Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. Age (>60 years) is a significant risk factor for developing severe COVID-19. To better understand the host response of the aged airway epithelium to SARS-CoV-2 infection, we performed an in vitro study using primary human bronchial epithelial cells from donors >67 years of age differentiated on an air–liquid interface culture. We demonstrate that SARS-CoV-2 infection leads to early induction of a proinflammatory response and a delayed interferon response. In addition, we observed changes in the genes and pathways associated with cell death and senescence throughout infection. In summary, our study provides new and important insights into the temporal kinetics of the airway epithelial innate immune response to SARS-CoV-2 in older individuals.
Highlights
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness
Our results demonstrated that air–liquid interface (ALI) differentiated epithelia generated from aged human bronchial epithelial cells (HBECs) donors are permissive to SARS-CoV-2 infection, resulting in the production of an infectious virus and a potent host response
We utilized the in vitro ALI culture model to study the virus replication kinetics and the host response following SARS-CoV-2 infection of a mucociliary epithelium generated using primary HBECs isolated from older individuals (>67 years old)
Summary
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. 1. Introduction with regard to jurisdictional claims in Coronavirus disease 2019 (COVID-19) is a global pandemic caused in response to infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a highly transmissible and pathogenic virus [1,2]. In vitro organotypic cell cultures of the human airway epithelium have been used extensively to help further our knowledge of SARS-CoV2 biology and the host response to infection [9].
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