A distinct innate immune signature marks progression from mild to severe COVID-19
A distinct innate immune signature marks progression from mild to severe COVID-19
Abstract Coronavirus disease 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease are still not fully understood. Excessive inflammation has been postulated to be a major factor in the pathogenesis of severe COVID-19 and innate immune mechanisms are likely to be central in the inflammatory response. We used 40-plex mass cytometry and targeted serum proteomics to profile innate immune cell populations from peripheral blood of patients with mild or severe COVID-19 and healthy controls. Sampling at different stages of COVID-19 allowed us to reconstruct a pseudo-temporal trajectory of the innate immune response. Despite the expected patient heterogeneity, we identified consistent changes during the course of the infection. A rapid and early surge of CD169+ monocytes associated with an IFNγ+MCP-2+ signature quickly followed symptom onset; at symptom onset, patients with mild and severe COVID-19 had a similar signature, but over the course of the disease, the differences between patients with mild and severe disease increased. Later in the disease course, we observed a more pronounced re-appearance of intermediate/non-classical monocytes and mounting systemic CCL3 and CCL4 levels in patients with severe disease. Our data provide new insights into the dynamic nature of the early inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identifies sustained pathological innate immune responses as a likely key mechanism in severe COVID-19, further supporting investigation of targeted anti-inflammatory interventions in severe COVID-19.
Raeber Miro E.、B?chli Esther、Rudiger Alain、Schaer Dominik J.、Bodenmiller Bernd、Chevrier St¨|phane、Adamo Sarah、Jacobs Andrea、St¨1ssi-Helbling Melina、Nilsson Jakob、de Souza Natalie、Zurbuchen Yves、Huber Lars C.、Cervia Carlo、Sivapatham Sujana、Boyman Onur
Department of Immunology, University Hospital Zurich (USZ)Clinic for Internal Medicine, Uster HospitalDepartment of Medicine, Limmattal HospitalDepartment of Internal MedicineDepartment of Quantitative Biomedicine, University of ZurichDepartment of Quantitative Biomedicine, University of ZurichDepartment of Immunology, University Hospital Zurich (USZ)Department of Quantitative Biomedicine, University of ZurichClinic for Internal Medicine, City Hospital Triemli ZurichDepartment of Immunology, University Hospital Zurich (USZ)Department of Quantitative Biomedicine, University of ZurichDepartment of Immunology, University Hospital Zurich (USZ)Clinic for Internal Medicine, City Hospital Triemli ZurichDepartment of Immunology, University Hospital Zurich (USZ)Department of Quantitative Biomedicine, University of ZurichDepartment of Immunology, University Hospital Zurich (USZ)||Faculty of Medicine, University of Zurich
医学研究方法基础医学临床医学
Raeber Miro E.,B?chli Esther,Rudiger Alain,Schaer Dominik J.,Bodenmiller Bernd,Chevrier St¨|phane,Adamo Sarah,Jacobs Andrea,St¨1ssi-Helbling Melina,Nilsson Jakob,de Souza Natalie,Zurbuchen Yves,Huber Lars C.,Cervia Carlo,Sivapatham Sujana,Boyman Onur.A distinct innate immune signature marks progression from mild to severe COVID-19[EB/OL].(2025-03-28)[2025-05-08].https://www.biorxiv.org/content/10.1101/2020.08.04.236315.点此复制
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