Long COVID Syndrome Update: The Connection Between Long COVID and Serotonin

by | Jan 8, 2024 | Blog, General Wellness

Even though we are mostly back to living our normal lives, COVID-19 is still very much around us. Though we have better strategies to reduce our risks and improve our recovery, long COVID syndrome is still a very much relevant problem. Experiencing chronic symptoms after the initial infection is not uncommon. 

Many individuals with long COVID have chronic health issues for a year or longer after infection. These symptoms can sometimes be debilitating or even disabling. Research is ongoing to reduce risk factors and support recovery from long COVID syndrome.

I consult with patients with long COVID regularly, and read research often about how to assist. In this article, I want to discuss an exciting new study that may help us uncover some of the mechanisms behind long COVID and may offer some new treatment options. It turns out, serotonin reduction may be behind some of your long COVID symptoms. So what is the connection between serotonin and long COVID? Let’s find out.

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 symptoms. 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 (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 (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 adult was absent from work for 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 much more than that. 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.

Current State of Research and Treatment

Even though COVID-19 has been around for four years, and long COVID is a commonly known condition, we still don’t understand all the mechanisms behind these chronic symptoms. Research is ongoing. In this article, I will share a new study that will help to untangle some of the underlying mechanisms behind long COVID and show us further hope in terms of treatment (3).

What Is Serotonin

Serotonin is a neurotransmitter. This means it is a chemical carrier of messages between nerve cells in your brain and across your body. It plays a role in many important bodily functions, including brain health, mood, sleep, digestion, bone health, wound healing, sexual desire, and blood clotting. Low serotonin levels may lead to various psychological and physical health issues. Low serotonin may lead to anxiety, depression, cognitive problems, fatigue, poor sleep, digestive issues, and some other problems (4).

As you may notice, some of these issues may be present in long COVID syndrome as well. Is this a coincidence? New research suggests it’s not. Let’s talk about the potential connection between serotonin reduction and long COVID. 

Serotonin Reduction and Long COVID

Researchers at the Microbiology, Pathology and Laboratory Medicine department and the Physical Medicine and Rehabilitations’ Post COVID Assessment and Recovery Clinic Department at the University of Pennsylvania looked at the blood and stool samples from various small animal models and clinical studies to evaluate and understand the effects of long-COVID infections (5). 

The study published in Cell has found that some patients with long-COVID syndrome still had traces of the SARS-CoV-2 virus in their stool even months after the initial acute infection. These results suggest that the virus is able to remain in the gut of some individuals for a long period of time, causing chronic long-COVID symptoms (3).

This residual virus in the gut is called the viral reservoir. The problem is this viral reservoir may disrupt the immune system and trigger the release of interferons. Interferons are proteins that help to fight the virus by causing inflammation and but also may be capable of decreasing the absorption of tryptophan in the gut.

Tryptophan is an amino acid. It also serves as a building block for serotonin and other neurotransmitters. As you know, serotonin carries messages between nerve cells in your brain and other body parts too. It is essential for digestion, sleep, memory, wound healing, mood, and other functions. It helps to support homeostasis in your body.

Serotonin is also necessary for regulating vagus nerve function. The term vagus nerve refers to a pair of nerves that help the main nerves of your parasympathetic nervous system. It assists communication between your brain and body. 

Your vagus nerve helps to manage stress and anxiety, regulate your mood, reduce blood pressure, decrease heart rate, lower inflammation, decrease pain, transfer information between your gut and brain, deliver information between your heart, lungs, and thoughts, regulate speech, and support swallowing. Vagus nerve problems may lead to both physical and psychological issues. 

Physical symptoms related to vagus nerve injury or poor vagal tone may include abdominal pain, nausea, vomiting, loss of gag reflex, lower stomach acid, unusual blood pressure, unusual heart rate, earache, or loss of voice. Psychological symptoms of poor vagus nerve function may increase high stress, chronic stress, being in a constant flight-or-fight mode, anxiety, depression, poor emotional regulation, decreased attention span, chronic pain, and inflammation. You may notice some of these digestive, cognitive, mental health, inflammation, and pain-related symptoms on the list of long COVID symptoms. This may be because lower serotonin levels in long COVID can cause poor vagus nerve function (6, 7).

To recap: Long COVID syndrome may lead to the reduction of tryptophan absorption in the body due to chronic inflammation from virus particles hanging around in the gut. Since tryptophan is critical for serotonin, this will lead to serotonin depletion and a disruption of vagus nerve signaling. Researchers speculate that low serotonin levels and poor vagus nerve function may be behind certain symptoms of long COVID syndrome, including memory loss, brain fog, poor concentration, fatigue, and sleep issues.

Potential Targets for Long COVID Recovery

Keeping up with ongoing research studies to understand long COVID is critical for finding the best treatment protocols for each patient. This research is remarkable from the perspective that it gives us specific biomarkers to look at and target instead of only relying on patients’ symptoms and personal descriptions of their experience to assess the problem and track progress.

Testing, however, may be difficult. The blood test that measures the amount of serotonin in your blood is typically used to test for tumours that produce serotonin outside of the brain. Blood and urine levels of serotonin are unreliable measures of your brain’s serotonin.  What’s important though is that the gut, also known as our second brain, has plenty of serotonin receptors and is involved in building serotonin from tryptophan. With cross-talk between the gut and the brain, and vagus nerve involvement in the communication, it’s easy to get excited about these new developments related to long COVID. 

So, though testing may be tricky, this new research suggests that targeting and improving serotonin and tryptophan levels may help to improve memory impairment or other long COVID symptoms. They found that serotonin precursors or selective serotonin reuptake inhibitors (SSRIs) may help. 

Some studies, including a 2023 research published in MedRxiv, found that using SSRIs may help to prevent or reduce long COVID symptoms (8). The recent results of this Penn research suggest that we can look at improving serotonin levels in long COVID patients with depleted serotonin to improve their health.

Tryptophan serves as a building block for not only serotonin but also niacin, melatonin, and other metabolites. Niacin helps to turn food into energy and it’s critical for your brain and mental health. Melatonin is essential to your circadian rhythm and sleep. Many long COVID patients experience issues with sleep, brain health, mental health, and digestion, and addressing underlying tryptophan absorption issues may help with these symptoms.

Long COVID is a complex problem. Each patient has a unique experience with a complicated set of symptoms. These new results suggest that the link between viral persistence, serotonin deficiency, and vagus nerve dysfunction may be among the underlying issues and are potential targets for treatment. 

In the next section, I will recommend some strategies to improve your serotonin levels and vagus nerve function naturally. These strategies may help without the use of SSRIs. Always consult your healthcare provider to see what’s right for your unique situation.

How to Improve Serotonin Levels

There are many strategies to improve long COVID syndrome depending on your personal situation, symptoms, and overall health. I have written about some general strategies that may help to calm long COVID symptoms in this article. Today, I want to specifically get into improving your serotonin levels to recover from long COVID and better your health.

Follow a Nutrient-Dense Diet and Eat Tryptophan-Rich Foods

Following a nutrient-dense diet is critical for your cognition, mental health, low inflammation levels, and overall health. Cut out inflammatory foods, including refined sugar, refined oil, sugary drinks, artificial ingredients, junk foods, and highly processed foods. Eat lots of greens, vegetables, fruits, herbs, spices, nuts, seeds, pseudograins, grass-fed meat, pasture-raised poultry, organic eggs, wild-caught fish and seafood, and wild game. 

Tryptophan is essential for your body to make serotonin (9). Poor tryptophan levels may lead to low serotonin and related issues. Tryptophan-containing foods to consider to improve your levels include turkey, salmon, eggs, nuts, pumpkin and other seeds, pineapples, and soybeans.

Get Some Sunlight

Sunlight is essential for normal mood levels. Sunshine helps to boost your vitamin D levels, but it also helps to improve your serotonin levels. Try to spend at least 15 to 30 minutes outside to get some sunlight. This can be more difficult in colder climates and in gloomier weather. Using light therapy is designed for Seasonal Affective Disorder (SAD) (10).

Move Your Body

Getting regular exercise may also help to boost your serotonin levels (11). Move your body throughout the day. Start your day with some stretching, rebounding, a short walk, or a yoga session. Get up to stretch and walk around regularly. Try an impromptu dance session while cooking or go for a walk with a friend during lunch. Exercise at least 20 to 30 minutes 5 days a week incorporating both cardiovascular exercise and strength and resistance training.

Socialize and Laugh More

Socializing with loved ones may help to support your serotonin levels (12). Spend time with supportive friends and family as much as you can. Seek out a supportive community through volunteer or other ways. Giving back is not only a great way to find a community, but it may also help to boost serotonin levels (13). Being around animals may also have similar benefits. Laughing more may also be just as important (14).

Try Some Supplementation

Certain supplements may help to improve your serotonin levels too. B vitamins, 5-HTP, magnesium, omega-3 fatty acids, L-Theanine, rhodiola, S-adenosylmethionine (SAM-e), and St John’s wort may all be great options for improving serotonin (15, 16, 17, 18, 19, 20, 21, 22).

Stimulate Your Vagus Nerve

Low serotonin levels may compromise vagus nerve function. In this article, you may learn more about the connection between your vagus nerve and histamine and some strategies to improve it. Stimulating your vagus nerve and improving its function may help to reduce some of your long COVID-related symptoms too.

Ways to improve your vagus nerve function include:

  • Meditation
  • Breathwork
  • Gratitude
  • Chanting or singing
  • Gargling
  • Laughter
  • Movement and exercise
  • Social connections
  • Acupuncture 
  • Massage therapy and bodywork
  • Nutrient-dense diet
  • Some supplements, including vitamin B12 and other B vitamins, vitamin D, magnesium, zinc, and omega-3 fatty acids (23, 24, 25, 26, 27)
  • Therapy, especially polyvagal therapy and EMDR

Personal Anecdote

During my trip to South America in June 2023, I contracted COVID and had an acute infection.  The strains by this time in the COVID cycle were notable for their effect on the digestive system. Likewise,  GI symptoms were predominant for me. During the 2 week period afterward, my mental fog was very noticeable, then thankfully cleared.  What remained, though, were daily headaches for weeks, including in the middle of the night, and stomach rumbling.  Things weren’t quite right with my digestion.  

I figured I had a “leaky gut”, and to repair it I first wanted to know my updated food sensitivities.  On myself, I did the mediator release test, which showed very high reactivity to potatoes, a staple in my gluten-free diet.  From the day I received my test results, in August 2023, and until now I have not eaten any potatoes, or products with potato in them.  And since that day, I have not had a single headache.  My digestive symptoms? They continued for a while longer, until I read the research paper summarized in this article.  I started taking a nighttime dose of 5-HTP (200 mg), and these symptoms resolved too!

Next Steps

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

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

Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.

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