Published on Tue Mar 30 2021

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

Sposito, B., Broggi, A., Pandolfi, L., Crotta, S., Ferrarese, R., Sisti, S., Clementi, N., Ambrosi, A., Liu, E., Frangipane, V., Saracino, L., Marongiu, L., Facchini, F., Bottazzi, A., Fossali, T., Colombo, R., Clementi, M., Tagliabue, E., Pontiroli, A., Meloni, F., Wack, A., Mancini, N., Zanoni, I.

The COVID-19 outbreak driven by SARS-CoV-2 has caused more than 2.5 million deaths globally. Most severe cases characterized by over-exuberant production of immune-mediators. Interferons of the type I (IFN-I) or type III

1
1
3
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.