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Preexisting comorbidities shape the immune response associated with severe COVID-19.
Kreutmair, Stefanie; Kauffmann, Manuel; Unger, Susanne; Ingelfinger, Florian; Núñez, Nicolás Gonzalo; Alberti, Chiara; De Feo, Donatella; Krishnarajah, Sinduya; Friebel, Ekaterina; Ulutekin, Can; Babaei, Sepideh; Gaborit, Benjamin; Lutz, Mirjam; Jurado, Nicole Puertas; Malek, Nisar P; Göpel, Siri; Rosenberger, Peter; Häberle, Helene A; Ayoub, Ikram; Al-Hajj, Sally; Claassen, Manfred; Liblau, Roland; Martin-Blondel, Guillaume; Bitzer, Michael; Roquilly, Antoine; Becher, Burkhard.
  • Kreutmair S; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland; German Cancer Consortium and German Cancer Research Center, Heidelberg, Partner Site Freiburg, Freiburg, Germany. Electronic address: kreutmair@immunology.uzh.ch.
  • Kauffmann M; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Unger S; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Ingelfinger F; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Núñez NG; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Alberti C; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • De Feo D; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Krishnarajah S; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Friebel E; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Ulutekin C; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Babaei S; Department Internal Medicine I, Eberhard-Karls University, Tuebingen, Germany.
  • Gaborit B; Université de Nantes, CHU Nantes, EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Service d'Anesthésie Réanimation chirurgicale, Hôtel Dieu, Nantes, France.
  • Lutz M; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Jurado NP; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Malek NP; Department Internal Medicine I, Eberhard-Karls University, Tuebingen, Germany; the Center for Personalized Medicine, Eberhard-Karls University, Tuebingen, Germany.
  • Göpel S; Department Internal Medicine I, Eberhard-Karls University, Tuebingen, Germany; the German Centre for Infection Research, Partner Site Tuebingen, Tuebingen, Germany.
  • Rosenberger P; the Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls University, Tuebingen, Germany.
  • Häberle HA; the Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls University, Tuebingen, Germany.
  • Ayoub I; Toulouse Institute for Infectious and Inflammatory Diseases, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
  • Al-Hajj S; Toulouse Institute for Infectious and Inflammatory Diseases, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
  • Claassen M; Department Internal Medicine I, Eberhard-Karls University, Tuebingen, Germany.
  • Liblau R; Toulouse Institute for Infectious and Inflammatory Diseases, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
  • Martin-Blondel G; Toulouse Institute for Infectious and Inflammatory Diseases, Université de Toulouse, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Toulouse, France; Department of Infectious and Tropical Diseases, Toulouse University Hospital, Toulouse, Fran
  • Bitzer M; Department Internal Medicine I, Eberhard-Karls University, Tuebingen, Germany; the Center for Personalized Medicine, Eberhard-Karls University, Tuebingen, Germany.
  • Roquilly A; Université de Nantes, CHU Nantes, EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Service d'Anesthésie Réanimation chirurgicale, Hôtel Dieu, Nantes, France.
  • Becher B; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. Electronic address: becher@immunology.uzh.ch.
J Allergy Clin Immunol ; 150(2): 312-324, 2022 08.
Article in English | MEDLINE | ID: covidwho-1983272
ABSTRACT

BACKGROUND:

Comorbidities are risk factors for development of severe coronavirus disease 2019 (COVID-19). However, the extent to which an underlying comorbidity influences the immune response to severe acute respiratory syndrome coronavirus 2 remains unknown.

OBJECTIVE:

Our aim was to investigate the complex interrelations of comorbidities, the immune response, and patient outcome in COVID-19.

METHODS:

We used high-throughput, high-dimensional, single-cell mapping of peripheral blood leukocytes and algorithm-guided analysis.

RESULTS:

We discovered characteristic immune signatures associated not only with severe COVID-19 but also with the underlying medical condition. Different factors of the metabolic syndrome (obesity, hypertension, and diabetes) affected distinct immune populations, thereby additively increasing the immunodysregulatory effect when present in a single patient. Patients with disorders affecting the lung or heart, together with factors of metabolic syndrome, were clustered together, whereas immune disorder and chronic kidney disease displayed a distinct immune profile in COVID-19. In particular, severe acute respiratory syndrome coronavirus 2-infected patients with preexisting chronic kidney disease were characterized by the highest number of altered immune signatures of both lymphoid and myeloid immune branches. This overall major immune dysregulation could be the underlying mechanism for the estimated odds ratio of 16.3 for development of severe COVID-19 in this burdened cohort.

CONCLUSION:

The combinatorial systematic analysis of the immune signatures, comorbidities, and outcomes of patients with COVID-19 has provided the mechanistic immunologic underpinnings of comorbidity-driven patient risk and uncovered comorbidity-driven immune signatures.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Metabolic Syndrome / Renal Insufficiency, Chronic / COVID-19 Type of study: Cohort study / Observational study / Prognostic study / Systematic review/Meta Analysis Limits: Humans Language: English Journal: J Allergy Clin Immunol Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Metabolic Syndrome / Renal Insufficiency, Chronic / COVID-19 Type of study: Cohort study / Observational study / Prognostic study / Systematic review/Meta Analysis Limits: Humans Language: English Journal: J Allergy Clin Immunol Year: 2022 Document Type: Article