Dysregulated host response in severe acute respiratory syndrome coronavirus 2-induced critical illness
Impaired immune response has been reported to be the cause of the development of coronavirus disease 2019 (COVID-19)-related respiratory failure. Further studies are needed to understand the immunopathogenesis and to enable an improved stratification of patients who are at risk for critical illness....
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
18 January 2021
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| In: |
Open Forum Infectious Diseases
Year: 2021, Jahrgang: 8, Heft: 3, Pages: 1-9 |
| ISSN: | 2328-8957 |
| DOI: | 10.1093/ofid/ofab019 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/ofid/ofab019
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| Verfasserangaben: | Shilpa Tiwari-Heckler, Conrad Rauber, Maria Serena Longhi, Inka Zörnig, Paul Schnitzler, Dirk Jäger, Thomas Giese, and Uta Merle |
| Zusammenfassung: | Impaired immune response has been reported to be the cause of the development of coronavirus disease 2019 (COVID-19)-related respiratory failure. Further studies are needed to understand the immunopathogenesis and to enable an improved stratification of patients who are at risk for critical illness.Thirty-two severely ill patients hospitalized with COVID-19 were recruited in our center at the University Hospital Heidelberg. We performed a comprehensive analysis of immune phenotype, cytokine, and chemokine profiling and leukocyte transcripts in patients with severe COVID-19 and compared critically ill patients who required mechanical ventilation and high-flow oxygen therapy and noncritically ill patient who received low-flow oxygen therapy.Critically ill patients exhibited low levels of CD8 T cells and myeloid dendritic cells. We noted a pronounced CCR6+ TH17 phenotype in CD4 central memory cells and elevated circulating levels of interleukin-17 in the critical group. Gene expression of leukocytes derived from critically ill patients was characterized by an upregulation of proinflammatory cytokines and reduction of interferon (IFN)-responsive genes upon stimulation with Toll-like receptor 7/8 agonist. When correlating clinical improvement and immune kinetics, we found that CD8 T-cell subsets and myeloid dendritic cells significantly increased after disconnection from the ventilator.Critical illness was characterized by a TH17-mediated response and dysfunctional IFN-associated response, indicating an impaired capacity to mount antiviral responses during severe acute respiratory syndrome coronavirus 2 severe infection. |
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| Beschreibung: | Gesehen am 09.06.2021 |
| Beschreibung: | Online Resource |
| ISSN: | 2328-8957 |
| DOI: | 10.1093/ofid/ofab019 |