Long-Haul Syndrome and Mast Cell Activation: The Connection

Fatigue, brain fog, aches and pains, headaches, shortness of breath, palpitations, dizziness, loss of taste and smell, and so on. Do you recognize any of these persistent symptoms since recovering from COVID-19? You may have long-haul syndrome.

Long-haul syndrome is a term used to describe chronic symptoms experienced by individuals who have recovered from their initial infection, but still have ongoing and sometimes debilitating symptoms. The exact cause of long-haul syndrome is not well understood yet. But new research suggests that mast cell Activation issues may be behind some of your ongoing symptoms.

In this blog, I will explore the latest research on Long-Haul Syndrome and Mast Cell Activation Syndrome. I will offer my best strategies to manage your symptoms, improve your health, and regain your quality of life.

What Is Long-Haul Syndrome?

Long-haul syndrome (LHS) is one of the terms used for the potential long-term effects of the COVID-19 infection. It is not one specific condition, but rather, a group of post-infection chronic symptoms. If you have long-haul syndrome, it means that you are still experiencing long-term symptoms and health issues even weeks, months, or years after recovering from your initial infection. Symptoms may vary from person to person (1, 2).

You may think that long-haul syndrome only affects those who had a severe infection. This is not the case. Many people with long-haul syndrome symptoms only had mild or moderate symptoms during their initial illness. Some long haulers were actually asymptomatic (3, 4). Unfortunately, your chronic symptoms may be related to the virus even if you only had a mild case.

If you are experiencing symptoms of long-haul syndrome, you are not alone. According to the Centers for Disease Control and Prevention (CDC), 1 in every 13 adults experienced long-lasting symptoms for 3 months or longer after their initial infection (5). According to a 2021 study published in the Clinical Nursing Journey, this number is much higher, and about 27% reported symptoms lasting after the infection (3).

Long-haul syndrome symptoms can last anywhere from a few weeks to several months or even years. According to the Public Health Agency of Canada, 80% of people with long-haul syndrome experienced ongoing symptoms between 4 and 12 weeks after recovering from their infection. About 60% reported symptoms lasting for 12 weeks or longer. About 10% of people with long-haul syndrome experience symptoms that were so severe that they were unable to go back to work (6).

Symptoms of Long-Haul Syndrome

Long-haul syndrome is a complex condition with over a hundred possible symptoms. Symptoms can greatly vary from person to person, they may vary anywhere from mild to severe. You may only have one or a few chronic issues, or you may have a laundry list of complaints.

The most common symptoms of long-haul syndrome may include (7, 8):

• Fatigue
• Insomnia and sleep problems
• Joint pain
• Muscle pain
• Loss of smell and/or taste
• Brain fog
• Trouble focusing and concentrating
• Memory issues
• Ongoing cough
• Shortness or breath
• Dizziness
• Headaches and migraines
• Hair loss
• Menstrual issues
• Digestive problems
• COVID toe
• Blood clotting
• Cardiovascular issues
• POTS-like symptoms
• General pain and discomfort

You may have other chronic symptoms related to post-viral issues. Additionally, long-haul syndrome can also seriously impact your mental health. Depression, anxiety, post-traumatic stress, and other emotional issues are common in those with chronic health issues.

Risk Factors for Long-Haul Syndrome

Long-haul syndrome is a new phenomenon, and we don’t fully understand all of the risk factors. Research is ongoing, and some of the current theories on possible risk factors include:

• Viral persistence and viral ghosts (9, 10)
• Mast cell activation syndrome (MCAS) (11, 12)
• Gut microbiome imbalance (13, 14)
• Autoimmune response causing widespread chronic inflammation (15, 16)
• Other dormant pathogens getting activated in your body (17, 18)
• Mitochondrial imbalance and cell danger response (19, 20)
• Persistent brainstem dysfunction (21, 22)
• Overlap of multiple conditions (23, 24)
• Mold exposure and fungal infections https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620017/

In this article, I will specifically discuss the possible connection between MCAS and long-haul syndrome.

Functional Medicine and Long-Haul Syndrome

Although long-haul syndrome is a new condition, post-viral health issues are not. You may develop post-viral fatigue and post-viral syndrome from the Epstein Barr virus (EBV), human herpes virus, cytomegalovirus, measles, and even the flu (25, 26, 27, 28, 29).

As a functional medicine practitioner, I’m experienced in working with patients with mast cell activation syndrome (MCAS), chronic fatigue syndrome (CFS), chronic Lyme disease, fibromyalgia, and other chronic health issues and immune imbalances, often triggered by infections. This experience helps me to support my patients in improving chronic symptoms of long-haul syndrome as well.

What Is Mast Cell Activation?

Think about your mast cells as the first responders of your immune system. They are an essential part of your body. Mast Cells are born in the bone marrow along with our red and white blood cells.  They migrate to places in the tissue near areas of interface where they can monitor for perceived threats to the body.  Mast Cells reside all over the body, in mucosal membranes, like the GI tract and respiratory tract, near the surface of the skin, near blood vessels and near nerves cells and in the brain! They contain hundreds of chemical messengers known as mediators, including histamine, heparin, leukotrienes, serotonin and other inflammatory chemicals called cytokines and chemokines.

When your body is exposed to an infection, a toxin, an allergen, or encounters some other trigger; your mast cells will come to your rescue. They will let your immune system know about the danger. In response to this danger, your mast cells will release their mediators in a process called degranulation.  This is an important protective mechanism that helps to fight invaders and support your recovery from infections, allergens, and toxins. But it is also in part why we have so many symptoms when we do get sick with a cold, COVID or the flu.  Symptoms are uncomfortable but we are reminded that our immune systems are doing their job!

However, in about 20% of the population, the mast cells can become overactive or dysregulated, releasing mediators even after the initial threat has passed. They may release chemicals even if there is no real danger in sight and they may start to react to otherwise non-dangerous substances, like the food we eat or smells of substances we previously tolerated. This creates havoc in your system causing widespread symptoms and chronic health issues. This is a condition known as Mast Cell Activation Syndrome.

Symptoms of MCAS may include:

• Rashes
• Hives
• Itching
• Headaches
• Fatigue
• Weakness
• Dizziness
• Heart palpitations
• Chest pain
• Low blood pressure
• Diarrhea, nausea, and other digestive issues
• Weight changes
• Poor appetite
• Anxiety and depression
• Vision changes
• Brain Fog and cognitive problems
• Cough, Shortness of breath and allergy-type symptoms

Long-Haul Syndrome, Mast Cell Activation, and Histamine Intolerance

Seeing an increasing number of patients with Long Haul Syndrome symptoms since the pandemic, I noticed something interesting. I realized that many of their symptoms are similar to symptoms of MCAS and histamine intolerance.

This may not be a coincidence. It’s possible that mast cell activation plays a role in long-haul syndrome. I wasn’t the only practitioner noticing this.

A 2020 paper by Dr. Theo Theoharides published in Annals of Allergy, Asthma, and Immunology, found a potential link between COVID-19 infection and mast cell activation (30). Dr. Theoharides explains that mast cells may release pro-inflammatory chemical messengers in patients with COVID-19. This may lead to severe symptoms and post-viral inflammatory issues. He recommends addressing MCAS with COVID-19 patients, especially if they have chronic inflammatory and allergic symptoms in multiple body systems. He suggests that blocking mast cells and their inflammatory compounds during infection may help to reduce symptoms severity and lower the risk of Long Haul Syndrome.

In a 2020 BBC report, Dr. Tina Peers, a practitioner who treats people with histamine intolerance and MCAS, noticed that her patient with long-haul syndrome symptoms also had increased histamine levels (31). Since then we have more scientific evidence backing these theories.

According to a 2020 study published in the International Journal of Infectious Diseases, the hyperinflammation associated with MCAS and associated with COVID-19 may lead to long-haul symptoms (32). Researchers found that medications prescribed for increased mast cell activity may help to reduce the risk of severe illness. They also found that the hyperinflammatory state related to mast cell dysfunction may also play a role in Long Haul Syndrome symptoms. Addressing mast cell activation issues may help to calm long-term issues as well.

A 2021 study published in the International Journal of Infectious Diseases looked at 136 patients with long-haul syndrome, 80 patients with MCAS, and 136 control subjects (33). Researchers found that long-haul syndrome symptoms mimicked the symptoms and severity of the symptoms of patients with MCAS. They also found that MCAS symptoms increased as a result of long-haul syndrome. The authors suggested that mast cell activation may be an underlying issue behind the pathophysiology of long hauler issues and targeting mast cells may be an appropriate therapeutic option.

Another 2021 study published in the European Journal of Allergy and Clinical Immunology also linked mast cell activation to long-haul syndrome (34). The authors found that the initial infection may lead to mast cell activation, inflammatory cytokine release, and inflammation, which may lead to chronic symptoms.

A 2022 review published in Virology Journal demonstrated that the hyperactivation of mast cells and the inappropriately increased release of inflammatory chemical mediators may be behind long-haul syndrome symptoms (35). Researchers believe that this may lead to a persistent inflammatory reaction, autoimmune mimicry, the reactivation of pathogens, and microbiome imbalance, which may all lead to chronic symptoms post-infection.

Another 2022 review published in the Journal of Immunology Research explained that mast cell activation associated with the infection may lead to female hormonal imbalance (36). This suggests that hormonal issues, menstrual imbalances, fertility issues, and endometriosis may be long-haul syndrome complications related to mast cell activation.

Research is still ongoing to understand the link between long-haul syndrome and mast cell activation. However, based on what we know, it seems like calming mast cells and addressing mast cell activation issues may be a smart option to improve your health and well-being.

A 2022 paper published in the British Journal of Hospital Medicine (London)  recommended addressing mast cell activation to support recovery from long-haul syndrome issues (37). Mast cell stabilizers, mast cell mediator blockers, anti-inflammatory agents, and self-management protocols were among some of their strategies. However, you may find improvements without using medications. In the next section, I will offer some natural options to improve mast cell activation issues.

Recommendations for MCAS and Long-Haul Syndrome

Do you have symptoms of MCAS and long-haul syndrome? Are you interested in supporting your body naturally? I recommend the following strategies to improve your health:

Follow an Anti-Inflammatory Diet

To reduce chronic inflammation and related symptoms, I recommend that you consume an anti-inflammatory diet. Remove inflammatory foods, including refined sugar and carbs, refined oils, gluten, food allergens, artificial ingredients, canned and processed meat, and overly processed foods. Focus on eating lots of greens, vegetables, sprouts, herbs, spices, nuts, seeds, organic grass-fed meat, organic pasture-raised poultry and eggs, and wild-caught fish.

Follow a Low-Histamine Diet

If you are dealing with histamine intolerance due to increased mast cell activation, I recommend following a low-histamine diet. Reduce your histamine load by removing high-histamine foods, including aged cheese, canned and cured meat, citrus, fermented food, vinegar, fermented alcohol, dried fruits, smoked fish, soured foods, and processed foods high in preservatives. Avoid histamine-liberating foods, including tomatoes, bananas, papaya, cow’s milk, shellfish, and wheat germ. These foods may trigger histamine release. Also, remove DAO enzyme-blocking foods and drinks, including alcohol, and caffeinated beverages like tea, coffee, and energy drinks.

Reduce Your Mast Cell Triggers

There are a variety of environmental factors that can trigger mast cell activation and related histamine release, complicating your recovery. If you are already dealing with mast cell issues related to Long Haul Syndrome, it’s critical that you reduce your other triggers. Common triggers of mast cell activation include allergens both food and environmental, mold and mycotoxins, other toxins, chemicals, heavy metals, and infections.

Follow a Healthy Lifestyle and Lower Your Histamine Bucket

Beyond mast cell activation and a high-histamine diet, other factors can increase histamine intolerance as well. I recommend that you lower your histamine bucket to reduce histamine intolerance by lowering stress, improving your sleep, moving your body regularly, and reducing exposure to environmental toxins. Following these healthy lifestyle strategies may also help to reduce chronic inflammation causing your long-haul syndrome symptoms.

Try Supplements for Mast Cell Activation

I recommend a few supplements that may help to calm your mast cells:

• Quercetin: Quercetin is a powerful flavonoid. It is found in many plant-based foods, including apples, berries, cherries, grapes, peppers, kale, snap peas, sprouts, cruciferous vegetables, and romaine lettuce. It is a potent anti-inflammatory and antioxidant-rich nutrient that also serves as a mast cell stabilizer that may lower your histamine levels naturally (38). I recommend taking this Quercetin supplement by Pure.
• DAO Enzymes: Diamine oxidase is an enzyme that naturally helps clean up histamine. However, if your body is unable to make enough DAO or you have too much histamine from extreme mast cell activation or histamine intolerance, you may need some help from DAO supplementation (39). I recommend taking HistDAO by Xymogen.
• Pycnogenol: Pycnogenol is made from the bark of the French maritime pine. It may help to stabilize your mast cells. It may also be a great anti-inflammatory, antiviral, antioxidant, and anti-thrombotic agent (40). By calming your mast cells and inflammation, it may help to address various chronic issues related to long-haul syndrome.
• HistaQuel: HistaQuel is a great supplement that includes both quercetin and luteolin. Luteolin is a powerful bioflavonoid with antioxidant and anti-inflammatory benefits (41).
• DHist – Ortho Molecular: DHist is a fantastic blend of flavonoids, antioxidants, proteolytic enzymes, and botanicals (42). It is great for mast cell activation, histamine intolerance, and allergies.

Try Some Other Supplements for Long Hauler

Beyond supplements for mast cell activation, I also recommend some supplements for specific long-haul syndrome symptoms and respiratory health:

• Perimine: I recommend supplementing with Perimine. This supplement is a patented extract of perilla seed, which is full of powerful antioxidant, anti-allergic, antimicrobial, anti-inflammatory, and neuroprotective benefits (43). It is a fantastic supplement for your respiratory health and to calm chronic inflammation associated with long hauler.
• Boluoke: Boluoke is made from lumbrokinase, an enzyme that’s been shown to be a highly effective treatment for a variety of conditions associated with hypercoagulation and hypoperfusion. It is a great supplement for blood clotting issues and circulatory health, which are common problems related to long-haul syndrome (44, 45). Other supplements I recommend for clotting issues include nattokinase and serratia.
• E’Lyte: Finally, I recommend E’Lyte for those with Postural Orthostatic Tachycardia Syndrome (POTS). POTS is an increasingly common long hauler issue. POTS may also increase your risk of severe symptoms from COVID-19 infection (46).

Next Steps

Are you experiencing symptoms of long-haul syndrome and/or mast cell activation syndrome? If you want to discuss anti-inflammatory or low-histamine diets to help support your symptoms, I welcome you to schedule a functional nutrition consultation with my nutritionist, Sarah. Visit our store for products to support your health.

And stay tuned for more information to help you uncover the root cause of your health issues, to improve your nutrition, repair your body, and regain your health naturally.

You can schedule your consultation with Sarah here.