Four potential pathways for severe complications from COVID 19 infection:


  1. Pulmonary epithelial cells (PECs) insulate and protect the pulmonary alveoli (lung air spaces) for the exchange of oxygen from the air we breathe into the hemoglobin (Hgb) in our blood. The PECs are directly damaged by the COVID 19 virus. Macrophages, a type of white blood cell (WBC), are attracted to the area of damage to fight the COVID virus, and these start an inflammatory response. If the inflammatory response in the lungs cycles out of control, patients develop Acute Respiratory Distress Syndrome (ARDS), which results from the pulmonary alveoli filling with inflammatory fluid and damaged cell debris. ARDS prevents the oxygen that we breathe from crossing the accumulated fluid to reach the hemoglobin (Hgb) in our blood.

  2. The Renin-Angiotensin-Aldosterone System (RAAS) regulates several things, including our blood pressure and our immune response. Special enzymes (ACE1 and ACE2) on the PECs activate the RAAS by converting non-active angiotensin-1 (AT1) to active angiotensin-2 (AT2). Normally, AT2 raises our blood pressure, but it can also stimulate macrophages to start an immune response. COVID 19 enters PECs and macrophages through the ACE2 enzymes that are attached to their cell membranes. Once inside the cell, COVID 19 damages the PECs and macrophages. The damaged cells attract more macrophages to the lungs, and these are also attacked by COVID 19. Ultimately, AT2 stimulates an overwhelming immune response, and ARDS develops in the lungs.

  3. Hemoglobin (Hgb) is a molecule that resides inside our red blood cells (RBCs). As the RBCs float by the pulmonary alveoli, each Hgb will pick up four molecules of oxygen. This oxygen is transported to our tissues, and the Hgb releases the oxygen to our cells. Oxygen keeps our cells and organs viable. The COVID 19 virus enters the RBCs and damages the (Hgb). Eventually, the cell wall of the RBCs is disrupted, and Hgb leaks into the bloodstream. The damaged Hgb carries less oxygen, but additionally, the free-floating Hgb (cell-free Hgb) creates an overwhelming immune response by the activation of macrophages and mast cells (another type of WBC). As more RBCs are damaged, the immune response of the macrophages and mast cells grows out of control. Secondarily, the immune response damages organs like the heart and kidneys, and ARDS develops in the lungs.

  4. Mast cells are the primary WBCs involved in allergic reactions. The COVID 19 virus starts an immediate allergic reaction by entering the mast cells, which causes them to release histamine and cytokines. Histamine creates swelling and inflammation, and the cytokines start an immune cascade through activation of macrophages and additional mast cells. As more cells are damaged, the immune response grows out of control. This contributes to damage to our organs and ARDS in our lungs.
The more fortunate amongst us may not activate any of these four pathways. Alternatively, a given individual could suffer one or more of these mechanisms of damage, and the degree of response in each area can be variable. Additionally, future research may reveal other types of damage that are not yet on this list.

A healthy immune response is necessary to fight infections, and the immune system returns to a normal level of activity as infections are controlled. The common mechanism for all four pathways of severe COVID 19 damage is an uncontrolled immune response. The endpoint of the severe immune response is damage to organs, including the lungs. If the fluid and cell debris fill the pulmonary alveoli with fluid, the resulting loss of oxygenation can be life-threatening.
The following is a compilation of vitamins, supplements, and medications, to build immunity against infection, to protect our cells against damage, to deliver oxygen to our tissues, and to minimize an uncontrolled immune or allergic response. All individuals should consult with their own physician for guidance on using any of these protocols either in the prevention or treatment of COVID 19 infection.

What to do before becoming infected with COVID 19

Vitamins and supplements to boost the immune system as a preventive measure:

Definitions: QD- once daily. BID- twice daily. TID- three times daily. QID- four times daily.

Vitamin A: (Retinoic acid). 5000 units QD. Increases IgA production. Antiviral.

Vitamin C: (Ascorbic Acid). 500 mg BID. Antioxidant. Antiviral. Decreases histamine release. Protects hemoglobin.

Vitamin D3: (1,25-dihydroxy-vitamin D3). 5000 units QD. Antiviral. Increases IgA production. Decreases ARDS damage to lungs.

Selenium: 55 mcg QD. Antiviral. Anti-asthmatic.

Zinc: 12-18 mg QD. Lozenge, syrup, or pill. Antiviral. Boosts T -cells for immune response. Decreases duration of viral infections.
Preventing an uncontrolled inflammatory response:

Melatonin: 10 mg QD. Antioxidant, anti-inflammatory, and immune enhancer. Improves anxiety by improving sleep. Protective against ARDS by decreasing oxidative injury, regulating cytokine response, and decreasing recruitment of macrophages.

Aspirin: 81 mg QD. OTC. Guards against platelet adhesion (blood clots). Protective to cardiac blood flow. Do not use in children.
Medications to prevent an allergic response:

Quercetin 1000 mg with bromelain 200 mg QD. OTC. Flavonoid. Anti-allergic. Anti-inflammatory. Antioxidant.

Antihistamines: OTC. Guard against mast cell allergic reaction.

  1. Benadryl, Claritin, Zyrtec, or Allegra, with or without the Pseudoephedrine.
Steroid Nasal Sprays: OTC. Guard against inflammation of nose and eyes.

  1. Flonase Allergy Relief (fluticasone propionate).

  2. Nasacort 24 Allergy (triamcinolone).

  3. Nasonex (mometasone furoate monohydrate).

What to do after becoming infected with COVID 19

Vitamins to boost the immune system for outpatient management:

Vitamin A: (Retinoic acid). 5000 units QD. Increases IgA production. Antiviral.

Vitamin B3: (Niacin or nicotinamide). 500-1000 mg BID-TID. Prevents lung damage. Decreases cytokine response.

Vitamin C: (Ascorbic Acid). 500 mg BID. Consider increasing to 500 mg QID. Antioxidant. Antiviral. Decreases histamine release. Protects hemoglobin.

Vitamin D3: (1,25-dihydroxy-vitamin D3). 5000 units QD. Antiviral. Increases IgA production. Decreases ARDS damage to lungs.

Vitamin E: (alpha tocopherol). 400 units QD. Consider increasing to 800 units QD. Antioxidant. Protects heart muscle.

Black Elderberry: (Sambucus nigra). 15 milliliters (1 tablespoon) QID. Antibacterial and antiviral against respiratory tract infections.

Selenium: 100 mcg QD. Antiviral. Anti-asthmatic.

Zinc: 34 mg QD. Lozenge, syrup, or pill. Antiviral. Boosts T -cells for immune response.

L-Arginine: 6 to 24 grams QD in three divided doses. Consider going to maximal dose. Produces Nitric Oxide (NO), which dilates vessels and increases blood flow. Decreases risk of blood clots.

L-Citrulline: 3-9 grams QD in three divided doses. Consider going to maximal dose. Converts to L-Arginine and then to NO. Dilates vessels, increases blood flow, decreases risk of blood clots.
Medications to respond to an inflammatory response for outpatient management:

Melatonin: 10-40 mg QD. Antioxidant, anti-inflammatory, and immune enhancer. Improves anxiety by improving sleep. Protective against ARDS by decreasing oxidative injury, regulating cytokine response, and decreasing recruitment of macrophages.

Aspirin, 81 mg. OTC. Guards against platelet adhesion (blood clots). Protective to cardiac blood flow. Do not use in children.

Motrin: (Ibuprofen). 800 mg TID. Over the counter (OTC). Minimizes inflammation. Excellent ability to cross blood-brain barrier for viral headache. May be contraindicated in hypertension and heart disease. Discuss with physician.

Celebrex: (Celocoxib). 200 mg BID. By prescription. Discuss with physician. Partial anti-viral. Minimizes inflammation. Excellent ability to cross blood-brain barrier for viral headache.
Medications to limit an allergic response for outpatient management:

Quercetin 1000 mg with bromelain 200 mg QD. OTC. Flavonoid. Anti-allergic. Anti-inflammatory. Antioxidant.

Antihistamines: OTC. Guard against mast cell allergic reaction.

  1. Benadryl, Claritin, Zyrtec, or Allegra, with or without the Pseudoephedrine.

Steroid Nasal Sprays: OTC. Guard against inflammation of nose and eyes.

  1. Flonase Allergy Relief (fluticasone propionate).

  2. Nasacort 24 Allergy (triamcinolone).

  3. Nasonex (mometasone furoate monohydrate).
Prednisone: 20 mg tablets. By prescription. 3 tablets QD x 3 days, then 2 tablets QD x 3 days, then 1 tablet QD x 3 days, then 1/2 tablet QD x 4 days, then STOP.

What you may face if you require advanced management

The big guns, but may not be your choice:

Oxygen: the biggest and most important of the big guns.

Nitric Oxide inhalation.

Vitamin B3. IV administration.

Vitamin C, (Ascorbate), 8 grams intravenous (IV) QD.

Melatonin. 30-60 mg QD.

IV Steroids.

Remdesivir. Antiviral. Inhibitor of viral replication.

Chloroquine/ Hydroxychloroquine. Under clinical trial.

Azithromycin: 500 mg QD for 10 days. (Dosing varies).
This was authored on April 16, 2020. Our understanding of mechanisms of damage from COVID 19 changes daily. Before taking any of these vitamins, supplements, or medications, you should first consult with your own physician. If you are taking any prescription medications or if you have any medical conditions, you and your physician should discuss how you would integrate any of this information for your own personal risks or benefits.

Stay safe and stay well.

Mark A. Piper, DMD, MD

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