BREAKING! International Study Validates That The Human Gut Also Serves As An Alternative Entry Route For The SARS-CoV-2 Virus That Can Also Be Food-Borne!

A new international meta-analysis study on published research data involving researchers from Italy, United States, Belgium, Portugal and France has found that the human gut can also serve as an alternative entry for the SARS-CoV-2 virus which past studies has shown can also be food-borne!


 
Hopefully, one South-East Asian country famous for stupid and fake claims of being able to cure various diseases including COVID-19 (In the early part of the pandemic, the primates claimed to have found a cure for COVID-19 and then even vaccines and then cures for Long COVID etc!) and their latest scam of nasal sprays that can act as a prophylaxis against the SARS-CoV-2 virus using a potential carcinogenic compound called hydroxypropyl methylcellulose, might not also come up with mouth sprays using the same compound! A subsequent high caseload of nose and mouth cancers will definitely overload the already incompetent medical services in that country!
 
The new meta study on the gut as an alternative entry route for the SARS-CoV-2 virus was conducted by researchers from the European Commission, Joint Research Centre-Italy, the US EPA at University of Wisconsin-Madison-USA, the European Commission, Joint Research Centre (JRC)-Belgium, Nova Medical School, Universidade Nova de Lisboa-Portugal, Seidor Italy Srl, the University of Urbino-Italy, the Cliniques Universitaires Saint-Luc, UCLouvain-Belgium, CEA, INRAE, Université Paris-Saclay-France and the Instituto Gulbenkian de Ciência-Portugal.
 
The human gut was already proposed as a potential alternative entry route for SARS-CoV-2 in the early part of the pandemic. This was mainly based on the high levels of SARS-CoV-2 receptor expressed in the gastrointestinal (GI) tract ie the ACE2 receptors and also the observations of GI disorders (such as diarrhea) in some COVID-19 patients and the detection of SARS-CoV-2 RNA in feces.
 
To date however, the underlying mechanisms remain poorly understood. It has been proposed that SARS-CoV-2 can productively infect enterocytes, damaging the intestinal barrier and contributing to inflammatory response, which might lead to GI manifestations, including diarrhea.
 
The study team reported a methodological approach to assess the evidence supporting the sequence of events driving SARS-CoV-2 enteric infection up to gut adverse outcomes.
 
Exploring current evidence from published peer reviewed studies permitted the study team to highlight knowledge gaps and current inconsistencies in the commentary about enteric infections and to guide further research.
 
Based on the current insights on SARS-CoV-2 intestinal infection and transmission, the study team also presented the potential implications on clinical practice, including on long COVID. A better understanding of the GI implication in COVID-19 is still needed to improve disease management and could help identify innovative therapies or preventive actions targeting the GI tract.
 
The study findings were published in the peer reviewed Journal of Clinical Medicine. https://www.mdpi.com/2077-0383/11/19/5691
 
Though primarily a respiratory disease, COVID-19 also causes gastrointestinal (GI) symptoms to varying degrees among patients, with symptoms like diarrhea, nausea, abdominal discomfort, and vomiting, among others. GI disorders are thought of as the direct consequences of SARS-CoV-2 infection, as viral RNA is dete cted in many patients’ fecal matter.
 
In fact, it has come to be believed that some of the newer emerged Omicron variants and sub-lineages exhibit a tropism towards the gastrointestinal tract!
 
The detailed mechanisms underlying diarrhea in COVID-19 are poorly known.
 
The study team evaluated whether the gut is an alternative entry for SARS-CoV-2 and thereby responsible for various GI disorders.
 
Clear Evidence of SARS-CoV-2 Gastrointestinal Infection
 
It was found that the small intestinal enterocytes express the highest levels of angiotensin-converting enzyme 2 (ACE2) in humans and co-express transmembrane protease, serine 2 (TMPRSS2).
 
Despite the fact that one past study did not observe any correlation between ACE2 expression and infectivity of cells in intestinal organoids, another moere detailed study observed SARS-CoV-2-infected cells in intestinal organoids regardless of surface ACE2 expression, suggesting an alternative entry mechanism or ACE2 downregulation post-infection.
 
Numerous other ACE2-knock-out (KO) experiments with intestinal organoids have indicated ACE2 as an obligatory receptor for viral entry. SARS-CoV-2 infection of human intestinal cells has been reported to lead to an innate response mediated by type III interferon (IFN).
 
Interestingly, researchers in a study observed pro-inflammatory and IFN-stimulated gene (ISG) expression profiles in infected and bystander cells in intestinal organoids.
 
However, SARS-CoV-2 replication was less efficient in human intestinal tissues ex vivo, with a robust innate response inducing types I and III IFNs. This contrasts observations in ex vivo lung tissues where the virus replicates more efficiently but triggers attenuated IFN responses.
 
SARS-CoV-2 viral RNA has been consistently detected in the stools of COVID-19 patients. The viral load in the fecal matter was as high as 107 copies/g, suggesting that IFN responses did not impair the enteric infection.
 
Aside from this, SARS-CoV-2 viral RNA has also been detected in untreated wastewater.
 
In another study where COVID-19 patients presented GI symptoms and underwent endoscopic examination, viral RNA was detected in the stomach, duodenum, and rectal specimens of those with severe disease. In contrast, viral RNA was detected only in the duodenum in non-severe patients.
 
Clear Evidence Of Damage To Intestinal Barrier Caused By SARS-CoV-2 Virus.
 
It has already been known that SARS-CoV-2 causes cytopathic effects in the lungs, triggering apoptosis in epithelial cells. Hence, SARS-CoV-2 can induce cell death leading to alterations to tight junctions, mucus layer, or the disruption of epithelial monolayer integrity.


            Graphical Study Abstract 

Similar disruption of intestinal barrier layers results in leaky gut ie increased intestinal permeability, which allows commensals and other pathogenic bacteria to move into lamina propia and subsequently enter the systemic circulation.
 
A past research reported that cell death in intestinal organoids following SARS-CoV-2 infection was not extensive.
 
However, contrastingly, in vitro studies with gut-derived organoids uncovered observable disintegration of organoids associated with apoptotic markers. Viable SARS-CoV-2 particles must reach the lumen of the gut as infectious virions to be able to replicate in the GI tract.
 
It was found that unlike enteric viruses, enveloped viruses could be eliminated by exposure to gastric juices and the mucus layer in the GI tract.
 
Corresponding author, Dr Laure-Alix Clerbaux from the European Commission, Joint Research Centre (JRC), Ispra-Italy told Thailand Medical News, “However, evidence suggests that SARS-CoV-2 remains stable across a wide range of pH, yet it lost infectivity in a gastric fluid of pH 1.5 to 3.5. Moreover, rapid inactivation of SARS-CoV-2 by enteric juice was observed in the colon’s lumen, implying that inactive SARS-CoV-2 particles reach the gut lumen. Alternatively, other cells such as lymphocytes or even bacteria may transport SARS-CoV-2 to the gut.”
 
Another past study observed SARS-CoV-2 replication in vitro in a bacterial growth medium. Fluorescence and electron microscopic examinations have shown the presence of SARS-CoV-2 particles inside bacteria.
 
Notwithstanding the excess ACE2 expression in the human gut and in vitro SARS-CoV-2 infection of enterocytes, the healthy human gut might not be permeable to viral entry due to antiviral responses, GI fluids, and multiple protective layers of the intestinal barrier.
 
However, there is evidence of intestinal SARS-CoV-2 infection, suggesting that the gut may become permissive to infection under some conditions.
 
Further detailed research is required to comprehensively delineate the conditions of in vivo SARS-CoV-2 infection of human enterocytes. Although viral RNA has been detected in patients’ stools, current data on recovering infectious viral particles from feces are contradictory.
 
Numerous, outstanding questions regarding the interactions between SARS-CoV-2 and the human gut still pervade. For instance, it remains to be established whether an active SARS-CoV-2 replication occurs in the intestine. Besides, certain conditions might make the gut susceptible to SARS-CoV-2 replication, albeit the underlying mechanisms remain poorly defined.
 
Also, whether GI symptoms, specifically diarrhea, are the direct consequences of SARS-CoV-2 infection of the GI tract or local/systemic immune activation remains unclear.
 
However current evidence moderately supports the notion of GI tract as an alternative portal for SARS-CoV-2 dissemination. Taken together, a better, more comprehensive understanding of the GI implications of COVID-19 is required to improve disease management and design innovative therapies.
 
Thailand Medical News would to add that various past studies have also shown that SARS-CoV-2 can be food-borne!
https://www.thailandmedical.news/news/breaking-u-s-study-finds-that-sars-cov-2-can-survive-on-frozen-or-refrigerated-meats-and-seafood-for-up-to-30-days,-validating-china-s-claims
 
Together all these data should serve as a warning that more precautions need to be undertaken not only in terms of preventing infections via the mouth but also in the proper handling of all food products.
 
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