Professor Malik Peiris, Dr. Michael Chan and team recently published a study evaluating the role of cigarette smoke on SARS-CoV-2-induced immune and inflammatory responses, and epithelial barrier integrity leading to airway epithelial damage.
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.
Fig. 1
Effect of cigarette smoke on SARS-CoV-2-induced morphological change and susceptibility to SARS-CoV-2 infection in airway epithelial cells.
A- Representative transmission electron micrographs of well-differentiated normal human bronchial epithelial cells (MOI = 0.1). m: mitochondria; vesicles are red arrows pointed. Scale bar, 2 μm.
B- Representative images of immunohistochemical staining with a polyclonal antibody against the SARS-CoV-2 nucleoprotein protein (MOI = 0.1). Positive cells are red-brown (black arrows). Scale bar, 50 μm. C mRNA expression of viral gene ORF1b (MOI = 2). Values are expressed as mean ± SEM (n = 5). **p < 0.01 for unpaired Student’s t-test. Ctrl, control; CSM, cigarette smoke medium; SCoV2, SARS-CoV-2; H, hours