Goblet Cell Hyperplasia Increases SARS-CoV-2 Infection in COPD

Abstract

SummarySARS-CoV-2 has become a major problem across the globe, with approximately 50 million cases and more than 1 million deaths and currently no approved treatment or vaccine. Chronic obstructive pulmonary disease (COPD) is one of the underlying conditions in adults of any age that place them at risk for developing severe illness associated with COVID-19. We established an airway epithelium model to study SARS-CoV-2 infection in healthy and COPD lung cells. We found that both the entry receptor ACE2 and the co-factor transmembrane protease TMPRSS2 are expressed at higher levels on nonciliated goblet cell, a novel target for SARS-CoV-2 infection. We observed that SARS-CoV-2 infected goblet cells and induced syncytium formation and cell sloughing. We also found that SARS-CoV-2 replication was increased in the COPD airway epithelium likely due to COPD associated goblet cell hyperplasia. Our results reveal goblet cells play a critical role in SARS-CoV-2 infection in the lung.

Immunohistochemistry for protein detection in PFA-fixed paraffin-embedded SARS-CoV-2-infected COPD airway epithelium

“…The authors recommend infection experiment with SARS-CoV-2 should be performed in a high biocontainment facility. Note: For developing this protocol, the work with SARS-CoV-2 was performed in the high biocontainment facility at the Rocky Mountain Laboratories (RML), NIAID, NIH in Hamilton, MT ( Osan et al., 2020 ). All infectious works followed standard operating procedures (SOPs) approved by the Institutional Biosafety Committee.…”

COVID-19 Gastrointestinal Symptoms and Attenuation of the Immune Response to SARS-CoV-2

“…12 They attribute this finding to increased MUC2þ goblet cell prevalence in distal small intestine, which colocalized with NP immunostaining, and their transmission electron microscopy images showing viral particles present primarily in exit vesicles of goblet cells. 12 This finding may corroborate findings from bronchial air-liquid interface cultures demonstrating tropism for goblet cells, 13 but were nevertheless surprising given relatively low ACE2 expression in intestinal goblet cell clusters, 5 evidence of goblet cell depletion in an infected patient's colonic biopsies, 9 and data from human intestinal organoids demonstrating enterocytes were susceptible to infection whereas goblet cells were not. 6,11 Livanos et al 12 also find evidence of NP staining in a nongoblet crypt base cell population but do not discern this population as Paneth, stem cells, or another population.…”

4’-Fluorouridine is a broad-spectrum orally efficacious antiviral blocking respiratory syncytial virus and SARS-CoV-2 replication

“…When comparing activity of 4'-FlU against SARS-CoV-2 and RSV in cultured cells and welldifferentiated HAEs, anti-SARS-CoV-2 potency was overproportionally lower in the organoid models. RSV tropism in the organoids is restricted to ciliated cells (30,31), whereas SARS-CoV-2 can reportedly be found in both ciliated and goblet cells (32)(33)(34)(35)(36)(37). Conceivably, 4'-FlU anabolism efficiency could be higher in ciliated than in goblet cells, affecting anti-SARS-CoV-2 impact in this system.…”