ReviewPurinergic signalling2022
A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.
Review in Purinergic signalling, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- The role of alveolar epithelial junctions in early lung injury and COVID-19-induced fibrosis.Histochemistry and cell biology · 2026Article
- Effect of subcutaneous lidocaine-hydroxypropyl-β-cyclodextrin (HP-β-CD) on quality of life in patients with post-COVID condition: a 36-week observational interrupted time series study.EClinicalMedicine · 2025Article
- The role of the P2X7 receptor in inactivated SARS-CoV-2-induced lung injury.Purinergic signalling · 2025Article
- Clinical and laboratory markers defining MIS-C and hyperinflammation in COVID-19: a cross-sectional study in a tertiary hospital.Advances in rheumatology (London, England) · 2025Article
- SARS-CoV-2 Infection and Alpha-Synucleinopathies: Potential Links and Underlying Mechanisms.International journal of molecular sciences · 2024Review
- Current treatment of Psoriasis triggered by Cytokine Storm and future immunomodulation strategies.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Editorial overview: "Purinergic immune cell regulation reveals novel pharmacological targets".Current opinion in pharmacology · 2024Article
- Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.PLoS biology · 2024Article
- Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Lidocaine reinforces the anti-inflammatory action of dexamethasone on myeloid and epithelial cells activated by inflammatory cytokines or SARS-CoV-2 infection.Biomedical journal · 2023Article
- Brain Renin-Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by SARS-CoV-2.Analytical cellular pathology (Amsterdam) · 2023Review
- Chemical Tools for the Study of DNA Repair.Accounts of chemical research · 2022Article
- Effect of Pirfenidone on Risk of Pulmonary Fibrosis in COVID-19 Patients Experiencing Cytokine Storm.Healthcare (Basel, Switzerland) · 2022Article
- Effects of Purinergic Receptor Deletion or Pharmacologic Modulation on Pulmonary Inflammation in Mice.ACS pharmacology & translational science · 2022Article
- Alterations in CD39/CD73 axis of T cells associated with COVID-19 severity.Journal of cellular physiology · 2022Article
- The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2.Frontiers in immunology · 2022Review
- Soluble P2X7 Receptor Is Elevated in the Plasma of COVID-19 Patients and Correlates With Disease Severity.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic receptors of the immune cells initiating the physiologic pro-inflammatory immune response. Persisting viral infection drives the ATP release even further leading to the activation of the P2X7 purinergic receptors (P2X7Rs) and a severe yet physiologic inflammation. Disease progression promotes prolonged vigorous activation of the P2X7R causing cell death and uncontrolled ATP release leading to cytokine storm and desensitisation of all other purinergic receptors of the immune cells. This results in immune paralysis with co-infections or secondary infections. We refer to this pathologic condition as hyperinflammation. The readily available and affordable P2X7R antagonist lidocaine can abrogate hyperinflammation and restore the normal immune function. The issue is that the half-maximal effective concentration for P2X7R inhibition of lidocaine is much higher than the maximal tolerable plasma concentration where adverse effects start to develop. To overcome this, we selectively inhibit the P2X7Rs of the immune cells of the lymphatic system inducing clonal expansion of Tregs in local lymph nodes. Subsequently, these Tregs migrate throughout the body exerting anti-inflammatory activities suppressing systemic and (distant) local hyperinflammation. We illustrate this with six critically ill COVID-19 patients treated with lidocaine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.