Airways tissue expression of type I interferons and their stimulated genes is higher in children than adults.

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 ß) 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/ß 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/ß 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/ß 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.

A founder effect at the EPCAM locus in Congenital Tufting Enteropathy in the Arabic Gulf.

Mutations of the EPCAM gene have been recently identified in Congenital Tufting Enteropathy (CTE), a severe autosomal recessive gastrointestinal insufficiency of childhood requiring parenteral nutrition and occasionally intestinal transplantation. Studying seven multiplex consanguineous families from the Arabic peninsula (Kuwait and Qatar) we found that most patients were homozygote for a c.498insC mutation in exon 5. The others carried a novel mutation IVS4-2A→G. Both mutations were predicted to truncate the C-terminal domain necessary to anchorage of EPCAM at the intercellular membrane. Consistently, immunohistochemistry of intestinal biopsies failed to detect the EPCAM protein at the intercellular membrane level. The c.498insC mutation was found on the background of a minimal common haplotype of 473kb suggesting a very old founder effect (5000-6000 yrs).