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Profound dysregulation of T cell homeostasis and function in patients with severe COVID‐19
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 ly...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251365/ https://www.ncbi.nlm.nih.gov/pubmed/33884644 http://dx.doi.org/10.1111/all.14866 |
Sumario: | 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. |
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