The Journal of infectious diseases · 2021
Critically Ill Coronavirus Disease 2019 Patients Exhibit Hyperactive Cytokine Responses Associated With Effector Exhausted Senescent T Cells in Acute Infection.
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Arcanjo Angélica, Guimarães Pinto Kamila, Logullo Jorgete, Leite Paulo Emílio Corrêa, Menezes Camilla Cristie Barreto, Freire-de-Lima Leonardo, Diniz-Lima Israel, Decoté-Ricardo Debora, Nunes Rodrigues-da-Silva Rodrigo, Geraldo Freire-de-Lima Celio, Almeida Filardy Alessandra, Lima-Junior Josué da Costa, Luiz Bertho Alvaro, De Luca Paula Mello, Mauro Granjeiro José, Coutinho Barroso Shana Priscila, Conceição-Silva Fátima, Savino Wilson, Morrot Alexandre
Аннотация
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.
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.