|We hope this information finds you and your loved ones healthy and safe at home. We want to reassure everyone that we are here for you and although we are not seeing patients with suspected SAR-CoV-2 infections in our clinic, we want to provide as much guidance to all of you in terms of prevention and steps to take in the event you have symptoms suggestive of this infection. If you have any symptoms consistent with COVID-19 (fever, dry cough, shortness of breath, diarrhea, cramping, new fatigue) please call our office immediately. Additionally, we want to update everyone as to what some of the current research is showing and help to clear up some of the speculation surrounding the virus.
SAR-CoV-2 Highly Contagious
This virus has certainly taken everyone by surprise at how quickly it has spread and how contagious it is. Epidemiologists have estimated that the virus will infect 70-80% of our population in two years — that’s over 200 million Americans. Currently, amongst those infected with the SAR-CoV-2 virus, 80% have mild or no symptoms, 20% need hospitalization, and 5% will need intensive care. It is still too early to tell the mortality rate as it has been ranging from 0.6% to as high as 15 % in elderly and those who have certain comorbidities such as cardiovascular disease, diabetes, and cancer. The mortality rate is higher than the flu but less than the SARS mortality rate which was approximately 16% and MERS mortality rates which was approximately 30%. The difference with some of these more fatal viruses is that people were not contagious until they showed symptoms as opposed to SARS-CoV-2 where people can be carriers and asymptomatic for 7-10, sometimes 14 days before they even show symptoms. There is evidence to demonstrate that patients can continue to shed the SARS-CoV-2 in stools for up to 31 days after being exposed.
SAR-CoV-2 in Tampa-Bay Area
I am on the Medical Staff at Baycare Hospitals and have been updated almost on a daily basis in regards to the cases. As of April 9th, Baycare has administered over 8.000 tests and of those, 450 tests have come back positive, which includes people from the drive-through testing sites. 57 people are currently admitted to Baycare hospitals, with 30 of those currently in the ICU. Only 10% of the ventilators at the Baycare hospitals are in use which is reassuring that the healthcare in our area does not appear to be overwhelmed. Most patients are going home and doing well.
How does SARS-CoV-2 enter into the Body?
One of the pieces to the puzzle in solving this pandemic is understanding how it enters and binds to the body. This particular virus enters via the mouth, eyes or nasal passage and then binds to receptors called ACE 2 which are in numerous cells of the body including the lungs, lining of blood vessels, and the GI tract. Therefore, when this virus attacks it can affect your breathing, blood pressure, your stools and can even affect your neurological systems.
People who have more ACE 2 receptor sites or “parking spaces” for the virus are deemed more vulnerable. Many conditions can lead to an up-regulation of this ACE 2 receptor which would increase one’s risk of viral load and this includes chronic inflammation and tissue damage, high blood pressure, smoking, and high blood sugar.
Drugs that block ACE 2 such as ACE inhibitors like Lisinopril and ARBs like Losartan have been shown to upregulate these receptors and there is controversy whether or not they increase risk because they increase sites available for the virus to bind. There is currently conflicting thought whether or not these drugs should be discontinued since some believe that discontinuing these drugs would leave the receptors completely empty like parking spots waiting for the virus to park. Based on the research thus far, patients who are on these medications for hypertension alone have a slightly elevated risk but not greater than originally expected. The AHA, the HFSA and the ACC recommend continuation of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin receptor blocker (ARB) medications for all patients already prescribed for indications such as heart failure, hypertension or ischemic heart disease. As new information is coming out every day, we plan to keep you updated should any of these recommendations change. Our office has compiled a list of everyone that is on these medications and will provide further information and updates as we learn more.
NLRP3 Inflammasome as a Key Inducer of Acute Lung Injury
The concern with COVID 19 (which is the infection caused by SARS CoV-2) is the progression into ARDS (acute respiratory distress syndrome) which is the result of a massive inflammatory response leading to lung tissue damage; some of you have heard this referred to as the “cytokine storm” in lungs. NLRP3 inflammasome activation has been shown to induce the production of various cytokines such as Interleukin 1 B; this is a potent pro-inflammatory cytokine implicated in the pathogenesis of ARDS because of its initiation of hypoxia (below normal oxygen levels in the blood).
Interesting Research on Melatonin
The elderly are particularly susceptible to the virus and while it is true that they often have comorbidities including cardiovascular disease and depressed immune systems, there seems to be something else emerging in the research which involves melatonin. Melatonin peaks in early childhood and starts to decline in puberty. It continues to decline during middle age and older people produce negligible amounts of melatonin. Recent research in several animal studies suggests that melatonin actually helps prevent the release of NLRP3, the inflammasome necessary to induce the cascade of events leading to cytokine storm. A study released on March 6, 2020 in China demonstrated that by increasing melatonin with the use of melatonin receptor agonists, they were able to prevent damaging effects of the ventilator-induced lung injury in rodent models. Another interesting fact is that none of the pregnant mothers infected by COVID- 19 admitted to the Zhongnan Hospital of Wuhan University in Wuhan China developed severe pneumonia or died; they have hypothesized that this is because melatonin secretion in the third-trimester pregnancy is more than double compared to the first trimester.
Nitric Oxide and Ascorbic Acid Inhibits NLRP3 Inflammasomes
Many of you have heard me speak about the importance of nitric oxide and how low levels greatly increase your risk of disease, particularly cardiovascular disease. Well, your immune system largely depends on nitric oxide as well to help transport immune mediators to fight off infection. It turns out that nitric oxide is produced in nasal passages as part of a defense system against bacterial and viral infections. Newborns have been found to have an extremely high level of nitric oxide in their barely developed paranasal sinuses. The levels of nitric oxide in nasal passages of infants match those found in healthy young adults, however as we continue to age our nitric oxide levels can decline.
There is emerging literature out of China, Italy, and South Korea, most observational studies but some small control studies on nitric oxide and Ascorbic acid inhibiting NLRP3 Inflammasomes. In rodent sepsis models nitric oxide was shown to inhibit NLRP3 inflammasome activation.
Furthermore, ascorbic acid was shown to support the production of nitric oxide, reduce oxidative stress, modulate the immune system and reduce cytokine storm, as well as other desirable effects. Ascorbic acid was shown to dose dependently inhibit NLRP3 Inflammasomes both in vivo and in vitro, leading to decreased interleukin I B production (pro-inflammatory mediator). The combined use of melatonin, as well as IV Vitamin C, may be a potentially effective treatment in COVID-19 especially for those with cardiovascular and hypertension comorbidities. IV Vitamin C is currently being used in New York as well as several hospitals across the country. It is currently in clinical trial as a treatment against COVID-19 and shows much promise.
Take home message for prevention: You can take Buffered Vitamin C (Ascorbic Acid) 1-2 grams a day and Melatonin 3mg at bedtime. Fullscripts seems to have a lot of vitamin C/ascorbic acid on backorder however this is something we have available at the office that we can mail out if you are in need. We also have ascorbic acid combined with quercetin which is an extremely strong antioxidant and thought to be helpful in protecting oneself against the damage of COVID 19; the product that we have is through Designs For Health and is in powder form. To boost
your Nitric Oxide levels, a well-researched patented product that has been clinically proven to raise nitric oxide is Neo40 Pro.
The Importance of Gut Health
We have discussed the importance of gut health in preventing disease given the fact that anywhere from 60-80% of your immune system resides alongside the GI tract. Research demonstrates that COVID-19 is very dominant in the GI tract and digestive symptoms predict worse outcomes. In those who became critically ill, 60% of patients without GI tract symptoms recovered versus 35% with GI symptoms. GI symptoms were not a predominant complaint from cases reported in China however over 50% of the cases in New York had GI disturbances as their initial presenting symptoms.
As mentioned earlier people who have chronic inflammation and increased intestinal permeability/leaky gut are thought to have increased ACE 2 receptors which allow the virus to bind to the cells and likely leak across the membrane and enter the bloodstream.
Now more than ever is a time to eat clean whole foods and avoid sugar, processed food, and unhealthy fats. Limit or stop alcohol as it may also suppress the immune system and depletes key nutrients. For those of you who we diagnosed with increased intestinal permeability/leaky gut, please continue your gut healing protocol. For those of you who suffer from chronic inflammation and suspect you have increased intestinal permeability, a simple strategy for you to take is to initiate a supplement with immunoglobulins such as Colostrum (Sovereign Labs), SBI Protect or Mega Mucosa (for non-dairy alternatives), as well as one of my favorite probiotics, MegaSporeBiotic which is currently in 14 clinical trials right now for healing the gut.
Stool Testing to Come
COVID-19 has been demonstrated to show up earlier in stool and persist longer than in the nasal pharyngeal track and therefore stool molecular methods are being developed as a surveillance tool to monitor patients to see if they continue to be a carrier. The additional benefit of this test is that someone who needs to be tested will be able to submit the sample themselves versus collecting nasopharyngeal swabs which has to be performed by a healthcare professional.
We are currently trying to secure these tests for our individual patients and corporate clients to see whether or not their employees have been infected and if so are they immune and ready to return to work. The test kits use rapid chromatographic immunoassays (like a home pregnancy test) to detect IgM and IgG antibodies to COVID-19 SARS-CoV-2 in the blood. IgM antibody is the type of antibody that rises generally within one week of initial infection whereas IgG appears about 14 days after infection.
Advantages of these types of tests include the following:
- Rapid results (under 15 minutes) versus the nasopharyngeal tests which take days
- Increased Accuracy: sensitivity (Most range around 85%) and specificity (~92%)
- CE approved and widely used in many European countries
- Whole blood testing likely remedies some false negatives inherent in respiratory swab samples
- Low cost
- Ease of use; no need for laboratory personnel, equipment or sample transport
We are trying to sort out the logistics of testing patients since we are trying to limit traffic through our office to protect our well patients and staff; we will keep everyone posted as to when this becomes available. We plan on testing those who feel they may have had the virus or been exposed but have not had any fever or upper respiratory symptoms for at least 21 days.
Controversies with Natural Supplements such as Elderberry
You may have read that natural immune-boosting agents such as Elderberry may contribute to cytokine storm however there is no evidence to support this. Elderberry, in particular, can induce pro-inflammatory cytokines but also anti-inflammatory cytokines and therefore it has a very neutral impact. What is interesting about Elderberry is that it may reduce the binding of the virus to the cells and therefore may be very helpful. However, if you develop symptoms suggestive of COVID-19 and notice increased shortness of breath when taking Elderberry you should stop.
Peptide Therapy and COVID-19
Many of you have heard me talk about peptides enthusiastically and several of you are on these therapeutically or preventatively at this time. Peptides are chains of amino acids that are found in our body but can decline with age and certain conditions. There are over 8000 peptides that have been identified in our bodies.
I have been using thymosin alpha 1 in particular for patients, for quite some time now, to help bring their immune systems back into homeostasis. It turns out that children have a robust, active thymus gland but as we age our thymus glands begin to involute which makes us more susceptible to infections and disease. Thymosin alpha 1 is thought to help restore functions of the thymus gland; it is thought to improve our bodies’ ability to detect viruses while also dampening the release of proinflammatory cytokines.
Better yet, new work recently in the MIT lab has produced a new peptide (23 amino acid chain) that binds to the spike protein of the SARS CoV-2 virus. This peptide is a copy of the a-helical portion of the ACE2 receptor. Blocking this binding interface represents a highly promising therapeutic strategy since it could potentially hinder SARS-CoV-2 from entering cells and replicating. They have started testing this specific peptide in animals.
Status of Treatments and Vaccines
Currently, there are no approved treatments for treating COVID 19 other than symptomatic care, supportive care with fluids and ventilators if necessary. However, there are over 75 different therapies, selected by Artificial Intelligence, being researched right now to see if they can treat the virus. A majority of these are medications that we currently use for existing diseases and we are trying to test and determine if they can be used to treat this new virus. Some of the more promising include:
- Plaquenil, (hydroxychloroquine) or chloroquine (a malaria drug) are medications used for autoimmune disease. This medication has been around for 60 years. The recommended dose is 200 mg twice a day for 10 days. This has been combined with the antibiotic Zithromax but has not been proven by clinical trials yet but seems to be promising. Plaquenil has possible side effects such as heart arrhythmias and should NOT be used unless discussed with a doctor. There is interesting evidence about COVID-19 that suggests SARS-CoV-2 may have the ability to dissociate iron from the porphyrin and bind to porphyrin itself. Porphyrins are essential for the function of hemoglobin — a protein in your red blood cells that links to porphyrin, binds iron, and carries oxygen to your organs and tissues. When the viral proteins bind to porphyrin, this causes alterations in the hemoglobin function, investigators claim and can be the cause of the additional lung damage and respiratory distress. Chloroquine has been shown to bind at a greater affinity to these viral proteins than the viral proteins to porphyrin, which could be one mechanism in which it is thought to work.
- Remdesivir, an antiviral drug developed for Ebola, given only intravenously.
- Convalescent plasma therapy, which means taking the blood of a recovered patient and extracting the antibodies from their blood and giving it to those who are sick. One small study in China demonstrated good effectiveness in critically ill patients. This is currently being studied and used at some institutions for the critically ill.
- Cytokine blocking drugs, (tocilizumab, sarilumab, etc.) which can reduce the inflammatory cytokine storm that can potentially lead to death.
- Interferon B, this drug has been developed in Cuba and can calm down an out of control inflammatory response. More data is needed but this seems promising.
- Vaccines will likely take 12 to 18 months to progress with human trials for safety and efficacy. The virus is already mutating which will make this process even more difficult.
My belief is that our biggest defense right now is our immune system. We previously emailed out ways to help boost your immune system and steps to take to reduce your risk for contracting the virus, please continue to use that as a reference.
As many of you know the conversation around this virus changes daily. My goal is to continue to provide you with the latest and most relevant news and research regarding this virus and more importantly what you can do to keep safe and strengthen your bodies to best fight it. Remember to eat a whole food diet rich in fiber and low in sugar, exercise, get your sleep, breathe, keep your toxins low, take key supplements, wash your hands, wipe down any surfaces that others come in to contact with, practice social distancing and stay home. As always we are here for you with any concerns and questions. Thank you all and stay safe.
Best in Health,
Dr. Tarin Forbes