Coronavirus-Intestin (UnlimPhoto)

Covid: Such a digestive disease?

We know that SARS-COV 2 colonizes the digestive tract, actively replicating there and even persisting in passing through the bloodstream for a long time, which could long explain COVID. Correcting vitamin D deficiency could play an important protective role.

Coronavirus gut (UnlimPhoto)

SARS-CoV-2 has been detectable in the digestive tract for a long time. The gut barrier plays a central role in the events leading from SARS-CoV-2 infection to serious complications. The latest studies suggest that SARS-CoV-2 disrupts the integrity of the biological, mechanical and immunological intestinal barrier. The diversity of the microbiota and the population of beneficial bacteria are reduced, as is the proliferation of pathogenic bacteria (dysbiosis).

A pre-existing dysfunction aggravated by SARS-COV-2

The spaces between the intestinal cells, the tight junctions (TJ), play an important role as a tight barrier. If this intestinal barrier is disturbed, the passage of bacteria, fungi and endotoxins into the circulation is possible. A pre-existing change in the gut barrier in patients with comorbidities (cardiovascular disease, obesity, diabetes and immunosuppression) promotes this harmful passage and makes them more vulnerable. [1]. The team of Prof. C. Devaux (CNRS – Marseille) has shown that in patients carrying SARS-CoV-2 in the gut, the virus can trigger damage to the barrier by disrupting these tight junctions and thus to the gastrointestinal ones symptoms of COVID-19 [2].

Long COVIDs: prolonged presence of SARS-COV2 in the digestive tract and circulating spikes

With no viral particles in the airways, 12.7% of patients had SARS-CoV-2 in their stools at 120 days and 3.8% were still excreting SARS-CoV-2 at 210 days [3]. In addition, viable virus was found in the cecum of 2 patients with long Covid symptoms at D+175 and D+462 days. This is the first study to demonstrate a viable virus in the digestive tract for so long [4]
In addition, the researchers were able to roughly identify either the spike protein, the N-nucleocapsid, or the S1 subunit in 31 long-COVID patients using ultrasensitive technology (Simoa) in the bloodstream 65% of COVID patients are delayed several months later. The authors suspect the presence of a active persistent virus reservoir of SARS-CoV-2 at the origin of their discovery [5].

Zonulin marker of altered gut permeability

Zonulin is a molecule that changes the tightness of the gut by opening up those tight junctions that unite the cells of the wall. Produced in excess, it can lead to unwanted compounds entering the body.
As of July 2021, a team has identified zonulin as a marker and potential therapeutic target in multisystem inflammatory syndrome (MIS-C or PIMS) affecting children [6].
A study showed that zonulin was significantly higher in the MIS-C group compared to a control group. However, zonulin opens the tight junctions (TJ) and allows the passage of highly pro-inflammatory viral particles into the circulation, but also endotoxins or lipopolysaccharides (LPS) of bacterial origin from the digestive tract. These results suggest that increased gut permeability may be involved in explaining severe COVID infection and MIS-C disease in children. [7].

An inflammatory bomb in the digestive tract

Pierre Sonigo (DR)
Pierre Sonigo (DR)

Pierre Sonigo, former INSERM research director and virus specialist, believes that “there is nothing in the body more pro-inflammatory than the endotoxins (LPS) of the bacterial wall”. . When gut permeability increases, a phenomenon called LPS translocation can occur. Permeability increases greatly in the event of a digestive infection. All of this is unfortunately common in the case of COVID. Digestive manifestations are also known to increase the risk of a severe form of COVID with shock.”

A hope for treatment in children with MIS-C

In children with MIS-C, the prolonged presence of SARS-CoV-2 in the gastrointestinal tract led to the release of zonulin with passage of SARS-CoV-2 antigens into the bloodstream, resulting in hyper-inflammation, according to a Massachusetts team General Hospital. the Larazotide, a zonulin inhibitor used in the treatment of celiac disease, would prevent the alteration of digestive permeability (tight junctions = TJ) and limit the passage of harmful antigens: this treatment would be well tolerated and useful as an adjuvant treatment. For example, 4 young MIS-C patients treated with larazotide saw a decrease in their spike protein levels to undetectable levels, faster improvement in gastrointestinal symptoms, and a trend towards a reduction in length of hospital stay. [8].

And vitamin D?

Vitamin D is known to be involved in inflammatory bowel disease and mediates intestinal permeability with tight connections.
Since 2007, experimental studies have shown that vitamin D3 can play a protective role in the mucosal barrier by maintaining the integrity of junctional complexes and the healing ability of the colonic epithelium. [9].
Vitamin D levels are also inversely correlated with symptom score and fecal zonulin. Mark this data the close relationship between vitamin D and the intestinal barrier [10].

Plasma endotoxin and zonulin decreased with increasing vitamin D levels. Analyzes showed a significant association between plasma zonulin levels and vitamin D levels. Again, this finding suggests a relationship between them Vitamin D deficiency and changes early signs of intestinal permeability. Therefore, determination of vitamin D levels and preventive correction of the deficiency may be warranted. [11].
Another study shows, both in vitro and in vivo, that vitamin D3 reduces the increased permeability of the intestinal mucosa. Finally, vitamin D3 treatment significantly decreased zonulin release levels [12].

Experimentally, in mice fed a vitamin D-deficient diet, a team found a significant decrease in colonic mucosa, a marked increase in pro-inflammatory cytokines, and increased levels of zonulin-1. According to the authors, vitamin D supplementation could be part of a therapeutic strategy for human diseases associated with intestinal barrier dysfunction (leaky gut). [13].

Severe vitamin D and MIS-C deficiency

Finally, 10 out of 31 young patients with MIS-C were severely vitamin D deficient with an average level of 7.2 ng/mL (desirable level is above 30 ng/mL or even 50 ng/mL). 90% with severe vitamin D deficiency had severe disease and an increased risk of heart damage [14]. The preventive effect of vitamin D is also suggested in a March 2021 mini-review of the scientific literature [15].

All of this data suggests that the change in digestive permeability associated with the invasion and presence of the replicative digestive virus is critical to understanding disease COVID—long COVID and MIS-C. Further studies and clinical trials are needed to determine the therapeutic effects of larazotide for the prevention of MIS-C, and correction of vitamin D deficiency in severe COVIDs and long COVIDs.

  • bibliography
    1) Assimakopoulos: SARS-CoV-2-Induced Viral Sepsis: The Role of Gut Barrier Dysfunction. Microorganisms 2022, 10, 1050. https://doi.org/10.3390/microorganisms10051050
  • 2) Osman IO, Devaux CA: Control of CDH1/E-cadherin gene expression and release of a soluble form of E-cadherin in SARS-CoV-2-infected Caco-2 gut cells: Physiopathological consequences for the gut forms of COVID-19. Front Cell Infect Microbiol. May 4, 2022;12:798767. doi: 10.3389/fcimb.2022.798767.
  • 3) Rubin R.: SARS-CoV-2 RNA can persist in the stool for months after the virus has left the respiratory tract. JAMA. 2022;327(22):2175-2176. doi:10.1001/jama.2022.7892
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  • 7) Kilic AO et al. Zonulin and claudin-5 levels in multisystem inflammatory syndrome and SARS-CoV-2 infection in children. J Pediatr Children’s Health. May 30, 2022 doi: 10.1111/jpc.16033. Epub before printing. PMID: 35638118.
  • 8) Yonker LM, Swank Z, Gilboa T, Senussi Y, Kenyon V, Papadakis L, Boribong BP, Carroll RW, Walt DR, Fasano A. Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children : A case series. Crit care explorer. 18 Feb 2022;10(2):e0641. doi: 10.1097/CCE.00000000000000641. PMID: 35211683; PMC ID: PMC8860335.
  • 9) Zhao H., et al. : Protective role of 1,25(OH)2 vitamin D3 in mucosal injury and epithelial barrier disruption in DSS-induced acute colitis in mice. BMC Gastroenterol. May 30, 2012;12:57. doi: 10.1186/1471-230X-12-57. PMID: 22647055; PMC ID: PMC3464614.
  • 10) Linsalata M, et al. The relationship between low serum vitamin D levels and altered gut barrier function in patients with IBS-diarrhea on a long-term low-FODMAP diet: novel observations from a clinical study. Nutrient. Mar 21, 2021;13(3):1011. doi: 10.3390/nu13031011.
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