Socially Distance SARS-CoV-2: Can We Boost Our Immune System?

The World Strains of SARS-CoV-2 on 4/6/2020.
Source: Nextstrain – Real-time tracking of pathogen evolution.

Typically, I relate various topics in the research world to tennis. However, the pandemic zeitgeist compels change for the moment. Instead of tennis, the research stories I delve into today provide actionable steps that can be used right now to buttress our immune systems – to help prevent SARS-CoV-2 from becoming COVID-19.

While social distancing and the standard infectious disease precautions rightfully dominate the major news outlets, maintaining our immune system’s armamentarium is also of import as it too, can help flatten the curve. Today, our story begins with a simple letter from a pathologist.

Zinc

Early on in the pandemic, Dr. James Robb, a physician with research expertise on Coronaviruses emailed family and friends, urging them to take infectious precautions against SARS-CoV-2. Most of his recommendations were standard, but peculiarly, he also included this statement:

“…Stock up now with zinc lozenges. These lozenges have been proven to be effective in blocking coronavirus (and most other viruses) from multiplying in your throat and nasopharynx…”

The email was leaked, frenziedly forwarded and seen by many as a metaphorical shot heard ’round the world. Despite there being evidence that zinc deficiency renders an individual more susceptible to upper respiratory tract infections, skeptics, proponents and even conspiracy theorists sprouted almost overnight in response. Was he crazy? Was he a genius? Was he both and about to be hounded by Fox Mulder? Despite not knowing which studies he was referring to, it seems he was at least barking up the right proverbial tree.

In this publication, Te Velthuis et al. summarily showed that zinc combined with a zinc ionophore impaired coronavirus (though not specifically SARS-CoV-2) viral replication. I know. You’re doing this right now. That’s fine, because that’s a great question. Simply put, an ionophore is a molecule that allows zinc to penetrate an otherwise highly regulated barrier into a cell’s interior – where viruses (including SARS-CoV-2) “live” their best life and replicate. But why are ionophores interesting?

Fascinatingly, chloroquine, currently one of the most intensely scrutinized drugs for treatment/prevention of SARS-CoV-2/COVID-19 happens to be a zinc ionophore. Take a look below and at the caption to better understand:

From left to right: Generally, the more green fluorescence, the more zinc has penetrated the cell. Box one (control) consists of cells taking a bath in 5 uM of zinc. Think of box two as eating a fistful of zinc lozenges and making your cells take a bath in 50 uM of zinc. Boxes three and four are repeats of the first two respectively, but with chloroquine acting as the ionophore. These show clear evidence of zinc penetrating into cells with the help of chloroquine.

As of today, chloroquine is just starting in large, human clinical trials and yet is already being used in special situations on the front lines. Given this is a prescription drug that requires monitoring of well-known side effects and is in shortage, this is not the currently recommended immune booster.

But.

Fascinatingly (again), quercetin, a flavonoid found in various fruits and vegetables is also a zinc ionophore. Guess who’s about to tell you to put down that Big Mac (don’t even start with the lettuce) you just ordered to your front door? So. The recommendations that we can extrapolate are: 1) don’t be zinc deficient and 2) up your intake of quercetin containing fruits and vegetables.

Vitamin D

In the past, I’ve written various things about sunlight and some of its benefits. Here in Boston, most of us are plausibly vitamin D deficient (even when not under quarantine). Unfortunately, that deficiency leaves our immune system a bit lacking. Martineau et al. published a meta-analysis of twenty-five randomized control trials to arrive at the conclusion that daily lower-dose Vitamin D supplementation is protective against acute upper respiratory tract infections. The protective effects were more significant in D-deficient folks, but supplementation still benefitted those that were not. Importantly, at daily higher-doses, the protective effect disappeared. You can look at their most telling data here. The recommendation we can extrapolate here is the daily supplementation of Vitamin D2 or D3, 800 – 2000 IU per dose.

The Land of Nod

With only experience to back this opening statement up, I believe I can safely say that only pathological Homo sapiens have ever wanted less sleep. Change my mind. Unfortunately as it turns out, less overnight sleep (or simply being awake during the daytime) impairs the ability of our immune system to do battle with pathogenic viruses.

Dimitrov et al. showed that in the event of sleep deprivation, stress and pathological conditions (e.g. cancer), your T-cells are less able to communicate with cells trying to alert them to the presence of a virus-infected cell (or a cancerous growth). Furthermore, they are less able to rid the body of said cells. As an aside for the curious, check out a beautiful microscopic example of the processes just discussed (not from the same study):

For those who do not want to delve into Dimitrov et al.’s research (how the immune system operates does get confusing rather quickly), suffice to say, one should strive to have uninterrupted sleep for more than 7 hours each night. Your viral bouncer T-cells will thank you for facilitating them in their perpetual front-line battles.

Summary

  • Eat zinc and quercetin containing foods with the goal of not being deficient in, or overdosed on either. Following the recommended dietary reference intake (DRI) for zinc is appropriate for a normal person. However because there is no well-studied DRI for quercetin, the recommendation is trickier. Some studies have suggested adverse effects when supplemented at 1 gram per day (this is significantly higher than the typical Western daily intake of 0-30 milligrams). In this setting, even increased intake is likely appropriate for a normal person.
  • Vitamin D supplementation is over-the-counter and generally safe. Particularly in the setting of standard vitamin D deficiency, daily vitamin D2 or D3 supplementation with 800 – 2000 IU per dose is appropriate for a normal person.
  • Sleep. More. Now. Help your T-cells fight viruses more effectively and flatten the curve.

Disclaimer: Always remember that human physiology is singularly complex. We are only now beginning to explore the world of personalized medicine, which ultimately seeks to provide individualized treatment and lifestyle recommendations. If you have any questions on whether these recommendations are appropriate for you as an individual with pre-existing conditions, discuss the idea with your primary care physician.

Primum non nocere

Thomas Sydenham

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