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. Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.
【저자키워드】 viral infection, Risk factors, 【초록키워드】 Treatment, SARS-CoV-2, coronavirus, Mortality, severe COVID-19, SARS-COV-2 infection, severity, Prospective Study, Infection, outcome, viral infections, pDCs, airway, Health, Viral load, mice, Patient, Prognostic marker, innate antiviral immunity, plasma, epithelial cells, HSV-1, recruitment, disease, SARS-CoV-2 infections, dendritic cell, COVID-19 patients, IFNα, marker, pulmonary diseases, Predictive, acute respiratory syndrome, secretion, circulating, CXCL12, potential therapeutic target, independent, identify, reduced, increase, reduce, exhibiting, CD123, COVID-19 negative, IFNλ, pDC, plasmacytoid dendritic cell, 【제목키워드】 SARS-COV-2 infection, severity, outcome, marker, Predictive, Interleukin-3,