Dr. Debasish Sarma Roy

July 27, 2020, 19:29:42   

"Every form of addiction is bad, no matter whether the narcotic be alcohol, morphine or idealism" - Carl Gustav Jung
For a large number Bengalis a common gas medicine first thing in the morning probably brings out as much charm as from a narcotic or an idealism; as perceived from a practice spanned over past three decades. Why? Reasons are diverse and may be an excellent topic for a good many of researchers.   
Well, now in the wake of the coronavirus crisis that heavenly feeling or should we call it a 'high' from a small piece of pantoprazole (or any of it's cousins) is no longer seems to be a good option to get into a blissful existence.  The consequential monograph coming to turmoil the tranquillity of Bengali minds from Christopher V. Almario, MD and colleagues, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, is titled as "Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors", and published in the American Journal of Gastroenterology this month. (Ref. - https://journals.

The researchers developed this hypothesis at the beginning of the COVID-19 pandemic when started to see a high incidence of GI symptoms and learned that the virus sheds into saliva, and thus can be swallowed into the stomach. "There is a reason we have acid in our stomach, namely, to kill pathogens before they enter the digestive tract," said Brennan M.R. Spiegel, MD, Cedars-Sinai. "Coronaviruses are easily destroyed at a gastric pH of less than 3, but survive in a more neutral pH." In the gastrointestinal tract presence of ACE-2 receptors, the docking zone for the virus to enter our body is bounteous, roughly 100 times more than any other organ including the lungs. No wonder that the virus finds the GI tract a suitable place to invade the body and spread unto other organs including lungs, brain etc. As the virus is shredded in the saliva in large amount, when this enters the stomach, in a person with normal stomach acid content, is killed quickly. But a person who consumes a stomach acid suppressant drug like a proton pump inhibitor (PPI) (pantoprazole, omeprazole, esompeprazole, rabeprazole, lansoprazole, dexlansoprazole, etc), or a histamine type-2 receptor antagonist (H2RA) (cimetidine, ranitidine, famotidine, nizatidine, etc) has a much higher stomach pH because secretion of hydrochloric acid by the stomach wall cells are blocked by these drugs.  As a result, lot of pathogens present in our food, or even those trapped in our nasal or upper respiratory mucus secretions and passively swallowed by us constantly are not destroyed in the stomach and raises the chance of infections. This is more so as the SARS-CoV-2 attaches to the ACE-2 receptors most plentifully present all along the entire GI tract. And so, it is not surprising that the “use of PPIs is associated with increased odds for reporting a positive COVID-19 test. The highest risk is seen among individuals taking PPIs twice daily—a common practice in both primary and secondary care —as they are nearly four times more likely to report COVID-19 positivity when compared to those not on PPIs" reported the researchers. And for those taking these drugs once a day, the risk is double than those who are non users.  

"The results of this large survey study, from an experienced team of clinicians and researchers, are intriguing and add novel, clinically relevant information to the rapidly evolving field of COVID-19 during this devastating pandemic," said Brian E. Lacy, MD, Co-Editor-in-Chief of the American Journal of Gastroenterology.  
What is more annoying, COVID-19 seems to be here to stay for a while. Klaus Stohr, the virologist who played a key role in 2003 WHO investigation that quickly identified coronavirus as the cause of SARS and also in many more epidemics, has recently said in an interview with Bloomberg "it is not the vaccine that's going to end the pandemic. The virus will end this pandemic by burning every piece of dry wood it will find". According to him by the end of this year or beginning of next year, half a billion doses of vaccines will be available. The world population is 7.5 billion, most of them living in countries where vaccine may not be available at all, says Dr. Klaus. As this virus is behaving like other respiratory viruses, there will be a significant rise in infections next winter, and that will be very serious. According to him by the middle of next year a significant portion of the world will have antibodies. That will increase gradually over time. Then there will be a third wave, and when that is over, 80% of world population may have antibodies. The majority of the world population will not receive a vaccine, he added, that the virus will continue to spread and it could take two to three years before the virus has affected a large majority of the population. 
Obviously, we need to take some long term planning to cope with the situation. No single strategy will be effective for all the localities, all the time. The goal is constant though, to minimize the loss of lives to a level as little as possible; and for countries like us to keep the economy floating at the same time. With a huge number of malnourished children and adults in our country even in the heights of its’ economic growth; presently the stark bites of a dwindling job market and economic hardship will prompt the population succumb easily to the virus or for that matter to many other pathogens like  measles, TB, diarrhoea, malaria, pneumonia, etc. 

The role of a stomach acid suppressant drug or more specifically a proton pump inhibitor is a serious one in the backdrop of the C-19 pandemic. This is not only because that this molecule opens up our largest collection of ports for the viral docking, as we have discussed at the beginning, but for much more important role it plays to alter the immune response of a healthy person as well as for its' role in the development of a lot of diseases which make a man vulnerable to serious complications once the virus is inside the body. And how is that done? The answer may stir up a lot of leaves and possibly a lot of denials, especially in our country, for a variety of reasons.  If we recapitulate the names of the underlying medical conditions those increase the risk for severe illness from COVID-19, here is the list – Chronic Kidney Disease, Diabetes Mellitus, Cancer, Chronic Obstructive Pulmonary Disease (COPD), Immunocompromised state, Serious heart conditions like Heart failure, Coronary artery disease, Cardiomyopathy, Obesity, etc. Besides these there are other diseases that may also pose increased risk, such as Bronchial asthma, Hypertension, Liver disease, Dementia, Pulmonary fibrosis, Smoking, etc.  Now the question is how PPIs affect these disease conditions, origin or propagation. 

If we go through an article published on PPIs in the New York based National Kidney Foundation, an organisation with repute and authority in this field, it mentions the side effects of PPIs as – 1. Increased chance of chronic kidney disease, 2. Acute interstitial nephritis, 3. Increased chance of heart attack(s), 4. Nutritional deficiencies (especially of iron, magnesium), 5. Increased chance of bone fracture and bone loss (osteoporosis), 6. Increased chance of dementia, 7. Increased chance of infection(s). (Ref. 
Our school curriculum teaches us environmental science, not to temper wrongly the world surrounding us. But what about the whole universe of diverse organisms we carry on and in us, that are as unique as our thumbprints or any other identifying marks for that matter? Experts now say these are far more important for the physical and mental wellbeing of the humankind than anything else we could probably presume.  In her book '10% Human' Alanna Collen, a PhD in evolutionary biology from the UCL, UK, writes "With just shy of 21,000 genes, the human genome is hardly bigger than that of The Worm (C. elegans). It is half the size of the rice plant, and even the humble water flea outstrips it, with 31,000 genes. None of these species can talk, create, or think intelligent thoughts. You might think, as the scientists entering the Genesweep pool did, that humans would have a great many more genes than grasses and worms and fleas. After all, genes make proteins, and proteins make bodies. Surely a body as complex and sophisticated as a human's would need more proteins, and therefore more genes, than a worm's? 

"But these 21,000 genes are not the only genes that run your body. We do not live alone. Each of us is a super organism; a collective of species, living side-by-side and cooperatively running the body that sustains us all. Our own cells, though far larger in volume and weight, are outnumbered ten to one by the cells of the microbes that live in and on us" she writes. That together, the microbes living on the human body contain 4.4 million genes, which collaborate in running our bodies alongside our 21,000 genes. By that count you are just half a percent human - she quipped. It is your genes that will determine how your immune system will react when an organism enters your body to cause a disease. It is these genes which will determine how you will react to stresses in your life, be it physical or mental. The same genes will predict whether pollen from a flower or dust from your floor or a protein in your well-garnished dish will kick start an asthmatic attack; or some flashing lights will get you into an epileptic convulsion; or a sudden fury into a catastrophic heart attack. Collective evidence of research every day is making it clear that these microbes hold the key in your life for health and happiness. Yes, happiness too, because depression, bipolar disorders, and even schizophrenia are now increasingly recognized being originated due to some genetic malfunction or other as may be influenced by the alteration of these microbes. 

PPIs are recognized to alter our gut flora at least in two ways. Reduction of stomach acid secretion lets in the malevolent bacteria which in turn disrupt the subtle 'eco system' unique for each individual. It may be worth mentioning here that no amount of capsules filled with 'friendly' bugs can actually replenish the exact balance of the unique individual microbial diversity in a given time. Secondly, PPIs not only affect your stomach's acid producing cells, these also target the proton pumps of the gut bacteria and fungi (yeasts), thereby changes the functions of these (remember that 4.4 million genes), and the overall impact falls upon your body functions. This way PPIs can and actually are responsible for the origin and continuation of a number of acute and chronic diseases, practically like you name it you have it fashion. Many of these diseases are again a risk factor for severe COVID-19 infection. 

In his interview with the Medscape mid-July, Dr. Anthony Fauci, one of the most revered names in the medical community and currently in charge of White House task force for pulling out the United States from corona crisis, declares in black and white –"We don't know. I have to tell you, I'm humbled by it that we don't know. We have so many people who have gotten sick, and we can't write a really good paper on delineating A-B-C-D or what's going on. We just don't know". That it is a mystery why this virus kills healthy international athlete teenager, and spares a centurion with multiple diseases. The answer may well lie in our use of PPIs, antibiotics, vitamins and other nutritional supplements that have shown to alter our microbial 'fingerprints' and thereby toiling our T-lymhocyte's programs so that sometimes they just ignore a major threat and sometimes gives a knee jerk reaction to a minor morbidity thereby kick-starting a cytokine storm, and the outcome may be grave, literally. Though these concepts are out there for many years, but the industry always could negate the findings.Degree of immune reactions vary grossly over time, place, persons, diet, constant physical and psycho-social changesin stressors, predisposing genetic traits (mostly unknown till date and for the sheer impossibility to gather complete genomic analysis of each of the study subjects, even then present day science can't predict which combination of genes will produce a particular disease). All of these make it impossible to recreate exactly similar modules to reproduce a study result. Hence the industry can always fool us by showing that the moon and the sun are equal in size as these two celestial bodies perfectly overlap each other during an eclipse!


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