Your immune system is like an intricate, highly complicated, well-oiled machine working behind the scenes 24 hours a day to keep you healthy and protect you from harmful invading microbes. But this complex machine relies on countless different compounds and nutrients to keep it running on all cylinders. If one of these critical compounds is thrown out of whack, it can send the whole system into a tailspin.

One of these key compounds your immune system relies upon is a little nutrient known as vitamin D. If something goes wrong in the supply chain of vitamin D being funneled to your immune system, it can put a major damper on your immune system's ability to function – leaving you vulnerable to invading pathogens. But if a shortage of this crucial compound can have such a profoundly negative effect on your immune system, it makes sense that restoring optimal levels of vitamin D can have the opposite effect – rebalancing and supercharging your immune system. 

Today we’re going to dive into part one of a two part series on addressing a condition that’s a master at dysregulating your immune system and zapping your vitamin D levels – a condition known as long COVID. We’ll dive into how vitamin D works in the body, the irreplaceable role it plays in your immune system, how a deficiency may be the underlying culprit causing lingering symptoms after a COVID infection, and most importantly, we’ll cover how we can tap into the power of this mighty nutrient to best support healing.

How Do You Get Vitamin D? The Vitamin D Pathway

You can obtain vitamin D either via your diet or through exposure to UVB rays from the sun. Once this raw form of vitamin D enters your body it must undergo a transformation process that goes something like this:¹

• Step 1: Raw vitamin D comes in the form of either cholecalciferol or ergocalciferol. These molecules are then transported to the liver where they undergo a process called hydroxylation that transforms them into a compound known as calcifediol. 
• Step 2: Calcifediol is then shuttled to the kidneys where it undergoes the next step in its transformation – becoming the hormonal form of vitamin D known as calcitriol. 
• Step 3: Once converted to calcitriol, these vitamin D metabolites are able to bind to vitamin D receptor sites on the outer membrane of most cells. 

This vitamin D pathway plays a major role in your immune system and its ability to properly fight off infections.

Vitamin D and Your Immune System: What Does Vitamin D Do for the Body?

Vitamin D is a potent regulator of your immune system. Just a handful of the ways vitamin D impacts the way your immune system includes:^2,3,4

• Activation of antimicrobial peptides (AMPs): When vitamin D binds to vitamin D receptors in your immune cells, it triggers an increase in the production of compounds known as antimicrobial peptides or AMPs. AMPs help to block pathogens from entering your cells while suppressing pathogen replication.
• Enhancement of phagocytosis: Vitamin D promotes autophagy in your immune cells – the process of encapsulating and neutralizing invading threats.
• T cell regulation: Vitamin D influences your immune cells in a way that prevents your immune system from spiraling out of control – pumping the brakes on the pro-inflammatory cascade so that your immune response doesn’t inadvertently cause more harm than good. 
• Enhancement of the integrity of mucosal barriers: The epithelial and mucosal cells that line your eyes, nose, mouth, and digestive tract are your first line of defense against potentially invading pathogens. Vitamin D plays a crucial role in maintaining and strengthening the integrity of these mucosal barriers by promoting the production of specific enzymes and proteins that seal the spaces between mucosal and epithelial cells.

Understanding the irreplaceable role vitamin D plays in immune system regulation is crucial when it comes to understanding the impact viral infections like COVID-19 have on your body.

How Viral Infections Like COVID Deplete Vitamin D

The coronavirus, more formally known as SARS-CoV-2 is a complex and rather tricky virus. This virus is typically contracted when it comes into contact with the mucosal surface of your mouth, nose, or eyes. Once it makes its way inside, it’s able to throw your immune system off-kilter and disrupt your vitamin D pathway in a couple of distinct ways:^5,6,7

An Overflow of Proinflammatory Cytokines 

Sars-CoV-2 is a master at camouflage – swiftly sneaking its way into human cells and then disguising itself so the initial infection goes undetected by the immune system. Once inside, it hijacks your cells and manipulates them to enhance its survival while jamming up any cellular exit channels – preventing the cell from releasing any signaling proteins that may sound the alarm and activate an immune response. 

As the virus renovates the inside of your cells and replicates, it eventually releases newly formed virions to infect new cells. Once these new virions exit the cell, the immune system catches on and launches an immune response. But by the time the immune system realizes there is a threat, the virus has replicated to a point that it triggers an exaggerated immune response – flooding the bloodstream with a massive influx of pro-inflammatory mediators in what’s known as a cytokine storm.

Downregulation of Vitamin D Receptors

In addition to triggering an overflow of cytokines and a massive spike in uncontrolled inflammation, SARS-CoV-2 can also downregulate the amount of vitamin D receptors on your cells. By blocking the activation of gene expression of vitamin D receptors, the coronavirus inhibits your cells' ability to bind to and utilize vitamin D even if adequate levels are available.

This out-of-control inflammation, dysregulation of the immune system, and depletion of cellular vitamin D also creates the perfect storm for another serious concern – the reactivation of dormant viral infections. 

How COVID Can Reactivate Latent Viral Infections

Once infected with the coronavirus, there is a massive spike in inflammation and your immune system is preoccupied with trying to neutralize the imminent threat. This creates an ideal scenario for latent viral infections that have been lying dormant within your cells to reactivate. Studies have found that a COVID-19 infection can be a potent activator of common latent viral infections such as:⁸

• Herpes simplex virus type 1
• Cytomegalovirus
• Parvovirus B19
• Epstein-Barr virus (EBV)

While reactivation of each of these latent viruses can present its own set of unique problems,  the Epstein-Barr virus (EBV) in particular has been identified as a major culprit in exacerbating symptoms associated with COVID. This is in part due to EBV’s potent ability to further deplete already dwindling Vitamin D levels in COVID patients.^9,10

COVID and Epstein-Barr Virus: A Vitamin D Depleting Duo

As you know, the coronavirus is able to downregulate vitamin D receptors on your cells. This in itself can quickly deplete vitamin D levels within your cells. But when you pair a COVID-19 infection with a reactivated EBV, it can spell double trouble. You see, The EBV contains proteins known as Epstein–Barr nuclear antigens or EBNA that directly impede Vitamin D signaling pathways by:¹¹ 

• Impeding calcitriol biosynthesis
• Binding to cofactors that block the binding of vitamin D to vitamin D receptor sites
• Binding to vitamin D receptors – rendering them inactive

This combination of effects triggered by coronavirus and EBV working in tandem can dramatically deplete Vitamin D levels – pushing the body into what’s known as a calcitriol crisis or an alarming lack of calcitriol. It’s speculated that this depletion of calcitriol is what may be triggering the lingering symptoms seen in the condition known as long COVID.

Could Long COVID Be Linked to a Vitamin D Deficiency?

Many patients recover from a COVID-19 infection within a few weeks. But others suffer from ongoing or new symptoms for weeks, months, or even years after initial infection and diagnosis. This subset of patients experiencing lingering, ongoing symptoms post-COVID are considered to have long COVID, also referred to as long-haul COVID.

According to studies, the top 15 most common symptoms seen in those struggling with symptoms of long COVID include:¹²

• Pain
• Breathing difficulties
• Hyperlipidemia
• Malaise and fatigue
• Hypertension
• Anxiety
• Intestinal issues
• Skin issues 
• High levels (glucose, cholesterol, BP)
• Abnormal heart results
• Migraine and/or headache
• GERD
• Sleep disorders
• Depression
• Abnormal organ tests

Interestingly, all of these symptoms can be directly related to a vitamin D deficiency. While the underlying mechanism triggering these persistent symptoms is likely more complex than just a simple deficiency in Vitamin D, studies have found that there is a clear and direct correlation between vitamin D levels and the severity and length of COVID-19 infection.

So can replenishing vitamin D levels be a solution when it comes to addressing the symptoms of long COVID?

Can Vitamin D Be Used to Treat Long COVID?

The answer is – yes. Vitamin D can be an important piece of the puzzle when it comes to treating the underlying imbalance contributing to the lingering symptoms seen in long COVID. You see, preventing COVID, reducing the severity of a COVID-19 infection, and giving your body the tools it needs to bounce back from an infection with the coronavirus requires a big-picture, multi-faceted approach.

And studies have found that replenishing and optimizing vitamin D levels can help your body ward off infection and recover on multiple fronts including:^13,14,15

• Enhancing mucosal immunity: Your mucosal immune system is not only the largest component of your entire immune system, it’s also the main site of coronavirus infection – with initial interaction with the virus almost always taking place on the mucosal surface of the mouth, nose, or eyes. Vitamin D can help strengthen your mucosal immune system and beef up this crucial barrier that blocks invading pathogens from successfully entering your body.  
• Boosting antimicrobial peptides (AMPs): Upping vitamin D levels boosts your immune cells' production of AMPs which not only block SARS-CoV-2 from entering cells but also suppresses the virus's ability to replicate.
• Increasing autophagy: If your immune system is overwhelmed and dysregulated it’s unable to lower viral levels enough to reach the tipping point necessary to neutralize the infection and begin moving back towards a balanced state. By stimulating autophagy – the engulfment of virions and damaged cells – vitamin D helps your immune system get a handle on the virus and begin working towards eliminating it from your body.
• Suppressing dormant virus reactivation: The reactivation of latent viral infections can significantly complicate COVID-19 infections and contribute to immune system overwhelm and dysregulation. Optimal vitamin D levels can prevent (or at the very least suppress) the reactivation of dormant viruses like EBV –  allowing the immune system to direct its resources toward addressing the coronavirus.

So how can we best tap into vitamin D’s potent immune-boosting powers?

How Is Vitamin D Being Used to Combat the Coronavirus?

While at first glance, it may make sense to simply up your vitamin D levels by eating vitamin D-rich foods and soaking up some sunshine, the truth is, replenishing vitamin D levels during or after a COVID-19 infection requires a little more in-depth approach. You see, because viral infections like coronavirus and EBV can majorly interfere with your ability to absorb and utilize vitamin D, simply upping vitamin D levels oftentimes isn’t quite enough.

Rather, you must increase vitamin D levels while simultaneously enhancing your body's ability to utilize it. And studies have found that one of the most effective ways to accomplish this is by pairing vitamin D in the form of calcifediol with a medication known as dexamethasone. Dexamethasone is a type of steroid that works to downregulate the inflammatory cascade – halting the uncontrolled inflammation and subsequent tissue damage triggered by the massive influx of proinflammatory molecules seen in a cytokine storm. 

Dexamethasone also induces the expression of vitamin D receptor sites on your immune cells – allowing more vitamin D to make its way into your cells and be utilized in combating invading pathogens.^16,17 By combining vitamin D in the form of calcifediol with dexamethasone, you can drastically improve vitamin D levels to heal the root dysfunction triggering the symptoms seen in lingering long COVID symptoms.

Are You Struggling With Symptoms of Long COVID?

If you’ve been struggling with lingering or hard-to-explain symptoms after contracting COVID-19, you’re not alone and you’re not at the mercy of this tricky virus. Upping your vitamin D levels and giving your immune system the support it needs are pivotal pieces of the puzzle when it comes to healing and restoring your health. But it’s important to not try and navigate this challenging time by yourself.

If you’re concerned you’re struggling with the symptoms of long COVID, I cannot overemphasize the importance of partnering with an experienced Integrative and Functional Medicine Practitioner to help identify the root cause of your symptoms and help you create an entirely personalized path to healing. There’s no one-size-fits-all when it comes to recovering from this complex condition and having an experienced professional who will treat you like the unique individual that you are is invaluable.

If you enjoyed this article and are looking for more ways to support your immune system or are just curious to learn more about the Functional Medicine approach, I encourage you to head over and browse through the hundreds of articles on my blog. And if you want to take it even deeper, I invite you to sign up for my email newsletter by entering your name and email address in the form below.

Now it’s time to hear from you. Were you surprised to learn the various ways COVID-19 can drastically deplete your vitamin D levels? If you’ve recovered from the lingering symptoms of long COVID, what healing strategies did you implement and what seemed to work best for you? Leave your questions and thoughts in the comments below!

Resources:

1. Vitamin D: Production, Metabolism and Mechanisms of Action – Endotext – NCBI Bookshelf (nih.gov)
2. Vitamin D and Immune Function – PMC (nih.gov)
3. Frontiers | Impact of vitamin D on immune function: lessons learned from genome-wide analysis (frontiersin.org)
4. Vitamin D, vitamin D receptor and tissue barriers – PMC (nih.gov)
5. How the coronavirus infects cells — and why Delta is so dangerous (nature.com)
6. COVID-19 infection: an overview on cytokine storm and related interventions | Virology Journal | Full Text (biomedcentral.com)
7. Vitamin D: A Role Also in Long COVID-19? – PMC (nih.gov)
8. Frontiers | Emergent Virus Reactivation in SARS-CoV-2-Negative Community Acquired Pneumonia Patients During the COVID-19 Pandemic (frontiersin.org)
9. Positive Epstein–Barr virus detection in coronavirus disease 2019 (COVID-19) patients | Scientific Reports (nature.com)
10. A Detailed Study of Patients with Long-Haul COVID–An Analysis of Private Healthcare Claims–A FAIR Health White Paper.pdf
11. EBNA1, EBNA2, and EBNA3 link Epstein-Barr virus and hypovitaminosis D in multiple sclerosis pathogenesis – ScienceDirect
12. COVID‐19 associated EBV reactivation and effects of ganciclovir treatment – Meng – 2022 – Immunity, Inflammation and Disease – Wiley Online Library
13. RETRACTED ARTICLE: Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease | Scientific Reports (nature.com)
14. Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D – PMC (nih.gov)
15. The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2 – PubMed (nih.gov)
16. Glucocorticoid Regulation of the Vitamin D Receptor – PMC (nih.gov)
17. IJERPH | Free Full-Text | The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2 (mdpi.com)