Monday, April 13, 2020

2019 Novel Coronavirus (CoVID-19): Part XII

2019 Novel Coronavirus (2019-nCoV (first named); COVID-2019 (later named disease); SARS-CoV-2 (final name of the virus causing COVID-2019), COVID-2019 Pandemic:
April 12, 2020 update Part 12
Paul Herscu ND, MPH
Herscu Laboratory

This is the twelfth piece of writing on the current epidemic. Please read Part 1Part 2Part 3Part 4Part 5Part 6 Part 7Part 8Part 9 Part 10 and Part 11 for context and also, please read my other writing on this site for a larger context on the overall topic of public health and epidemics.

It has been a very long road, my friends, these past three and a half months. A lot has happened, and really, it has been a confusing period of time for many of us. In this Update, I focus on our natural medicine efforts over these months, on why I have urged us all to take these actions and then share my thoughts and hypothesis on why some people fall severely ill.

My main focus over the three and a half months has been, and will remain, on keeping people out of the hospital. I explain why below. Our first goal has been to keep people from developing the illness to start with. However if they do develop COVID-19, the goal has been to keep it the mildest version possible. Towards that end, the two main tools we use are natural therapies, mentioned in Update 7 and homeopathy described in Update 8. The idea is to have people react/adapt to the virus, move through the illness without becoming severely ill, and then move on with their lives. And if we do our job well, and the stars align, that is how it plays out. 

One of our main tools is to use homeopathy, as it helps people respond early to the virus and have only subclinical or minor manifestations of the illness. We have now treated 170+ folks that have tested positive for COVID-19. The people we put on this supplementation plan and were able to receive an individualized homeopathic remedy too have done well enough. No one has been admitted into the hospital yet (touch wood). This for me is a main, most important point. We need our patients to stay out of the hospital when possible. Partly that is to save personnel and resources for those already severely ill with COVID-19 and/or other unrelated complaints. Simply, I use the hospital admission as a proxy for how well or poorly things are going. 

To be clear. Obviously, if a person’s health deteriorates to serious condition, there is no better place to be than the hospital. If we can keep the person healthy enough to not end up in the hospital, we can avoid several unknowns. As a result, the main focus for Amy and I remains helping with prevention and keeping the disease in those who have it in its mildest form possible.
To help us all understand how people are dying: 

The first is ARDS. The main reason we hear about death is ARDS, as a consequence of sepsis and pneumonia. This makes sense, pneumonia and sepsis are common causes of ARDS, and frankly, treating people with ARDS in the finest hospitals does not lead to great results. In this paper, which I co-authored with others in Critical Care Medicine, we explored a novel and hopeful approach to treating ARDS. With ARDS, mechanical ventilation (MV) comes in, as part of a life-saving aid. However, as many of us remember, there have been an enormous number of deaths at first when MV was incorporated as part of the hospital treatment protocol. People died from the procedures, until doctors found the correct modifications to ventilator strategies, including an incremental Positive End-Expiratory Pressure (PEEP), Low Tidal Volume Ventilation (LTVV), as well as other specific overarching changes to the application of MV. With those changes, many people still died, but they died from ARDS, rather than the injury caused to the alveoli by the high pressures of the intervention. It takes time to develop accurate strategies for sure and the MV approaches are being modified daily with information shared among facilities. Clearly, infections lead to pneumonia, which leads to ARDS, but I think in this instance, it could be that we are repeating history, and we have not yet developed the correct strategy. Some people are dying from ARDS, and some people may be injured from improper strategies here, which continue to be refined. As an MD colleague of mine working in the ICU described to me, eventually they had to ventilate carefully with very high numbers, as for example in the setting of extreme hypoxemia there was nothing left for them to do but to increase oxygen up to 100% with PEEP despite the fact that it may be harmful and may damage the lungs. 

Similarly, in ARDS we prefer not to give too much fluid, to keep the lungs dry. But here, the patients are coming in, often after a week or two of fever, loss of appetite, extreme distress. It is likely that the majority experience hypovolemia which worsens coagulopathy and prompting Multiple Organs Dysfunction (MODS). It is a new situation that demands modified protocols that may not be optimal for other pathophysiologic reasons at this time. If we can skip ALL of this mess, these questions and potential problems, then it is better for all involved. Even the people we spoke with that have developed mild pneumonia have been able to remain at home, and did not need to be admitted in the hospital and have not progressed to further disease.

The second reason people are dying involves Multiple Organs Dysfunction Syndrome (MODS). For a variety of reasons, both septic and other, some patients begin to have at least two organs show physiologic derangement, in addition to the organ system symptoms that brought the patient into the hospital. This is a kind of continuum, as the situation worsens from reversible organ damage to potentially irreversible organ damage and to the point where the patient can die. This cause of death is not mentioned often in the news, but can be considered an end result of an uncontrolled inflammatory response, such as we find with sepsis. This is not an easy situation to deal with if the driving cause is unclear in terms of what sent the person into this state in the first place. Yes, you try to fix the hypoxemia, but mostly, it is still a tricky thing to deal with here. So again, spend most of your efforts on the healthy, mostly healthy or slightly ill people, to keep the presentation at those levels, so hopefully we are able to keep people from falling into these critical states. 

The third cause of death is Coagulopathies, which is when the blood has issues with clotting, either not clotting enough or over-clotting. This situation has also not been mentioned much yet, but will be shortly. In fact, I believe perhaps a very large majority of the patients that have died have had some element of coagulopathy. I believe this is an important piece of the puzzle. Often patients fulfill the criteria for DIC (disseminated intravascular coagulation) as per the International Society of Thrombosis and Haemostasis (ISTH.) Oddly, despite thrombocytopenia (low platelets) and low fibrinogen levels, they do not bleed much at all. There are several treatment options here, including blood replacement, but it is unclear whether this might actually make things better or worse. And it is not clear why patients develop this, or if treatments are helping or not. 

Very related to the issue of coagulopathy is the very important question and something that I am sure will be explored further going forward, is the effect of ACE-Is and ARBs in disease progression. There is heated debate of either or both drug classes either hindering or encouraging disease progression, via the ACE2 receptor. There are theories and quoted results on both sides of the debate. But if we leave this receptor site question aside for a moment, I think looking at potential coagulation issues that are modified by these classes of drugs, might help us better understand their role here. If there is DIC developing, and if they are not overly hemorrhaging, perhaps the potential benefits we may find from these drugs may relate to lowering coagulation problems. Just a thought. 

Here is one hypothesis I would like to share that might explain these three things that happen as listed above.
  1. In an article on ChemRxiv, we read SARS-CoV-2 virus “attacks heme, on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images.” Where if this is the case chloroquine may help prevent this from happening. 
  2. This leads to extreme high pCO2 up to 100%, a CO2-narcosis, with depression of breathing center, and respiratory acidosis.
  3. This leads in the direction of a blood disorder, which may lead to the coagulopathies.  
  4. At some point this may lead to ARDS. 
  5. Mechanical Ventilation (MV) is started, with the normal strategies. 
  6. However, ARDS, which is difficult to treat in the best of situations, is not the only thing happening here. While MV is pushing air into the lungs, the lungs are not working properly in terms of gas exchange due to both the ARDS and the heme issue. The MV settings may be really off, and if it’s the blood that’s at the same time the issue, then in addition to the MV, addressing the blood heme issues primarily or concurrently is paramount.
  7. If not, as a result, ARDS worsens.
  8. If not, as a result, coagulopathies worsen. 
  9. As a further impact, Multiple Organ Dysfunction Syndrome MODS develops.
  10. The patient may die. 

The solutions should address the ARDS/MV setting primarily, while addressing underlying coagulopathy, if present, which is likely. The solution here may be simpler than we think if we focus on the assumptions. I believe this model of what goes wrong has merit. But the issue is that we don’t know yet for sure. No one does. So, until we do know how to handle this heartbreak of a situation, keeping our focus on prevention and aggressive treatment of early disease is essential. And if we succeed here, then I think a great thing will have been done. 

Several of my colleagues have placed most of their focus on the treatment of the hospitalized severely ill patients, which is highly commendable. For me, working to prevent that progression into that severe state in the first place is where I chose to place my focus. If we can keep people on this side, I think that this is really fine work. And it is a powerful thing to help yourself and give your people the ability to help themselves. At the very least it helps the odds, or so it has seemed to us thus far. I hope this explains the constant harangue from us. Do the everyday simple things delineated in update # 7 that may be proving effective at keeping the symptoms at the mild side, this is my hope for me, for my family, friends, colleagues, and my patients. I am repeating those recommendations below to underscore their importance and to try one last time to urge you into action on this front.

PREVENTION STRATEGIES TO CONSIDER (aside from all the good public health measures you should take seriously and follow aggressively)

·       Perfect time to cut down on alcohol and sugar and refined foods
·       Vitamin C 1,000mg
·       Vitamin D, 2,000IU-5,000IU depending on your Vitamin D status
·       Zinc 10-15mg
·       Elderberry (Sambucas nigra) one teaspoon syrup daily
·       Mushroom Immune Formula that has several mushrooms, 2-3 times a week
·       Resveratrol (may work with MERS-Cov) 500mg
·       Get out and go for a walk each day/exercise at home
·       Good rest, and enough sleep
·       Stay hydrated
·       Keep in touch with loved ones, for their sake and yours. The health impact of social isolation is also not good!
·       Don’t panic
You can read further on these details about these approaches, with references, from Amy’s piece here.

STRATEGIES TO CONSIDER IF IN CONFINED SPACE (Ship/airplane/triage center with close proximity to others/jail, aside from public health measures to the best of your ability:

·       Same as above, but double everything
·       Use of Zinc/propolis lozenges during confinement
·       There are any number of throat sprays that that contain antiviral antibacterial herbs, to take when you enter a confined space. These can contain Echinacea angustifolia & purpurea, Propolis, Hyssopus officinalis (hyssop), Zanthoxylum clava-herculis (southern prickly ash bark), Monarda fistulosa (wild bergamot/beebalm), Ligusticum porteri (osha).

STRATEGIES TO CONSIDER IF EXPOSED OR IF MILD SYMPTOMS ARISE aside from all the public health measures you should continue:

·       Same as above, at the same dosage as above.
·       Elderberry teaspoon syrup three teaspoons daily
·       Mushroom Immune Formula that has several mushrooms, 2 times a day
·       Resveratrol (may work with MERS-Cov) 500mg, three times a day
·       Vitamin A 10,000IU
·       Ligusticum ½ dropper or 30 drops three times a day
·       Throat sprays
·       Add more medicinal antivirals that contain any number of the following:
    • Medicinal Mushrooms (species Royal Sun Blazei, Cordyceps, Resishi, Maitake, Lion’s Mane, Chaga and Mesima) 150 g each
    • Andrographis paniculataSambucas nigraZingiber officinale: 800 mg
    • Echinacea Extract Blends: 100 mg
    • Elderberry fruit extract 4:1 (Sambucas Nigra) 500-600mg
    • Larch Arabinogalactan 100mg
    • Resveratrol

I try hard not to mention any label or company above. There is one last thing that I take, but have not mentioned it before here, since it is a product I put together for our practice. Let me describe what it is and how you can make it yourself from supplements you can buy online or at a store near you. We had put together a product some time ago to help support our aging patient population, of which I am one! It contains four supplements: zinc, low dose lithium orotate, lemon balm, and bacopa. We chose these for a variety of reasons and put together at very low doses for a hormetic effect. (To read more about hormesis here’s a compelling piece by Amy in the Huffington Post.) But such doses were difficult to find. I had patients cutting tablets and measuring dosages which became cumbersome. Here is the website that contains the product with the dosages I was after. But again, please note that all 4 supplements are readily available. You can find these at most larger health food stores or online, buy these four supplements from any number of companies, open the capsules and roughly divide each capsule into the similar amount. Aside from the ease and dosage, there is nothing special or unique about the formulation I put together. Mostly it was for the ease of my patients. I take one a day. Two of the ingredients are also antiviral, the zinc and the lemon balm. The lemon balm also is calming, important right now as anxiety is so rampant. And the low dose lithium helps in general with mood, while the bacopa helps with memory and focus, also victims of our over-stressed moment.

I want to end on an optimistic note. None of the people we spoke to have ended up in the hospital. With the very first update on this virus, in January, I felt that the mortality rate, when all is said and done will be in the 1% or less range. There is nothing that has changed my mind on this. It is just that the science has to catch up here, and we are trying to buy time for all our people until it does. 

In the next update, I would like to discuss how we come out of this lockdown, what is a reasonable pathway and where do we go with public health measures then. 

In health, 
Paul Herscu ND, MPH