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1.
Annali dell'Istituto Superiore di Sanita ; 58(2):81-84, 2022.
Article in English | ProQuest Central | ID: covidwho-1904403

ABSTRACT

Besides the timely detection of different SARS-CoV-2 variants through surveillance systems, functional and modelling studies are essential to better inform public health response and preparedness. Here, an overview on the knowledge available so far on SARS-CoV-2 variants are discussed by different expertises.

2.
Ann Ist Super Sanita ; 58(2): 81-84, 2022.
Article in English | MEDLINE | ID: covidwho-1903735

ABSTRACT

Besides the timely detection of different SARS-CoV-2 variants through surveillance systems, functional and modelling studies are essential to better inform public health response and preparedness. Here, the knowledge available so far on SARS-CoV-2 variants is discussed from different perspectives, in order to highlight the relevance of a multidisciplinary approach in countering the threat posed by this insidious virus.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306566

ABSTRACT

Background: While pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a pre-requisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown.Methods: We performed a retrospective analysis of single cell data repositories. This data was then validated at both gene and protein level by performing qRT-PCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues.Findings: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels, only in the fetal intestine and kidney and is not expressed in the fetal lung. The placenta is also negative for the two proteins both during development and at term.Interpretation: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the GI tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid.Funding Information: This work was made possible by an MRC / UKRI COVID-19 Rapid response initiative grant (MR/V028480/1).Declaration of Interests: The authors declare no conflicts of interest related to this work or its developments. DC is founder, shareholder, and consultant of Next Generation Diagnostic SRL.Ethics Approval Statement: Human fetal tissues were obtained with consent through the Human Developmental Biology Resource (HDBR;REC 18/LO/0822 – IRAS 244325;Project ID 2000478). Placental samples were obtained at delivery of an uncomplicated, full-term pregnancy (median 39 weeks PCW [Range 38+1 -39+4] for 6 patients recruited through the EVERREST Prospective Study as normal controls (National Research Ethics reference 13/LO/1254), NCT02097667 registered 31st October 2013[10].

4.
Nat Commun ; 12(1): 6610, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1521737

ABSTRACT

COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission.


Subject(s)
COVID-19/pathology , Intestinal Mucosa/virology , Organoids/virology , SARS-CoV-2/physiology , Stomach/virology , Virus Replication/physiology , Aborted Fetus , Aged , Animals , COVID-19/virology , Cell Line , Child , Child, Preschool , Chlorocebus aethiops , Humans , Infant , Intestinal Mucosa/pathology , Middle Aged , Organoids/pathology , SARS-CoV-2/isolation & purification , Stomach/pathology
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