute COVID-19 Severity and Mortality.” Journal of Clinical Investigation (2024).

MLA Click to copy
Gygi, Jeremy P., et al. “Integrated Longitudinal Multiomics Study Identifies Immune Programs Associated with Acute COVID-19 Severity and Mortality.” Journal of Clinical Investigation, 2024.

BibTeX Click to copy

@article{jeremy2024a,
  title = {Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality},
  year = {2024},
  journal = {Journal of Clinical Investigation},
  author = {Gygi, Jeremy P. and Maguire, Cole and Patel, Ravi K. and Shinde, Pramod and Konstorum, A. and Shannon, Casey P. and Xu, Leqi and Hoch, Annmarie and Jayavelu, N. and Haddad, Elias K. and Reed, Elaine F and Kraft, Monica and McComsey, Grace A. and Metcalf, Jordan and Ozonoff, Al and Esserman, D. and Cairns, Charles B. and Rouphael, N. and Bosinger, S. and Kim-Schulze, S. and Krammer, F. and Rosen, Lindsey B. and van Bakel, H. and Wilson, Michael and Eckalbar, W. and Maecker, H. and Langelier, Charles R. and Steen, Hanno and Altman, Matthew C. and Montgomery, R. R. and Levy, Ofer and Melamed, Esther and Pulendran, B. and Diray-Arce, J. and Smolen, K. and Fragiadakis, G. and Becker, Patrice M. and Sekaly, R. and Ehrlich, Lauren I. R. and Fourati, Slim and Peters, Bjoern and Kleinstein, S. and Guan, Leying}
}

Abstract

BACKGROUND Patients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. METHODS We performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes. RESULTS Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness. CONCLUSION Our longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill. TRIAL REGISTRATION ClinicalTrials.gov NCT04378777. FUNDING NIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).