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Critically Ill Coronavirus Disease 2019 Patients Exhibit Hyperactive Cytokine Responses Associated With Effector Exhausted Senescent T Cells in Acute Infection

2021; Oxford University Press; Linguagem: Inglês

10.1093/infdis/jiab425

1537-6613

Angélica Arcanjo, Kamila Guimarães‐Pinto, Jorgete Logullo, Paulo Emílio Corrêa Leite, Camilla Cristie Barreto Menezes, Leonardo Freire‐de‐Lima, Israel Diniz-Lima, Débora Decoté‐Ricardo, Rodrigo Nunes Rodrigues‐da‐Silva, Célio Geraldo Freire-de-Lima, Alessandra A. Filardy, Josué da Costa Lima‐Junior, Álvaro Luiz Bertho, Paula Mello De Luca, José Mauro Granjeiro, Shana Priscila Coutinho Barroso, Fátima Conceição‐Silva, Wilson Savino, Alexandre Morrot,

Long-Term Effects of COVID-19

Abstract Background Coronavirus disease 2019 (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. Methods In this study, we report that severe acutely infected patients have high levels of both type-1 and type-2 cytokines. Results Our results show abnormal cytokine levels upon T-cell stimulation, in a nonpolarized 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. Of note, we demonstrated for the first time an increased frequency of CD3+CD4+CD28−CD57+ T cells with expression of programmed death 1, one of the hallmarks of T-cell exhaustion. Conclusions 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.