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Sci Immunol ; 5(49)2020 07 10.
Article in English | MEDLINE | ID: covidwho-639363

ABSTRACT

Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1ß-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1ß-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunophenotyping , Influenza A virus/immunology , Influenza, Human/immunology , Interferon Type I/metabolism , Pneumonia, Viral/immunology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Cells, Cultured , Coronavirus Infections/blood , Coronavirus Infections/virology , Female , Healthy Volunteers , Humans , Inflammation/immunology , Influenza, Human/blood , Influenza, Human/virology , Interleukin-1beta/metabolism , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , RNA-Seq , SARS-CoV-2 , Single-Cell Analysis , Transcriptome , Tumor Necrosis Factor-alpha/metabolism
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