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1.
Immunity ; 54(4): 753-768.e5, 2021 04 13.
Article in English | MEDLINE | ID: covidwho-1385739

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.


Subject(s)
Immunity/genetics , Virus Diseases/immunology , Antigen Presentation/genetics , Cohort Studies , Hematopoiesis/genetics , Humans , Interferons/blood , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Myeloid Cells/immunology , Myeloid Cells/pathology , Prognosis , Severity of Illness Index , Systems Biology , Transcriptome , Virus Diseases/blood , Virus Diseases/classification , Virus Diseases/genetics , Viruses/classification , Viruses/pathogenicity
3.
iScience ; 24(1): 101947, 2021 Jan 22.
Article in English | MEDLINE | ID: covidwho-974141

ABSTRACT

The pandemic 2019 novel coronavirus disease (COVID-19) shares certain clinical characteristics with other acute viral infections. We studied the whole-blood transcriptomic host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using RNAseq from 24 healthy controls and 62 prospectively enrolled patients with COVID-19. We then compared these data to non-COVID-19 viral infections, curated from 23 independent studies profiling 1,855 blood samples covering six viruses (influenza, respiratory syncytial virus (RSV), human rhinovirus (HRV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), Ebola, dengue). We show gene expression changes in COVID-19 versus non-COVID-19 viral infections are highly correlated (r = 0.74, p < 0.001). However, we also found 416 genes specific to COVID-19. Inspection of top genes revealed dynamic immune evasion and counter host responses specific to COVID-19. Statistical deconvolution of cell proportions maps many cell type proportions concordantly shifting. Discordantly increased in COVID-19 were CD56bright natural killer cells and M2 macrophages. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of the host response to SARS-CoV-2.

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