Multi-cohort Analysis of Host Immune Response Identifies Conserved Protective and Detrimental Modules Associated with Severity Across Viruses

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2021 Mar 25

PMID 33765435

Citations 36

Authors

Hong Zheng

Aditya M Rao

Denis Dermadi

Jiaying Toh

Lara Murphy Jones

Michele Donato

Yiran Liu

Yapeng Su

Cheng L Dai

Sergey A Kornilov

Minas Karagiannis

Theodoros Marantos

Yehudit Hasin-Brumshtein

Yudong D He

Evangelos J Giamarellos-Bourboulis

James R Heath

Purvesh Khatri

Affiliations

Soon will be listed here.

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.

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