Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

Human endogenous retroviruses (HERVs) have been studied and proposed as relevant cofactors in several autoimmune diseases, including type 1 diabetes (T1D), though with controversial results and no study at disease onset. In order to gather further information on the potential role of HERVs in the development of T1D we assessed the transcription levels of pol genes of HERV-H, HERV-K, and HERV-W in peripheral leucocytes from 37 children and adolescents with new-onset T1D and 50 age-matched control subjects. A PCR real time Taqman amplification assay was used to evaluate HERV transcripts with normalisation of the results to glyceraldehyde-3-phosphate dehydrogenase. The expression levels of HERV-H-pol gene and HERV-W-pol gene were significantly higher in diabetic patients than in control subjects. Conversely, no significant difference emerged in the expression levels of HERV-K-pol gene between diabetic patients and controls. The activation of HERV-H and HERV-W in new-onset T1D suggests their importance in the pathogenesis of the disease and supports targeted therapeutic attempts to hinder their activation.

Chronic hepatitis C virus (HCV) infection is associated with several hepatic and extrahepatic complications, including cancers and autoimmune disorders, whose frequency is reduced but not abolished after drug-induced viral clearance. The causes of these complications and of their persistence are ill-defined. Human endogenous retroviruses (HERVs) are remnants of ancestral infections and constitute 8% of the human genome. Most HERV elements are inactive, but some are transcribed. HERV overexpression is associated with many cancers and autoimmune diseases with a putative pathogenetic role. Several viral infections trigger HERV activation, but there are no studies on HCV-infected subjects. We assessed, through a PCR real-time amplification assay, the transcription levels of the pol genes of HERV-H, -K, and -W, and of their repressor TRIM28 in white blood cells (WBCs) of vertically infected children, both before and after therapy with direct-acting antivirals (DAAs). The results documented significantly higher expressions of HERV-H-pol and HERV-K-pol, not of HERV-W-pol, in HCV-infected subjects as compared to age-matched controls. HERV RNA levels remained unchanged after DAA-driven viral clearance. No significant variations in transcription levels of TRIM28 were observed in infected subjects. Our findings demonstrate HERV-H-pol and HERV-K-pol overexpression in subjects with chronic HCV infection, without variations after a positive response to DAAs; this might justify their predisposition to cancers and autoimmune disorders that persist after a DAA-induced resolution of viremia.

Background: The aim of this study was to investigate the efficacy of Lactobacillus rhamnosus ATCC 53103 together with the maternal diet avoidance of cow’s milk in treating infantile colic. Methods: Forty-five colicky breastfed infants were consecutively randomized to receive L. rhamnosus for 28 days at a dosage of 5 × 10⁹ cfu per day or placebo. Faecal samples were collected from each subject before starting supplementation and at the end of the study period and were immediately analysed. Faecal calprotectin was detected via a quantitative assay. The total bacterial load and selected bacterial species were evaluated using real-time TaqMan PCR. Results: After supplementation for 28 days with Lactobacillus rhamnosus ATCC 53103, median full-force daily crying was reduced (104 versus 242 min, p < 0.001) and the values of faecal calprotectin decreased significantly (p = 0.026). Furthermore, the probiotic increased the abundance of Lactobacillus (p = 0.048) and total bacteria (p = 0.040); all these effects were not observed in the placebo group. Conclusion: Infants treated with Lactobacillus rhamnosus ATCC 53103 for 28 days, in association with the elimination of cow’s milk from the maternal diet, presented some interesting features related to the effect of this probiotic treatment: reductions in crying time and faecal calprotectin, with increased total bacteria and Lactobacillus. To validate these results, a double-blind, placebo-controlled trial on a larger cohort is required.