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Nicotine Upregulates ACE2 Expression and Increases Competence for SARS-CoV-2 in human pneumocytes

Fabrizio Maggi, Alfredo Rosellini, Pietro Giorgio Spezia, Daniele Focosi, Lisa Macera, Michele Lai, Mauro Pistello, Antonio de Iure, Carlo Tomino, Stefano Bonassi, Patrizia Russo
ERJ Open Research 2021; DOI: 10.1183/23120541.00713-2020
Fabrizio Maggi
1Department of Medicine and Surgery, University of Insubria, Varese, Italy
2Laboratory of Clinical Microbiology, ASST dei Sette Laghi, Varese, Italy
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Alfredo Rosellini
3Virology Division, Pisa University Hospital, Pisa, Italy
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Pietro Giorgio Spezia
4Department of Translational Research, University of Pisa, Pisa, Italy
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Daniele Focosi
5North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy
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Lisa Macera
3Virology Division, Pisa University Hospital, Pisa, Italy
4Department of Translational Research, University of Pisa, Pisa, Italy
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Michele Lai
4Department of Translational Research, University of Pisa, Pisa, Italy
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Mauro Pistello
3Virology Division, Pisa University Hospital, Pisa, Italy
4Department of Translational Research, University of Pisa, Pisa, Italy
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Antonio de Iure
6Experimental Neurophysiology, IRCSS San Raffaele Pisana, Rome, Italy
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Carlo Tomino
7Scientific Direction, IRCSS San Raffaele Pisana, Rome, Italy
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Stefano Bonassi
8Clinical and Molecular Epidemiology, IRCSS San Raffaele Pisana, Rome, Italy
9Department of Human Sciences, and Quality of Life Promotion San Raffaele University, Rome, Italy
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Patrizia Russo
8Clinical and Molecular Epidemiology, IRCSS San Raffaele Pisana, Rome, Italy
9Department of Human Sciences, and Quality of Life Promotion San Raffaele University, Rome, Italy
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  • For correspondence: patrizia_russo@hotmail.it patrizia.russo@uniroma5.it
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Abstract

The COVID-19 pandemic has a variable degree of severity according to underlying comorbidities and life-style. Several research groups have reported an association between cigarette smoking and increased severity of COVID-19. The exact mechanism of action is largely unclear.

We exposed low ACE2-expressing human pulmonary adenocarcinoma A549 epithelial cells to nicotine and assessed ACE2 expression at different times. We further used the nicotine-exposed cells in a virus neutralisation assay.

Nicotine exposure induces rapid and long-lasting increases in gene and protein expression of the SARS-CoV-2 receptor ACE2, which in turn translates into increased competence for SARS-CoV-2 replication and cytopathic effect.

These findings show that nicotine worsens SARS-CoV-2 pulmonary infection and have implication for public health policies.

Footnotes

This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.

Conflict of interest: Dr. maggi has nothing to disclose.

Conflict of interest: Dr. rosellini has nothing to disclose.

Conflict of interest: Dr. spezia has nothing to disclose.

Conflict of interest: Dr. focosi has nothing to disclose.

Conflict of interest: Dr. macera has nothing to disclose.

Conflict of interest: Dr. lai has nothing to disclose.

Conflict of interest: Dr. pistello has nothing to disclose.

Conflict of interest: Dr. de iure has nothing to disclose.

Conflict of interest: Dr. tomino has nothing to disclose.

Conflict of interest: Dr. bonassi has nothing to disclose.

Conflict of interest: Dr. russo has nothing to disclose.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received September 30, 2020.
  • Accepted January 24, 2021.
  • ©The authors 2021
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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Nicotine Upregulates ACE2 Expression and Increases Competence for SARS-CoV-2 in human pneumocytes
Fabrizio Maggi, Alfredo Rosellini, Pietro Giorgio Spezia, Daniele Focosi, Lisa Macera, Michele Lai, Mauro Pistello, Antonio de Iure, Carlo Tomino, Stefano Bonassi, Patrizia Russo
ERJ Open Research Jan 2021, 00713-2020; DOI: 10.1183/23120541.00713-2020

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Nicotine Upregulates ACE2 Expression and Increases Competence for SARS-CoV-2 in human pneumocytes
Fabrizio Maggi, Alfredo Rosellini, Pietro Giorgio Spezia, Daniele Focosi, Lisa Macera, Michele Lai, Mauro Pistello, Antonio de Iure, Carlo Tomino, Stefano Bonassi, Patrizia Russo
ERJ Open Research Jan 2021, 00713-2020; DOI: 10.1183/23120541.00713-2020
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