Intro

Our world is facing an epidemic of Long COVID over the next decade. Assuming at least 10% of COVID-19 survivors develop long COVID, which is likely underestimated, it is estimated that 5 million people are facing long COVID globally. Long COVID affects multiple systems in the body and therefore requires a multidisciplinary approach. It is a shared opinion amongst several specialists that a functional medicine approach will be needed to rehab these patients back to health. While we are still in the beginning stages of understanding this chronic disease, there are some emerging ideas on how to treat Long COVID as well as some nutritional supplements that may offer a complete or partial solution.

Defining Long Covid

The now accepted technical name for Long Covid is Post Acute Sequelae of CO-V-2 (PASC). While a widely accepted definition is lacking, there seems to be some consensus on the approximate timing of symptoms and the type of symptoms common to a diagnosis of PASC. Onset is typically anywhere from 2-8 weeks after a confirmed or suspected COVID-19 infection and may persist up to 6-months or more. Common symptoms include: fatigue, dyspnoea (shortness of breath), cognitive dysfunction, headache, myalgia, chest pain, joint pain, smell and taste dysfunction, cough, hair loss, insomnia, wheezing, rhinorrhea, autonomic dysfunction (POTS), cardiac and gastrointestinal issues.

Risk Factors

Some of the clearly defined risk factors for developing long COVID include: More than 5 initial symptoms, initial disease severity, female sex, pre-existing comorbidity, prior psychiatric disorder, and old age. There are also certain biomarkers in blood samples that appear to have a correlation with Long COVID including: Increased levels of D-dimer, CRP, IL6, procalcitonin, troponin-1, BUN, neutrophils and decreased levels of lymphocytes.

Pathophysiology

Although the exact mechanisms behind what causes PASC in not completely understood recent research has pointed towards a few mechanisms. For some Long Covid sufferers there seems to be evidence of long term tissue damage in the cardiovascular, pulmonary and neurological systems. There is also prevalence of unresolved inflammation, viral persistence, gut dysbiosis and autoimmunity.

Treatments

The obvious question that everyone would like know is if there are treatment interventions to both prevent and alleviate the symptoms of PASC. The most conventionally accepted treatments thus far are: Personalized rehabilitation programs (light aerobic and breathing exercises), analgesics, antidepressants, ivabradine (for POTS like symptoms) and antihistamines. It is also accepted that treatment to regulate immune and mitochondrial function would be useful. This is perhaps where naturopathic and functional medicine can make an enormous impact.

There is emerging research looking into nutraceutical compounds to help prevent and treat PASC, here is an overview:

Mitochondrial Support: The mitochondria is an energy producing organelle within every cell of our body. In high school science we are taught that the mitochondria is the “power plant of the cell”. Disruptions in mitochondrial function can lead to fatigue, muscle pain, headache and immune dysfunction. COVID-19 infections seems to disrupt mitochondrial function through mechanisms still being investigated but include oxidative stress and alterations in genetic mutation.

Co-factor nutrients that help support mitochondrial function are being investigated for use in treating COVID-19 infection and PASC. These nutrients include: L-Carnitine, Alpha lipoic acid and Coenzyme Q10. A CoQ10 deficiency has been reported in COVID-19 patients and therefore supplementation with this particular compound is of great interest amongst researchers.

Inflammation: Inflammation seems to be driving a lot of the symptomatology in PASC. Inflammatory compounds have been identified in multiple organ systems including the brain, lungs, pancreas and heart. As such one natural anti-inflammatory compound has been identified as being a possible adjuvant therapy in both COVID-19 infection and PASC.

Curcumin is a compound derived from Turmeric and has anti-inflammatory, anti-viral, anticoagulant, anti-platelet and cytoprotective properties. There has been some evidence to suggest that 1000mg of a turmeric supplement restored smell and taste in individuals who lost these senses following COVID-19 infection. Furthermore in vitro studies have demonstrated that curcumin can inhibit coronavirus from entering the cell, and can disrupt some of the signing processes of the virus.

Immune System: Many of the complications of COVID-19 can be attributed to a dysfunctional response of the immune system, either over-reactive or under-reactive. Many compounds that have a direct and indirect role in proper immune system activity are showing promise in treating COVID-19 infection and PASC.

Vitamin D acts as an immune activity regulator, helping to both increase and decrease immune activity as is appropriate to the situation. Some studies have demonstrated that vitamin D supplementation after COVID-19 infection is associated with less ICU admissions and decrease mortality. Another study demonstrated that a combination of vitamin D, selenium and zinc was able to mitigate the course of respiratory complications with COVID-19 infection. It is likely that co-factors and nutrients which help support normal immune activity can shorten the duration of PASC and alleviate symptoms.

Gastrointestinal: Symptoms affecting the gastrointestinal tract are both common in COVID-19 infection and PASC. There is evidence that COVID-19 and its associated spike protein can persist in the gastrointestinal tract for months after confirmed infection.

Autoimmune type syndromes are commonly seen with PASC. One hypothesis for this outcome is a type of molecular mimicry between spike protein and healthy tissue. Spike protein can enter through a compromised digestive tract into the blood stream. Once in the blood stream the immune system can create auto-antibodies in response.

Maintaining a healthy gut/body barrier is emerging as a possible area of treatment in COVID-19 infection and PASC. A healthy environment of commensal bacteria strengthens the gut/body barrier as well as driving the production of healing compounds such as butyrate.

Butyrate is a short chain fatty acid that is produced by beneficial bacteria in our gastrointestinal tract. Butyrate can cross the blood brain barrier and influence regeneration of damaged nerve cells. Probiotic strains belonging to the Lactobacillus and Bifidobactrium categories are

essential for Butyrate production. While probiotic supplementation can assist in developing a healthy gut environment most of the benefit comes from eating foods which help these probiotics thrive. A diet rich in fibre and polyphenols is therefore essential in influencing the growth of beneficial butyrate producing probiotics. Fruit, veggies, and polyphenols like curcumin, luteolin and resveratrol are likely an important part of what will be a holistic approach to treating PASC.

Conclusions: The COVID-19 virus has turned out to be a multifaceted disrupter of homeostasis in a large percentage of those who have been infected. A functional medicine approach to treatment is likely going to have the most profound impact in addressing PASC. We are already starting to see some natural compounds (L-Carnitine, Alpha Lipoic Acid, Coenzyme Q10, Curcumin, Vitamin D, Selenium Zinc and probiotics) having an impact of this ill defined syndrome. More properly funded research in the area of nutraceuticals and functional medicine for treatment of PASC is much needed. In the meantime Naturopathic Doctors and Functional Medicine Physicians have many tools to start treating PASC with safe and effective protocols.

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