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

Alan Bénard (), Anne Jacobsen, Maximilian Brunner, Christian Krautz, Bettina Klösch, Izabela Swierzy, Elisabeth Naschberger, Malgorzata J. Podolska, Dina Kouhestani, Paul David, Torsten Birkholz, Ixchel Castellanos, Denis Trufa, Horia Sirbu, Marcel Vetter, Andreas E. Kremer, Kai Hildner, Andreas Hecker, Fabian Edinger, Matthias Tenbusch, Petra Mühl-Zürbes, Alexander Steinkasserer, Enrico Richter, Hendrik Streeck, Marc M. Berger, Thorsten Brenner, Markus A. Weigand, Filip K. Swirski, Georg Schett, Robert Grützmann and Georg F. Weber ()
Additional contact information
Alan Bénard: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Anne Jacobsen: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Maximilian Brunner: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Christian Krautz: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Bettina Klösch: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Izabela Swierzy: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Elisabeth Naschberger: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Malgorzata J. Podolska: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Dina Kouhestani: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Paul David: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Torsten Birkholz: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Ixchel Castellanos: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Denis Trufa: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Horia Sirbu: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Marcel Vetter: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Andreas E. Kremer: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Kai Hildner: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Andreas Hecker: University Hospital
Fabian Edinger: University Hospital
Matthias Tenbusch: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Petra Mühl-Zürbes: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Alexander Steinkasserer: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Enrico Richter: University Hospital
Hendrik Streeck: University Hospital
Marc M. Berger: University Hospital Essen, University Duisburg-Essen
Thorsten Brenner: University Hospital Essen, University Duisburg-Essen
Markus A. Weigand: Heidelberg University Hospital
Filip K. Swirski: Massachusetts General Hospital and Harvard Medical School
Georg Schett: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Robert Grützmann: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
Georg F. Weber: Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-21310-4

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