Alterations in CD39/CD73 Axis of T cells associated with COVID-19 severity

Dorneles, Gilson Pires; Teixeira, Paula C.; Silva, Igor da; Schipper, Lucas de Lima; Filho, Paulo Santana; Rodrigues, Luiz Carlos; Bonorino, Cristina; Peres, Alessandra; Fonseca, Simone Gonçalves; Monteiro, Marta Chagas; Boeck, Carina Rodrigues; Eller, Sarah; Oliveira, Tiago Franco de; Wendland, Eliana Márcia; Romão, Pedro R T

doi:10.1101/2021.09.18.21263782

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…Moreover, it has been proposed that P2X7R antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients ( Ribeiro et al., 2021 ). Contrasting with these findings, it was reported that plasma levels of ATP are lower in mild and severe adult COVID-19 patients compared with healthy controls ( Dorneles et al., 2021 ). We here found higher plasma concentrations of ATP in children with severe and non-severe COVID-19 compared with healthy children.…”

Section: Discussionmentioning

confidence: 83%

Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19

Russo

Raiden

Algieri

et al. 2022

Front. Cell. Infect. Microbiol.

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Severe COVID-19 in children is rare, but the reasons underlying are unclear. Profound alterations in T cell responses have been well characterized in the course of adult severe COVID-19, but little is known about the T cell function in children with COVID-19. Here, we made three major observations in a cohort of symptomatic children with acute COVID-19: 1) a reduced frequency of circulating FoxP3+ regulatory T cells, 2) the prevalence of a TH17 polarizing microenvironment characterized by high plasma levels of IL-6, IL-23, and IL17A, and an increased frequency of CD4+ T cells expressing ROR-γt, the master regulator of TH17 development, and 3) high plasma levels of ATP together with an increased expression of the P2X7 receptor. Moreover, that plasma levels of ATP displayed an inverse correlation with the frequency of regulatory T cells but a positive correlation with the frequency of CD4+ T cells positive for the expression of ROR-γt. Collectively, our data indicate an imbalance in CD4+ T cell profiles during pediatric COVID-19 that might favor the course of inflammatory processes. This finding also suggests a possible role for the extracellular ATP in the acquisition of an inflammatory signature by the T cell compartment offering a novel understanding of the involved mechanisms.

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Section: Discussionmentioning

confidence: 83%

Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19

Russo

Raiden

Algieri

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The innate immune response, as the first line of defense against the infection, plays an outsized role in promoting inflammatory dysfunction, changing metabolic processes, and promoting malfunction of the adaptative immune response, such as T cells exhaustion and inadequate B cells/antibody response (1,26). HMGB1 and ATP stand out among the alarmins increased during COVID-19 infection (16)(17)(18)27). Although the pathogenic role of HMGB1 in COVID-19 remains to be explored in animal models, studies in culture systems demonstrated that HMGB1 up-regulates ACE2 expression, the main SARS-CoV-2 gateway on cellular membrane (17,19).…”

Section: Discussionmentioning

confidence: 99%

HMGB1 correlates with severity and death of COVID-19 patients

Vicentino

Fraga-Junior

Palazzo

et al. 2022

Preprint

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SARS-CoV-2, the causative agent of the ongoing COVID-19, has spread worldwide since it was first identified in November 2019 in Wuhan. Since then, it was already demonstrated an exuberant inflammation, cytokine storm, endothelium dysfunction, platelets hyperactivation and aggregation, following T cell exhaustion leading to severe multi-organ damage and death of COVID-19 patients. Here, we sought to identify molecular biomarkers of disease severity in a Brazilian cohort of COVID-19 patients by measuring the serum levels of endogenous danger signals. Our data revealed that ICU patients that are critically ill, at the early hyperinflammatory phase of COVID-19 (around 12-25 days after hospital admission) display higher serum levels of the classical alarmin HMGB1. Serum levels of HMGB1 were positively correlated with cys-leukotrienes, D-dimer, AST, and ALT. Notably, we verified that HMGB1 levels above 125.4 ng/mL is the cut off that distinguishes the patients that are at higher risk of death. Serum levels of extracellular ATP, PGE<2, LTB4, cys-LTs, and tissue factor were also elevated in the serum of ICU patients. In conclusion, we propose that serum levels of HMGB1 serve as prognostic biomarker of risk of death in patients suffering from severe COVID-19.

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“…In addition, HLA‐DR diminished expression has been reported in myeloid‐derived suppressor cells from patients with COVID‐19, 23 as well as in monocytes (CD14+ cells) from critically ill patients 24 . Because COVID‐19 evokes both inflammatory and anti‐inflammatory responses, CD39/CD73 on leucocytes could also help monitor patients with COVID‐19 25,26 . CD39 and CD73 are surface enzymes on monocytes, and T and B cells that could elicit an anti‐inflammatory 27,28 or even an immunosuppressive response 29 .…”

Section: Introductionmentioning

confidence: 99%

Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID‐19 patients with pre‐existing comorbidities

Madera‐Sandoval,

Cérbulo‐Vázquez,

Arriaga‐Pizano

et al. 2023

Clinical Translational Sci

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The difficulty in predicting fatal outcomes in COVID‐19 patients impacts the general morbidity and mortality due to SARSCoV2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre‐existing co‐morbidities. A cohort of one hundred and forty‐seven patients hospitalized for severe COVID‐19 was included in a descriptive, observational, single‐center, and prospective study. Patients were recruited during the first COVID‐19 pandemic wave (April‐Nov, 2020). Data were collected from the clinical history while immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leukocytes. Patients were grouped according to the outcome in survivor or non‐survivor. The prognostic value of leukocytes, cytokines or HLA‐DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the decease group. Mixed hypercytokinemia, including inflammatory (IL‐6) and anti‐inflammatory (IL‐10) cytokines, was more evident in deceased patients. In the decease group, lymphopenia with a higher Neutrophil‐Lymphocyte Ratio value was present. HLA‐DR expression and the percentage of CD39+ cells were higher than non‐COVID‐19 patients but remained similar despite the outcome. ROC analysis and cut‐off value of Neutrophil‐Lymphocyte Ratio (69.6%, 9.4), percentage Neutrophil‐Lymphocyte Ratio (71.1%, 13.6), IL‐6 (79.7%, 135.2 pg/mL). The expression of HLA‐DR, CD39, and CD73, as many serum cytokines (other than IL‐6) and chemokines levels do not show prognostic potential compared to Neutrophil‐Lymphocyte Ratio and percentage Neutrophil‐Lymphocyte Ratio values.

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Alterations in CD39/CD73 Axis of T cells associated with COVID-19 severity

Cited by 5 publications

References 45 publications

Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19

Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19

HMGB1 correlates with severity and death of COVID-19 patients

Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID‐19 patients with pre‐existing comorbidities

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