Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in Chronic Obstructive Pulmonary Disease.
Jaspreet OsanSattya N TalukdarFriederike FeldmannBeth Ann DeMontignyKailey JeromeKristina L BaileyHeinrich FeldmannMasfique MehediPublished in: Microbiology spectrum (2022)
Chronic obstructive pulmonary disease (COPD) is one of the underlying conditions in adults of any age that place them at risk for developing severe illnesses associated with COVID-19. To determine whether SARS-CoV-2's cellular tropism plays a critical role in severe pathophysiology in the lung, we investigated its host cell entry receptor distribution in the bronchial airway epithelium of healthy adults and high-risk adults (those with COPD). We found that SARS-CoV-2 preferentially infects goblet cells in the bronchial airway epithelium, as mostly goblet cells harbor the entry receptor angiotensin-converting enzyme 2 (ACE2) and its cofactor transmembrane serine protease 2 (TMPRSS2). We also found that SARS-CoV-2 replication was substantially increased in the COPD bronchial airway epithelium, likely due to COPD-associated goblet cell hyperplasia. Likewise, SARS-CoV and Middle East respiratory syndrome (MERS-CoV) infection increased disease pathophysiology (e.g., syncytium formation) in the COPD bronchial airway epithelium. Our results reveal that goblet cells play a critical role in SARS-CoV-2-induced pathophysiology in the lung. IMPORTANCE SARS-CoV-2 or COVID-19's first case was discovered in December 2019 in Wuhan, China, and by March 2020 it was declared a pandemic by the WHO. It has been shown that various underlying conditions can increase the chance of having severe COVID-19. COPD, which is the third leading cause of death worldwide, is one of the conditions listed by the CDC which can increase the chance of severe COVID-19. The present study uses a healthy and COPD-derived bronchial airway epithelial model to study the COVID-19 and host factors which could explain the reason for COPD patients developing severe infection due to COVID-19.
Keyphrases
- sars cov
- chronic obstructive pulmonary disease
- respiratory syndrome coronavirus
- lung function
- coronavirus disease
- induced apoptosis
- angiotensin converting enzyme
- single cell
- early onset
- cell cycle arrest
- angiotensin ii
- cystic fibrosis
- air pollution
- signaling pathway
- end stage renal disease
- high glucose
- newly diagnosed
- stem cells
- drug induced
- endoplasmic reticulum stress
- oxidative stress
- chronic kidney disease
- genome wide
- ejection fraction
- dna methylation
- high resolution
- cell death
- endothelial cells
- case report
- binding protein
- atomic force microscopy
- respiratory tract
- high speed