Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Generation of Cytotoxic T cells and Dysfunctional CD8 T Cells in Severe COVID19 Patients

Version 1 : Received: 26 August 2022 / Approved: 29 August 2022 / Online: 29 August 2022 (14:30:57 CEST)

How to cite: Gozzi-Silva, S.C.; Oliveira, L.D.M.; Alberca, R.W.; Pereira, N.Z.; Yoshikawa, F.S.; Pietrobon, A.J.; Yendo, T.M.; Andrade, M.M.; Ramos, Y.Á.L.; Brito, C.A.; Oliveira, E.A.; Beserra, D.R.; Duarte, A.J.D.S.; Sato, M.N. Generation of Cytotoxic T cells and Dysfunctional CD8 T Cells in Severe COVID19 Patients. Preprints 2022, 2022080496 (doi: 10.20944/preprints202208.0496.v1). Gozzi-Silva, S.C.; Oliveira, L.D.M.; Alberca, R.W.; Pereira, N.Z.; Yoshikawa, F.S.; Pietrobon, A.J.; Yendo, T.M.; Andrade, M.M.; Ramos, Y.Á.L.; Brito, C.A.; Oliveira, E.A.; Beserra, D.R.; Duarte, A.J.D.S.; Sato, M.N. Generation of Cytotoxic T cells and Dysfunctional CD8 T Cells in Severe COVID19 Patients. Preprints 2022, 2022080496 (doi: 10.20944/preprints202208.0496.v1).

Abstract

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

Keywords

SARS-CoV-2; COVID-19; T-lymphocytes; antiviral response; cytotoxic factors

Subject

BIOLOGY, Other

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