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Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed.AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells.Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins.HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

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Background: The vertical transmission of severe acute respiratory coronavirus-2 (SARS-CoV-2) remains highly debated. Here, we evaluated SARS-CoV-2-transmission in newborns with intrauterine conditions. Methods: This was a prospective, observational and multicentric study involving 13 Spanish hospitals included in the GEStational and NEOnatal-COVID cohort. Pregnant women with microbiologically confirmed SARS-CoV-2 infection during any trimester of pregnancy or delivery and their newborns were included from March to November 2020. Demographic, clinical and microbiological data were also obtained. Viral loads were analyzed in different maternal and newborn biological samples (placenta, breast milk and maternal blood; urine, meconium and newborn blood). Results: A total of 177 newborns exposed to SARS-CoV-2 were included. Newborns were tested by reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs within the first 24–48 hours of life and at 14 days of life. In total 5.1% were considered to have SARS-CoV-2 infection in the neonatal period, with 1.7% considered intrauterine and 3.4% intrapartum or early postnatal transmission cases. There were no differences in the demographic and clinical characteristics of the pregnant women and their newborns’ susceptibility to infections in their perinatal history or background. Conclusions: Intrauterine transmission of SARS-CoV-2 is possible, although rare, with early postnatal transmission occurring more frequently. Most infected newborns remained asymptomatic or had mild symptoms that evolved well during follow-up. We did not find any maternal characteristics predisposing infants to neonatal infection. All infected newborn mothers had acute infection at delivery. Although there was no presence of SARS-CoV2 in cord blood or breast milk samples, SARS-CoV-2 viral load was detected in urine and meconium samples from infected newborns.

Background Chagas disease (CD) is an emergent disease in Europe, due to immigration. The aims of this study are to describe the epidemiological characteristics of a cohort of Chagas infected pregnant women in Spain, to assess the vertical transmission (VT) rate and evaluate the usefulness of the PCR in the diagnosis of congenital infection in the first months of life. Methods A descriptive, retrospective study including Chagas seropositive pregnant women who were attended at three tertiary hospitals in Madrid, from January 2012 to September 2016. Infants were examined by PCR at birth and 1 month later and serologically studied at 9 months or later. Children were considered infected when the parasite was detected by PCR at any age or when serology remained positive without decline over the age of 9 months. Results We included 122 seropositive-infected pregnant women, 81% were from Bolivia and only 8.2% had been treated before. 125 newborns were studied and finally 109 were included (12.8% lost the follow-up before performing the last serology). The VT rate was 2.75% (95% CI: 0,57–8,8%). Infected infants had positive PCR at birth and 1 month later. All of them were treated successfully with benznidazole (PCR and serology became negative later on). All non-infected children presented negative PCR. The mean age at which uninfected patients had negative serology was 10.5 months. Conclusions The VT rate is in keeping with literature and confirms the need to carry out a screening in pregnant women coming from endemic areas. PCR seems to be a useful tool to provide early diagnosis of congenital CD.