Alterations in T and B cell function persist in convalescent COVID-19 patients.
Autor: | Shuwa HA; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Shaw TN; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK.; Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3FL, UK., Knight SB; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK.; Department of Respiratory Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK., Wemyss K; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., McClure FA; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Pearmain L; Wellcome Trust Centre for Cell Matrix Research, The University of Manchester, Manchester M13 9PT, UK.; Division of Infection, Immunity, and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Prise I; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Jagger C; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Morgan DJ; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Khan S; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Brand O; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Mann ER; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK.; Maternal and Fetal Health Centre, Division of Developmental Biology, School of Medical Sciences, Faculty of Biology, Medicine, and Health, The University of Manchester, 5th Floor, St. Mary's Hospital, Oxford Road, Manchester M13 9WL, UK., Ustianowski A; Regional Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK., Bakerly ND; Department of Respiratory Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK., Dark P; Division of Infection, Immunity, and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK.; Intensive Care Department, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK., Brightling CE; Department of Respiratory Sciences, University of Leicester, Leicester LE3 9QP, UK., Brij S; Department of Respiratory Medicine, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK., Felton T; Division of Infection, Immunity, and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Simpson A; Division of Infection, Immunity, and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Grainger JR; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Hussell T; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Konkel JE; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK., Menon M; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Room 2.16, Core Technology Facility, 46 Grafton Street, Manchester, M13 9PL, UK. |
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Jazyk: | angličtina |
Zdroj: | Med (New York, N.Y.) [Med (N Y)] 2021 Jun 11; Vol. 2 (6), pp. 720-735.e4. Date of Electronic Publication: 2021 Mar 31. |
DOI: | 10.1016/j.medj.2021.03.013 |
Abstrakt: | Background: Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined. Methods: Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3-6 months of convalescence. Findings: We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8 + T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6 + B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10 + B cells was associated with the resolution of lung pathology. Conclusions: Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Funding: Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving. Competing Interests: The authors declare no competing interests. (© 2021 The Author(s).) |
Databáze: | MEDLINE |
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