Research News: Washington University Study Shows That Individuals With Barrett’s Esophagus Have Increased Susceptibility To COVID-19

Research News: A new study by researchers from Washington University School of Medicine- St. Louis has found that individuals with Barrett’s Esophagus have increase susceptibility to COVID-19 disease.


 
Barrett’s esophagus is a condition in which the lining of the esophagus changes, becoming more like the lining of the small intestine rather than the esophagus. This occurs in the area where the esophagus is joined to the stomach. It is believed that the main reason that Barrett’s esophagus develops is because of chronic inflammation resulting from Gastroesophageal Reflux Disease (GERD). Barrett’s esophagus is more common in people who have had GERD for a long period of time or who developed it at a young age. It is interesting that the frequency or the intensity of GERD symptoms, such as heartburn, does not affect the likelihood that someone will develop Barrett’s esophagus.
 
COVID-19, caused by SARS-CoV-2, is a global pandemic, spurring exigent need for determining how the virus is transmitted and what increases disease susceptibility. Gastrointestinal (GI) symptoms are prominent in COVID-19, and live virus is detected along the GI tract and in stool. SARS-CoV-2 enters host cells via its transmembrane spike glycoproteins that bind host ACE2 protein on the cell surface, an interaction facilitated by spike protein cleavage catalyzed by host type II transmembrane serine protease TMPRSS22 . Thus, concurrent cellular expression of ACE2 and TMPRSS2 determines cellular tropism for SARS-CoV-2. Surveys of ACE2 and TMPRSS2 in GI tissues have shown abundant expression in human intestines. However, the low pH of gastric secretions as well as emulsifying conditions of the small and large intestinal inactivate the virus, limiting access of infective virus to distal GI tissues via the GI tract lumen.
 
In this research, the study team shows that individuals with intestinal metaplasia (i.e. ectopic intestinelike cells in their esophagus as in Barrett’s esophagus) would have increased potential for viable, ingested virus to interact with a receptive host epithelium. Thus, intestinal metaplasia could present a previously unappreciated orogastric route for viral entry in individuals with this condition.
 
The study findings were published in the peer reviewed journal: Gastroenterology. https://www.gastrojournal.org/article/S0016-5085(21)00091-3/fulltext#%20
 
To date there is no evidence so far indicates that food or drinks can transmit the virus that causes COVID-19, but the study team suggests that people with problems in the upper gastrointestinal (GI) tract may be vulnerable to infection after swallowing the virus.
 
Simply by studying tissues from patients with a common disorder called Barrett's esophagus, the study team found that although cells in a healthy esophagus cannot bind to the SARS-CoV-2 virus, esophageal cells from patients with Barrett's have receptors for the virus, and those cells can bind to and become infected by the virus that causes COVID-19.
 
Dr Jason C. Mills, MD, PhD, Senior Investigator told Thailand Medical News, “There is no evidence yet that people with Barrett's esophagus have higher rates of COVID-19 or are at any greater risk, but part of the reason is because that hasn't been studied. Now that we've connected these dots, it may be worthwhile to look and see whether people with Barrett's have higher rates of infection."
 
One of the reasons that it has been considered safe to eat and drink most foods during the pandemic is that they are unlikely to carry viral particles. And even if some viral particles are attached to food, the stomach acid is able to neutralize the SARS-CoV-2 virus.(However note that many studies are  now showing now that food can be carriers of the virus and people can infected by touching them and then somehow passing the virus to their noses, eyes or ears.) https://www.thailandmedical.news/news/coronavirus-news-chinese-authorities-report-of-sar-cov-2-coronavirus-being-found-on-ice-cream-in-the-city-of-tianjin-could-the-virus-be-food-borne
 
However when stomach acid backs up, people develop a disorder called gastric reflux that can cause long-term damage to the esophagus. In those with reflux disease, which affects about one in five people in the U.S., acid from the stomach backs up into the esophagus, causing heartburn and damaging the lining of the esophagus.
 
It has been observed that over time, some people with reflux, the cells in the esophagus change and begin to resemble intestinal cells. Intestinal cells have receptors that can bind to the novel coronavirus, so Dr Mills and his colleagues reasoned that in Barrett's patients, the cells that line the esophagus also would develop receptors that can bind to the virus and become infected.
 
Furthermore standard medical management for patients with Barrett's esophagus is to suppress gastric acid secretions with drugs such as proton pump inhibitors.
 
However by reducing stomach acidity, those drugs may inadvertently make it possible for the virus to pass through the stomach and into the intestine, where even the normal, healthy cells carry receptors for SARS-CoV-2.
 
Interestingly many patients with COVID-19; most of whom contract it by breathing in the viral particles; develop GI symptoms such as abdominal pain and diarrhea. The virus also has been found in the stool of COVID-19 patients.
 
But this new study demonstrates that under the right circumstances, the virus also may have an impact in the upper part of the GI tract. As a result, Dr Mills, a professor of medicine, of developmental biology, and of pathology and immunology and his team believe esophageal cells in Barrett's patients are potential gateways for infection.
 
Dr Ramon U. Jin, MD, PhD, the paper's co-first author and a clinical fellow in the Division of Medical Oncology who studies Barrett's esophagus because it is a major risk factor for cancer of the esophagus added, "You can imagine that if someone already has low levels of the virus in their respiratory tract, that individual could swallow some respiratory secretions, and the virus could infect cells in the esophagus to make them sicker that way."
 
The other co-first author, Jeffrey W. Brown, MD, PhD, is an instructor in medicine in the Division of Gastroenterology.
 
The study team for this research  analyzed tissues from 30 patients with Barrett's esophagus and found that cells in the tissue samples all had receptors for the SARS-CoV-2 virus, which normal esophagus cells lack.
 
The team built and cultured mini organs from those and other esophagus tissue samples. Some of the sample organs were built with cells that came from healthy people while others came from patients with Barrett's esophagus.
 
The study team built the mini esophaguses, called organoids, in a dish to learn how those model organs interacted with the SARS-CoV-2 virus.
 
It was found that the virus was able to bind to and infect mini organs built from tissue from people with Barrett's esophagus. Moreover, the more the cells in a specific patient's mini esophagus culture resembled intestine, the more the virus bound to and infected that culture.
 
Dr Mills added, "The worry would be that, particularly for Barrett's patients, there even may be a susceptibility to infection from foods containing viral particles. This study provides data to indicate that we need to take a closer look to investigate whether a substantial portion of the population may be susceptible to infection through what they swallow."
 
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