Airways tissue expression of type I interferons and their stimulated genes is higher in children than adults
Narjes Saheb Sharif-Askari,
Fatemeh Saheb Sharif-Askari,
Shirin Hafezi,
Zaina Kalaji,
Mohamed Temsah,
Saleh Almuhsen,
Habiba S. Alsafar,
Qutayba Hamid,
Rabih Halwani
Affiliations
Narjes Saheb Sharif-Askari
Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
Fatemeh Saheb Sharif-Askari
Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates
Shirin Hafezi
Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates
Zaina Kalaji
Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates
Mohamed Temsah
Department of Pediatrics, College of Medicine, King Saud University, Saudi Arabia
Saleh Almuhsen
Immunology Research Laboratory, Department of Pediatrics, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
Habiba S. Alsafar
Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Department of Biomedical Engineering, College of Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; Department of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
Qutayba Hamid
Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; Meakins-Christie Laboratories, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada
Rabih Halwani
Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; Prince Abdullah Ben Khaled Celiac Disease Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Saudi Arabia; Corresponding author.
There is emerging evidence that age-dependent differences in susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with stronger innate immune response in the upper respiratory tract in children compared to adults. The efficient induction of interferon (IFN) alpha and beta (α and β) signaling, and interferon-stimulated genes (ISGs) is fundamental to the host antiviral response. In-silico transcriptomic analyses was conducted to determine the expression levels of IFN α/β pathway genes as well as 524 human ISGs in upper and lower airways of children and adults at baseline and post respiratory infections including coronavirus disease 2019 (COVID-19). To validate our in-silico analysis, we conducted qRT-PCR to measure ISGs levels in children and adult's nasal epithelial samples. At baseline, children had significantly higher levels of IFN α/β and ISGs genes compared to adults. More distinction was also seen in bronchial compared to nasal basal levels. Children nasal epithelial cells exhibited superior antiviral IFN α/β and associated ISGs response following ex-vivo poly (I:C) treatment model, and in clinical samples of SARS-CoV-2 infected patients. This was also confirmed in nasal epithelial samples using qRT-PCR validation. No gender-based difference in type I IFN levels across both age groups were observed. Understanding the biological basis for children resistance against severe COVID-19 is a challenge that has substantial clinical importance. More mechanistic studies are needed to carefully quantify how much of early IFN levels is needed to bypass the viral evasion mechanism and prevent its further replication and dissemination to lower airways and the rest of the body.
