Research ArticleCORONAVIRUS

Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19

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Science Immunology  10 Jul 2020:
Vol. 5, Issue 49, eabd1554
DOI: 10.1126/sciimmunol.abd1554

Cytokine drivers of COVID-19

By carrying out single-cell RNA sequencing analyses on immune cells in the blood, Lee et al. have compared immune responses in patients with mild and severe COVID-19 with immune responses in severe cases of influenza. They report TNF/IL-1β–driven inflammation as defining characteristics of COVID-19 that was relatively weak in the response to influenza. By further comparing the transcriptomes of mild and severe cases of COVID-19, they found type I interferons to be key drivers of inflammation in severe COVID-19. By profiling the immune responses to SARS-CoV-2 and flu in parallel, Lee et al. have shed new light on the similarities and differences between the immune responses to these two distinct respiratory viruses.


Although most severe acute respiratory syndrome coronavirus 2 (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 sequencing 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 hyperinflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the tumor necrosis factor/interleukin-1β (TNF/IL-1β)–driven inflammatory response as compared with severe influenza. In classical monocytes from patients with severe COVID-19, type I interferon (IFN) response coexisted with the TNF/IL-1β–driven inflammation, and this was not seen in patients with milder COVID-19. We documented type I IFN–driven inflammatory features in patients with severe influenza as well. On the basis of this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.

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