Nicotine upregulates ACE2 expression and increases competence for SARS-CoV-2 in human pneumocytes

• Main Authors: Fabrizio Maggi, Alfredo Rosellini, Pietro Giorgio Spezia, Daniele Focosi, Lisa Macera, Michele Lai, Mauro Pistello, Antonio de Iure, Carlo Tomino, Stefano Bonassi, Patrizia Russo
• Format: Article
• Language: English
• Published: European Respiratory Society 2021-04-01
• Series: ERJ Open Research
• Online Access: http://openres.ersjournals.com/content/7/2/00713-2020.full

The coronavirus disease 2019 (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 angiotensin-converting enzyme 2 (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 severe acute respiratory syndrome coronavirus 2 (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 implications for public health policies.