Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients

SARS-CoV-2 感染的严重程度与 COVID-19 患者呼吸道干扰素分布的关系

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作者:Benedetta Sposito, Achille Broggi, Laura Pandolfi, Stefania Crotta, Roberto Ferrarese, Sofia Sisti, Nicola Clementi, Alessandro Ambrosi, Enju Liu, Vanessa Frangipane, Laura Saracino, Laura Marongiu, Fabio A Facchini, Andrea Bottazzi, Tommaso Fossali, Riccardo Colombo, Massimo Clementi, Elena Tagliab

Abstract

The COVID-19 outbreak driven by SARS-CoV-2 has caused more than 2.5 million deaths globally, with the most severe cases characterized by over-exuberant production of immune-mediators, the nature of which is not fully understood. Interferons of the type I (IFN-I) or type III (IFN-III) families are potent antivirals, but their role in COVID-19 remains debated. Our analysis of gene and protein expression along the respiratory tract shows that IFNs, especially IFN-III, are over-represented in the lower airways of patients with severe COVID-19, while 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; also, IFN expression varies with abundance of the cell types that produce them. Our data point to a dynamic process of inter- and intra-family production of IFNs in COVID-19, and suggest that IFNs play opposing roles at distinct anatomical sites.

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