Summary 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. Graphical abstract Highlights • Conserved host response distinguishes non-severe and severe viral infections • Increased hematopoiesis, myelopoiesis, and myeloid-derived suppression with severity • Protective and detrimental modules define trajectories for mild and severe outcomes • Interferon response is decoupled from the protective response in severe outcomes Viral infections induce a conserved host response distinct from bacterial infections, but whether this conserved response distinguishes severity is unclear. Zheng et al. analyzed >5000 bulk and single-cell transcriptome profiles from patients infected with one of 16 viruses, including SARS-CoV-2, Ebola, and chikungunya. They identified protective and detrimental host response modules that distinguish patients with mild or severe outcomes.
【저자키워드】 COVID-19, systems immunology, pan-virus analysis, conserved host response to viruses, multi-cohort analysis, 【초록키워드】 viruses, SARS-CoV-2, viral infection, Influenza, severity, disease severity, Infection, host response, outcome, virus, diagnostics, Single-cell RNA sequencing, global pandemic, outcomes, Cohort, cells, Patient, Mild, trajectory, age, Ebola, interferon response, Bacterial infections, single-cell, Protective, Immune cell, detrimental, Chikungunya, Abstract, profile, cohorts, Hematopoiesis, host-directed therapy, blood transcriptome, IMPROVE, defined, analyzed, conserved, induce, accelerate, Increased, transcriptome profile, 【제목키워드】 severity, Host immune response, Protective, Analysis, detrimental, identify, virus, conserved,