ArticleFrontiers in immunology2022
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Understanding neuroinflammation in post-COVID-19 syndrome: biological mechanisms, diagnostic biomarkers, and therapeutic prospects.Translational psychiatry · 2026Review
- The role of the P2X7 receptor in inactivated SARS-CoV-2-induced lung injury.Purinergic signalling · 2025Article
- Purinergic signaling in the battlefield of viral infections.Purinergic signalling · 2025Review
- Altered CD73-Adenosine Signaling Linked to Infection in Patients undergoing hemodialysis.Journal of inflammation research · 2025Article
- T Regulatory Cell Subsets Do Not Restore for One Year After Acute COVID-19.International journal of molecular sciences · 2024Article
- Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS.Molecular biology reports · 2024Review
- Article
- Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.Brain sciences · 2024Review
- ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.Frontiers in immunology · 2024Article
- Adenosine AFrontiers in pharmacology · 2024Article
- Transcriptome and machine learning analysis of the impact of COVID-19 on mitochondria and multiorgan damage.PloS one · 2024Article
- Elevated CD39+T-Regulatory Cells and Reduced Levels of Adenosine Indicate a Role for Tolerogenic Signals in the Progression from Moderate to Severe COVID-19.International journal of molecular sciences · 2023Article
- The role of Pannexin-1 channels, ATP, and purinergic receptors in the pathogenesis of HIV and SARS-CoV-2.Current opinion in pharmacology · 2023Review
- Purinergic signaling pathway in severe COVID-19.Current opinion in pharmacology · 2023Review
- The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections.Pathogens (Basel, Switzerland) · 2023Review
- Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies.Frontiers in immunology · 2023Article
- Editorial: Hypoxia and inflammation: A two-way street.Frontiers in immunology · 2023Article
- Differential expression patterns of purinergic ectoenzymes and the antioxidative role of IL-6 in hospitalized COVID-19 patient recovery.Frontiers in immunology · 2023Article
- Characterization of Regulatory T Cells in Patients Infected byTropical medicine and infectious disease · 2022Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients' cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.
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