An Integrative Medicine Approach to Long COVID

When someone is struggling to function because of brain fog, it's usually a symptom that is hard to quantify and easy for others to dismiss. It also happens to be one of the most common manifestations of Long COVID. We all have tired days when mental processes are not at their peak. But, Long COVID symptoms, like brain fog, can have a far more significant impact than symptoms felt when acutely fighting the flu or lacking a few hours of sleep. A study in the UK has found that the level of functional cognitive impairment in Long COVID can be similar to a level of intoxication that would make driving illegal in the UK or equal to ten years of brain aging. 

Three years into the COVID-19 pandemic, around 65 million people worldwide are estimated to have lingering effects, from mild to debilitating, from a past COVID infection. This is a condition known as Long COVID. It affects between 10% and 50% of those who recover from a COVID infection. At least some of the cases resolve slowly over time. 

When it first started appearing, it was quickly recognized as sharing many traits with other illnesses that occur after an acute viral infection, such as Myalgic Encephalitis (ME), also known as Chronic Fatigue Syndrome (CFS) and POTS. Thus the knowledge from those fields, along with HIV research, has significantly contributed to the accelerated development of knowledge around Long COVID. And, Long COVID research may also yield valuable insight into those conditions.

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What is Long COVID?

Long COVID is not just one illness but a collection of disorders that occur after the acute phase of infection with the SARS-coV-2 virus. These prolonged illnesses may last for weeks to years or more after the initial illness. Many individuals with post-COVID conditions report being unable to sustain their previous levels of function in work and daily life for months after the initial infection. Given the number of people infected during the pandemic, this population struggling to function at their previous levels is quite large, significantly impacting the whole. In healthy younger individuals, such as teens, the rate of spontaneous improvement over time appears promising. However, there are still millions of individuals struggling, many of whom have had to reduce or stop work.

Mechanistic studies are ongoing to understand why Long COVID may develop and provide insights into better treatments. The following categories have been identified that help consider the reasons and causes of Long COVID symptoms, though much is still not understood:

Organ Damage From the COVID Infection

Acute inflammation during a COVID infection can leave lasting damage to the lungs, heart, kidney, or brain. In some cases, damage can also occur as a result of being hospitalized for the illness. 

Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysfunction 

Low cortisol levels leading to overall HPA axis dysfunction may result if antibodies cross-react with and damage adrenocortical receptors via molecular mimicry.

ME/CFS and Dysautonomia 

It is estimated that 50% of individuals with Long COVID meet the criteria for ME/CFS. Since Long COVID symptoms and ME/CFS symptoms significantly overlap, this could be an explanation for many sufferers. 

Impaired Microbiota-Gut-Brain (MGB) Axis Signaling

The MGB is the communication pathway between the gut and the brain. Dysbiosis, an imbalance in the gut microbiome, as a result of the infection is also implicated in the development of ongoing symptoms. 

Chronic Low-Grade Inflammation 

One theory is that the virus may persist in small pockets in the body, triggering ongoing low-level inflammation as part of the ongoing immune response. 

Autoimmune Processes

There are similarities between segments of COVID proteins and human proteins, creating the opportunity for molecular mimicry to trigger autoimmune processes, which may explain some of the persistent symptoms of Long COVID.

Post-ICU Syndrome

For patients treated in the ICU, post-ICU syndrome is another consideration that may overlap with or exacerbate other factors.

Long COVID Symptoms

Long COVID has been connected with up to 200 different symptoms. The specific symptoms an individual may experience are likely to be related to specific mechanisms at play in their situation (i.e., someone with lung damage experiencing ongoing shortness of breath). 

Overall, some of the most commonly occurring symptoms in those experiencing Long COVID are: 

• Fatigue
• Feeling unwell after exercise (post-exertional malaise)
• Difficulty thinking and focusing (Brain fog) (85% prevalence)
• Memory issues (79% prevalence) 
• Body Aches
• Shortness of breath
• Heart Palpitations

Reactivation of latent diseases such as shingles (varicella-zoster virus), Epstein Barr Virus (EBV), Lyme infection, or Cytomegalovirus infection (CMV) can occur.

There are also many shared symptoms between Long COVID and Mast Cell Activation Syndrome (MCAS), provoking investigation into a possible mechanism. Some of these symptoms include:

• Fatigue
• Brain fog
• Headaches
• Insomnia
• New allergies
• Anaphylaxis
• Dizziness
• Fast heart rate
• Changes in sensitivities to medications

Dysautonomia (POTS and ME/CFS) also share many symptoms with Long COVID. Specific trends that may suggest looking into this more might be experiencing heart palpitations or dizziness on standing.

Why Do Some People Get Long COVID?

While the exact mechanisms for Long COVID are not fully understood, some trends have been observed about who tends to be at higher risk. Factors increasing the risk of developing long COVID include: 

Severe Cases of COVID

A more severe case of COVID may increase the risk of developing Long COVID, although it is also commonly seen in those who had mild to moderate illness. Rates are lower among those infected during the omicron vs. earlier waves of the pandemic.

Gender and Race

Being female, Hispanic, or Latino are risk factors. Females are thought to have a higher risk of Long COVID due to the more robust immune response to the initial infection, which may lead to immune dysregulation. Hispanics are prone to more severe initial infections, which may in part explain the increased rate of Long COVID.

Age

Age over 40 is related to an increased risk of Long COVID.

Lower Income

Having a lower income and lower educational level or living in a rural area is associated with higher rates of Long COVID, likely partly due to being unable to rest adequately during the first weeks after developing COVID-19.

Environmental Factors

Living or working in a building with water damage and toxic mold has been associated with higher rates of Long COVID. 

Pre Existing Medical Conditions

Having certain conditions prior to the COVID infection increases the risk of Long COVID. Some of the common medical conditions that have been associated with Long COVID are type 2 diabetes, a reactivation of EBV, connective tissue disorders, attention deficit hyperactivity disorder (ADHD), chronic hives (urticaria) and environmental allergies (allergic rhinitis).

Functional Medicine Labs to Personalize Treatment for Long COVID Patients

Because Long COVID is not just one illness and can affect multiple organs in the same person, there is no single standard test to identify it. There is not even a set of tests to run on all patients. But, based on the specific presentation, additional information may be obtained to help direct treatment through the following concepts.

All Long COVID patients should have a complete blood count with differential (CBC with diff) and a complete metabolic panel (CMP) to check coagulation, kidney and liver function, and blood sugar levels. 

Heart Disease and a hyper-coagulable state can develop after COVID. It's important to screen for excessive clotting via a troponin test in post-COVID patients because of the potential to develop a life-threatening clot. In addition, a lipid panel, inflammatory markers, such as hs-CRP, and other cardiac markers like fibrinogen, D-dimer, and ferritin, may be useful to check along with an EKG or other testing as fits the individual's condition.

Diabetes can be a risk factor but also a component of Long COVID, so Long COVID patients should, at minimum, be screened with a fasting glucose test (also generally included as part of a CMP). If there is reason to suspect this specifically, additional diabetes tests may also make sense.

HPA Axis function can be screened with stress response labs, which may be useful since viruses impact the stress response.

As digestive function is often disrupted and dysbiosis may be a contributing factor, a functional GI screen could provide valuable and actionable information. 

If an individual has a known or suspected past exposure to toxic mold or water-damaged buildings, a urine mycotoxin test can give some insight into current body stores.

If you suspect Mast Cell Activation Disorders (MCAS), you might pursue additional testing since there are many shared symptoms between this condition and Long COVID.

Integrative Medicine Treatment for Long COVID Patients

Patients with Long COVID due to heart, lung, or kidney damage impacting organ function should be managed as needed for those resulting conditions, including with medications to maintain function if necessary. 

Any clearly reactivated infections (Epstein-Bar, Cytomegalovirus, etc.) should also be treated. These viruses respond well to Vitamin C, herbs such as garlic, astragalus, green tea, ginger, Echinacea, black cumin, licorice, St. John's Wart, and a Mediterranean Diet.

If dysbiosis is identified, it should be treated with standard functional or naturopathic medicine methods. Prebiotics, probiotics, ginger, and zinc help reestablish a healthy microbiome.

If stress hormone (HPA Axis) patterns appear dysfunctional with testing, this can be addressed with standard functional medicine treatments. Adaptogenic herbs are particularly helpful for rebalancing the stress response.

If Mast Cell Activation Syndrome (MCAS) is suspected and identified, it should be treated. Low histamine diets have been shown to help treat this condition.

If mold toxicity is suspected and identified, it should also be treated, including removal from triggering locations or remediation of those places.

Nutrition 

In general, a plant-based, whole-food diet will provide high levels of anti-inflammatory phytonutrients and antioxidants that can help to reduce excess inflammation. Focusing on omega-3 fatty acids, such as from flax, chia hemp seeds, and fatty fish like wild-caught salmon or even supplemented as fish oil can also help reduce chronic inflammation. Similarly, cooking with turmeric, ginger, and garlic can provide a nutritional baseline that supports a less reactive inflammatory response. Any known food allergens should be avoided to diminish a potential immune flare from food. 

In addition, Vitamins B, C, D, and E and the flavonoids Quercetin and Luteolin can protect against neuroinflammation and oxidative stress (a possible cause of brain fog) in the context of Long COVID. 

Complementary and Alternative Medicine

Many herbs have been studied in the context of Long COVID. These mostly fall into the categories of antivirals, antiinflammatories, energy-boosting herbs, and nervous system calming herbs. Herbs effectively used for anxiety include valerian, passionflower, kava-kava, hops, and lemon balm. Herbs effectively used for depression include St. John's Wort and Rhodiola, and for mixed depression-anxiety, lavender and guarana have been effective. 

For cognitive health, Ginkgo, lavender essential oil, melissa (lemon balm) essential oil, and myrrh essential oil have been used effectively for Long COVID. 

For heart issues related to Long COVID, Hawthorne has been helpful.

In addition, Chinese Medicine (CM) herbs have been widely used according to Chinese Medicine diagnostics in the treatment of COVID and appear to help significantly in the resolution of symptoms. 

For those experiencing symptoms of trauma (PTSD or PICUS) or significant psychiatric symptoms of Long COVID, stress-lowering treatments, including massage, meditation, and yoga, may help alleviate symptoms of stress. Due to the stress-immune system connection, it is also worth considering more lasting therapies for any trauma symptoms, such as EMDR, somatic therapy, or psychedelic-assisted therapy, where available legally or as part of a clinical trial.

Summary

As the world emerges from the acute phases of the COVID pandemic, many are still dealing with life-altering after-effects of a COVID infection. This area is getting a lot of research attention, and there are some things we already know from a functional medicine perspective that can help improve the function and quality of life of those struggling. 

Basic health-promoting lifestyle habits, reducing stress to the degree possible, and managing body systems that are not functioning in balance may all lead to significant improvements.