Cell
Volume 184, Issue 19, 16 September 2021, Pages 4953-4968.e16
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Article
The interferon landscape along the respiratory tract impacts the severity of COVID-19

https://doi.org/10.1016/j.cell.2021.08.016Get rights and content
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Highlights

  • IFN expression in COVID-19 varies based on location, viral load, age, and severity

  • IFN-λ1 and IFN-λ3 drive protective ISGs in the upper airways of mildly ill patients

  • Critical patients express IFN-αβ and IFN-λ2 and have low ISGs and high p53 expression

  • Epithelial cells efficiently produce protective IFN-λ1, while cDCs express IFN-λ2,3

Summary

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.

Keywords

interferon
Type I IFN
Type III IFN
COVID-19
SARS-CoV-2
dendritic cell
epithelial cell
pattern recognition receptor
lung
airways

Data and code availability

  • Targeted transcriptomics data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the Key resources table.

  • Gene expression matrix from targeted transcriptomics, Gene expression matrix from qPCR experiments, cytokine expression matrix from multiplex analysis of BALF, Plasma and supernatants of phagocytes are deposited at Mendeley and are publicly available as of the date of publication. The DOI is listed in the Key resources table.

  • The code used to analyze the data is available upon request to the corresponding authors.

Cited by (0)

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These authors contributed equally

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These authors contributed equally

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Present address: INSERM U1104 Centre d'Immunologie de Marseille-Luminy (CIML), Marseille 13000, France

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Lead contact

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Twitter: @Lo_Zanzi