The Connection Between Spike Protein and Long COVID

by | Feb 7, 2024 | Blog, General Wellness

COVID-19 has changed our lives. For some people, COVID-19 is a short-term infection that they completely recover from within a week or two. For others, it may turn into longer-term health issues called long COVID. 

Long COVID syndrome is characterized by a variety of chronic symptoms that stick around for at least 3 months after the initial infection. Some may experience long COVID symptoms for a year or longer. Symptoms may vary from person to person, but they may be severe or even disabling in some.

I have written about long COVID in this and this article before. In my last article, I discussed new research on the potential connection between serotonin reduction and long COVID. In this article, I want to discuss the potential connection between the spike protein and long COVID and how to address it. Let’s dive into some new research.

What Is Long COVID?

Long COVID syndrome refers to a condition when people are still experiencing long-term symptoms and ongoing health issues weeks, months, or even a year after recovering from an initial COVID-19 infection. Long COVID is not COVID-19, but a group of chronic symptoms after the infection is resolved. Your long COVID  symptoms may be very different from the symptoms you experience during your acute COVID-19 illness. Some people experience mild to moderate. Others may experience severe post-COVID symptoms.

According to the Public Health Agency of Canada, about 15% of individuals develop long-term issues after COVID-19 infection in Canada (1). According to the Centers for Disease Control and Prevention (CDC), about 1 in 5 individuals will develop some symptoms of long COVID post-infection in the United States (2). About 47% of them may experience symptoms for a year or longer. 21% of long COVID patients reported that their symptoms often or always limit their regular activities. 74.1% of those with long COVID have missed school or work as a result of their symptoms. The average missed day is 20 days (1). 

Symptoms of Long COVID

Symptoms of long COVID vary from person to person. Some people may struggle with only one ongoing problem, others may have all of the common and some other less common symptoms. You may experience mild, medium, or severe long COVID symptoms. 

Though reports suggest over 100 possible symptoms or difficulties with daily activities, common symptoms of long COVID syndrome include (1):

  • Fatigue
  • Sleep problems
  • Brain fog, trouble concentrating, and decreased memory
  • Joint pain or muscle pain
  • Shortness of breath or ongoing cough
  • Loss of smell and/or loss of taste
  • Hair loss and rashes
  • General pain and discomfort

Additionally, long COVID syndrome may also affect your emotional and mental health. It may increase anxiety, depression, and post-traumatic stress.

You may learn more about long COVID in this article.

What Is a Spike Protein?

COVID-19 is a type of coronavirus (CoV). Just like other coronaviruses, the components of the viral genome of COVID-19 are packaged into a helical nucleocapsid which is enveloped by a lipid bilayer. Its viral envelope is made up of 3 different proteins, including the membrane protein (M), the envelope protein (E), and the spike protein (S). In this article, I want to discuss the functions of the spike protein further.

So, what is a spike protein? It is a highly glycosylated, large type I transmembrane fusion protein. Depending on the actual virus, it is formed by 1,160 to 1,400 amino acids. In COVID-19, the spike protein is 1273 amino acids long (3). Spike proteins also provide the well-known spike-shaped protrusions found on the surface of the virus.

Membrane proteins and envelope proteins mainly play a role in virus assembly. Spike proteins, on the other hand, play a critical role in perforating and getting into the host cell. Thus, they play a major role in initiating an acute COVID-19 infection. 

Spike proteins have two functional subunits. The N-terminal S1 subunit is responsible for the globular head, while the C-terminal S2 subunit creates the stalk of the spike protein. The S2 subunit is also embedded into the viral envelope.

When the COVID-19 virus meets the host cell, first, the S1 subunit will recognize the host cell, and then bind to its receptors. The S2 subunit will fuse its viral envelope with the host’s cell membrane. This fusion has two steps, including the heptad repeat (HR) region 1 and 2 (or HR1 and HR2). 

Without the spike protein, the COVID-19 virus may not be able to interconnect and communicate with the host cells. Thus, without the spike protein, it may not be able to cause an infection. Thus, it’s not surprising that the spike protein has become a target for vaccine and antiviral research and solutions (4, 5). 

In the next sections, you will learn how the spike protein may play a role in not just acute COVID-19, but in long COVID syndrome as well. We will discuss how targeting the spike protein may help to improve long COVID.

The Connection Between Spike Protein and Long COVID

Research on long-term COVID syndrome is ongoing. We still don’t have a complete understanding of the mechanisms behind the issue. Recent research has found that the COVID-19 spike protein may be responsible for not only the acute infection but long COVID as well.

It seems that the virus is not completely gone in long COVID patients. The body’s immune response to the remaining virus may cause chronic inflammation and persistent symptoms (6). A 2022 study published in Clinical Infectious Diseases has found that a large number of long COVID participants still had spike protein circulating in their body, possibly causing symptoms (7).

A 2022 review published in Molecular Neurobiology has also found that the remaining spike protein may be responsible for long COVID symptoms (8). They found that the spike protein may damage the endothelium and may be able to cross the blood-brain barrier (BBB), leading to perivascular inflammation. It seems that these spike proteins may also share antigenic epitopes with human molecular chaperons, which may lead to the release of inflammatory cytokines, chronic inflammation, and autoimmune issues.

Moreover, some antibodies produced against the spike protein, instead of neutralizing, may change their conformation. As a result, they may bind to its receptor. This may cause the spike protein to enter the brain. It may also trigger the activation of the microglia, causing neuroinflammation. It seems that the spike protein may have neurotoxic effects. This may explain the phenomenon of long COVID and some of its symptoms, cognitive symptoms in particular (8).  

Strategies for Managing Spike-Protein-Related Long COVID Symptoms

Ongoing research is exploring strategies to manage spike-protein-related long COVID symptoms. A 2023 review published in Microorganisms has looked at the pathophysiology of spike protein issues in long COVID, as well as post-COVID-19-Vaccine Syndrome, and looked at therapeutic intervention options (9). Their recommendations include establishing a healthy microbiome, inhibiting the binding of spike protein to prevent ongoing damage, clearing the spike protein, and restoring homeostasis after the damage is done.

Another 2023 review published in Medicine and Pharmacology has also looked at the pathology of long COVID and spike protein-related symptoms (10). Researchers explored how improving autophagy and mitophagy through fasting and other strategies may help to improve spike protein-related pathology and long COVID symptoms. 

Autophagy is the natural cleansing and renewal process of your body on a cellular level. It helps to remove damaged and old ones and replace them with healthy and new cells. Mitophagy is a specific autophagic mechanism that helps to clean out and replace damaged mitochondria.

Without further ado, let’s look at some of the strategies for spike protein-related long COVID symptoms recommended in these articles:

Improve the Gut Microbiome

Researchers found that people with long COVID syndrome and post-vaccine syndrome tend to have severe dysbiosis, particularly low Bifidobacterium levels (9). Following a gut-friendly, anti-inflammatory, nutrient-dense diet with lots of green vegetables, herbs, spices, fruits, and clean animal protein is critical. Adding foods rich in prebiotic fiber, probiotic-rich fermented foods, a daily probiotic supplement, and glucomannan may help to improve the gut microbiome and decrease inflammation and related symptoms (9).

Reduce the Risk of Spike Protein Damage

As we discussed, the prolonged presence of spike proteins may be an underlying issue behind long COVID. This may likely happen due to the cleavage of the spike protein into S1 and S2 subunits. Targeting cleavage may serve as a therapeutic option, including cleavage by furin, trypsin, or trans-membrane serine protease. Frankincense may help to bind to furin (10). 

Inhibiting Spike Protein Binding

According to the 2023 review published in Medicine and Pharmacology, “one of the most direct therapeutic mechanisms is to seek compounds which disrupt the ACE2/Spike interface, either through binding ACE2 or spike in isolation or disrupting the interface itself” (10). Researchers found that metformin, a diabetes medication, may help with this. Quercetin, curcumin, N-Acetyl cysteine (NAC), cloves, rutin, and emodin are natural compounds that may also help to inhibit spike protein binding (10). 

Clearing Spike Protein Through Autophagy

Clearing spike protein is a critical part of reducing your risk of long COVID-related issues and improving recovery. Improving autophagy is one of the best ways to do this (9). Fasting is one of the best ways to improve autophagy. Intermittent fasting is a simple and effective way to experience the benefits of fasting. It is a type of fasting strategy that cycles between a period of fasting and non-fasting within a day. 

If you haven’t practiced intermittent fasting before, it’s easiest to start with a 12-hour fasting window. Stop eating after dinner at 7 pm. You will be fasting overnight and will be ready for your next meal 12 hours later, the next day at 7 am. Gradually increase your fasting window until you find what works for you. 

The most popular intermittent fasting method is 16 hours of fasting and 8 hours reserved for your meals, but you may find that a slightly longer or shorter window works better for you. It’s critical that you eat nutrient-dense foods and meet your caloric needs during the eating period. You are simply shortening your eating window and maybe the number of meals in a day, not your nutrients. 

If you are feeling well with intermittent fasting, you may try an extended fast. A great way to do this is a juice cleanse or bone broth cleanse for 1 to 3 days. It is a good way to give your digestion a break while still consuming nutrients through liquids. You may also try a water fast for a day. However, it’s important that you work with your healthcare provider before embarking on a fasting protocol.

Other ways to improve autophagy, mitophagy, and mitochondrial function may include, according to the two reviews (9, 10):

  • Using an infrared sauna
  • Increasing flavonoid consumption
  • Using phenolic compounds
  • Drinking coffee
  • Moving your body, especially endurance exercise
  • Increasing the production of nitric oxide through exercise, ultraviolet A light, and cold stress
  • Trying cold exposure, such as cold plunges or cold showers
  • Using light therapy, such as red light therapy
  • Using melatonin for mitochondrial biogenesis
  • Using certain nutrients, including vitamin C, NAC, magnesium, lipoic acid (LA), and acetyl-l-carnitine (ALCAR)
  • Trying certain herbs and nutritional compounds, including quercetin, green tea polyphenols, EGCG mulberry, licorice, curcumin, rutin, tangeretin, Amla, eriocitrin, sudachitin, and nobiletin, 
  • Using hyperbaric oxygen
  • Trying ozone therapy

Recovering Your Body from Damage

Finally, you have to address any lingering inflammation, normalize immune processes, and allow your body to recover from any damage. Diet, nutrients, and herbs may help with this. However, sometimes medication is necessary. For example, some people may experience blood clots due to long COVID, which may need to be addressed through pharmaceuticals (9). An interesting natural health product for clotting issues is nattokinase. 

Consider Some Supplements to Aid Recovery

According to the 2023 review published in Microorganisms, the following supplements may support your recovery (9):

  • Vitamin C may offer antioxidant and immune support
  • Vitamin D may have immunomodulatory benefits
  • NAC may have anti-inflammatory, antioxidant, and cellular metabolism support benefits
  • Glutathione may have anti-inflammatory, antioxidant, and cellular metabolism support effects
  • Quercetin may offer anti-inflammatory effects and stop spike-ACE2 interactions
  • Melatonin may have anti-inflammatory, antioxidant, and cellular metabolism support benefits
  • Curcumin may help to inhibit spike-ACE2 interaction and virus encapsulation
  • Resveratrol may offer anti-inflammatory and anit-thrombotic benefits
  • Zinc may offer nutritional and immune health support
  • Magnesium may offer nutritional and mitochondrial benefits
  • Fish oil may serve as an anti-coagulant and anit-inflammatory substance
  • Nutmeg may help as an anti-coagulant
  • Sage may help to stop virus replication
  • Cinnamon may have immune modulatory benefits
  • Thyme may offer antioxidant and anti-inflammatory effects
  • Propolis may be beneficial for immunomodulation and influencing ACE2 signaling pathways
  • Cloves may be anti-inflammatory, anti-thrombotic and may support autophagy
  • Milk thistle may be a great antioxidant and anti-inflammatory herb
  • Licorice may have immunomodulatory and anti-inflammatory effects
  • Cardamon may have anti-inflammatory benefits
  • Ginger may have anti-inflammatory effects
  • Prunella vulgaris may help to block spike protein
  • Andrographis may help to reduce viral load
  • Algae may have immunomodulatory effects
  • Limonene may have anti-inflammatory benefits
  • Nattokinase is an anti-coagulant and may help to degrade spike protein
  • Luteolin may reduce inflammation
  • St. John’s Wort may help to reduce inflammation
  • Emodin may help to block spike-ACE2 interaction
  • Apigenin may help as an antioxidant
  • Fisetin may be a senolytic
  • Frankincense may bind to protease furin and offer a positive impact

Next Steps

If you are experiencing symptoms of long COVID, the nutritional and lifestyle strategies may help with your symptoms. I recommend that you consult a healthcare provider well-versed in long COVID before taking any supplements or embarking on any strict protocol. Long COVID varies from patient to patient and it’s critical that we consider your personal health and circumstances before creating a personalized treatment strategy to address your unique set of symptoms and health challenges.

If you are experiencing symptoms of long COVID or recently had a COVID-19 infection, I invite you to schedule a consultation with me here to see if you can benefit from the strategies listed in this article. 

If you are dealing with any chronic health issues for advice on how to improve your nutrition and health, I welcome you to start a functional medicine consultation with me for further personalized guidance. You may book your consultation here

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