Emerging Theories That May Help Us Solve the COVID-19 Puzzle

I should be writing this at the beginning of all my articles in the last month but due to the fact that we are all living in real time and the information coming out is changing moment by moment even the best scientist’s theories on how to combat this illness continue to evolve.  Although things could certainly change as larger studies come forth, for the moment I wanted to share with you some exciting new details that are emerging theories, which could affect future treatment development.

Current Theory and Treatment for Coronavirus

Currently COVID-19 is being treated as a dysfunction of the lower respiratory tract. It’s primary symptoms are:(1) 

1. Fever
2. Cough
3. Shortness of breath

Interestingly, a large number of COVID-19 patients also report a loss of taste and smell. In mild cases of COVID-19, the virus will run its course and resolve on its own. But if this disease progresses to a critical level, patients spiral into a state of severe hypoxemia – where the body is unable to effectively deliver life-sustaining oxygen to the rest of the body. Without adequate oxygen delivery, vital organs and tissues are starved of oxygen and begin shutting down – which can eventually lead to death.

The current treatments assume that coronavirus is causing a build-up of liquid (instead of air) in the alveoli – making it difficult for oxygen to transfer through the fluid and make its way into the bloodstream. To counteract oxygen deprivation caused by this build up of fluid, COVID-19 is currently being treated as a case of acute respiratory distress, also known as ARDS. The standard treatment for ARDS is mechanical ventilation – which will force air into the alveoli in hopes of transferring oxygen into the blood.

The problem is, treating COVID-19 with ventilation isn’t working like it should. In fact, some doctors have observed that the use of ventilators may even be harming some patients. So that brings up the question – what if our current understanding of COVID-19 is wrong?

Emerging ideas on the virus…

There is mounting evidence suggesting that our initial understanding of exactly how coronavirus impacts the body may be incorrect.

Consider these mysteries of COVID-19:

1. Patients are showing blood oxygen levels so low that they should be life-threatening, but without showing the typical signs of distress that are expected when the same levels are reached due to lung dysfunction. (2)
2. Doctors are saying that ventilators aren’t working as well as they should be and may even be harming some people. (2)
3. Many patients report a loss of taste and smell, typically associated with zinc deficiency, not respiratory disease.
4. Researchers have noted that the pathological mechanism that causes the damage to the body remains a mystery. (3)
5. Twenty percent of COVID-19 patients have cardiac damage. (4)
6. Fatality rates, even among places with robust testing in place, are wildly different.

These discrepancies have hinted at a new culprit as well as new possible solutions. So, should we be treating COVID-19 differently? To answer that question, first let’s look at exactly how a healthy body is designed to deliver oxygen to your tissues.

How Our Cells Are Designed Carry Oxygen

As you inhale air, oxygen enters your lungs and reaches the alveoli which is lined with a layer of cells that creates the barrier between your lungs and your bloodstream. Oxygen molecules pass through this barrier and attach themselves to a protein called hemoglobin that is bound to your red blood cells. Once your red blood cells have picked up oxygen, they set off to begin delivering it to the rest of the tissues in your body.

Think of your red blood cells like little rafts that are responsible for picking up oxygen and carrying it to your tissues which rely on oxygen for survival. And think of hemoglobin like people on the raft working as a delivery crew – tasked with receiving, holding, and dropping off oxygen molecules. Without the “delivery crew” of hemoglobin proteins, the raft is useless.

It’s also important to understand a little more about the structure of hemoglobin. A vital component of hemoglobin proteins are heme groups – which are embedded in the hemoglobin and are responsible for binding and releasing oxygen molecules.These heme groups are a metal complex and contain iron as the central metal atom, with each iron molecule capable of carrying one oxygen molecule.5 These iron rich heme groups are critical – without them your cells are unable to transport the oxygen your tissues depend on.

This understanding the body carries oxygen has sparked speculation about how COVID-19 may be exerting it’s devastating effects by creating more reactive oxygen species causing tissue damage and hypoxia.

A New Theory on COVID-19’s Mechanism of Injury

One the most puzzling aspects of COVID-19, is that despite fitting most of the criteria under the definition of acute respiratory failure there is one glaring contradiction. With the coronavirus, there appears to be hypoxia or low oxygen saturation in the blood rather than respiratory distress as seen in classic respiratory failure. Meaning many patients present with severe hypoxia with nearly normal respiratory function.6 This remarkable combination is almost never seen in severe cases of ARDS.

Interestingly, it may be creating a clinical picture similar to someone suffering from severe malaria or altitude illness.

Could COVID-19 Be affecting Oxygen Carrying Capacity?

In COVID-19’s final and severe stages, the lungs are severely damaged. But new information on this virus’s cellular process in the body is revealing that the final condition of the lungs and accompanying respiratory failure may actually be more of a case of massive oxidative stress overload disrupting the capacity of hemoglobin to carry oxygen to tissues rather than an outright attack on the air sacs in the lungs.

The theory on coronavirus affecting the blood’s oxygen carrying capacity is related to the fact that increased intracellular oxidative stress is at the core of all pathogenic infections.  This is often referred to as an increase in reactive oxygen species or ROS.  This ROS production is at the core of much of the damage we are seeing not only to the blood’s ability to deliver oxygen to the tissues, causing severe hypoxia or low oxygen but also damaging all tissues they come in contact with.  As Integrative and functional medicine doctors, we often measure markers of oxidative stress in our patient’s urine to determine if this process is out of control.  One such marker is lipid peroxides.  According to Dr. Tom Levy the intracellular levels of Vitamin C, magnesium and glutathione largely affect the oxidative stress which could damage the tissues, one reason why you are seeing Vitamin C being used in hospitals to treat the virus.  Stay tuned as I will be writing more about Vitamin C in upcoming blog articles.

This cascade of events would explain:

1. Why as many as one in five COVID-19 patients have cardiac damage.
2. Why IV nutrients that target cardiovascular function are beneficial.
3. Why many people experience a loss of taste and smell.
4. Why anti-malarial medications are showing promising results.

This would also explain why ventilators aren’t working quite like we’d expect. Ventilators work by forcing more air into the lungs, so more oxygen can be delivered to the blood. This is helpful when there’s liquid or inflammation in the lungs, and the blood is working normally – like in pneumonia. However, if there is an issue due to the fact that oxidative stress (ROS) has altered the blood’s ability to properly carry this oxygen, then a ventilator can’t do its job. Right now, the Journal of the American Medical Association indicates that COVID-19 patients are candidates for “early, invasive ventilation”. But if we’re ventilating patients who are struggling to keep their little oxygen boats afloat in the bloodstream due to massive oxidative stress, ventilation will do little good and could even cause damage.(8)

This theory would also give us some more insight as to why certain populations may be more at risk of contracting COVID-19.

This Might Explain Why Anti-malarial Medications are Being Considered for Treatment.

Hydroxychloroquine, also known as Plaquenil, is an anti-malarial medication that is showing promise as a potential treatment for COVID-19. If coronavirus is in fact attacking red blood cells, similar to the way malaria does, then it would make sense why an anti-malarial drug would be beneficial for coronavirus patients. But how exactly could hydroxychloroquine be exerting these antiviral effects?

Research is finding that it might be due to hydroxychloroquine’s relationship with the mineral zinc. You see, hydroxychloroquine is a zinc ionophore – meaning it enhances your body’s ability to allow zinc into your cells.9  When intracellular concentrations of zinc are increased, it displays broad spectrum antiviral activity in a few ways:

1. Zinc inhibits the actions of certain proteins necessary for the completion of different phases of the virus’s life cycle – essentially halting its ability to reproduce(10)
2. Zinc supports a robust immune response by aiding in the production of cytokines and the modulation of immune cells(10)
3. Zinc acts as a powerful antioxidant and prooxidant – neutralizing the oxidative stress caused by toxic overload of iron that has been dumped into the blood from the burst cells(11,12)

Interestingly, one of the initial symptoms reported by many coronavirus patients is a loss of taste and smell. This lack of taste and smell can be caused by a zinc deficiency. Perhaps the action of hydroxychloroquine helping zinc enter cells is part of the reason the drug has benefitted some COVID-19 patients.13 It’s important to note that in order for hydroxychloroquine to work, there must be adequate zinc levels available to allow into the cells – so hydroxychloroquine must be administered in conjunction with zinc to be most effective against COVID-19.

Hydroxychloroquine has shown promise (as well as a risk of severe cardiac arrhythmia in certain patients) but the way the drug functions has given us some powerful insights and may give us answers into how we can save more lives.

The Connection Between COVID-19 and Altitude Sickness

Another interesting connection is the fact that COVID-19’s clinical presentation is quite similar to another respiratory illness – high altitude pulmonary edema, also known as altitude sickness. In both COVID-19 and high altitude pulmonary edema clinical findings include:(14)

1. A decreased ratio of arterial oxygen levels to inspired oxygen
2. Hypoxia (low oxygen levels) and tachypnea (abnormally rapid breathing)
3. Low carbon dioxide levels
4. A ground glass appearance in the lung tissues
5. Elevated fibrinogen levels
6. Diffuse alveolar damage

In altitude sickness, the lungs are functioning fine – there are just inadequate levels of oxygen to process to properly meet the needs of the body. Clinical findings similar to altitude sickness would make sense if COVID-19 is in fact causing a dysfunction of red blood cells through production of massive oxidative stress rather than a direct problem with the lungs.

So What Are Potential Options to Quench Oxidative Stress?

Even with all of the information that points to COVID-19 creating massive oxidative stress, there are still a lot of unknowns. The downside of this is of course the trial and error and continued research that needs to take place before we have real answers. The upside, is that this information gives us an array of new potential treatment options to consider:

High Dose Vitamin C:

High doses of vitamin C are garnering attention as a powerful way to potentially mitigate the effects of coronavirus. These ultra-high doses of vitamin C are speculated to fight the massive immune response and subsequent respiratory failure seen in coronavirus infection by:(15,16)

1. Suppressing the over-reactive inflammatory response in the lungs
2. Minimizing the accumulation of immune cells in the tissues of the lungs
3. Decreasing the release of cytokines (chemical messengers involved in the immune response)
4. Slowing down the viruses ability to reproduce and spread
5. Neutralizing the oxidative stress caused by the massive amounts of iron floating around in the bloodstream

Ideally, high dose vitamin C can be delivered intravenously, where it is more easily absorbed and utilized intracellularly. But oral vitamin C can also be beneficial if taken correctly. While regular over the counter oral vitamin C causes diarrhea, liposomal Vitamin C at frequent intervals does not, and is an effective way to increase intracellular levels. Several  New York hospitals have approved intravenous vitamin C as a therapy for the first time ever in studies being conducted on the virus.

Glutathione:

Glutathione is a potent antioxidant naturally found in most of the cells in your body. Glutathione plays a few major roles in immune function including:

1. Functioning as a signaling molecule – helping balance inflammation levels and modulating immune system response(17)
2. Reducing oxidative injury by neutralizing harmful toxins (18)
3. Regulating cellular proliferation and apoptosis(19)

There is a growing mountain of evidence finding that the most effective way to take glutathione may be through inhalation. Inhaled glutathione (aerosolized or nebulized) is already being used in the treatment of a variety of respiratory-related conditions and has been garnering attention as a possible treatment option for COVID-19.(20)

Inhaled Hydrogen:

The inhalation of concentrated hydrogen gas is another potential treatment option due to its powerful antioxidant properties. Inhaling hydrogen gas has been found to:(21,22)

1. Reduce oxidative-stress induced damage
2. Reduce cellular apoptosis
3. Improve gas exchange in the lungs
4. Block the production of proinflammatory mediators

Inhaled hydrogen gas may be particularly effective when paired with other anti-oxidative therapies such as IV vitamin C and inhaled glutathione.

Other Antiviral Drugs:

A number of other antiviral medications are being studied for their potential to treat COVID-19. These include:

1. Methylene Blue: Methylene Blue is a medication that has been used in the treatment of malaria due to its powerful antiviral properties – killing the virus at an impressive speed. (23) It’s also used in the treatment of a condition known as methemoglobinemia – a condition in which individuals have too much methemoglobin which is a form of hemoglobin that is much less effective at carrying oxygen. Methylene blue works by converting methemoglobin into a type of hemoglobin that can more effectively transport oxygen.(24)
2. Remdesivir: Remdesivir is another antiviral drug used for Ebola. Remdesivir is showing benefit in solid studies – a small but well-conducted study on severe cases in the US, Canada, Europe, and Japan concluded that Remdesvir caused clinical improvement in 68% of patients. (25)
3. Favipiravir: Favipiravir is a powerful anti-viral agent that inhibits the virus from replicating and spreading. (26) It has been approved in China and Japan for the treatment of influenza and is undergoing research to determine its potential efficacy in treating COVID-19. (27)

Hyperbaric Treatment:

Hyperbaric treatment works in two ways. First, inspired oxygen concentration is increased to nearly 100%. Secondly, ambient pressure is increased to about three times higher than the air pressure we normally breathe. This combination is designed to essential “hyper oxygenate” your blood – improving oxygen delivery to your tissues.(28)

Hyperbaric treatment may be an effective adjunct therapy to help COVID-19 patients recover, especially when administered early.

Could This Bring Us One Step Closer to Finding a Cure for COVID-19?

There are still many unknowns when it comes to coronavirus. The only thing we know for certain is that we are in a race against time. I hope we will continue to search for clues and change course when wrong.

I urge my fellow clinicians and researchers to examine this virus and its mechanism of action with fresh eyes. We entered into this field knowing we were signing up for being lifetime students. This current pandemic is calling us to rise to the occasion – the world is counting on us to find the answers it needs.

In my own practice, I will continue to give my patients and readers the most up-to-date tools they need to protect themselves amidst this pandemic. Until we have a solid understanding of this virus, I will continue to seek new information to do my part in fighting back against COVID-19 and update you when we find more information to help patients get well.

Give Your Immune System the Support It Needs  

Along with continued research to identify the root cause of COVID-19, I am also working on equipping our clinic to offer treatments to support your immune system during this time. Based on our current understanding we may consider offering some of the following options.

1. IV Vitamin C and Glutathione: A powerful combination of two of the most potent antioxidants delivered intravenously so they can be immediately used by the cells to combat oxidative damage.
2. Inhaled Glutathione: Inhaling glutathione delivers it directly to your lung cells – replenishing their antioxidant stores that are quickly used up when fighting inflammation.
3. Inhaled Hydrogen: Pairing inhaled hydrogen’s impressive anti-inflammatory effects with Vitamin C and glutathione makes for a robust and powerful trio of antioxidant therapies.
4. Nasal Ozone: Ozone gas held in the sinuses helps your body more effectively uptake oxygen and activates a healthy immune response.  Ozone should not be inhaled as may damage the lungs.

And fortunately, Flatiron Functional Medicine is certainly not the only place that you may be able to receive these powerful therapies to support the immune system. Many other providers have the resources and training to deliver them as well – so please seek out a reputable and trusted clinician in your area to learn more about these options.