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Your First Line of Defense Against Viral Infections

By Dr. Michael Murray

In this article:


The worldwide pandemic due to the novel COVID-19 coronavirus has brought focus to prevention – both in terms of reducing the risk of infection through “social distancing” and good hygiene as well as measures to bolster the immune system. But even before our immune system comes in contact with a coronavirus or any microorganism, there are natural barriers to infection. As it relates to COVID-19, the first line of defense is the lining of the airways or respiratory tract – nasal cavity, sinuses, throat, trachea, and bronchi.

The Importance of the Mucous Membranes in Our Airways

In order for any virus to infect the throat, sinuses, airways or lungs it must first pass through or enter the body through the mucous membrane. It is the first barrier to infection; the immune system is the second line of defense. There are two routes for COVID-19 to enter the lungs and cause serious damage. The primary route is through the respiratory tract, the other is through the gastrointestinal tract.

The respiratory tract mucous membrane that lines our airways is the first line of defense against COVID-19. It consists primarily of cells known as ciliated epithelial cells. These cells have their external surface covered by hair-like structures called cilia. The cilia are formed into bundles and act like brushes to move the respiratory tract secretions, microorganisms, and debris up and eventually out the nose or mouth. On top of the ciliated epithelial cells are two layers of mucus. The mucus is produced by another type of epithelial cell called a goblet cell. A thinner version of mucus lies intermixed with the cilia bundles while a thicker layer sits on top of that layer. The mucus is composed of mucin, which refers to a network of proteins complexed with sugars.

The mucous membrane and mucus are specially designed to protect against any microorganism or particles from getting into the lungs. Inside the lungs are specialized epithelial cells that do not have cilia. Nor are there goblet cells in the lungs. In the lungs, there are only very thin epithelial cells, connective tissue, and blood capillaries all designed to perform the function of delivering oxygen to the blood and exchanging it for carbon dioxide. When particulate matter or microorganisms make it to the lungs it is a very serious situation as there is very little protection there. The importance of the health of the mucus and the lining of the airways in preventing COVID-19 infection cannot be overstated as conditions associated with poor functioning of this line of defense is associated with an increased risk of more serious infection.

Preventing the Gastrointestinal Route of Infection

The secondary route of COVID-19 entering the body is through the gastrointestinal tract. Within the GI tract, there are a number of protective factors beyond the mucus lining. The most notable additions are digestive secretions such as stomach acid and digestive enzymes. The immune system structure in the gut is also much larger. If COVID-19 is able to avoid these protective factors and infect the GI tract it is able to enter the bloodstream and also infect the lungs. Interestingly, this ability of coronaviruses to travel from the gut to the lungs was confirmed with Middle East respiratory syndrome coronavirus (MERS-CoV) by increasing the gastrointestinal replication of the virus by infecting animals with viruses orally while at the same time giving them an acid-blocking drug known as a proton pump inhibitor. Obviously, this begs an answer to the question “Does taking a proton pump inhibitor increase the risk for viruses that can attack the lungs by increasing the secondary route of access to the lungs?” The answer is yes.

Another factor that greatly increases the risk of the secondary route of infection is a lack of digestive enzymes. It is well established that pancreatic enzyme insufficiency is a major risk factor for all viral respiratory infections. In fact, enzyme replacement therapy is the key medical approach to reduce the risk of lung infections in these patients. Enzymes that digest protein, proteases, are able to digest not only proteins in food but also the proteins on the cell walls of the virus. Viruses contain proteins protruding from their cell membranes that play critical roles in the infection process. Without these proteins, the virus simply cannot enter human cells. Supplemental proteases are also effective in supporting the mucus barrier in the airways as well.

What Determines the Severity of COVID-19 Infection?

The difference between a mild vs. a severe COVID-19 infection appears to be based on a few things. Most important the viral load that a person is initially exposed to. If exposure is a small dose of COVID-19, in most cases in healthy individuals it will lead to mild or moderate symptoms. If the viral load a person is exposed to is quite high, then it greatly increases their risk for a more severe infection. That is why healthcare workers are especially vulnerable. 

Another factor that determines the severity of COVID-19 may be the ability of the virus to travel down the respiratory tract into the lungs. A respiratory tract viral infection generally starts in the nose and travels down the airways. The deeper it goes, the more serious or severe the infection. Remember the lung cells have little protection. During a viral infection of the lungs, not only are the lung epithelial cells damaged by the infecting virus, but they are also damaged by the body’s immune response to the infection. If the response and clean up by the immune system are quick, the infection can be contained and cleared in a few days. But if the immune response is either insufficient or overly aggressive, it can lead to significant damage.

How to Support the First Line of Defense 

From the above discussion, it should be clear that the first step in supporting our host defenses against COVID-19 or any organism that targets the respiratory tract is to support the production of an effective mucous barrier. Here are some key strategies: 

  • Adequate hydration.
  • Supply key nutrients for epithelial function and the production of mucin (the components of mucus).
  • Utilize protease enzyme formulas.
  • Consider supplementing with N-acetylcysteine (NAC).

Adequate Hydration is Key

Water is critical to the health of the mucous membranes. The mucin that the epithelial cells make is made “dry” otherwise there would not be enough space in the cell itself. Mucins are able to bind 1,000 times their weight in water. Without sufficient water, they are not able to grow. Remember grow toys? Those cheap little toys that get bigger after you leave them in water. That is how mucus is formed. So, sufficient water is critical to mucus function. Humidifiers may help keep the airways moist, but ensuring sufficient hydration from the inside out is critical to proper barrier function. 

Key Nutrients to Support an Effective Mucous Barrier

A deficiency of any essential vitamins and minerals can lead to an altered mucous barrier. The epithelial cells need a constant supply of nutrients in order to replicate properly as well as perform both their structural role as well as manufacturing role. It is not just mucin that these cells manufacture, they also manufacture many other protective substances critical in fighting off viruses and harmful organisms. Taking a multiple vitamin and mineral formula is crucial. Take one that provides at least the recommended dietary intake level for key nutrients like vitamin AC, and DB vitamins; and zinc as these nutrients are especially important. Since most multivitamins now contain beta-carotene as the vitamin A source, I would also recommend taking additional vitamin A in the form of retinol. This form has more direct anti-infective action.

Vitamin A

Vitamin A was the first fat-soluble vitamin to be discovered, but that is not the only reason why it was called “A” – it was given the name to signify its “anti-infective” properties. Vitamin A is absolutely critical to the health and function of mucous membranes. Vitamin A deficient individuals are more susceptible to infectious diseases, in general, but especially viral infections. Vitamin A supplementation has been shown to produce significant benefits in improving immune function during viral infections, especially when fighting respiratory tract viruses. 

Dosage ranges for vitamin A reflect the intent of use. During the cold and flu months to support the health of the mucosa and immune system, a dosage of 3,000 mcg (10,000 IU) for men and 1,500 mcg (5,000 IU) for women is safe. During an acute viral infection, a single oral dosage of 15,000 mcg or 50,000 IU for one or two days is safe as long as there is ZERO chance of pregnancy. Because high doses of vitamin A during pregnancy can cause birth defects, women of childbearing age should not supplement with more than 1,500 mcg (5,000 IU) of vitamin A per day. The same warning applies during lactation.

Vitamin D

Vitamin D is also important to take a little extra of than what is typically found in a multiple vitamin and mineral formula. There is a growing body of science that shows low levels of vitamin D increase the risk of viral respiratory infections. Since we can make vitamin D in our skin when it interacts with sunlight, there is obviously a natural tendency for many people to make less vitamin D during the winter months. Supplementing the diet with additional vitamin D can help prevent this winter-time drop in vitamin D levels. 

Beyond that, it appears that vitamin D functions in the body in a way that prevents viruses from infecting cells. Research has shown that vitamin D supplementation prevents respiratory infections in adults and children. During the winter months, most vitamin D experts recommend taking 5,000 IU per day for adults and children over 10 years of age. For children under the age of 1 year the dosage is 1,000 IU; for children between the ages of 2-4 years 2,000 IU; and for children between the ages of 4 through 9 the suggested dose is 3000 IU daily. 

Utilize Protease Enzyme Formulas

Certain protease enzymes have shown benefits in improving the composition, physical characteristics, and function of mucus. Proteases are often used in digestive formulas to aid in the breakdown of dietary protein. When taken on an empty stomach away from food, these proteases are absorbed into the bloodstream to exert systemic effects including effects on mucus. 

The best-studied protease is mucolase - a special fungal protease with confirmed actions on respiratory tract mucus. One clinical study looked at the effect of mucolase on mucus in patients with chronic bronchitis. The patients were randomly assigned to receive either the protease or a placebo for ten days. While the placebo had no effect on the mucus, mucolase produced significant changes in both viscosity (thickness) and elasticity (stretchiness) at the end of treatment. In fact, the improved mucus structure and function was apparent up to eight days after the end of treatment.

In another ten-day double-blind study, mucolase was shown not only to improve the viscoelasticity of mucus, but also to reduce airway inflammation.  Other proteases like bromelain and serratia peptidase have shown similar effects. Mucolase, bromelain, and serratia peptidase decrease the thickness of the mucus while at the same time increasing mucus production as well as dramatically increasing the ciliary transport of the mucus. The net effect is the production of much more mucus that is effective in neutralizing microbes and moving them out of the body. In addition to enhancing the mechanical effects of mucus, proteases may enable special protective factors within mucus to more effectively neutralize invading organisms. Some of the protective factors secreted in mucus are secretory IgA, various white blood cell-derived protease inhibitors that block viruses, nitric oxide, and lactoferrin.

N-Acetylcysteine and Respiratory Health

N-acetylcysteine (NAC) is a sulfur-containing amino acid that has an extensive history of use as a mucus modifying agent to support the respiratory tract. It is also used in the body to form glutathione – the major antioxidant for the entire respiratory tract and lungs. People who are exposed to smoke or other respiratory toxins, who suffer from conditions associated with inflammation such as diabetes, obesity, and other chronic conditions have lower levels of glutathione. Low levels of glutathione may lead to risk factors for more severe outcomes with COVID-19. NAC supplementation can boost glutathione levels and help protect the lungs and respiratory tract.

NAC is also a mucus modifying agent. It has been used orally with great success as well as in hospitals through breathing tubes to help people dealing with inefficient or thick mucus in acute and chronic lung conditions such as emphysema, bronchitis, chronic asthma, and cystic fibrosis. NAC helps to reduce the viscosity of bronchial secretions. NAC has also been found to improve the ability of cilia in the respiratory tract to clear mucus, increasing the clearance rate by 35%. As a result of these effects, NAC can improve bronchial and lung function, reduce cough, and improve oxygen saturation in the blood when the respiratory tract is being challenged. To reduce the risk of infection and boost glutathione levels in the lungs, the dosage is generally 500 to 1,000 mg daily. For use in reducing mucus thickness, the typical dosage is 200 mg three to four times daily.

References: 

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  3. Braga PC, Moretti M, Piacenza A, Montoli CC, Guffanti EE. Effects of seaprose on the rheology of bronchial mucus in patients with chronic bronchitis. A double-blind study vs placebo. Int J Clin Pharmacol Res. 1993;13(3):179-85.
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  10. Kesic MJ, Hernandez M, Jaspers I. Airway protease/antiprotease imbalance in atopic asthmatics contributes to increased influenza A virus cleavage and replication. Respir Res. 2012 Sep 19;13:82.
  11. Santus P, Corsico A, Solidoro P, Braido F, Di Marco F, Scichilone N. Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine. COPD. 2014 Dec;11(6):705-1.
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