Critically Ill Coronavirus Disease 2019 Patients Exhibit Hyperactive Cytokine Responses Associated With Effector Exhausted Senescent T Cells in Acute Infection
Angélica Arcanjo, Kamila Guimarães‐Pinto, Jorgete Logullo, Paulo Emílio Corrêa Leite, Camilla Cristie Barreto Menezes, Leonardo Freire‐de‐Lima, Israel Diniz-Lima, Débora Decotè-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
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.