@article {Maggi00713-2020, author = {Fabrizio Maggi and Alfredo Rosellini and Pietro Giorgio Spezia and Daniele Focosi and Lisa Macera and Michele Lai and Mauro Pistello and Antonio de Iure and Carlo Tomino and Stefano Bonassi and Patrizia Russo}, title = {Nicotine Upregulates ACE2 Expression and Increases Competence for SARS-CoV-2 in human pneumocytes}, elocation-id = {00713-2020}, year = {2021}, doi = {10.1183/23120541.00713-2020}, publisher = {European Respiratory Society}, 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.FootnotesThis 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.}, URL = {https://openres.ersjournals.com/content/early/2021/01/28/23120541.00713-2020}, eprint = {https://openres.ersjournals.com/content/early/2021/01/28/23120541.00713-2020.full.pdf}, journal = {ERJ Open Research} }