Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses.

Document Type

Article

Publication Date

3-16-2021

Publication Title

Immunity

Keywords

2019-nCoV; washington; seattle; isb; conserved host response to viruses; covid-19; multi-cohort analysis; pan-virus analysis; systems immunology

Abstract

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.

Department

Institute for Systems Biology

Department

Allergy & Immunology

Department

Institute for Systems Biology

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