Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by respiratory illness and an exaggerated immune response. Age (>60 years) is a significant risk factor for developing severe COVID-19. However, the underlying mechanisms of how aging impacts SARS-CoV-2 infection and the host response are largely unknown. Therefore, we performed an in vitro study to characterize the host response to SARS-CoV-2 infection using primary human bronchial epithelial cells from donors >67 years of age differentiated on 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 observe changes in genes and pathways associated with cell death and senescence throughout infection. In summary, our study provides important insights into the temporal kinetics of the airway epithelial innate immune response to SARS-CoV-2 in older individuals. Overall design: mRNA profiling of primary human bronchial epithelial cells (HBECs) from normal, nonsmoker, aged individuals (>67 years old) either uninfected or infected with SARS-CoV-2 as a function of time post-infection (24, 48, 72 and 96 hr)