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Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and
Jeremy P Gygi1, Cole Maguire2, Ravi K Patel3
1Yale School of Medicine, New Haven, Connecticut, USA.
The Journal of Clinical Investigation
|May 1, 2024
Summary
This study reveals how COVID-19 progresses by tracking immune system changes over time. Understanding these immune cascades, like cytokine storms and T cell dysfunction, can help develop better treatments for hospitalized patients.
Area of Science:
- Immunology
- Virology
- Genomics
Background:
- COVID-19 patients show varied outcomes despite similar initial severity.
- Understanding immune responses throughout the disease course is key to explaining progression heterogeneity.
Purpose of the Study:
- To systematically evaluate molecular and cellular profiles during COVID-19 progression.
- To link immune program coordination with heterogeneous clinical outcomes.
Main Methods:
- Deep immunophenotyping and longitudinal multiomics modeling in 1,152 COVID-19 Cohort (IMPACC) participants.
- Integration of 10 distinct molecular and cellular assays.
Main Results:
- Disease severity correlates with a temporal cascade: immunosuppressive metabolites, inflammatory cytokines, coagulation, neutrophil extracellular traps, and T cell dysregulation.
- A distinct cascade, predicting mortality in critically ill patients, involves reduced immunoglobulins (Igs), B cells, and dysregulated interferon (IFN) responsiveness.
- Disrupted balance between IFN-stimulated genes and IFN inhibitors is a key biomarker for COVID-19 mortality and impaired viral clearance.
Conclusions:
- Longitudinal multiomics profiling reveals temporal immune coordination explaining COVID-19 progression.
- Findings offer insights for targeted therapy development in hospitalized and critically ill COVID-19 patients.
