Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections

Bénard, Alan; Jacobsen, Anne; Brunner, Maximilian; Krautz, Christian; Klösch, Bettina; Swierzy, Izabela; Naschberger, Elisabeth; Podolska, Malgorzata J.; Kouhestani, Dina; David, Paul; Birkholz, Torsten; Castellanos, Ixchel; Trufa, Denis; Sirbu, Horia; Vetter, Marcel; Kremer, Andreas E.; Hildner, Kai; Hecker, Andreas; Edinger, Fabian; Tenbusch, Matthias; Mühl-Zürbes, Petra; Steinkasserer, Alexander; Richter, Enrico; Streeck, Hendrik; Berger, Marc M.; Brenner, Thorsten; Weigand, Markus A.; Swirski, Filip K.; Schett, Georg; Grützmann, Robert; Weber, Georg F.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNα and IFNλ levels when compared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatment with recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating pDCs into the airways by stimulating CXCL12 secretion from pulmonary CD123(+) epithelial cells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potential therapeutic target for pulmunory viral infections.