DIFFERENTIAL IFN GENES EXPRESSION in the UPPER AIRWAYS of CHILDREN and ADULTS

ABSTRACT

Background: Children generally develop a mild disease after SARS-CoV-2 infection;it has been shown (Loske J al., 2021) that higher basal expression of relevant pattern recognition receptors may result in a stronger early innate antiviral than in adults. However, how the early interferon (IFN) response differs from that in adults is not fully characterized. Hence, we aimed to investigate the expression of several IFN-related genes in nasopharyngeal (NP) cells from children and adults with asymptomatic or mild COVID-19, not requiring hospitalization. Methods: Children and adults attending emergency departments (ED) of Sapienza University Hospital, to perform SARS-CoV-2 molecular tests, were enrolled from November 2020 to February 2021, after informed consent was obtained. RNA from residual NP swabs was purified and 200 ng were reverse transcribed. Gene expression of genes coding for type I and III IFNs and for the well-known markers of IFNs' activation, ISG15 and ISG56, was measured by exonuclease-based Real time PCR assays with relative quantification to the invariant gene GUS (the 2-ΔCt method). Results: Residual NP cells from a total of 132 children and adults were included in the study;56 had SARS-CoV-2 positive results and 76 resulted negative. The expression of all tested genes showed a moderate significant inverse correlation with age, with the exception of ISG15. Participants were further stratified in age groups (< 16;16-35;36-65 years) resulting in 25 SARS-CoV-2 negative and 26-positive children;14 SARS-CoV-2 negative and 16-positive young adults and 37 SARS-CoV-2 negative and 14-positive adults. In SARS-CoV-2 negative samples, higher levels of all study genes were found in children, while significantly decreasing in young and elderly adults. Among SARS-CoV-2 positive samples, those from children showed significantly higher levels of type I IFNs and of IFN lambda2 whereas ISG15 was far more elevated in adults. Moreover, levels of all type I IFNs, and of IFN lambda2, were significantly higher in individuals with no symptoms (65% of children and 44% of the young adults), whereas ISG15 was elevated in those with a mild COVID-19. Conclusion: The higher baseline expression of IFN-related genes in children may prompt a quicker activation of the IFN response after SARS-CoV-2 infection and contribute to effective control of viral replication;the higher ISG activation in adults may be caused by the inflammatory response and associated to COVID-19 symptoms.