Long COVID: New Research And Functional Medicine Tools

Over a year and a half into the global pandemic, we are still uncovering the mysteries of COVID-19. One such mystery is why a significant portion of COVID cases continue to experience symptoms of COVID months after the infection is no longer detected in the body. 

Today’s article is going to dive into this topic and uncover how understanding COVID as a vascular disease, or even an autoimmune disease, may shed some light into why some recover from COVID and others persist with a host of systemic symptoms. 

Keep reading to learn:

• What is long COVID or long haulers COVID
• How prevalent it is
• Who it affects
• What symptoms to look out for
• What we can learn about the root causes of COVID through a functional medicine lens
• And, most importantly, simple strategies and interventions to support recovery from long COVID

Let’s get started! 

What Is Long COVID?

Long COVID, COVID long haulers and post-acute COVID syndrome all describe a collection of symptoms experienced after a SARS-CoV-2 infection, the virus that causes COVID-19. Symptoms are widespread, and have some overlap with COVID symptoms, with fatigue and shortness of breath being common. 

In some cases, symptoms persist from the original COVID illness and in other cases, a person recovers from acute COVID-19 and then long haulers symptoms appear sometime later. One paper defines the timeframe of long COVID as symptoms beyond 12 weeks after the initial infection or positive test. (Source 1) 

How Prevalent Is Long COVID?

A recent Swiss study found that 26 percent of those with COVID in 2020 reported they were not fully recovered six to eight months after the initial infection. (Source 3) Another study reports the prevalence of long haulers to be over 30 percent. (Source 4)

A review of 25 studies from around the world found rates of long COVID to vary between 4.7 percent and 80 percent depending on the population studied and criteria used. (Source 5)

Covid is a small blood vessel disease:

Dr. William Li is the Medical Director of the Angiogenesis Foundation, an internal medicine doctor and vascular biologist at the forefront of Covid-19 research. He was interviewed on a recent podcast with Functional Medicine leader, Dr. Mark Hyman. You can listen to the episode here. 

Dr. Li explains that Long COVID is a vascular disease instead of a respiratory one. The SARS-CoV-2 virus gets into the endothelial cells of blood vessels creating inflammation and damage to these cells. Of note, each of us has over 60,000 miles of blood vessels in the body. (Source 2)

This is why COVID 19 symptoms go well beyond respiratory symptoms and cause blood clots, stroke, heart failure, gastrointestinal issues and more. It really becomes a systemic disease instead of only affecting the lungs. (Source 2)

With a team of international researchers conducting autopsies of tissues from those who died from COVID-19, Dr. Li was able to see the vascular damage throughout the body and in organs. (Source 2)

In long haulers, many continue to have breathing problems, even though CT scans and other tests look clear, but using artificial intelligence to reconstruct blood vessels from the scans, the deficiency in micro-vascularization of the lungs remains. Dr. Li compares this to a skin wound that won’t heal. (Source 2)

Long hauler’s is characterized by both widespread damage to the epithelium of blood vessels as well as system-wide chronic inflammation. 

Those with long COVID presentations test negative for the coronavirus (SARS-CoV-2) using the diagnostic testing for active virus. Some wonder if the virus remains in the body, however, hidden in an undetectable reservoir. 

Dr. Li reports that 41 percent of those with long haulers improve after receiving a COVID vaccine, suggesting that it offers a reboot to the immune system, disrupting the rut of inflammation that long haulers seem to be stuck in. (Source 2)

Long COVID Symptoms

In the study mentioned above where 26 percent of participants had long COVID, 89 percent had symptoms at diagnosis of acute COVID and 19 percent were hospitalized. Six to eight months later of those with persistent symptoms, 55 percent reported fatigue, 25 percent reported shortness of breath and 26 percent reported depression. In addition, 10 percent of those who were previously hospitalized were re-hospitalized months later. (Source 3)

Dr. Li estimates long haulers to be a collection of over 100 symptoms. The link between the symptoms is endothelial damage and inflammation. Some of the symptoms reported in studies include:

• Fatigue
• Shortness of breath
• Rapid heart beat
• Muscle weakness
• GI symptoms
• Ringing in the ears
• Cognitive and mental impairments
• Chest pain
• Joint pain
• Loss of taste and smell
• Cough
• Headache
• Skin rashes
• Hair loss
• Weight loss
• Insomnia
• Thyroiditis
• Onset or worsening of diabetes (Source 1, 2, 3, 4, 6)

It’s common in long COVID to have multiple, overlapping symptoms that affect quality of life. 

Who Is At Risk For Long COVID?

Who’s at risk? In short, everyone. It appears to disproportionately affect women, those who initially showed symptoms of acute COVID, those with more severe disease, including those who were hospitalized, as well as those who are older. (Source 5, 6)

However, long haulers COVID is also present in younger populations and seen in those who are healthy, who may have only had mild COVID symptoms for none at all. 

Long COVID has also been reported in children. (Source 7)

Long COVID Functional Medicine Perspective – Is Long COVID an Autoimmune Disease?

Functional medicine takes a systems view and this is so relevant for long COVID, since we see the effects throughout the body. It’s time to break down the walls between specialties and work together to understand the root causes. 

In addition to being a microvascular disease, long COVID shows similarities with autoimmune diseases. Autoimmune disease is characterized by inflammation and autoantibodies (antibodies to self-tissue). Autoimmune disease usually has a trigger. Functional medicine has been aware of viral triggers for autoimmunity for some time.  

Autoantibodies have just recently been discovered in COVID-19. In autoimmunity, overactive immune cells produce toxic webs of protein and DNA called NETs (neutrophil extracellular traps). In COVID patients, anti-NET antibodies have been discovered that shield the toxic NETs from being broken down. Those with these antibodies were more likely to develop severe COVID and the associated inflammatory storm. The same anti-NET antibodies are seen in antiphospholipid syndrome, which is an autoimmune disease. (Source 8)

Recent research shows that immune cross reactivity may play a role in long COVID. Researchers applied several human SARS-CoV-2 antibodies to 55 tissue proteins. The study found that SARS-CoV-2 reacted with 28 of them including barrier proteins (such as those seen in leaky gut), thyroid proteins and brain tissue. This research offers a potential mechanism for why we see so many symptoms with long COVID and why there may be a link to autoimmune disease. (Source 9)

In yet another study, working to identify potential root causes of long COVID, researchers discovered that 66.7 percent of long haulers experienced a reactivation of the Epstein Barr virus (the virus that causes mononucleosis) compared to only 10 percent of controls. (Source 4) 

Functional Medicine Tools And Action Steps For Long COVID

Because of the widespread microvascular damage, inflammation and immune dysregulation seen in long COVID, it is unlikely that a single pill or treatment will “fix” the problem. Instead, we need to look at it from multiple angles and work to understand root causes in each individual. 

Here are some tools to consider to tip the balance toward healing and reduce inflammation:

1. Adopt an anti-inflammatory diet. Eat a whole food diet and consider an elimination diet to identify food sensitivities. Eliminating the most allergenic foods like gluten, dairy, eggs, nuts and soy for 30-60 days is a solid start.

2. Heal leaky gut. Along with diet change consider gut health supplements such as probiotics, prebiotics and butyrate that help to balance the immune system (tone down Th-17 cells and increase T-Regs). Phosphatidylcholine is highly effective for leaky gut as well. Read more about how to heal leaky gut here.

3. Stress less. Stress actually slows blood vessel growth. (Source 2) Since COVID and long COVID can be very stressful, consider some adrenal support such as liposomal vitamin C, B vitamins and apoptogenic herbs to support resilience during times of stress.  

4. Incorporate gentle movement and exercise. With long COVID, you may have to start slow, but exercise helps to grow blood vessels. (Source 2)

5. Prioritize sleep. Sleep is required for the body to repair and improves immunity. If you are having trouble sleeping, consider incorporating a gentle sleep aid such as melatonin. As a bonus, melatonin is anti-inflammatory and being used by functional medicine practitioners for COVID patients. 

6. Breathe. Breathing exercises help to strengthen the lungs and oxygenate the body as well as reduce stress and promote healing. 

7. Reduce toxin exposures. Daily exposure to environmental toxins are source of inflammation often overlooked that add to the body burden. Simple strategies include drinking filtered water, filtering indoor air and using non-toxic cleaning and personal care products. 

8. Incorporate supplements to reduce inflammation in the body. Liposomal curcumin and liposomal glutathione are at the top of the list for effectiveness. 

9. Support mitochondria. Mitochondria are essential for energy and may be damaged in the fallout from COVID. Liposomal NAD+ is a supplement to consider here to rebalance mitochondrial energy production and help to lessen the fatigue associated with long COVID. 

10. Stimulate nitric oxide production. Nitric oxide is a signaling molecule that dilates blood vessels so they can repair themselves. The precursor to nitric oxide is l-arginine, an amino acid that can be taken as a supplement or found in functional foods such as beet juice or beet powder. 

11. Optimize vitamin D levels. Vitamin D deficiency correlates with Covid-19 risk. Black women are at higher risk as they are more likely to be deficient in this critical immune nutrient. (Source 10) 

If you are suffering from long COVID symptoms, please work with your functional medicine doctor for a personalized treatment protocol that includes dietary, lifestyle and supportive supplements. 

Hope for the Future in Covid-19 Treatment:

As a potential ray of hope, German researchers have developed mini-antibodies or nanoantibodies that are smaller than the antibodies naturally made by the immune system.  In recent work, these  seem to be highly efficient at rendering the virus inactive and may offer a potential pharmaceutical treatment for COVID and long COVID. (Source 11)  More research is needed, but I’ll be watching closely in order to expand this toolkit for supporting long haulers. 

Core Med Science offers many of the supplements outlined above that may offer long COVID sufferers support from multiple angles. Core Med Science’s products are formulated with a clinically proven liposomal delivery. Unlike competitor products which use up to 12% alcohol, our liposomal products are alcohol free and use non-Chinese, non-GMO vitamin C and Glutathione. 

Targeting nutrition to support the root causes of long COVID carries little risk and may jump-start or speed up the healing process. 

References:

1. Montani, D., Savale, L., Beurnier, A., Colle, R., Noël, N., Pham, T., Monnet, X., & Humbert, M. (2021). Multidisciplinary approach for post-acute COVID-19 syndrome: time to break down the walls. The European respiratory journal, 58(1), 2101090. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112007/ 
2. The Doctor’s Farmacy. (2021). Long-Haul COVID and the Mysteries of Coronavirus: A Path To Healing. Episode 171. Episode: https://drhyman.com/blog/2021/05/19/podcast-ep171/ 
3. Menges, D., Ballouz, T., Anagnostopoulos, A., Aschmann, H. E., Domenghino, A., Fehr, J. S., & Puhan, M. A. (2021). Burden of post-COVID-19 syndrome and implications for healthcare service planning: A population-based cohort study. PloS one, 16(7), e0254523. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274847/ 
4. Gold, J. E., Okyay, R. A., Licht, W. E., & Hurley, D. J. (2021). Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens (Basel, Switzerland), 10(6), 763. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233978/ 
5. Cabrera Martimbianco, A. L., Pacheco, R. L., Bagattini, Â. M., & Riera, R. (2021). Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review. International journal of clinical practice, e14357. Advance online publication. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236920/ 
6. Yong S. J. (2021). Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infectious diseases (London, England), 1–18. Advance online publication. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146298/ 
7. Brackel, C., Lap, C. R., Buddingh, E. P., van Houten, M. A., van der Sande, L., Langereis, E. J., Bannier, M., Pijnenburg, M., Hashimoto, S., & Terheggen-Lagro, S. (2021). Pediatric long-COVID: An overlooked phenomenon?. Pediatric pulmonology, 56(8), 2495–2502. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242715/ 
8. Zuo, Y., Yalavarthi, S., Navaz, S.A., Hoy, C.K., Harbaugh, A., Gockman, K., Zuo, M., Madison, J.A., Shi, H., Kanthi, Y., & Knight, J.S. (2021). Autoantibodies stabilize neutrophil extracellular traps in COVID-19. JCI Insight. In Press Preview. Full text: https://insight.jci.org/articles/view/150111 
9. Vojdani, A., Vojdani, E., & Kharrazian, D. (2021). Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases. Frontiers in immunology, 11, 617089. Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/33584709/ 
10. Cozier, Y. C., Castro-Webb, N., Hochberg, N. S., Rosenberg, L., Albert, M. A., & Palmer, J. R. (2021). Lower serum 25(OH)D levels associated with higher risk of COVID-19 infection in U.S. Black women. PloS one, 16(7), e0255132. Full text: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255132 
11. Guttler, T., Aksu, M., Dickmanns, A., Stegmann, K.M., Gregor, K., Rees, R., Taxer, W., Rymarenko, O., Schunemann, J., Dienemann, C., Gunkel, P., Mussil, B., Krull, J., Teichmann, U., Grob, U., Cordes, V.C., Dobbelstein, M., & Gorlich, D. (2021). Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies. EMOB J. Advance Online Publication. Full text: https://www.embopress.org/doi/abs/10.15252/embj.2021107985