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COVID, Volume 4, Issue 9 (September 2024) – 3 articles

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11 pages, 780 KiB  
Hypothesis
Could the Spike Protein Derived from mRNA Vaccines Negatively Impact Beneficial Bacteria in the Gut?
by Alberto Rubio-Casillas, Mark Fabrowski, Carlo Brogna, David Cowley, Elrashdy M. Redwan and Vladimir N. Uversky
COVID 2024, 4(9), 1368-1378; https://doi.org/10.3390/covid4090097 - 25 Aug 2024
Viewed by 2174
Abstract
The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development. Nevertheless, concerns of experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects [...] Read more.
The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development. Nevertheless, concerns of experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects and destroys specific bacterial strains in the GM. The present manuscript hypothesizes that the synthetic spike protein could create changes in the composition and the functioning of the GM by entering the intestinal cells after vaccination and impairing the symbiotic relationship between intestinal cells and the GM. An experimental protocol to test the hypothesis is suggested. Full article
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13 pages, 4052 KiB  
Article
The Role of Intestinal Epithelial Permeability in Multisystem Inflammatory Syndrome in Children: A Case–Control Study
by Cathal Roarty, Clare Mills, Claire Tonry, Helen E. Groves, Chris Watson and Thomas Waterfield
COVID 2024, 4(9), 1355-1367; https://doi.org/10.3390/covid4090096 - 24 Aug 2024
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Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after SARS-CoV-2 infection, with gastrointestinal symptoms a prominent feature. This syndrome has been proposed to be triggered by persistent SARS-CoV-2 antigenemia due to increased intestinal epithelial permeability. We obtained evidence for this in this study. [...] Read more.
Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after SARS-CoV-2 infection, with gastrointestinal symptoms a prominent feature. This syndrome has been proposed to be triggered by persistent SARS-CoV-2 antigenemia due to increased intestinal epithelial permeability. We obtained evidence for this in this study. Methods: In a single-centre study, we recruited 83 children and analysed blood samples to quantify the circulating markers of increased intestinal permeability following SARS-CoV-2 infection. Publicly available proteomics MIS-C datasets were also accessed to assess the evidence for increased intestinal permeability. We further quantified SARS-CoV-2 antigenemia and the humoral response to SARS-CoV-2 spike protein. Results: Following SARS-CoV-2 infection, healthy children demonstrated no dysregulation of the intestinal epithelial barrier. In MIS-C, considerable increases in markers of epithelial dysfunction were observed, with similar increases noted in febrile controls. Furthermore, we found little evidence of persistent SARS-CoV-2 antigenemia in MIS-C. Conclusions: Our results suggest that although increased intestinal epithelial permeability is a feature of MIS-C, it is not unique to the condition, and persistent SARS-CoV-2 antigenemia does not occur. Full article
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17 pages, 3316 KiB  
Article
ESCRT Protein VPS4A Is Required for the Formation of Replication Centers and Replication of Human Coronavirus 229E (HCoV-229E)
by Rinki Kumar, Rebecca Kaddis Maldonado, Neil D. Christensen, Maria C. Bewley, John M. Flanagan, Nicholas J. Buchkovich and Leslie J. Parent
COVID 2024, 4(9), 1338-1354; https://doi.org/10.3390/covid4090095 - 24 Aug 2024
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Abstract
Human coronavirus 229E (HCoV-229E) is an alpha coronavirus that infects humans and bats. In common with all positive-strand RNA viruses, 229E infection causes rearrangements of the host’s intracellular membranes to form replication organelles, a highly conserved and vital step in the viral replication [...] Read more.
Human coronavirus 229E (HCoV-229E) is an alpha coronavirus that infects humans and bats. In common with all positive-strand RNA viruses, 229E infection causes rearrangements of the host’s intracellular membranes to form replication organelles, a highly conserved and vital step in the viral replication cycle. Here, we investigated the role of the ESCRT protein VPS4A in 229E infection. We found that functional VPS4A was required for the formation of replication organelles and localizing viral RNA to these structures in host cells to facilitate viral genome replication. We validated this effect using small molecule inhibitors to VPS4A, significantly reducing virus replication. We also showed that other ESCRTS, like CHMP4B, were required for the virus replication step, whereas VPS37A was involved in the post-replication stages. The absence of a functional VPS4A prevented the remodeling of membranes to form viral replication centers and, therefore, exposed the viral RNA, triggering an inflammatory immune response as indicated by elevated levels of IL-6. Interestingly, we observed the role of VPS4A to be similar for the OC43 coronavirus, indicating it could be conserved across all four coronavirus genera, including SARS-CoV-2. Understanding more about the replication of coronaviruses is imperative to finding more effective ways to control them. Full article
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