Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm

Jesus Gonzalez-Rubio

Carmen Navarro-Lopez

Elena Lopez-Najera

Ana Lopez-Najera

Lydia Jimenez-Diaz

Juan Navarro-Lopez

Alberto Najera

^{Centre for Biomedical Research, School of Medicine, University of Castilla-La Mancha, Albacete, Spain}

^{Hospital General La Mancha Centro, Servicio de Salud de Castilla-La Mancha, Ciudad Real, Spain}

^{Gerencia de Atención Primaria, Salud de Castilla y Leon, Avila, Spain}

^{Gerencia de Emergencias Sanitarias, Salud de Castilla y Leon, Spain}

^{Centre for Biomedical Research, School of Medicine, University of Castilla-La Mancha, Ciudad Real, Spain}

Edited by: Haichao Wang, Feinstein Institute for Medical Research, United States

Reviewed by: Alain Simard, Northern Ontario School of Medicine, Canada; Jens D. Mikkelsen, Rigshospitalet, Denmark; Outi S. Salminen, University of Helsinki, Finland

*Correspondence: Lydia Jimenez-Diaz se.mlcu@zenemij.aidyl

Juan D. Navarro-Lopez se.mlcu@orravaN.nauJ

Alberto Najera se.mlcu@arejan.otrebla

This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

†These authors have contributed equally to this work

Edited by: Haichao Wang, Feinstein Institute for Medical Research, United States

Reviewed by: Alain Simard, Northern Ontario School of Medicine, Canada; Jens D. Mikkelsen, Rigshospitalet, Denmark; Outi S. Salminen, University of Helsinki, Finland

Received 2020 Apr 27; Accepted 2020 May 28.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients.

Keywords: cholinergic anti-inflammatory pathway, nicotine, Cytokine Release Syndrom (CRS), SARS-CoV-2 (virus), COVID- 19, lung

Acknowledgments

The authors thank Dr. Isabel Najera for helpful comments that greatly improved the manuscript. This manuscript was released as Pre-print at https://osf.io/chd2k/ on 2020/04/16 that has not been peer-reviewed (32).

Footnotes

Funding. This work was supported by University of Castilla-La Mancha Research Programme 2020-GRIN-28705.

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