Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV2 Infection Severity

Leonardo Lupacchini
,
Fabrizio Maggi
ORCID logo ,
Carlo Tomino
,
Chiara De Dominicis
,
Cristiana Mollinari
,
Massimo Fini
,
Stefano Bonassi
,
Daniela Merlo
,
Patrizia Russo
*
Version 1 : Received: 17 December 2020 / Approved: 18 December 2020 / Online: 18 December 2020 (13:24:14 CET)

A peer-reviewed article of this Preprint also exists.

Lupacchini, L.; Maggi, F.; Tomino, C.; De Dominicis, C.; Mollinari, C.; Fini, M.; Bonassi, S.; Merlo, D.; Russo, P. Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity. Molecules 2021, 26, 101. Lupacchini, L.; Maggi, F.; Tomino, C.; De Dominicis, C.; Mollinari, C.; Fini, M.; Bonassi, S.; Merlo, D.; Russo, P. Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity. Molecules 2021, 26, 101.

Abstract

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective is to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1, 48 h or continuously with 10-7 M Nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-beta-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca+2, ATP and EMT were evaluated by ELISA and/or western blotting. (3) Results: Nicotine induced through α7-nAChR (i) increase in cell viability (ii) cell proliferation; (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation (v) EGFR/pEGFR over-expression; (vi) increase in basal Ca+2 concentration, (vii) reduction of ATP production; (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that Nicotine potentiates viral infection it is likely that Nicotine is involved in SARS-CoV-2 infection and severity

Keywords

Cell Proliferation; EMT; Mitochondrial Dysfunction; nAChR; Nicotine; SARS-CoV-2

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (2)

Comment 1
Received: 18 December 2020
Commenter:
Ernesto de Bernardis

The commenter has declared there is no conflict of interests.
Comment: It's a very interesting series of observations but I don't think at this stage it is possible to extrapolate them with confidence to predict the effect of nicotine on SARS-CoV-2 infection of that cell line, let alone a whole human being.
I would recommend a more nuanced approach when jumping from the many interesting, and thought-provoking findings, to pharmacological effects in a complex organism.
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Response 1 to Comment 1
Received: 28 December 2020
Commenter:
patrizia russo

The commenter has declared there is no conflict of interests.
Comment: dear Dr. Ernesto De Bernardis
firstly the paper is in press to Molecules.
Thanks for your comment. We have now an accepted paper by ERJ open research that when A549 cells are treated with nicotine and infected with SARS-CoV-2 these cells, not permissive to infection by SARS-CoV-2, are massively infected with a large cytopathic effect

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