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

2021; Cell Press; Volume: 184; Issue: 19 Linguagem: Inglês

10.1016/j.cell.2021.08.016

1097-4172

Benedetta Sposito, Achille Broggi, Laura Pandolfi, Stefania Crotta, Nicola Clementi, Roberto Ferrarese, Sofia Sisti, Elena Criscuolo, Roberto Spreafico, Jaclyn M. Long, Alessandro Ambrosi, Enju Liu, Vanessa Frangipane, Laura Saracino, Sara Bozzinì, Laura Marongiu, Fabio A. Facchini, Andrea Bottazzi, Tommaso Fossali, Riccardo Colombo, Massimo Clementi, Elena Tagliabue, Janet Chou, Antonio E. Pontiroli, Federica Meloni, Andreas Wack, Nicasio Mancini, Ivan Zanoni,

Long-Term Effects 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 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.