The interferon landscape along the respiratory tract impacts the severity of COVID-19

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...

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Published in:Cell Vol. 184; no. 19; p. 4953
Main Authors: Sposito, Benedetta, Broggi, Achille, Pandolfi, Laura, Crotta, Stefania, Clementi, Nicola, Ferrarese, Roberto, Sisti, Sofia, Criscuolo, Elena, Spreafico, Roberto, Long, Jaclyn M, Ambrosi, Alessandro, Liu, Enju, Frangipane, Vanessa, Saracino, Laura, Bozzini, Sara, Marongiu, Laura, Facchini, Fabio A, Bottazzi, Andrea, Fossali, Tommaso, Colombo, Riccardo, Clementi, Massimo, Tagliabue, Elena, Chou, Janet, Pontiroli, Antonio E, Meloni, Federica, Wack, Andreas, Mancini, Nicasio, Zanoni, Ivan
Format: Journal Article
Language:English
Published: United States 16.09.2021
Subjects:
Age Factors
Aging - pathology
COVID-19 - genetics
COVID-19 - immunology
COVID-19 - pathology
Epithelial Cells - pathology
Epithelial Cells - virology
Gene Expression Regulation
Humans
Interferons - genetics
Interferons - metabolism
Leukocytes - pathology
Leukocytes - virology
Lung - pathology
Lung - virology
Respiratory Distress Syndrome - pathology
Respiratory Distress Syndrome - virology
Respiratory System - virology
Severity of Illness Index
Viral Load
COVID-19
lung
SARS-CoV-2
Type III IFN
airways
epithelial cell
interferon
Type I IFN
dendritic cell
pattern recognition receptor
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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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.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2021.08.016