tsunninleemd

Dated: April 21, 2020

by Tsun-Nin Lee, M.D.
Director
Academy of Pain Research
April 20, 2020

Introduction

The attached video report on the application of traditional Chinese medicine (TCM) therapeutics in the treatment of COVID-19 infections in China has placed TCM in a positive light (https://vimeo.com/academyofpainresearch/review/407254717/299bddab9c) Unfortunately, it lacks specifics that would allow a modern physician to apply the information clinically. Furthermore, highly potent and lifesaving TCM therapeutics have taken a backseat in managing critically ill patients, according to the report. Another deficiency is the report’s failure to outline a clear-cut and overall credible strategy to combat this deadly disease with TCM. Though it mentions a number of treatment formulae in mild to moderate cases, it does not include a unified approach to dealing with the pathophysiology of COVID-19 illnesses, which is one of the important foci of the following article.

Discussion is raging on regarding the treatment for COVID-19 infections, generally focusing on two known solutions: antiviral medications and vaccines, both of which require a long time to develop. However, in the battle against COVID-19, time is of the essence. TCM-based therapies have been available for millennia against infectious diseases during past epidemics. Approximately 1,800 years ago in the Eastern Han Dynasty, Zhang Zhong Jing (張仲景) was the taishou (太守, equivalent to the position of mayor) of today’s Changsha in Hunan. Despite his prominent social status, he had to watch helplessly as almost one-third of his clansmen died in a rampaging epidemic. This family tragedy prompted him to learn everything he could about medicine, eventually making him the most respected physician in the long history of China. Zhong’s extensive clinical experience and highly systematic and analytical approach to various infectious diseases and chronic medical conditions culminated in the compilation of his clinical findings and therapeutic methodology in 傷寒論 (Cold Injury Thesis), from which many herbal formulae are still widely used today. Unfortunately, despite the plethora of knowledge accumulated by numerous prominent physicians throughout the ages in the treatment of clinical syndromes caused by infectious diseases, these highly effective tools have fallen by the wayside with the advent of antibiotics, to the distinct disadvantage of modern societies.

There is no reason that Chinese herbal medicine and modern therapeutics such as the use of antibiotics cannot be integrated for the greater good of patients, especially at this critical juncture when no effective antiviral medications have been proven effective. The substrate of Chinese medicine in the treatment of infections is not the invading organisms themselves, but rather the host’s response to those infections. In other words, its main action is to stimulate the body’s own immune system to fight off the infective agents. Exactly how is this priming of the immune system accomplished? What are the physiological mechanisms involved? Based on my theoretical work, TCM’s therapeutic modalities, which include acupuncture, moxibustion, and herbal medicine, are all acting directly on the central nervous system, which in turn modulates the immune system to focus its attack on the invading microorganisms such as bacteria and viruses. The mechanism of action may be explained in a somewhat simplistic manner as follows. The therapeutic formula is not meant to kill the infective agents directly, but rather to direct the host’s natural defenses to do so. Unlike in a real battle, it does not bring tanks, artillery, smart bombs, cruise missiles, or troops to the war theater. Rather, the formula functions more like a team of military advisors who know the enemy’s exact game plan. The team will anticipate the enemy’s next point of attack to direct the body’s armed forces to hold the line, thwarting its advance. Anticipating the enemy’s strategy allows the formula to direct the body’s immune system to mount effective counteroffensives. The TCM treatment, though not a vaccine, behaves like one. Vaccines enable the host to recognize the enemy early on and mobilize the body’s countermeasures against it. Without the vaccine or any kind of TCM intervention, the body is at a loss, not knowing how to react to the enemy’s onslaughts. It will take a considerable amount of time to learn about the enemy’s tactics before it can coordinate its efforts against it. On the other hand, both vaccines and TCM formulae are capable of coordinating the body’s defense intelligently, shortening the reaction time to put a stop to the enemy’s advance at an early stage. As Sunzi says in the Art of War, “知彼知己，百戰不殆,” or “Know thy enemy. Know thyself. Victorious always.” To gain further insight into the tremendous potential of TCM in the treatment of COVID-19 infections, let’s take a closer look at the first component of the motto, “Know thy enemy.”

COVID-19 is a Yin Virus

COVID-19 is yin in nature because it likes a cold and wet environment. To ensure its survival, it has the proclivity to induce and maintain a cold environment in the host to allow it to thrive and propagate its species. Individuals with a yin, or cold and wet, constitution are the ideal hosts for the virus. Individuals of advanced age, especially with comorbidities such as chronic kidney diseases, diabetes, and cardiovascular conditions often suffer from yang deficiency states and are particularly prone to contracting COVID-19 pneumonia because their bodies’ conditions are ideally suited for the virus to thrive in. As the virus expands its territory, the host’s condition continues to deteriorate; cold begets cold and wet begets wet, eventually causing the host’s demise. The yin nature of COVID-19 is also evident by its prolonged survival on cold objects such as metallic surfaces and its destruction when the environmental temperature exceeds 57ºC, as well as the explosive number of cases in Wuhan in the depths of winter.

Due to its yin nature, the COVID-19 virus is rather sneaky; it can be waiting in the wings for quite some time before it rears its ugly head, sometimes after a prolonged incubation period. In some cases, the test for COVID-19 may turn positive again in patients who have recovered from the acute phase, once again affirming its covert or yin nature. My guess is that it may even have the potential to linger in the body indefinitely, just like the hepatitis B or hepatitis C viruses, though this hypothesis has not yet been proven. It can be quiet and indolent for a long time, as in the case of tuberculosis, which can lay dormant for a very long time, only to reactivate and attack when the host becomes weak or immunosuppressed. Hence mycobacteria tuberculosis also behave as yin organisms.

The COVID-19 Virus Produces and/or Aggravates the Wetness or Dampness Syndrome

It has been observed on the frontlines by many critical care clinicians that COVID-19 victims often behave as if they were suffering from high altitude pulmonary edema (HAPE) rather than acute respiratory distress syndrome (ARDS). High altitude sickness is a yang deficiency state because oxygenation is an energy-producing process—a yang process, so to speak—making a lack of oxygen equivalent to a lack of yang. This yang-deficient (yin-dominant) state is characterized by excessive water (a yin element) that gravitates toward the lungs (a yin organ), causing the patient to drown in his own fluids, leading to pulmonary edema. There is little wonder that coca, a local remedy for high altitude sickness in the Andes in Peru, is a yang-promoting substance, whereas Diamox, a modern medication used as a diuretic, is employed for the same purpose: getting rid of the water (yin) to preserve the yang. The following is a brief summary of the work done by Professor Liu Liang (劉良), Department of Forensic Medicine, Tung Ji (同濟) Medical University, who performed autopsies on patients who died from COVID-19 infections in China. According to a published report in the Journal of Forensic Medicine in China entitled “General Observations from the Post-Mortem Examination of COVID-19 Patients,” the lungs of those who died from COVID-19 pneumonia are filled with grayish white exudate on the dissected surface of the lungs, and the bronchioles are filled with tenacious fluid that plugs up the alveoli where gas exchange normally takes place, thereby preventing oxygen from being transported. The report further observes that the use of mechanical ventilation forcing oxygen into the lungs may have resulted in pushing the fluid into the lung tissues to obstruct the small airways and alveoli. This observation seems to be in agreement with the opinion of many frontline clinicians in the West that regular protocols for mechanical ventilation may not be appropriate—and may have actually resulted in a high mortality rate of patients on respirators. According to the teachings of TCM, COVID-19 pneumonia is characterized by shortness of breath due primarily to the excessive production of phlegm, which should be removed by phlegm-dispersing herbal formulae.

A Brief Primer on Cold Injury Thesis and the Five Elements Theory

To have a sensible discussion about TCM’s approach to illnesses caused by COVID-19, it is necessary to have a basic understanding about the Cold Injury Thesis, which considers the body to be composed of six different divisions, physiologically functioning like layers from outside to inside, each containing various quantities and qualities of yin and yang. Beginning from the body’s exterior, the divisions are named as follows:

1. Tai Yang (Greater Yang) 太陽
2. Shao Yang (Lesser Yang) 少陽
3. Yang Ming (Radiant Yang) 陽明
4. Tai Yin (Greater Yin) 太陰
5. Shao Yin (Lesser Yin) 少陰
6. Jue Yin (Extreme Yin) 厥陰

These dividing layers may also be viewed as lines of defense. As the pathological force advances in many infectious processes, the lines of defense may fall one by one, leading to the eventual demise of the host. An assault on any division will manifest specific symptom complexes. Equally specific remedies can then be administered to win back the lost territories. Infective agents may target one layer at a time, or more than one layer simultaneously, sometimes posing diagnostic challenges. These six divisions, in modern medical terms, are likely to represent the body’s systematic and specialized neuroimmunoendocrinal responses to infections.

Another important fundamental principle of TCM is the five elements theory, which essentially defines the pathophysiological functions of each organ system by assigning an element to it to illustrate the regulation of interactions among these organ systems according to the concept of the generation cycle—water generates wood, which generates fire, which generates earth, which generates metal, which generates water—versus the suppression cycle — water suppresses fire, which suppresses metal, which suppresses wood, which suppresses earth, which suppresses water. For instance, liver excess (wood) may cause extreme anger, generating over-activities in the heart (fire), leading to rapid heartbeats and high blood pressure that are often found in Grave’s disease (hyperthyroidism). Too much wood (liver excess) can also suppress earth (stomach), as anger can also lead to a gut-wrenching experience, literally. The five elements are merely symbols embodying the rules governing the processes of excitation and inhibition among the body’s different physiological and organ systems.

The Target Organ System of the COVID-19 Virus

Professor Didier Raoult, the French physician who performed the initial clinical study using a combination of hydroxychloroquine and azithromycin to treat COVID-19 pneumonia, reported significant improvement in patients on this regimen, although the rationale behind its efficacy has not been adequately elucidated. Hydroxychloroquine, a medication originally used for the treatment of malaria, is also used to treat rheumatoid arthritis, lupus, and other autoimmune conditions. It is interesting to note that both rheumatoid arthritis and lupus are cold and wet conditions according to TCM analysis, primarily affecting patients with excessive elements of water and wood in their constitution, where water represents the kidney system and wood the liver/gallbladder system. Malaria or malaria-like illnesses are typical of disease states of the shao yang (lesser yang) system, which also belongs to the wood element, which in turn represents the liver/gallbladder system. A prominent feature of malaria is alternating hot and cold, or fever and chills. According to an old adage of TCM, “無痰不成瘧,” that is “If there is no phlegm, there can be no malaria-like disease.” Based on TCM analysis, hydroxychloroquine may very well have a regulating effect and phlegm-dispersing characteristics for the shao yang (liver/gallbladder) system, and that may explain why it is efficacious in the treatment of a variety of medical conditions, such as rheumatoid arthritis and lupus, that also feature excessive phlegm in the liver/gallbladder system. A typical shao yang disease usually presents with one or more of the following symptoms: dry throat, bitter taste in the mouth, pain in the thorax, cough, shortness of breath, or alternating fevers and chills. When qi, or energy, is excessive in the water (kidney) and wood (liver) elements systems, the gastrointestinal functions represented by the earth element will be suppressed, because wood suppresses earth. Diarrhea is also present in some cases, and about 20% of COVID-19 patients may experience a transient loss of taste, a clinical sign that the gastrointestinal functions (the earth element) have been impaired. Therefore, hydroxychloroquine need not have the ability to kill the virus as long as it has the capacity to regulate the liver/gallbladder system, thus making the internal environment inhospitable to the viral invaders. This inhospitable environment will frustrate the virus’s attempt to grow and multiply. And to be therapeutic, these medications do not even have to possess any invitro activities against the virus. As a matter of fact, early treatment with TCM herbal formulae can frequently prevent mild cases from progressing to more severe cases, using the lung-clearing toxin eliminating decoction that combines the following four formulae derived from the Cold Injury Thesis:

1. 麻杏石甘湯: Ma huang almond ginseng licorice decoction, to expel heat from the lungs
2. 小柴胡湯: Bupleurum minor decoction, to regulate the shao yang system
3. 五苓散: Five ling powder, consisting of five separate ingredients, to rid the body of excessive phlegm
4. 射干麻黃湯: She gan ma huang decoction, to suppress heat in the lungs

My criticism about these formulae is that they are not sufficiently tonifying and not warming enough because the majority of COVID-19 patients are qi-deficient and cold. While hydroxychloroquine appears to be effective on its own, the French study suggests that combining it with azithromycin may be even more effective. Examining the effects of azithromycin from the standpoint of TCM, one can understand why it may work in this situation, whether or not it possesses any antiviral properties. Azithromycin, or macrolides as a class, may be used to promote gastrointestinal motility; hence it may be regarded as a tonifying agent for the gastrointestinal system (the earth element), enhancing its abilities to stand up against the liver/gallbladder system (wood). Consequently, the combination of hydroxychloroquine and azithromycin will create an internal environment much less favorable to the virus, preventing it from overwhelming the host’s defenses. This simple theoretical framework adequately explains why the combination may be effective. More importantly, this therapeutic concept may be extrapolated to include a whole host of treatment avenues comprising the TCM armamentarium. In other words, in this particular clinical setting, these modern drugs are being used like herbs in TCM and not as antiprotozoals (hydroxychloroquine) and antibiotics (azithromycin) in modern medicine.

Expanding the Armamentarium with TCM Approaches

Now that we have a fair understanding of the enemy, including its tactics, we should take inventory of our weaponry to better adhere to the second part of Sunzi’s motto “Know thy enemy, know thyself” and win the war. Accordingly, our strategy is as follows:

I. Herbal formula to warm up the body
II. Herbal formula to rid the body of excessive fluid or phlegm
III. Tonifying formula to strengthen the qi
IV. Herbal formula to control, regulate, or suppress the excess in the liver/gallbladder
system (wood)
V. Tonifying formula for the gastrointestinal system (earth)

The formulae above may be combined or administered separately. The following TCM herbal formulae are generally safe and effective, if properly prescribed and administered:

I. True martial decoction (真武湯) for its warming effect
II. Rehmannia eight (金匱腎氣湯) for tonification or both yin and yang
III. Bupleurum minor (小柴胡汤) or chai hu, gan jiang, gui zhi decoction
(柴胡桂枝干姜湯) to regulate the liver/gallbladder system
IV. Six gentlemen decoction (六君子湯) to tonify the GI functions and to disperse phlegm

There are, of course, additional potent formulae for the critically ill, including ma huang fu zi xi xing decoction (麻黃附子細辛湯) and green dragon minor decoction (小青龍湯) for wet lungs. The greatest utility of these formulae from the Cold Injury Thesis may be applicable for certain critical conditions of COVID-19 pneumonia. Unfortunately, these have not been adequately deployed to combat the recent COVID-19 pandemic, essentially squandering the precious knowledge painstakingly assembled by Zhang Zhong Jing, who was canonized as the Saint of Chinese medicine.

Additional Observations

Quite a number of frontline clinicians utilizing mechanical ventilation to treat COVID-19 pneumonia have experienced disappointing results, marked by a high mortality rate. The following factors should be considered.

First, high pressure ventilation may cause injury by pushing the mucus deep into the lung tissue or drying up the mucous, making it more tenacious and further preventing gas exchange. Second, the respiratory drive is usually controlled by the rhythmic neural circuit within the brainstem, characterized by its own unique rhythm. If the respirator’s breathing cycles are not synchronized with this internal rhythm, usually in the pressure control or volume control settings, they may impede the internal qi, causing disruption to the body’s natural rhythm and resulting in more harm than good. Third, heavy sedation is often prescribed to reduce the anxiety of intubated patients. Unfortunately, all sedatives are cold in nature, suppressing neural activities in the brain and thereby disabling the central command that plays a crucial role in coordinating various bodily functions to achieve a better internal environment, which is essential in winning the battle against the marauding viral invaders.

Other treatment modalities that can stimulate the body’s immune system to defend against COVID-19 should also be employed. AuricuLeetherapy, a unique proprietary therapy in which points on the ear are injected with minute amounts of medications, may also be called into action. There will be more on that subject in future communications.

Designing a Therapeutic Protocol for Clinical Trial Using Traditional Chinese Medical Agents

Based on the discussion so far, the main therapeutic strategy is to tonify the gastrointestinal system and regulate the liver/gallbladder system to harmonize the internal environment, making it less favorable to the survival of the virus. There is a reasonable probability that the combination of hydroxychloroquine and azithromycin may accomplish this goal. However, concerns may be raised about the side effects of these medications. From my own analysis, excessive wood and water are a common finding in the constitutions of patients suffering from rheumatoid arthritis, lupus, or type 2 diabetes. Surprisingly, in a recent clinical trial conducted in India, hydroxychloroquine used for the treatment of type 2 diabetes was found to be more effective for glycemic control and weight loss than the recently developed type 2 diabetes drugs DPP4 inhibitor and SGLT2 inhibitor. Based on the very same theoretical model, it may be possible to substitute artemisinin for hydroxychloroquine. Artemisinin is a derivative of the Chinese herb qinghao, which was used to treat malaria as early as two thousand years ago. Tu Youyou shared the 2015 Nobel Prize for her discovery, isolation, and application of the chemical compound qinghaosue (qinghao extract) in the treatment of malaria. On the whole, it is more effective than the other antimalarial drugs and is now the first-line treatment for falciparum malaria. This drug has a favorable side effect profile, yet it is more potent than hydroxychloroquine. Additionally, it will only be used for the short term in the treatment of COVID-19 pneumonia, mitigating some of the worry about its long-term effects. Azithromycin, on the other hand, is being used as a tonifier for the gastrointestinal system and thus may be substituted for with the six gentlemen decoction, or girotate, both of which possess warming, tonifying, and phlegm-dispersing functions, at the same time reducing GI upset, a common side effect of artemisinin. By simply adjusting the dosages of these formulae, they may be used to treat COVID-19 infections of varying degrees of severity. After all, the currently available treatments for gravely ill patients are only supportive in nature, with both patients and doctors forced to wait for the patients’ own immune response to kick in. Unfortunately, the efficacy of that immune response is not a given. On the other hand, if the above theoretical model is correct, significant clinical improvement should be discernible within a few days. The potential for harm with these generally safe therapeutic agents is unlikely, while the potential benefits may include reduced severity of illness, shortened hospital stays, and, most importantly, life-saving results for many.