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A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.
Hasan, Djo; Shono, Atsuko; van Kalken, Coenraad K; van der Spek, Peter J; Krenning, Eric P; Kotani, Toru.
  • Hasan D; , Kasterlee, Belgium. djohasan@gmail.com.
  • Shono A; Department of Anaesthesiology and Critical Care Medicine, School of Medicine, Showa University, Tokyo, 142-8666, Japan.
  • van Kalken CK; , Hoorn, The Netherlands.
  • van der Spek PJ; Department of Pathology & Clinical Bioinformatics, Erasmus MC, Erasmus Universiteit Rotterdam, 3015 CE, Rotterdam, The Netherlands.
  • Krenning EP; , Rotterdam, The Netherlands.
  • Kotani T; Department of Anaesthesiology and Critical Care Medicine, School of Medicine, Showa University, Tokyo, 142-8666, Japan.
Purinergic Signal ; 18(1): 13-59, 2022 03.
Article in English | MEDLINE | ID: covidwho-1694363
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adenosine Triphosphate / Receptors, Purinergic / Purinergic P2X Receptor Antagonists / Cytokine Release Syndrome / COVID-19 / Inflammation / Lidocaine Type of study: Case report Limits: Humans / Male / Middle aged Language: English Journal: Purinergic Signal Year: 2022 Document Type: Article Affiliation country: S11302-021-09814-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Adenosine Triphosphate / Receptors, Purinergic / Purinergic P2X Receptor Antagonists / Cytokine Release Syndrome / COVID-19 / Inflammation / Lidocaine Type of study: Case report Limits: Humans / Male / Middle aged Language: English Journal: Purinergic Signal Year: 2022 Document Type: Article Affiliation country: S11302-021-09814-6