COVID-19 So Far: How It Works and What We’ve Been Doing to Treat It
Imagine that there is a small, rogue state known to attack by infiltrating its enemies armies, gaining recruits, and then using those recruits to destroy those armies. This is what viruses do. They are acellular microorganisms, smaller than bacteria, that cannot grow or reproduce without a living cell. Like a parasite, they invade living cells and then replicate and keep themselves alive by using the cell’s machinery.
COVID-19 is an especially concerning “rogue state” because it invades cells called ACE2, which are concentrated deep inside the lungs [1]. This is why it causes severe upper respiratory symptoms, in addition to affecting the blood (through clotting), brain (through strokes and direct neurological damage), heart and kidneys (on account of clotting and oxidative stress), and the immune system (through what is called the cytokine storm).
From what doctors and researchers have learned so far, most patients are oxygen-deprived (hypoxic) without showing symptoms of respiratory distress. This means that their bodies are starved of oxygen from the virus’s attack on ACE2 cells, perhaps due to clotting in the lungs, while their lungs are still functioning [2].
So treatment for coronavirus seems to be shaping up as follows. Rely less on ventilators, which can do damage to the lungs in themselves, reserving them for cases where there is severe respiratory distress. In cases of hypoxia without respiratory distress, oxygenation is now being recommended, along with blood clot medication.
But why does the virus get so bad that we need these treatments? The immune system is like an extremely powerful army. Its soldiers are trained to recognize enemy infiltrators from “rogue states” like coronaviruses. They have powerful weapons at their disposal. Soldiers are excellent at following commands. How does the body’s amazing defense system fail to resist the takeover?
These lines of questioning expand our thinking when it comes to treating COVID-19. Providing oxygen, a ventilator, or blood clotting medication doesn’t address the reasons why the body needs those treatments in the first place.
If we can find treatments that actually help the body use its innate healing mechanisms, we won’t just be treating symptoms. We will be engaging in a truly therapeutic treatment, by caring for the patient in a comprehensive manner. Therapeutics manages specific problems, such as disease or pain, with therapies such as drugs, surgery, or counseling, while using diet, exercise, and mental factors for prevention of disease as well.
And there is where NAD, a coenzyme present in every living cell, could prove to be important.
Preclinical Research Suggests Key Immune Response Regulator, NAD, Is Depleted in COVID-19 Infection
Imagine that within the incredible army that is the immune system, there is an extremely important general. That general is always one of the first who is informed of an infiltration. But in the case of COVID-19, the virus has figured out a way to make sure that this general is nowhere to be found. The cells that are under attack keep trying to send messages, but there’s no one on the other end!
The “general” in this analogy is NAD (NAD+ is the name of its oxidized form). NAD is a major modulator of metabolism, since it is required to convert macronutrients into energy. It’s also needed for the interaction between the metabolism and the immune system, and an important regulator of the immune system itself.
A new study, conducted jointly at the University of Iowa, Oregon Health & Science University, and the University of Kansas, has shown that “coronaviruses, including SARS-CoV-2, the causative agent of COVID-19, greatly disturb the NAD system.” [3]
COVID-19 has a gene that can take out the “general” in our analogy. Functional Medicine Practitioner Dr. Inna Lukyanovsky, in an email exchange I had with her, explains as follows:
“Corona, including SARS-CoV-2, that causes COVID-19, disturbs the NAD+ system. Cells, animals and a deceased patient infected with SARS-CoV-2 turn on three to eight different so-called PARP genes which encode enzymes that use NAD+ as part of an apparent innate immune response.”
In the words of Dr. Lukyanovsky, the virus depletes cellular NAD “up to 70%” by turning off two gene pathways used for NAD production. The cell then has a reduced ability to respond to the signals being sent that they are under attack.
Without enough NAD, something called mTOR, a protein that conducts cell growth and has been implicated for its role in cancer, cardiovascular disease, obesity, and diabetes, goes haywire. It’s like mTOR is a trigger-happy lieutenant general who can be really good at their job, but needs someone of higher rank — like NAD — to keep them in check. Otherwise they just start blowing everything up.
New research on the role of mTOR cytokine storms in patients with Castleman Disease may have implications for treating cytokine storms in COVID patients.
“With iMCD, just as with COVID-19, it is the body’s hyper-response that’s deadly rather than the disease itself, and this study gives us new clues about why the immune cells are out of control and what we can do to rein them in” [4]
Think of the role of mTOR and NAD in COVID this way. Imagine the damage that mTOR could cause if it were hijacked by an enemy whose sole intent is to infiltrate and replicate. COVID-19, it’s being hypothesized, takes out the “general” NAD, and then takes over the protein in the body that controls cellular growth. That’s like invading an army, assassinating its general, and then taking over its recruiting office. The army is growing, but it’s serving a different master [5].
Given we now know that this coronavirus reduces NAD, making our immune system dysregulate, we can ask: Can we treat patients suffering from the virus by replacing NAD? Would the body then be able to mount an innate immune defense against the hijacked mTOR?
Can Supplements That Increase NAD+ Benefit Those Infected With Coronavirus?
NAD has been studied since the 1960s, and supplementing NAD+ has been around for decades. Supplements that increase NAD+ is getting more popular, as more data comes out in support of the benefits. Research thus far has concentrated on benefits when it comes to anti-aging, improving metabolism, preventing cell damage, and improving sleep.
Since NAD tends to decrease as we get older, the over 55 population, which experiences more severe symptoms of COVID, may potentially benefit from supplementation. NAD levels are also reduced in people with malabsorption problems, sleep issues, weight problems, and addictions.
Supplementing NAD+ is not as simple as popping a pill full of NAD molecules. NAD is quite the dynamic molecule. What does that mean? Check out this diagram:
Dizzy? Me too.
While scientists are still studying its many facets, there are a few different ways to supplement NAD+. Direct NAD supplementation through IV is widely available, and is commonly used to treat withdrawal symptoms from addiction, though its effectiveness in this regard has yet to be proven [6]. Higher doses can have side effects like insomnia, fatigue, and anxiety.
NMN is a stable precursor to NAD+, which is readily available in pill or liposomal, as well as injected, form, and has undergone clinical trials to determine its safety.
NR, another precursor, was recently found to be a powerful, highly bioavailable supplement to boost NAD+ levels [7] https://pubmed.ncbi.nlm.nih.gov/27721479/
What’s more, Dr. Lukyanovsky told me that in COVID cases “the Infected cells specifically seek out nicotinamide riboside (NR) to replenish NAD+ levels in the face of viral infection, a type of immune stress.”
The science is in its early stages, and more time is needed to discover whether boosting NAD+ through NR supplementation or other means may support innate immunity to the coronavirus.
But I for one will be tracking the developing research about our COVID arsenal closely, since NAD+ supplementation shows promise, along with other means of boosting innate immunity such as vitamin C, zinc, glutathione, and vitamin D.
Have you been thinking about innate immunity boosters during coronavirus too? If you have, maybe we’ll run into each other, outside in the sun, taking in our vitamin D. We’ll share a zinc loaded steak and enjoy some vitamin C rich strawberries for dessert, and chat about glutathione and NAD+ boosters.
[1] https://www.technologyreview.com/2020/04/15/999476/explainer-how-does-the-coronavirus-work/
[3] https://www.biorxiv.org/content/10.1101/2020.04.17.047480v3
[5] https://www.nature.com/articles/s41421-020-0153-3
[7] https://pubmed.ncbi.nlm.nih.gov/27721479/