Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals
Bharathiraja Subramaniyan,
Jason L. Larabee,
Manish Bodas,
Andrew R. Moore,
Anthony W. G. Burgett,
Dean A. Myers,
Constantin Georgescu,
Jonathan D. Wren,
James F. Papin,
Matthew S. Walters
Affiliations
Bharathiraja Subramaniyan
Department of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Jason L. Larabee
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Manish Bodas
Department of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Andrew R. Moore
Department of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Anthony W. G. Burgett
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Dean A. Myers
Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Constantin Georgescu
Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Jonathan D. Wren
Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
James F. Papin
Department of Pathology, Division of Comparative Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Matthew S. Walters
Department of Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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.
