Dysregulated host response in severe acute respiratory syndrome coronavirus 2-induced critical illness

• Verfasst von: Tiwari-Heckler, Shilpa [VerfasserIn]
• Verfasst von: Rauber, Conrad [VerfasserIn]
• Verfasst von: Longhi, Maria Serena [VerfasserIn]
• Verfasst von: Zörnig, Inka [VerfasserIn]
• Verfasst von: Schnitzler, Paul [VerfasserIn]
• Verfasst von: Jäger, Dirk [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Verfasst von: Merle, Uta [VerfasserIn]
• Titel: Dysregulated host response in severe acute respiratory syndrome coronavirus 2-induced critical illness
• Verf.angabe: Shilpa Tiwari-Heckler, Conrad Rauber, Maria Serena Longhi, Inka Zörnig, Paul Schnitzler, Dirk Jäger, Thomas Giese, and Uta Merle
• E-Jahr: 2021
• Jahr: 18 January 2021
• Umfang: 9 S.
• Teil: volume:8
• Teil: year:2021
• Teil: number:3
• Teil: pages:1-9
• Teil: extent:9
• Fussnoten: Gesehen am 09.06.2021
• Titel Quelle: Enthalten in: Open Forum Infectious Diseases
• Ort Quelle: Oxford : Oxford University Press, 2014
• Jahr Quelle: 2021
• Band/Heft Quelle: 8(2021), 3, Seite 1-9
• ISSN Quelle: 2328-8957
• DOI: doi:10.1093/ofid/ofab019
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1760127116

Abstract

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.