Profound dysregulation of T cell homeostasis and function in patients with severe COVID‐19
| Autor: | Sujana Sivapatham, Sarah Adamo, Dominik J. Schaer, Melina Stüssi-Helbling, Stéphane Chevrier, Miro E. Raeber, Esther Baechli, Jakob Nilsson, Lars C. Huber, Andrea Jacobs, Liliane Yang, Alain Rudiger, Carlo Cervia, Bernd Bodenmiller, Onur Boyman, Yves Zurbuchen |
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| Přispěvatelé: | University of Zurich, Bodenmiller, Bernd, Boyman, Onur, Nilsson, Jakob |
| Rok vydání: | 2021 |
| Předmět: |
T cell
Immunology Cell T cells 610 Medicine & health macromolecular substances Disease Lymphocyte Activation Asymptomatic SARS‐CoV‐2 Flow cytometry COVID‐19 medicine COVID-19 lymphopenia SARS-CoV-2 Homeostasis Humans Autoimmunity and Clinical Immunology Immunology and Allergy Cytotoxic T cell Mass cytometry 2403 Immunology medicine.diagnostic_test business.industry Cross-Sectional Studies medicine.anatomical_structure 10033 Clinic for Immunology 2723 Immunology and Allergy Original Article 10029 Clinic and Policlinic for Internal Medicine ORIGINAL ARTICLES medicine.symptom business 11493 Department of Quantitative Biomedicine |
| Zdroj: | Allergy Allergy, 76 (9) |
| ISSN: | 1398-9995 0105-4538 |
| Popis: | Background Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID-19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill-defined in COVID-19. Methods We prospectively enrolled individuals with mild and severe COVID-19 into our multicenter cohort and performed a cross-sectional analysis of phenotypic and functional characteristics of T cells using 40-parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. Results Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID-19. Individuals with severe COVID-19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4+T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin-7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses. Conclusion Our study suggests that severe COVID-19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery. Allergy, 76 (9) ISSN:0105-4538 ISSN:1398-9995 |
| Databáze: | OpenAIRE |
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