Doctor offers coronavirus protection advice

NEW YORK - Internist and author of medical books, Leo Galland M.D., has authored this information on what he recommends at coronavirus protection options.

He says he has written this to supply useful and practical information for those concerned about the present coronavirus epidemic and also to correct some misinformation that is circulating:

April 5, 2020

I have written this to supply useful and practical information for those concerned about the present corona virus pandemic and also to address some misinformation that has been circulating. I have decided to focus on what is unique about COVID-19, as opposed to general anti-viral measures, because the world has not seen anything like this in a hundred years.

BACKGROUND: AN EMERGING PICTURE

Corona viruses are a family of viruses made from RNA instead of DNA. There are many species that produce respiratory and gastrointestinal illness in humans and animals. Four strains cause the common cold. The pandemic corona virus, technically called SARS-CoV-2, first identified in Wuhan, China, causes the disease labeled COVID-19, which has certain distinctive features: Chinese data indicate that 80% of infected people have minimal symptoms and do not seek medical attention, whereas 15% become moderately to severely ill with cough and shortness of breath and 5% require intensive care. About half the Chinese patients admitted to hospitals did not have a fever and a fifth failed to develop fever despite having pneumonia, so—unlike with influenza—the presence or absence of fever is not a useful diagnostic aid. 

COVID-19 appears to spread readily from person to person, usually as droplets from coughing or sneezing.  A cough or sneeze may send a virus-containing droplet as far as 27 feet, coasting on turbulent airflow. A study from the National Institutes of Health found that droplets containing SARS-CoV-2 may remain airborne for 3-4 hours, but they start losing infectivity rapidly. Within 66 minutes, the droplets have lost half their potency. SARS-CoV-2 is also shed in stool, and for a quarter of the people studied it persisted in stool after respiratory swabs had become negative. Food-borne or water-borne infection is possible but not yet demonstrated. Corona viruses remain viable on surfaces for several days (more about this below), but spread of infection from touching of a contaminated surface has not yet been demonstrated.

The incubation period from exposure to illness is 2 to 14 days, with an average of 5 days. Unlike the flu, COVID-19 appears to start gradually with fatigue, aches and pains and a sore throat or mild dry cough or occasionally a stuffed or runny nose, sometimes nausea and loss of appetite. For some people, the first symptom is abdominal pain without respiratory complaints. Loss of smell and taste occurs frequently. Some people experience diarrhea. The initial respiratory symptoms typically last about 5 days and are followed by recovery. This is Phase One, and for 80% of people it is the only phase.  For 20%, however, Phase Two starts after 5 days, with increasing cough and shortness of breath, symptoms of pneumonia. Neurological symptoms like seizures and strikes have been described. Whether sick or well, infected people shed the virus in secretions for several weeks and may still be contagious 8 days after symptoms end.

Because people who are infected but not sick are able to infect others, widespread dissemination has already occurred and will continue. For this reason, locations that implemented widespread testing (as in Germany) or early shelter-in-place orders (California, Washington state) are seeing reduced spread and mortality. Despite misleading early reports, morbidity (the degree of illness) is the same for young adults as for those aged 50-65.

Patients hospitalized with COVID-19 are frequently co-infected with bacteria and with other viruses (over 50% in a Chinese retrospective study), so antibiotics may have a positive impact.  The mortality rate of COVID-19 varies with the population being studied. The clearest data for mortality among ambulatory, well-fed individuals comes from the Diamond Princess cruise ship, because all of the 3500 people on board were tested. So far, 706 have tested positive for the virus and 9 have died, a case fatality rate of 1.4%. This is over 10 times greater than the typical seasonal flu. A re-calculation of the case fatality rate in Wuhan produced a similar figure, 1.38%.  The risk of severe illness is greater in men than in women and increases with advancing age, high blood pressure, diabetes, and heart, lung or kidney disease. Immune suppression by itself does not appear to increase morbidity or mortality. Patients receiving cancer chemotherapy or transplant drugs do not show increased risk or severity of corona virus disease.

It is not presently known whether recovery from infection with COVID-19 produces immunity to the virus. There are reports of apparent re-infection, but they might represent inaccuracies of testing or the flare-up of an infection that had been suppressed and not cured. In China, the rate of false negatives for nasal or oral swabs was 10-30%.  

PERSONAL PROTECTION

Avoidance of exposure should be the number one strategy and has received the most attention. Methods of avoidance are described in the section below called Anti-Viral Hygiene. By avoiding infection, you help prevent spread to other people and benefit the entire community. Quarantines will delay the spread of infection and reduce the burden on the health care system, but they are not designed to eradicate the virus. Most people in the U.S. are likely to be exposed to COVID-19 over the next year.

If you are exposed, there are measures you can take, based on the biology of the virus, which may diminish the likelihood of severe illness. These are not treatments for disease; they are preventive strategies to help place you among the 80% with mild to minimal illness and they have the greatest chance of succeeding if they are implemented before you are exposed. If it becomes possible to expand the 80% with trivial illness from COVID-19 to 90%, the social benefit will be enormous.

CORONAVIRUS BIOLOGY, WHAT YOU NEED TO KNOW

In order to cause disease, any virus must enter a human cell, replicate, and damage the cell, escaping to infect adjacent cells. For COVID-19, there are 3 enzymes that play a critical role in this sequence. They are named ACE-2, Furin and 3-CL protease.

ACE-2

COVID-19 enters human cells by attaching to a protein on the cell surface called ACE-2. The pattern of COVID-19 pneumonia on CT scan matches the distribution of ACE-2 in the lungs. ACE-2 is actually an enzyme with strong beneficial effects in the organs that produce it. When corona virus binds to ACE-2, the protein loses its enzyme activity. In the words of one scientist, COVID-19 produces “ACE-2 exhaustion”.  Some scientists believe that ACE-2 exhaustion is responsible for the severity of pneumonia and for catastrophic effects like heart failure, blood clots and circulatory collapse. I believe that all the clinical manifestations of COVID-19 can be traced to ACE-2 destruction by the virus.

Laboratory studies have shown that restoring ACE-2 dramatically reduces the severity of pneumonia in animals with many types of lung injury, infectious or toxic, including those infected with SARS CoV-1, a close relative of SARS-CoV-2. The resilience of ACE-2 may explain the diversity of responses to corona virus infection. ACE-2 activity is highest in young animals and decreases with age. Conditions associated with death from COVID-19 infection (advanced age, diabetes, high blood pressure, heart disease, kidney disease) are all associated with diminished baseline ACE-2 activity. Because the gene for ACE-2 is located on the X-chromosome, women may have more ACE-2 than men. The second phase of COVID-19, the progression from a minor viral illness to severe pneumonia, may reflect ACE-2 exhaustion, occurring several days after the initial symptoms. This protocol for protection will present aids to enhancing ACE-2 resilience.

FURIN

In order for the COVID-19 virus to lock on ACE-2, the surface of the virus (the viral spike proteins) must first be altered by an enzyme called Furin. Furin is present in all human cells; unlike ACE-2, it is not indispensible. Furin plays a role in the spread of cancer and various infections and there are drugs designed to block Furin. Some dietary components and herbal compounds have been shown to inhibit Furin activity. 

A recent detailed analysis of the evolution of this virus through genetic analysis suggests the following conclusion: COVID-19 has been around for a long time as a source of occasional illness in humans. A series of mutations increased its sensitivity to Furin, allowing the virus to bind much more tightly with ACE-2, making it far more contagious and virulent, and creating the present pandemic. This research makes Furin an attractive target for slowing the spread of infection.

3 CL-PROTEASE

Once they have entered human cells, corona viruses produce damage and spread to other cells by creating an enzyme called 3CL protease. Although several enzymes may be involved in viral replication and spread, 3CL protease is the most important for the corona virus family. It has been called “the Achilles heel” of corona virus and is the subject of new anti-viral drug development. Some dietary flavonoids inhibit 3CL protease in laboratory studies and for that reason may limit severity of infection.

IMMUNE BALANCE

In order to accomplish the steps just described, viruses need to avoid the natural, intrinsic protection provided by the human innate immune system, a series of cells and proteins that kill viruses on contact. Corona viruses have many mechanisms for evading the innate immune system, so it isn’t clear that stimulating innate immunity will offer much protection. Weakened innate immunity may increase susceptibility to illness, so measures to optimize innate immunity are warranted. Once pneumonia develops and disease severity increases, the role of the immune system changes. Much of the damage is due to over activity of immune responses, which is termed a “cytokine storm.” Immune modulating therapies need careful handling during Phase Two of COVID-19 infection.

PROTECTION THROUGH NUTRITION

A few dietary components have shown anti-corona virus effects in laboratory studies, including results in animals. Some of these have a long history of human use for treating infections.

ACE-2 enhancement

Regular aerobic exercise and a plant-based whole foods diet are associated with improved ACE-2 function. Natural substances shown to enhance ACE-2 function include curcumin (a set of flavonoids found in the spice turmeric), resveratrol (a polyphenol found in red grapes and other foods), rosmarinic acid (a polyphenol found in spices like rosemary and oregano), Panax notoginseng (an herb used in some traditional Chinese medicines—the active Panax fractions for strengthening ACE-2 are called saponins), and alpha-lipoic acid (an anti-oxidant). ACE-2 as an enzyme produces a peptide called Ang 1-7, which is responsible for many of its cellular benefits. Ang 1-7 is made up of 7 amino acids and can be absorbed if taken orally. Availability of Ang 1-7 as a nutraceutical is desirable, but presently elusive.

Resveratrol has a number of beneficial effects on corona virus infection beyond ACE-2 support; it inhibits the growth of the deadly MERS corona virus by multiple mechanisms. In addition, resveratrol diminishes the kind of inflammation associated with corona virus infection.

Inhibition of Furin

Natural substances that inhibit Furin activity include the herb Andrographis paniculata, a staple of traditional Chinese medicine (the active fractions are called andrographolides), the flavonoid luteolin (found in celery, thyme, green peppers and chamomile tea), and an extract of noni leaf (Morinda citrifolia, the leaf not the fruit). In addition to inhibiting Furin, luteolin was shown to directly block the entry of SARS-Co-V-1 into cells by sticking to the surface spike protein.

3CL protease inhibition

Elderberry fruit (Sambucus nigra) and the medicinal herb Houttuynia cordata both inhibit the viral enzyme 3-CL protease and have been shown to inhibit corona virus activity in cells. Elderberry seems to be most effective if started before infection occurs. It may be contra-indicated in Phase Two of COVID-19, because of its immune boosting effects. Elderberries’ 3CL protease inhibition is related to its content of flavonoids, especially those called anthocyanins, and its immune stimulating activity is related to its complex sugars (polysaccharides). If taking elderberry, make sure its flavonoid or anthocyanin content has been standardized. Elderberry extracts are safer than raw elderberry fruit. The leaves, bark and roots of elderberries contain a toxic substance, which is removed by cooking or extraction. Concerns have been raised about the immune stimulating effects of elderberries. These are addressed in the next section, because they apply to all immune enhancing therapies.

There are several dietary flavonoids that inhibit corona virus 3CL protease. The most studied are luteolin and quercetin, which is found in both elderberry and Houttuynia. Food sources of quercetin include onions, apples and many other fruits. Quercetin is presently being studied in China as a drug treatment for COVID-19, based on research initiated at McGill University. Other flavonoids with potent 3CL protease inhibition in laboratory studies include herbacetin, which is primarily found in ground flax seed (not in flax seed oil but in the husk) and theaflavin gallates, which are abundant in black and puerh tea. Green tea and oolong tea were inactive in this study.  As long as you maintain hydration, black tea with elderberry concentrate may be the beverage of choice. Do not add milk to your tea, as milk interferes with theoflavin absorption.

Immune Balance

There is a growing consensus that broad-based attempts to enhance immune function will not help and may hurt people suffering from COVID-19. Immune modulation for COVID-19 should vary with the stage of infection: pre-exposure/asymptomatic, Phase One/Phase Two. Some immune enhancers are sufficiently anti-inflammatory that they have a place in each stage; others should only be used for prevention or early asymptomatic infection.

For prevention, enhancement of innate immunity is reasonable, given the proclivity of this virus to sicken people who are older and therefore likely to have sub-optimal innate immune defenses. The innate immune system is present at birth and is ready to attack microbes on contact. Its function is supported by adequate sleep and moderate exercise. The most important dietary component for its maintenance is protein. Protein deficiency impairs innate immunity, but there is no evidence that excess dietary protein improves it beyond the effects of a normal healthy diet. Your protein intake in grams should be about half your lean body weight in pounds.

For symptomatic infection, anti-inflammatory approaches that prevent hyper-reactivity of the innate immune system are warranted.  A key driver of the inflammatory damage in COVID-19 is a protein complex called the NLRP3 inflammasome. Quieting this complex should be a major treatment goal.

Pre-illness enhancement of innate immunity: The safest substances are vitamin D, low dose melatonin, probiotics, prebiotics and mushrooms.

Vitamin D. Almost everyone should supplement with Vitamin D through the winter, but the dose needs to be individualized over a range of 1000 to 5000 IU/day. Vitamin D is best absorbed with a large meal. (A recent review cautioned about a possible pro-inflammatory effect of vitamin D. That report failed to recognize the different forms of vitamin D in the body. The common supplemental form of vitamin D is cholecalciferol, or vitamin D3. In the liver D3 is converted to 25-hydroxyvitamin D3, which is the main circulating form of vitamin D. At sites of inflammation and in the kidneys, 25-hydroxyvitamin D is converted to the most active form, calcitriol. Except in cases of severe deficiency, there is little relationship between vitamin D supplementation and levels of calcitriol. No observation that relates calcitriol level to inflammation has any impact on optimal vitamin D3 supplementation).

Melatonin is a hormone made by the pineal gland at the base of the brain. It supports anti-viral immunity and also helps to control NLRP3. Your body makes melatonin in the dark, mostly between 2-3 AM. Melatonin synthesis decreases with age, which may be one factor contributing to the impact of age on the outcome of COVID-19.  Don’t watch late night television or use a video screen after midnight. Limit artificial lighting at night. Cherry juice contains low levels of melatonin (about 40 micrograms in 8 ounces). Drinking cherry juice (about 16 ounces a day) can significantly increase blood levels of melatonin. You can also take low dose melatonin as a supplement, about one half milligram (0.5 mg) around 10 PM. If you get sick, you may need more. At higher doses, melatonin inhibits the NLRP3 inflammasome. The anti-inflammatory effect of melatonin may be enhanced by high doses of vitamin C.

Medicinal and dietary mushrooms contain polysaccharides that can stimulate innate anti-viral immunity. The best to take in anticipation of SARS-CoV-2 exposure are turkey tail (Coriolus or Trametes versicolor) and reishi (Ganoderma lucidum). In addition to enhancing innate immunity, they can stimulate release of immune balancing, anti-inflammatory cytokines.

Probiotics and prebiotics may impact innate immunity by creating a gut microbiome that stimulates the immune system. Research in this area is in its infancy. Prebiotics with the best evidence for immune stimulation include beta-glucans, arabinogalactans and galacto-oligosaccharides. These are readily available as powders. Probiotics with the best evidence for immune stimulation are Lactobacillus species, especially Lactobacillus plantarum, which is found in sauerkraut and other fermented plant foods, and spore-forming bacteria of the genus Bacillus, which are normally found in soil. Several preparations are commercially available. Because COVID-19 has many mechanisms for evading innate immunity, even when it is strong, immune enhancement by itself is not a promising approach for preventing severe infection.

Elderberry polysaccharides have been shown to enhance innate immunity and prevent viral infections in air travelers. To be rich in polysaccharides, the elderberry extract must be produced by ultra filtration, not by solvent extraction.

Several physicians advise that zinc and vitamin A should be taken to prevent or treat COVID-19. My view is that vitamin A and zinc should only be supplemented if blood levels are low, because of the potential toxicity of high levels of these nutrients. Vitamin A may cause liver toxicity. Zinc is much more complex. Zinc has been advocated at doses of 30 to 75 milligrams per day for its alleged direct anti-vital effects and for its inhibition of certain enzymes involved in viral transport and replication. This advice ignores the physiology of zinc. Levels of zinc in plasma, even when they are low, are about 10 times greater than those needed for inhibition of viral enzymes. The concentration of zinc inside cells is over 200 times higher than needed. Almost all the zinc within cells is bound to proteins, so that the concentration of free zinc is negligible, almost a million times lower than what is needed to inhibit viral-associated enzymes. There is no way that zinc supplementation will impact the level of free intracellular zinc. But high dose zinc supplementation will produce deficiency of copper, and copper is a natural inhibitor of Furin. Many integrative physicians make the mistake of measuring zinc in red blood cells or whole blood to establish zinc status; this is inaccurate, because intracellular zinc reflects the levels of zinc-containing proteins, which is not a guide to zinc deficiency or adequacy. Plasma zinc is much more meaningful. Inflammation leads to a sequestration of zinc in the liver, however, so in severe inflammatory states, plasma zinc also becomes an unreliable index of zinc status. Finally, dietary zinc supplementation increases the risk of bowel inflammation due to overgrowth of the pathogenic bacteria, Clostridum difficile. Dietary zinc increases toxin-production and virulence of C. difficile in laboratory animals and in humans. Hospitalization, especially when associated with the use of antibiotics or acid-suppressing drugs, is a major risk factor for C. difficile colitis. Zinc supplementation should not be used freely, but with caution.

Immune Modulation during Symptomatic Infection

The lung damage of advanced corona virus pneumonia is due to an overactive immune response, so some immune boosting therapies should be used only for prevention or early infection and not for severe illness. Fortunately, many of the substances already mentioned decrease inflammation and specifically down-regulate the NLRP3 inflammasome: resveratrol, luteolin, curcumin, andrographolides, and melatonin. There are many other dietary components that modulate NLRP3. Among these, black cumin seed (Nigella sativa and Nigella indica) has the most robust history of medicinal and clinical use. Their active ingredient is thymoquinone. Look for a product that specifies thymoquinone content (desirable is 5%). 

If you suffer from an autoimmune disease, it may not be advisable to use melatonin, mushrooms, elderberry, prebiotics or probiotics that stimulate innate immune function. If you become  sick with symptoms of COVID-19, you should stop the use of medicinal mushrooms elderberry and immune-enhancing pre- or probiotics.

ANTI-VIRAL HYGIENE

The first step is to develop these habits: Wash your hands with soap and water for 20 seconds before eating, touching your face, after being with other people and when you return home. A face wash is also a good idea.  Soap is the ideal anti-coronavirus cleanser, because it destroys the virus’s protective envelope. Do not use antibacterial soap; it will not kill viruses and will only damage your skin’s microbiome.

COVID-19 remains viable on surfaces like plastic and stainless steel for 48 hours, on cardboard for about 24 hours and on copper for 4 hours. The infectivity of the virus declines with time. After 6-7 hours on steel or plastic, half the particles have lost viability. The viral half-life on copper is under one hour. Use caution with objects or surfaces that are possibly contaminated; avoid touching doorknobs or elevator buttons with your hands.

The following cleansers will kill most viruses, including corona viruses, on hard surfaces with 30 seconds of contact: 70% alcohol, 0.5 % hydrogen peroxide, 0.1 % bleach (hypochlorous acid). The studies have been done on hard nonporous surfaces, so alcohol, peroxide or bleach will work on counter tops but may not work the same on your skin or other porous surfaces. If you choose to use bleach, make sure you do not mix it with ammonia, because the combination produces a deadly gas. Purelle hand sanitizer is 70% alcohol and might be an adequate substitute for soap, but remember that contact needs to be maintained for 30 seconds. Clean door knobs, phones and keyboards daily or more often.

Microwave ovens can kill some strains of corona virus that contaminatie food. In the one study done, death occurred in 20 seconds. . For helpful information about handling food safely, view this YouTube video: https://youtu.be/sjDuwc9KBps

The use of face masks has become a major strategy in the government’s attempts to stop the spread of COVID-19. The CDC has recently reversed its advice that asymptomatic people should not wear face masks in public.  This is long overdue but has created a great deal of confusion: what type of mask? How effective is each kind? Is there a downside? A review of 34 studies found that simple masks, even homemade ones, have a significant protective effect on viral spread through communities.

https://www.washingtonpost.com/outlook/2020/03/28/masks-all-coronavirus/.

Here are links to other articles that attempt to guide readers in making choices about masks:

https://www.popsci.com/story/diy/make-diy-face-masks/

https://www.aol.com/article/lifestyle/2020/03/24/how-to-make-a-face-mask-that-is-effective-against-coronavirus/23960274/

https://www.nbcnews.com/health/health-news/making-your-own-face-mask-some-fabrics-work-better-others-n1175966

https://slate.com/technology/2020/04/comprehensive-guide-masks.html?v

Face masks aside, the old rules still apply: If you are sick, stay home and wear a surgical mask around other people. N95 respirators are fairly uncomfortable when worn for extended periods of time and should be reserved for health professionals. When coughing or sneezing, cover your nose and mouth with your forearm or with a tissue and dispose of the tissue in a closed container. Avoid shaking hands. Social distancing prevents viral spread; try staying six feet away from other people, especially if you’re sick.

Various metals are being touted for their anti-viral effects. Do not fall for the hype. Copper and its alloys like bronze are the most potent of the anti-viral metals. However, several hours of copper exposure are needed to eliminate COVID-19, unlike cold viruses, which are killed in 60 seconds. Because the mechanisms by which different metals kill viruses tend to be similar, it is unlikely that metals like zinc or silver will be effective at killing COVID-19. Furthermore, the silver preparations tested in scientific studies are different from the colloidal silver that is sold in health food stores, so colloidal silver sprays cannot be relied upon for protection. High levels of zinc kill some corona viruses but are less effective than copper. Although some doctors advocate the use of zinc lozenges to prevent COVID-19, zinc lozenges are unlikely to achieve time of contact or concentration needed to kill this virus. The main side effect of zinc is nausea, a symptom that plagues many people with COVID-19.

OLD DRUGS REPURPOSED

Ever since the SARS-CoV-1 epidemic, which lasted from 2002 to 2004, scientists have been searching for drugs (old and new) to improve the outcome of corona virus infection. There are two categories of established, readily available, FDA-approved drugs that are promising:

1. Anti-parasitic drugs: The anti-malarials, chloroquine and hydroxycholoroquine (Plaquenil), have received the most attention. A research paper from China published last month demonstrated potent killing of COVID-19 by these drugs in laboratory studies, with hydroxychloroquine being superior. Plaquenil is generally used as an immune modulator for autoimmune diseases or as an enhancer of antibiotic effectiveness for infections like Lyme disease. It is typically taken for months or years at a time. In humans, Plaquenil has been shown to rapidly reduce the number of live COVID-9 particles; the addition of the antibiotic azithromycin improved the Plaquenil response, so that there was no live virus left after 6 days.  Clinical trials with Plaquenil and azithromycin are underway in the U.S.  Both these drugs may cause life-threatening cardiac arrhythmias; they must only be taken under medical supervision. Ivermectin, a drug for eradicating worms, has recently been shown to decrease the entry of SARS-CoV-2 into cells by a factor of 5000, with just one application. Ivermectin is inexpensive and has a high safety profile. It will undoubtedly be the subject of clinical trials. Nitazoxanide (Alinia), approved for treatment of the parasite Giardia lamblia, has been proposed as a useful add-on to Plaquenil. Alinia has anti-viral activity and also up-regulates anti-viral defenses by boosting Type 1 interferon production.
2. The anti-malarials, chloroquine and hydroxycholoroquine (Plaquenil), have received the most attention. A research paper from China published last month demonstrated potent killing of COVID-19 by these drugs in laboratory studies, with hydroxychloroquine being superior. Plaquenil is generally used as an immune modulator for autoimmune diseases or as an enhancer of antibiotic effectiveness for infections like Lyme disease. It is typically taken for months or years at a time. In humans, Plaquenil has been shown to rapidly reduce the number of live COVID-9 particles; the addition of the antibiotic azithromycin improved the Plaquenil response, so that there was no live virus left after 6 days.  Clinical trials with Plaquenil and azithromycin are underway in the U.S.  Both these drugs may cause life-threatening cardiac arrhythmias; they must only be taken under medical supervision.
3. Ivermectin, a drug for eradicating worms, has recently been shown to decrease the entry of SARS-CoV-2 into cells by a factor of 5000, with just one application. Ivermectin is inexpensive and has a high safety profile. It will undoubtedly be the subject of clinical trials.
4. Nitazoxanide (Alinia), approved for treatment of the parasite Giardia lamblia, has been proposed as a useful add-on to Plaquenil. Alinia has anti-viral activity and also up-regulates anti-viral defenses by boosting Type 1 interferon production.

1. Antihypertensives, a class called ARBs (angiotensin receptor blockers), which are normally used to reduce blood pressure and protect kidney function. ARBs increase ACE-2 activity and have been proposed as a treatment to promote healing of the lung in corona virus pneumonia. A recent study from China demonstrated through indirect measures that ACE-2 function declines with viral load and severity of COVID-19 pneumonia. For people already taking blood pressure medication, the inclusion of an ARB may improve the response to COVID-19 infection.  The Federal government is sponsoring a trial of the ARB losartan for amelioration of COVID-19. However, the ARB that most enhances ACE-2 levels in humans is olmesartan (Benicar). Of all the ARBs, olmesartan has the greatest impact on immune function. One caveat: a rare but serious autoimmune complication of olmesartan has been described by the Mayo,  severe diarrhea mimicking celiac disease and/or lymphocytic colitis.

There is misinformation circulating on the Internet that attributes a high death rate with COVID-19 to ARBs and another class of drugs called ACE inhibitors. This opinion is speculative and based on no evidence; it reflects a faulty understanding of corona virus biology and the role of ACE-2 exhaustion in determining disease outcome. A recent study from China found no association between the use of ACE inhibitors or ARBs and severity of COVID-19.  

NUTRITIONAL STRATEGIES FOR CONFRONTING THE CHALLENGE OF COVID-19

1. Before symptoms begin: Enhance anti-viral immunity with vitamin D, prebiotics, probiotics, mushrooms (turkey tail  or reishi), low dose melatonin, and elderberry Consume flavonoids and other plant-based polyphenols for 2 purposes Support ACE-2 activity Build up cellular levels to inhibit the action of 2 critical protease enzymes (Furin and 3CL-protease).
2. Enhance anti-viral immunity with vitamin D, prebiotics, probiotics, mushrooms (turkey tail  or reishi), low dose melatonin, and elderberry
3. Consume flavonoids and other plant-based polyphenols for 2 purposes Support ACE-2 activity Build up cellular levels to inhibit the action of 2 critical protease enzymes (Furin and 3CL-protease).
4. Support ACE-2 activity
5. Build up cellular levels to inhibit the action of 2 critical protease enzymes (Furin and 3CL-protease).

Substances include curcumin, luteolin, resveratrol, quercetin, Andrographis, and elderberry. Ground flax seed and black tea may also be helpful.

1. If symptoms have already started, or once symptoms begin, do not take elderberry, mushrooms, prebiotics, or probiotics, unless advised to by a knowledgeable health care provider.  Continue to use or begin taking curcumin, luteolin, resveratrol, quercetin, melatonin and Andrographis. Add thymoquinone (from black cumin seed) and Houttuynia cordata, if available.  
2. If symptoms are severe or if they do not improve within 3 days, you must consult a medical professional.

SELECTED REFERENCES FOR HEALTH PROFESSIONALS (more will follow when I have time)

1. The role of ACE-2 in COVID-19                 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088566/
2. Resveratrol and ACE-2                                      https://www.ncbi.nlm.nih.gov/pubmed/29407880
3. Resveratrol vs. the MERS coronavirus (MERS does not use ACE-2 for entry into cells, so this study demonstrates other anti-coronavirus actions of resveratrol. The authors recommend resveratrol as treatment for MERS.) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307780/
4. Curcumin and ACE-2                                     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651552/
5. No association between prior use of ACE inhibitors or ARBs and severity of COVID-19  https://www.ncbi.nlm.nih.gov/pubmed/32120458
6. Coronavirus disease is not increased in immune suppressed  patients   https://www.ncbi.nlm.nih.gov/pubmed/32196933
7. Serum angiotensin 2 is directly related to viral load and disease severity in Chinese patients with COVID-19. This is the only paper that supplies actual evidence, not speculation. The authors call for the use of ARBS to ameliorate COVID-19.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088566/

1. ARBs protect against ARDS and may be good for COVID-10 patients   (opinion) https://mbio.asm.org/content/11/2/e00398-20.long
2. A role for ARBs in the body’s defense against COVID-19 (opinion) https://www.ncbi.nlm.nih.gov/pubmed/32129518
3. In vitro effectiveness of hydroxychloroquine vs chloroquine against COVID-19 https://www.ncbi.nlm.nih.gov/pubmed/32150618

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078228/

1. Open label study of hydroxychloroquine plus azithromycin on viral load. Study was recently expanded to 90 patients (not published). https://www.ncbi.nlm.nih.gov/pubmed/32205204  https://www.physiciansweekly.com/hydroxychloroquine-azithromycin-for-covid-19-new-clinical-trial-results/?pi=bf9bcad6b92e7b06e54503f8ffcd4c8f2346114e526a9a4329e78dc67a2b8c38&utm_medium=email&utm_campaign=COVID-19%20Newsletter%20-%20Clinical%20Trial%20copy&utm_content=COVID-19%20Newsletter%20-%20Clinical%20Trial%20copy+CID_763763c39bd3e0f8b73fc0f885ed80f3&utm_source=Email%20marketing%20software&utm_term=Read%20More%20Now
2. Ivermectin prevents  SARS-CoV-2 from entering cells

https://www.sciencedirect.com/science/article/pii/S0166354220302011?fbclid=IwAR2qec5DTgwa0jko3kDE6TebtgBBBmcwYhzuk7IrPQO9htTAP-i72spNcek

1. Research on quercetin as treatment for COVID-19 (McGill Tribune)

http://www.mcgilltribune.com/sci-tech/montreal-researchers-propose-a-treatment-for-covid-19-170320/

1. The role of mast cells in COVID-19 infection (luteolin inhibits mast cells)

https://www.biolifesas.org/biolife/2020/02/04/mast-cells-contribute-to-coronavirus-induced-inflammation-new-anti-inflammatory-strategy/

1. Anti-viral effects of microwave ovens

https://www.ncbi.nlm.nih.gov/pubmed/15223557

1. The origins of SARS-CoV-2 and the role of Furin and ACE-2: https://www.nature.com/articles/s41591-020-0820-9
2. Unique structure and function of the SARS-CoV-2 spike protein https://www.cell.com/cell/fulltext/S0092-8674(20)30262-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420302622%3Fshowall%3Dtrue
3. The role of furin in the spread of SARS https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092861/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114094/

1. Nice review from the American Nutrition Association; what’s lacking is an emphasis on Furin and on enhancement of ACE-2 activity

 https://theana.org/COVID-19

1. Zinc supplementation decreases resistance to C. difficile colitis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101143/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219639/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067591/

However, among patients receiving fecal transplants for recurrent C difficile colitis, low plasma zinc increases risk of recurrence and zinc supplementation is protective. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199870/

Leo Galland M.D.
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Coronavirus Protection