tetano
Editor, Senior Moderator
Virol J
. 2023 Apr 11;20(1):65.
doi: 10.1186/s12985-023-02008-z.
SARS-CoV-2 infection aggravates cigarette smoke-exposed cell damage in primary human airway epithelia
Rui Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Kenrie Pui-Yan Hui[SUP] #[/SUP][SUP] 2 3 [/SUP], Yingmin Liang[SUP] 1 [/SUP], Ka-Chun Ng[SUP] 3 [/SUP], John Malcolm Nicholls[SUP] 4 [/SUP], Mary Sau-Man Ip[SUP] 1 [/SUP], Malik Peiris[SUP] 2 3 [/SUP], Michael Chi-Wai Chan[SUP] 5 6 [/SUP], Judith Choi-Wo Mak[SUP] 7 8 [/SUP]
Affiliations
Abstract
Background: The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic with over 627 million cases and over 6.5 million deaths. It was reported that smoking-related chronic obstructive pulmonary disease (COPD) might be a crucial risk for COVID-19 patients to develop severe condition. As cigarette smoke (CS) is the major risk factor for COPD, we hypothesize that barrier dysfunction and an altered cytokine response in CS-exposed airway epithelial cells may contribute to increased SARS-CoV-2-induced immune response that may result in increased susceptibility to severe disease. The aim of this study was to evaluate the role of CS on SARS-CoV-2-induced immune and inflammatory responses, and epithelial barrier integrity leading to airway epithelial damage.
Methods: Primary human airway epithelial cells were differentiated under air-liquid interface culture. Cells were then exposed to cigarette smoke medium (CSM) before infection with SARS-CoV-2 isolated from a local patient. The infection susceptibility, morphology, and the expression of genes related to host immune response, airway inflammation and damages were evaluated.
Results: Cells pre-treated with CSM significantly caused higher replication of SARS-CoV-2 and more severe SARS-CoV-2-induced cellular morphological alteration. CSM exposure caused significant upregulation of long form angiotensin converting enzyme (ACE)2, a functional receptor for SARS-CoV-2 viral entry, transmembrane serine protease (TMPRSS)2 and TMPRSS4, which cleave the spike protein of SARS-CoV-2 to allow viral entry, leading to an aggravated immune response via inhibition of type I interferon pathway. In addition, CSM worsened SARS-CoV-2-induced airway epithelial cell damage, resulting in severe motile ciliary disorder, junctional disruption and mucus hypersecretion.
Conclusion: Smoking led to dysregulation of host immune response and cell damage as seen in SARS-CoV-2-infected primary human airway epithelia. These findings may contribute to increased disease susceptibility with severe condition and provide a better understanding of the pathogenesis of SARS-CoV-2 infection in smokers.
Keywords: Airway epithelial cells; COVID-19; Cigarette smoking; SARS-CoV-2.
. 2023 Apr 11;20(1):65.
doi: 10.1186/s12985-023-02008-z.
SARS-CoV-2 infection aggravates cigarette smoke-exposed cell damage in primary human airway epithelia
Rui Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Kenrie Pui-Yan Hui[SUP] #[/SUP][SUP] 2 3 [/SUP], Yingmin Liang[SUP] 1 [/SUP], Ka-Chun Ng[SUP] 3 [/SUP], John Malcolm Nicholls[SUP] 4 [/SUP], Mary Sau-Man Ip[SUP] 1 [/SUP], Malik Peiris[SUP] 2 3 [/SUP], Michael Chi-Wai Chan[SUP] 5 6 [/SUP], Judith Choi-Wo Mak[SUP] 7 8 [/SUP]
Affiliations
- PMID: 37041586
- DOI: 10.1186/s12985-023-02008-z
Abstract
Background: The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic with over 627 million cases and over 6.5 million deaths. It was reported that smoking-related chronic obstructive pulmonary disease (COPD) might be a crucial risk for COVID-19 patients to develop severe condition. As cigarette smoke (CS) is the major risk factor for COPD, we hypothesize that barrier dysfunction and an altered cytokine response in CS-exposed airway epithelial cells may contribute to increased SARS-CoV-2-induced immune response that may result in increased susceptibility to severe disease. The aim of this study was to evaluate the role of CS on SARS-CoV-2-induced immune and inflammatory responses, and epithelial barrier integrity leading to airway epithelial damage.
Methods: Primary human airway epithelial cells were differentiated under air-liquid interface culture. Cells were then exposed to cigarette smoke medium (CSM) before infection with SARS-CoV-2 isolated from a local patient. The infection susceptibility, morphology, and the expression of genes related to host immune response, airway inflammation and damages were evaluated.
Results: Cells pre-treated with CSM significantly caused higher replication of SARS-CoV-2 and more severe SARS-CoV-2-induced cellular morphological alteration. CSM exposure caused significant upregulation of long form angiotensin converting enzyme (ACE)2, a functional receptor for SARS-CoV-2 viral entry, transmembrane serine protease (TMPRSS)2 and TMPRSS4, which cleave the spike protein of SARS-CoV-2 to allow viral entry, leading to an aggravated immune response via inhibition of type I interferon pathway. In addition, CSM worsened SARS-CoV-2-induced airway epithelial cell damage, resulting in severe motile ciliary disorder, junctional disruption and mucus hypersecretion.
Conclusion: Smoking led to dysregulation of host immune response and cell damage as seen in SARS-CoV-2-infected primary human airway epithelia. These findings may contribute to increased disease susceptibility with severe condition and provide a better understanding of the pathogenesis of SARS-CoV-2 infection in smokers.
Keywords: Airway epithelial cells; COVID-19; Cigarette smoking; SARS-CoV-2.