Written by Alison Proffitt
For the millions of patients still experiencing fatigue, brain fog, racing heartbeats, and a constellation of other symptoms months or years after contracting the coronavirus, Dr. George Schatz has a message: The rules of conventional medicine are not enough. He spoke last week Integrative Healthcare Symposiuma physician from the Andrew Weil Center for Integrative Medicine, has developed a multi-layered, systematic framework for understanding and treating long Covid, one that begins not with prescriptions, but with the roots of trees.
“When a tree starts to lose leaves, we don’t pick the leaves, paint them green, and stick them back on the tree with supplements and/or medications,” Schatz told the audience. “Sometimes we have to do it to relieve suffering – and that’s good in the short term – but we treat the roots of the tree.”
Root cause on symptom management
Schatz opened his talk by challenging the standard clinical approach to long Covid, arguing that the symptom-to-diagnosis-to-treatment model is failing these patients. A single individual can make dozens of diagnoses based on symptoms alone, while underlying drivers remain unaddressed, he said. Its alternative: a functional medicine approach that works backwards from symptoms through mechanisms to pathophysiology.
The clinical framework he described functions like a pyramid. First, he advised ruling out any significant diseases through laboratory workup. In his practice, he looks for organ dysfunction, unmasked underlying comorbidities, metabolic dysfunction, and autoimmune diseases.
Then build a foundation of the basics: sleep, stress management, diet, and movement. “These things are necessary for good health, but they are not sufficient,” Schatz stressed. “If you’re not sleeping eight hours a night, if you’re not moving your body, if you’re not managing stress — it’s going to be very difficult to help you, and there’s no way around that.”
He noted that he saw patients invest in expensive, sophisticated treatments that ultimately failed because the foundational work was never done. “They collapsed because they didn’t put the steps in first,” he said.
Middle classes: identifying root causes
Once the foundations are firmly in place, Schatz turns to identifying what he describes as the underlying mechanisms most prevalent in long Covid patients. Three phenotypes stood out in his clinical experience—all common but difficult to assess or treat: dysphoria or POTS, dysregulation of tryptophan metabolism, and mast cell dysfunction.
Postural orthostatic tachycardia syndrome, or POTS. One of the most common problems in his practice, Schatz said he rarely needs a formal tilt table test to identify POTS. If a patient has post-coronavirus fatigue and reports a dramatically elevated heart rate with activities like showering, “I’ve got this — let’s not waste time figuring out anything else except the subtype of POTS.”
He presented several patient cases where thiamine (vitamin B1) supplementation proved transformative. Drawing on the work of researchers Derek Lonsdale and Chandler Mars, Schatz described patients with hypovolemia, a subtype driven by thiamine deficiency that affects brainstem structures that regulate heart rate. He explained that the mechanism is that without adequate thiamine, the brain cannot metabolize glucose properly; The result is mitochondrial dysfunction, impaired autonomic reflexes, cerebral hypoperfusion, and ultimately the classic set of POTS symptoms. One patient experienced complete resolution of the tachycardia and associated symptoms within 2 weeks of starting thiamine supplements. Another, with overlapping EDS and mast cell activation, saw significant objective improvement in heart rate and even reversal of the diagnosis of heart failure after careful titration of thiamine doses.
“Not all thiamine is thiamine,” Schatz cautioned, noting that the most bioavailable form—lithiamin—is superior to standard formulations due to its superior absorption and ability to cross the blood-brain barrier. He uses thiamine therapeutically and diagnostically: if a patient improves by 50%, that pretty much tells him how much this mechanism has affected his image.
Mast cell activation. The second major phenotype addressed by Schatz is mast cell activation disorder (MCAD), which he said should be ruled out in long Covid patients — particularly because mast cell reactivity can prevent patients from tolerating other treatments. He described a simple clinical guideline for suspicion: symptoms extending across the skin (hives, facial flushing), respiratory (allergic reactions), and gastrointestinal (irritable bowel syndrome-like) symptoms together strongly suggest mast cell involvement. It relies heavily on clinical diagnosis and response to treatment rather than the cumbersome laboratory work traditionally required, and emphasizes low-histamine dietary approaches combined with targeted medications.
Dysregulation of tryptophan metabolism. In perhaps the most biochemically detailed part of the talk, Schatz described what he called the third most common phenotype: inactivation of the kynurenine pathway. Most people know that tryptophan is a precursor to serotonin and melatonin, but Schatz noted that only about 5% to 10% of tryptophan goes this way. The lion’s share, about 90%, goes towards NAD+ production via the kynurenine pathway.
He explained that in long Covid, viral infection and resulting immune activation upregulate the enzyme IDO (indoleamine 2,3-dioxygenase) in the periphery and TDO (tryptophan 2,3-dioxygenase) in the brain. This acutely shunts tryptophan toward the kynurenine pathway—and toward the production of quinolinic acid, a neurotoxin and NMDA receptor agonist. The result is brain fog, depression, nerve cell damage, and a depletion of both serotonin and melatonin. At the same time, the pathway becomes less efficient at producing NAD+, leading to a lack of cellular energy and extreme fatigue.
Elevated kynurenic acid levels are actually more predictive of long Covid than a positive antigen test, Schatz said, citing emerging research. The constellation of distinct clinical features—fatigue, brain fog, depression, and disrupted sleep—matches this biochemical picture almost perfectly.
His therapeutic approach targets multiple points in the pathway simultaneously: suppressing IDO/TDO activity with specific supplements and medications, including low-dose naltrexone, pushing tryptophan toward the serotonin/melatonin branch, raising NAD+ levels with precursors, and antagonizing the NMDA receptor to counteract the neurotoxic effects of quinolinic acid. Ketamine, which is increasingly used in long Covid clinics, works largely through this latter mechanism, he noted. Resveratrol has also been shown in his protocol for many patients, with notable improvements in fatigue and depression.
Putting It Together: Cases and Cautions
Throughout the conversation, Schatz discussed patient cases that demonstrated the strength and complexity of the framework. A college student suffering from brain fog and depression for two years saw significant improvement with supplements targeting the tryptophan pathway. A 46-year-old woman with fibromyalgia, worsening anxiety, low energy, and sleep disturbance responded quickly to a targeted supplement protocol that addresses the same pathway. A patient with EDS, mast cell activation, POTS, and liver complications — who couldn’t tolerate most treatments — finally found her footing when the mast cell reaction in her GI tract was addressed first, allowing her to tolerate everything else.
Ready meals
Schatz concluded by returning to the pyramid metaphor: Build from the bottom, one block at a time. Foundation work comes first, always. Then identify the root cause mechanisms—dysphoria, mast cell activation, and tryptophan pathway inactivation—that maintain the disease. Address these things specifically and systematically, and “you give the body enough of what it needs to be able to heal, and then you go from there.”
