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. 2021 Aug 24:jiab425. doi: 10.1093/infdis/jiab425

Critically ill COVID-19 patients exhibit hyperactive cytokine responses associated with effector exhausted senescent T cells in acute infection

Angélica Arcanjo 1,#, Kamila Guimarães Pinto 2,#, Jorgete Logullo 3, Paulo Emílio Corrêa Leite 4, Camilla Cristie Barreto Menezes 5, Leonardo Freire-de-Lima 3, Israel Diniz-Lima 6, Debora Decoté-Ricardo 6, Rodrigo Nunes Rodrigues-da-Silva 7, Celio Geraldo Freire-de-Lima 3, Alessandra Almeida Filardy 2, Josué da Costa Lima-Junior 8, Alvaro Luiz Bertho 8, Paula Mello De Luca 8, José Mauro Granjeiro 4,9, Shana Priscila Coutinho Barroso 10, Fátima Conceição-Silva 8, Wilson Savino 11,12,13, Alexandre Morrot 5,8,13,
PMCID: PMC8513399  PMID: 34427670

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, SARS-CoV-2 coronavirus, Immunopathology, Exhausted/senescent T cells

Supplementary Material

jiab425_suppl_Supplementary_Figure_S1

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Supplementary Materials

jiab425_suppl_Supplementary_Figure_S1

Articles from The Journal of Infectious Diseases are provided here courtesy of Oxford University Press

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