Pictured: SARS-CoV-2 cells attach to ACE-2 receptors.
by Kimberly Rivers
“You heard it here first, COVID-20,” said Dr. Sabine Hazan on Sept. 16 during a discussion with the Ventura County Reporter at the offices of Ventura Clinical Trials and ProgenaBiome in Ventura. “We are already starting to see COVID-20-associated diarrhea and rectal bleeding.”
She agreed to talk about findings in a ProgenaBiome report currently undergoing peer review. It is the first study she is aware of that finds the entire genome — along with 33 different mutations — in the stools of those with SARS-CoV-2.
The paper, “Detection of SARS-CoV-2 from Patient Fecal Samples by Whole Genome Sequencing,” authored by Dr. Andreas Papaoutis, Jordan Daniels, Skylar Steinberg, Dr. Brad Barrows and Dr. Sabine Hazan (all with ProgenaBiome) and Dr. Thomas Borody and Dr. Siba Dolai of the Center for Digestive Diseases. (1)
That paper reports on the existence of hundreds of thousands of replicas of the complete genome of the virus in the stool samples of people who tested positive by nasal swab PCR testing, both symptomatic and asymptomatic. By using Next Generation Sequencing (NGS) the researchers identified 33 unique variations of the virus, indicating a high propensity for mutations, potentially making treatment by something as fine-tuned as a vaccine extremely challenging.
The report also shows the initial findings of the clinical trial studying whether a combination treatment protocol called HAZDPaC (which includes hydroxychloroquine, azithromycin, zinc and Vitamins C and D) or high dosages of Vitamin C, D and Zinc alone (the placebo in the trial) may prove effective in eradicating the virus from the gut, where it could potentially cause long-lasting problems if left to “percolate.”
Eleven of 14 trial participants were positive (nasal swab PCR) for the virus. Eight of those people were not treated and the full virus genome was found in each of their stool samples. A total of 33 unique mutations of the virus were identified in those eight participants. The remaining three people who had the virus were treated for 10 days with HAZDPaC or high dosages of Vitamin C; when retested, they had no trace of the virus in their stools.
Three additional trial participants served as the “control.” Two were negative (nasal swab PCR); one was not tested. None were treated and no virus was detected in stools.
Until the report is printed as a peer reviewed paper (currently in process) it cannot be relied upon for other clinical study or purposes. But Hazan is confident of the findings’ ultimate confirmation through peer review.
The drug hydroxychloroquine, one component of the HAZDPaC protocol, has long been used to treat malaria, lupus and arthritis. It became a political hot topic when President Donald Trump touted it as a potential treatment for COVID-19 in the early days of the pandemic. Cries went up across the political spectrum, with many questioning his motive for promoting a drug that hasn’t been tested for this use.
When Hazan and her colleagues placed ads seeking participants for the trial, the lab received crank calls from folks levying attacks for studying hydroxychloroquine.
Hazan also has been contacted by network television stations. She has refused to speak with them, however, saying, “No, I’m not going to be your scapegoat for this political battle that you have. The media should not interfere with science, because it biases the doctors from writing the prescriptions, it biases the patients from wanting to enroll in the study. It stops us from seeing an answer.”
“Science and medicine should never be politicized,” said an exasperated Hazan.
Hazan explained the process of isolating the virus, standing at a white board and illustrating as she talked.
“A tiny little sample of stool” is transferred “into a pipette,” she explained, drawing a small triangular vial. The process of preparing the samples for NGS involves purifying DNA or RNA from the stool sample and performing numerous complex steps to identify nucleotide sequences of bacteria and viruses. “About 60 percent is your DNA. Then you’ve got the bacteria.”
Or, rather, bacteria, virus and fungi — numerous families of each, with possibly thousands of strains.
“So we capture all this bacteria, and then maybe 0.1 percent or less is virus,” Hazan continued. “If we want to zoom in from the beginning on just the RNA viruses, we use a different purification protocol that enriches for our targets of interest. . . . From there we just focus on the [species of virus] and break it down.” This is when viruses in the gut (herpes, rotavirus, coronaviruses and others) are mapped. As there are many strains in the species of coronavirus, “you have to find the COVID-19.”
Hazan says it’s important to understand how existing testing works to understand why preventing or treating the virus, or developing a vaccine, is so challenging.
“So when you look at the PCR [test], if this is the virus,” she said, drawing an elongated cylinder with an asymmetrical head and tail, ”It’s got many spikes. It’s got a 1a region, a 3a region,” other parts of the virus that have been mapped by researchers.
She explained that as the virus was studied, certain “segments” of the virus were found in most infected people. These are the segments of the viral RNA the PCR test looks for and, when found, they generate a positive test result for the SARS-CoV-2 virus.
These segments of the virus are usually found in infected patients — but not always.
“There are some people [with the virus] who may have variations in the sequence of the conserved regions, which may result in false negative results,” because the test doesn’t find the segments it was designed to find.
Hazan also pointed out that the “conserved region” may represent a fragment of an inactivated, non-infectious virus, “a piece that is shed, making it a false positive test or a positive test in a patient that is no longer actively infected.”
Another issue has plagued researchers such as Hazan.
“The problem is, this virus mutates,” she said, drawing a second cylinder, but this one with a differently shaped head and tail. “These two [strains of the same virus] are completely different.”
“So how does a vaccine work? A vaccine works by mimicking the targeted virus so your immune system can identify it and develop a preemptive response,” she continued. Later, when the vaccinated person is exposed to the conserved version of the coronavirus, “your body recognizes it, and the vaccine works. But what happens when the virus mutates and is no longer the conserved form recognized by the immune response produced by the vaccine? It may be less effective or not effective at preventing infection. Due to this, multiple booster vaccinations may be required to keep up with the most current strain.”
Which makes the stool research all the more exciting. Hazan and her colleagues have found the complete virus genome (not just segments) every time in the stool samples of those with the virus.
Coronavirus in the gut and stools
Once a person gets coronavirus, whether they have symptoms or not, Hazan said that they may need to be treated. “If you don’t get rid of it, and you let it percolate in your body, you run a risk of long-term complications of COVID.”
Hazan and her team found copies of the full genome of the virus in just one tiny stool sample. That finding was the same for each person with the virus. This means the virus is setting up shop in the gut, and relies on favorable conditions in that environment to replicate. To understand what that means, you have to understand what happens in the gut.
The coronavirus latches onto the body with an ACE-2 receptor, which is needed for the virus to replicate.
“It’s a lock and key mechanism,” Hazan explained, noting that the virus attaches to that receptor cell and is able to replicate inside the cell.
“Where are the ACE-2 receptors in the body?” she posited. “The brain. That is why people have loss of smell, seizures and neurological problems. Blood, [the virus] attaches in the blood vessel and creates an anticoagulant problem. The testicles, gallbladder. But where is the biggest organ?”
The small bowel and the cecum, both packed with ACE-2 receptors. When unhealthy, the area resembles an empty drive-in movie theater for the coronavirus, with plenty of parking and the gut access pathway. “The small bowel, if you stretch it out, is the same size as a tennis court.”
“If it sits in there, it’s multiplying millions [of times],” said Dr. Brad Barrows, medical director with ProgenaBiome. “What we found in our study, in only a little tiny poop, we found thousands of copies of the whole genome, the whole thing. Not little specks, the whole thing.”
The initial protocols used in the FDA trial were formulated as a hypothesis to reach the ACE-2 receptors but also to destroy the virus. The treatment ProgenaBiome is using occupies those spots. Zinc fills up the ACE-2 receptors so there is nowhere for the virus to “park,” helping to maintain the gut barrier. Vitamins C and D boost the good gut bacteria.
Hydroxychloroquine’s role is to raise the pH of the lysosome, or stomach of the cells.
“If you change the pH in lysosome with medication, you change the pH…to 9 or 9.5. It’s a super alkaline environment and the virus disappears, it cannot replicate on the next cell. And so you stop the reproduction.” (2)
With nowhere to go and unable to replicate, the virus is quickly evacuated by the bowel.
“At least that’s the hypothesis from the mechanism of action of all these products brought together as one formula. It’s not a one-pill solution,” said Hazan. She thinks earlier studies involving hydroxychloroquine were flawed because they were only using that one drug approach.
Finding the full virus genome in the feces of those with the virus raises a public health issue. Hazan emphasized that all wastewater from toilets or other restrooms that are treated (with bleach, chlorine, etc.) kill the virus. But she highlighted the risk when people don’t have access to sanitary restrooms (beaches, riverbeds or other areas where fecal matter will not be treated). Compared to the short fragments found in the upper respiratory tract (expelled when talking or coughing), this can create a situation where live virus is spreading.
It also creates an added urgency to address the issue of homeless individuals who may have the virus — although Hazan did point out that, in general, homeless individuals have fairly healthy microbiomes as they are living in closer contact with the earth and in a less sterile environment.
And because of the way the virus can lodge in the gut, any treatment “needs to focus not just on the respiratory [system] but on making sure the gut” is healthy.
Treatment for all
So far, this self-funded trial (researchers aren’t receiving any money from, say, pharmaceutical companies) has just 20 participants, so far. In a separate trial, Hazan has partnered with Dr. Thomas Borody, the pioneer of fecal transplants, using another inexpensive formula — ivermectin (an antiparasitic), doxycycline and zinc.
“More trials are on their way as we need a cheap solution for all,” Hazan said. “This virus requires everyone to be treated and protocols and consents need to be followed and obtained.” She referred to Borody’s success in eradicating H. pylori, a common bacteria infection of the stomach that can lead to gastric cancer, using a mix of available antibiotics (3). “Our hope is to provide therapy for all using combination therapy.”
Members of the public who have tested positive for SARS-CoV-2 and are interested in participating in or otherwise supporting the FDA-approved clinical trial or who want to have their gut microbiome sequenced (for a subsidized fee) can contact Ventura Clinical Trials at 805-339-0549 or online at www.venturaclinicaltrials.com
- ProgenaBiome Report: https://www.researchsquare.com/article/rs-48863/v1