The functional medicine approach to chronic and acute COVID-19

Functional medicine is patient-centered, science-based, and about underlying causes, said Joel Evans, MD, at the 2022 Integrative Healthcare Symposium in New York City.

Evans, a board-certified OB/GYN, who is the chief of medical affairs at the Institute for Functional Medicine, talked about the functional medicine approach to chronic and acute novel coronavirus (COVID-19) on Saturday morning.

The functional medicine model, he said, uses a detailed understanding of each patient’s genetic, biochemical, and lifestyle factors and leverages that data to direct personalized treatment plans that lead to improved patient outcomes.

Genetics is very exciting, according to Evans. “It shouldn’t surprise you that genetics play a very important part in COVID-19. The problem is we don’t know what to do with that information, with the emphasis on, yet.”

He said genetics are important because it helps practitioners identify high-risk individuals and understand underlying mechanisms which assist in designing treatment plans.

There’s been a quest to find genes that drive severe COVID-19 and what’s emerged are genetic variants strongly associated with developing the virus and becoming very ill. People with a variant of chromosome 3 are twice as likely to be hospitalized with COVID-19, Evans said.

According to Evans, people are walking around with abnormal immune profiles, whether that’s due to a previous infection, virus, mast cell issue, or genetics.

Evans said an integrated network analysis shared new genes suggesting COVID-19 chronic effects and treatment. According to functional analysis, vascular remodeling and fibrosis could be possible long-term systemic effects of the infection.

When you look at areas where genetics are overlapping with COVID-19, there’s so many different areas, he said. “It gives me comfort to know there is a lot of research going on here.”

Genomic approaches have been used to identify disease susceptibility and severity in COVID 19.

Evans talked about structural variations, which are defined as genetic variants involving larger regions of an individual genome. As these remain difficult to detect, structural variations have not yet been investigated with respect to their relationship with COVID-19.

A multi-valent vaccine in development is based on genetics, he said, adding that long-term immunity to coronaviruses likely stems from T cell activity.

Evans then talked about biochemistry and comorbidities such as include cancer, chronic kidney disease, chronic obstructive pulmonary disease, an immunocompromised state from solid organ transplant, obesity, serious heart conditions, sickle cell disease, and type 2 diabetes mellitus.

Long-haul COVID-19 has similar biochemistry, he said.

He pointed to analyses of 10 longitudinal studies and electronic health records in the United Kingdom that revealed poor pre-pandemic mental health is associated with higher risk of long COVID-19, as is poor general health, asthma, and obesity.

“The presence of these comorbidities has to inform our decision-making, for prevention or treatment whether we’re talking about acute COVID or long COVID,” he said.

He said biochemical imbalances, such as mitochondrial function and oxidative stress, hyperglycemia, inflammation, and immune system function seen in those chronic diseases, must also inform clinical decisions for prevention and treatment for both acute and chronic COVID-19.

Practitioners also need to pay attention to lifestyle factors such as nonrestorative sleep, sedentarism, obesity, gut health, nutrition, stress, isolation and loneliness, smoking, and implicit bias, when treating and preventing COVID-19.

“There is such good data on lifestyle that you may not be aware of that I think will blow you guys away,” Evans said. “Everything here is so important.

He added that these lifestyle factors – every single one of them - are also associated with mitochondrial function and oxidative stress, hyperglycemia, inflammation, and immune system function.

Therefore, genetics overall health, biochemical imbalances and lifestyle are all interrelated when it comes to acute and chronic COVID-19, he said.

Evans then shared how to use this information to make personalized treatment plans. He said it’s important, to preemptively before infection, improve these biochemical imbalances.

He said integrative physicians need to work on reducing inflammation and oxidative stress, as well as addressing each of these lifestyle factors.  

For prevention of acute COVID-19 Evans talked about potential risk reduction from modifiable factors. He said if an individual doesn’t have one of the four major cardiometabolic risk factors – obesity, diabetes, hypertension or heart failure, there is a 64 percent of protection against severe disease. He said a vegetarian diet is also helpful in reducing risk in acute COVID-19.

Evans talked about a variety of supplements patients can be taking to lower their risk such as vitamin D, vitamin C, omega-3 fatty acids, curcumin, and quercetin.

When it comes to pre-exposure to acute COVID-19, Evans recommended practitioners address reducing viral exposure load, comorbidities, inflammation and oxidative stress, immune system resilience and resistance, and patients’ environment.

According to Evans, if a patient has been exposed to COVID-19 but not exhibiting symptoms, they should be taking melatonin, elderberry, resveratrol, curcumin, quercetin, epigallocatechin gallate (EGCG), leeks, and nettles.

Evans said that even though the Centers for Disease Control and Prevention said people should quarantine for five days if exposed to COVID-19, he uses 14 days in his personal and professional life.

Evans defined Post Acute Sequelae of SARS‐C0V‐2 (PASC) as a collection of symptoms during or following a confirmed or suspected case of COVID‐19 and which continue for more than 28 days. He shared statistics from a study conducted by the National Institutes of Health (NIH) that evaluated 3,700 international patients, mostly white females between 30 and 60 years of age, living in U.S. More than 50 percent never sought hospital care, only eight percent were admitted, and approximately 60 percent had symptoms for greater than six months.

When you talk to a patient you’ll know if they have long COVID or not, Evans said.

The most common symptoms of PASC include fatigue, post‐exertional malaise, and cognitive dysfunction. Exercise, mental activity, and stress were all triggers, which practitioners should be mindful of during treatment.

Evans said when people started running, symptoms got worse for people with COVID. He recommended patients don’t get back to exercising too quickly. “It’s really very mild stuff that they feel comfortable doing.”

Immune health is critical, according to Evans. If a patient doesn’t have any symptoms or a mild case, its because they have a robust immune response. He pointed to a study that concluded those that develop severe disease have an abnormal inflammatory immune response even at the time of diagnosis.

Common immunologic findings of severe COVID-19 infection include impaired interferon signature (Type I & III); neutrophilia; aberrant activation of monocytes/macrophages; T cell depletion (especially CD4+ and CD8+); depletion of NKT cells; T cell exhaustion (positive for markers PD-1, Tim-3); and elevated pro-inflammatory cytokines and other mediators such as bradykinin.

“We have known about this months ago, this is nothing new, but we have to keep speaking about it so that it catches on because what is important here is the invention you can do with simple lifestyle interventions and supplements, if necessary,” he said.

With PASC, immune recovery is complex with signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation. It’s this immune dysfunction that is associated with long COVID-19, he said.  

“Long-haulers represent a very significant public health concern, and there are no guidelines to address their diagnosis and management,” Evans said.

Evans also talked about vaccines. One study found that previous variants have shown protection against long-haul syndrome if vaccinated, by about 50 percent.

He said the functional medicine approach to PASC is reducing and resolving inflammation, optimizing mitochondrial efficiency, normalizing immune signatures, improving cell membrane and microvascular health, and ensuring gut health.

Evans stressed the importance of addressing patients’ unique vulnerabilities and consider dietary, lifestyle, pharmaceutical, nutraceutical, and botanical interventions where appropriate. This needs to be done in a way that is culturally appropriate and free of implicit bias, he said.

He closed his plenary with sharing his thoughts about the clinician as healer.

“Our patients are scared, they don’t tell us that directly, initially," he said. "They’re stressed, they’re not taking great care of themselves. We have to find a way to connect with our patients so that they will discuss these issues in an honest way and sometimes it will be the first time they are speaking about these issues out loud.”

In addition, Evans said the best way to get patients to get into that space of opening up is for practitioners to do this work themselves.

“I want to see more integrated practitioners,” he said. “We have to become integrated and do all we can do to achieve optimal health.”