tetano
Editor, Senior Moderator
Allergy
. 2021 Apr 21.
doi: 10.1111/all.14866. Online ahead of print.
Profound dysregulation of T cell homeostasisand function in patients with severe COVID-19
Sarah Adamo[SUP] 1 [/SUP], St?phane Chevrier[SUP] 2 3 [/SUP], Carlo Cervia[SUP] 1 [/SUP], Yves Zurbuchen[SUP] 1 [/SUP], Miro E Raeber[SUP] 1 [/SUP], Liliane Yang[SUP] 1 [/SUP], Sujana Sivapatham[SUP] 2 3 [/SUP], Andrea Jacobs[SUP] 2 3 [/SUP], Esther Baechli[SUP] 4 [/SUP], Alain Rudiger[SUP] 5 [/SUP], Melina St?ssi-Helbling[SUP] 6 [/SUP], Lars C Huber[SUP] 6 [/SUP], Dominik J Schaer[SUP] 7 [/SUP], Bernd Bodenmiller[SUP] 2 3 [/SUP], Onur Boyman[SUP] 1 8 [/SUP], Jakob Nilsson[SUP] 1 [/SUP]
Affiliations
Abstract
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 prominentfeature 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 tomild 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 na?veT cells, skewing toward CD4[SUP]+[/SUP] T follicular helper cells and cytotoxic CD4[SUP]+[/SUP] 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 extensiveT cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery.
Keywords: COVID-19; SARS-CoV-2; T cells; lymphopenia.
. 2021 Apr 21.
doi: 10.1111/all.14866. Online ahead of print.
Profound dysregulation of T cell homeostasisand function in patients with severe COVID-19
Sarah Adamo[SUP] 1 [/SUP], St?phane Chevrier[SUP] 2 3 [/SUP], Carlo Cervia[SUP] 1 [/SUP], Yves Zurbuchen[SUP] 1 [/SUP], Miro E Raeber[SUP] 1 [/SUP], Liliane Yang[SUP] 1 [/SUP], Sujana Sivapatham[SUP] 2 3 [/SUP], Andrea Jacobs[SUP] 2 3 [/SUP], Esther Baechli[SUP] 4 [/SUP], Alain Rudiger[SUP] 5 [/SUP], Melina St?ssi-Helbling[SUP] 6 [/SUP], Lars C Huber[SUP] 6 [/SUP], Dominik J Schaer[SUP] 7 [/SUP], Bernd Bodenmiller[SUP] 2 3 [/SUP], Onur Boyman[SUP] 1 8 [/SUP], Jakob Nilsson[SUP] 1 [/SUP]
Affiliations
- PMID: 33884644
- DOI: 10.1111/all.14866
Abstract
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 prominentfeature 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 tomild 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 na?veT cells, skewing toward CD4[SUP]+[/SUP] T follicular helper cells and cytotoxic CD4[SUP]+[/SUP] 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 extensiveT cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery.
Keywords: COVID-19; SARS-CoV-2; T cells; lymphopenia.