tetano
Editor, Senior Moderator
J Infect Dis
. 2021 Aug 24;jiab425.
doi: 10.1093/infdis/jiab425. Online ahead of print.
Critically ill COVID-19 patients exhibit hyperactive cytokine responses associated with effector exhausted senescent T cells in acute infection
Angélica Arcanjo[SUP] 1 [/SUP], Kamila Guimarães Pinto[SUP] 2 [/SUP], Jorgete Logullo[SUP] 3 [/SUP], Paulo Emílio Corrêa Leite[SUP] 4 [/SUP], Camilla Cristie Barreto Menezes[SUP] 5 [/SUP], Leonardo Freire-de-Lima[SUP] 3 [/SUP], Israel Diniz-Lima[SUP] 6 [/SUP], Debora Decoté-Ricardo[SUP] 6 [/SUP], Rodrigo Nunes Rodrigues-da-Silva[SUP] 7 [/SUP], Celio Geraldo Freire-de-Lima[SUP] 3 [/SUP], Alessandra Almeida Filardy[SUP] 2 [/SUP], Josué da Costa Lima-Junior[SUP] 8 [/SUP], Alvaro Luiz Bertho[SUP] 8 [/SUP], Paula Mello De Luca[SUP] 8 [/SUP], José Mauro Granjeiro[SUP] 4 9 [/SUP], Shana Priscila Coutinho Barroso[SUP] 10 [/SUP], Fátima Conceição-Silva[SUP] 8 [/SUP], Wilson Savino[SUP] 11 12 13 [/SUP], Alexandre Morrot[SUP] 5 8 13 [/SUP]
Affiliations
Abstract
COVID-19 can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm. We herein report that severe acutely infected patients have high levels of both type-1 and type-2 cytokines. Our results show abnormal cytokine levels upon T cell stimulation, in a non-polarized profile. Furthermore, our findings indicate that this hyperactive cytokine response is associated with a significantly increased frequency of late-differentiated T cells with particular phenotype of effector exhausted/senescent CD28 -CD57 + cells. Interestingly, we demonstrated for the first time an increased frequency of CD3 +CD4 +CD28 -CD57 + T cells with expression of programmed death 1 (PD-1), one of the hallmarks of T cell exhaustion. These findings reveal that COVID-19 is associated with acute immunodeficiency, especially within the CD4 + T cell compartment and points to possible mechanisms of loss of clonal repertoire and susceptibility to viral relapse and reinfection events.
Keywords: COVID-19; Exhausted/senescent T cells; Immunopathology; SARS-CoV-2 coronavirus.
. 2021 Aug 24;jiab425.
doi: 10.1093/infdis/jiab425. Online ahead of print.
Critically ill COVID-19 patients exhibit hyperactive cytokine responses associated with effector exhausted senescent T cells in acute infection
Angélica Arcanjo[SUP] 1 [/SUP], Kamila Guimarães Pinto[SUP] 2 [/SUP], Jorgete Logullo[SUP] 3 [/SUP], Paulo Emílio Corrêa Leite[SUP] 4 [/SUP], Camilla Cristie Barreto Menezes[SUP] 5 [/SUP], Leonardo Freire-de-Lima[SUP] 3 [/SUP], Israel Diniz-Lima[SUP] 6 [/SUP], Debora Decoté-Ricardo[SUP] 6 [/SUP], Rodrigo Nunes Rodrigues-da-Silva[SUP] 7 [/SUP], Celio Geraldo Freire-de-Lima[SUP] 3 [/SUP], Alessandra Almeida Filardy[SUP] 2 [/SUP], Josué da Costa Lima-Junior[SUP] 8 [/SUP], Alvaro Luiz Bertho[SUP] 8 [/SUP], Paula Mello De Luca[SUP] 8 [/SUP], José Mauro Granjeiro[SUP] 4 9 [/SUP], Shana Priscila Coutinho Barroso[SUP] 10 [/SUP], Fátima Conceição-Silva[SUP] 8 [/SUP], Wilson Savino[SUP] 11 12 13 [/SUP], Alexandre Morrot[SUP] 5 8 13 [/SUP]
Affiliations
- PMID: 34427670
- DOI: 10.1093/infdis/jiab425
Abstract
COVID-19 can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm. We herein report that severe acutely infected patients have high levels of both type-1 and type-2 cytokines. Our results show abnormal cytokine levels upon T cell stimulation, in a non-polarized profile. Furthermore, our findings indicate that this hyperactive cytokine response is associated with a significantly increased frequency of late-differentiated T cells with particular phenotype of effector exhausted/senescent CD28 -CD57 + cells. Interestingly, we demonstrated for the first time an increased frequency of CD3 +CD4 +CD28 -CD57 + T cells with expression of programmed death 1 (PD-1), one of the hallmarks of T cell exhaustion. These findings reveal that COVID-19 is associated with acute immunodeficiency, especially within the CD4 + T cell compartment and points to possible mechanisms of loss of clonal repertoire and susceptibility to viral relapse and reinfection events.
Keywords: COVID-19; Exhausted/senescent T cells; Immunopathology; SARS-CoV-2 coronavirus.