SARS-CoV-2 infection, Post COVID-19 Symptoms and Acupuncture
By Joseph Audette, MD
There is a growing literature on persistent or long-haul post-COVID symptoms that can significantly impact quality of life. For example, data from the Assistance Publique–Hôpitaux de Paris in France has found that post-COVID symptoms tend to affect woman more than men (4:1 ratio), can occur without a previous significant medical history and are not associated with abnormal serological evidence of ongoing infection or immune activation such as elevated c-reactive protein or lymphocytopenia. Potential work up to exclude more serious issues could include COVID-19 serology, antinuclear antibodies to rule out an autoimmune reaction to exposure to the virus, a transthoracic echocardiography to rule out myopericarditis, as well a chest computed tomographic scan to rule out more concerning lung pathology.
The Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome created a post-acute outpatient service for patients discharged from the hospital for acute COVID-19. Patients were asked to retrospectively recount the presence or absence of symptoms during the acute phase of COVID-19 and whether each symptom persisted at the time of the visit. More than one symptom could be reported. The EuroQol visual analog scale was used to score quality of life from 0 (worst imaginable health) to 100 (best imaginable health) before COVID-19 and at the time of the visit. The mean time after recovery from the acute COVID-19 infection was 60 days and 87.4 % of the population reported the persistence of at least one symptom with the most common being fatigue and dyspnea. Among the 143 patients sampled, 44.1% reported that these persistent symptoms had a significant effect on worsening quality of life. Other symptoms that persisted included joint pain, chest pain, cough, anosmia, and sputum production.
The renin-angiotension (RAS) pathways play a critical role in both the acute respiratory distress of patients and potentially in the long haul symptomatology that many patients feel after clearing the virus. RAS is a known regulator of blood pressure but also plays a role in local tissue homeostasis. Angiotensin-converting enzyme (ACE) and ACE2 act to regulate a homeostatic balance in the system. When ACE predominates, pathological cell proliferation, inflammation, fibrosis and thrombosis predominate. In contrast when ACE2 predominates, there is activation of a protective pathway that stimulates the reduction in inflammation as well as anti-fibrotic and anti-thrombotic effects. Coronaviruses are classified into four different genus, in which 3 species (α HCoV-NL63, SARS-CoV, and SARS-CoV-2) have ACE2 as a receptor. SARS-CoV-2 (the virus related to COVID-19) has a longer incubation period in our cells, but then has a faster viral peak (3 days) after onset compared to the other Coronaviruses. This leads to a peak of viral load before symptoms become manifest and the immune response at this early phase is still low. This makes early disease identification difficult, and as a consequence, makes treatment with antivirals ineffective because the viral load has reached its peak before symptoms are manifest. Antiviral agents are best administered during the replication phase of the virus. The high replication capacity of SAR-CoV-2 is directly related to the coupling to ACE2 and cell infection. With this coupling, there is a concomitant reduction of ACE2 in the infected organs, tipping the balance towards the pathological consequences of ACE being predominant. The resultant hypoxia stimulates angiogenesis further altering the alveolar respiratory function. Hypoxia is also found to stimulate the hypoxia-inducible factor (HIF) that creates a feed forward vicious cycle, causing further shift towards the expression of ACE and inhibiting ACE2. The imbalance of ACE and ACE2 also has a primary role in inducing the uncontrolled inflammatory reaction to SAR-CoV-2 and subsequent cytokine storm seen in the severe cases of COVID-19.
The balance of ACE and ACE2 can also be affected by medical comorbidities and this may be involved in the increased risk for severe responses to COVID-19 infection in patients with diabetes, cardiovascular diseases, and obesity. A common finding in these patients is a higher expression of the protease ADAM17. ADAM17 has a pro-inflammatory and pro-fibrotic effect in chronic kidney disease as well as playing a key role in the ACE, ACE2 balance. It is responsible for the cleavage of the extracellular component ACE2 from the cell, leading to increase soluble ACE2 and decreasing the local tissue action of ACE2 to regulate and balance the pro-inflammatory activity of ACE.
From a Traditional Chinese Medicine (TCM) point of view COVID-19 infection is due to an invasion of pathological heat leading to the body’s response that includes four phases of the invasion of external pathogenic factors including activation of Defensive or wei qi, qi disturbance, nutrient or ying qi disturbance, and blood disturbance. Initially, the symptoms stay on the surface in the Tai Yang Zone with fever, headaches and sweating. Then, if the defensive qi is not strong enough to expel the pathogenic factor, the qi disturbance penetrates deeper affecting the Yang Ming Zone and causing symptoms in the lungs and intestines. Depending on an individual’s constitutional weakness, the lungs versus the intestines may be more or less involved. In this phase, the organ pathology is more functional and, although the patient may have many symptoms, the actual organ is not damaged. For example, imaging of the lungs would remain clear. The next phase is when the these layers of Qi defense fail and the nutrient or ying qi is affected, leading to more overt organ pathology. This is when the pathological heat is no longer kept at the surface of the body, but starts to invade more deeply to the organ level. This is when pneumonia develops and more serious respiratory issues that may require hospitalization and respiratory support. The fourth phase is when the heat invades the blood. This can be extremely serious and leads to the vascular and cardiac issues seen with COVID. From a TCM point of view, this would be viewed as a Liver disturbance with blood stagnation and blood heat. This is also when organ parenchymal damage occurs.
In the Wanzhou and Chongqing districts of China, a study analyzed cases of COVID-19. From a TCM point of view, presentations were characterized as an invasion of a damp heat with the development of “heat obstructing lung syndrome” (30%,), dampness obstructing syndrome (16%), and cold dampness stagnating lung syndrome (12%). The goal of treatment focused on strengthening the lungs and clearing heat and dampness with additional treatment focused on strengthening Qi and nourishing Yin.
From an herbal point of view, the Chinese national health commission issued a notice recommending a herbal preparation specifically targeted at COVID-19 called Qing Fei Pai Du Tang (QFPDT or QPT). Active ingredients in the concoction include quercetin, luteolin, kaempferol, naringin, and isorrine and preliminary studies show effects on a number of immune signally pathways including TNF and NF-kB which can act to inhibit the uncontrolled inflammatory response seen in COVID-19.
Some early retrospective data suggests that use of QPT during hospitalization of COVID-19 led to a lower morality (8939 patients included, 28.7% received QPT). The crude mortality was 1.2% (95% confidence interval [CI] 0.8% to 1.7%) among the patients receiving QPT and 4.8% (95% CI 4.3% to 5.3%) among those not receiving QPT.
From an acupuncture point of view, depending on the phase of infection, different point considerations are at play. In the acute phase, the goal is to expel the pathological heat and clear dampness so the lungs and other organs do not get obstructed. Treatment would focus on the Tai Yang and Yang Ming zones, using immune points such as Nagano’s tonsillar points LI 11, GV 14 and TW 16 to expel heat with KD 6, BL 23 and CV 6 or CV 4 to nourish and mobilize Qi. In addition, at every phase, the goal should be to nourish points for the lungs and digestive system such as LU 5, SP 6, CV 12 (Stomach Mu) and ST 36 (ST Qi line from a Japanese point of view) together with the Back Shu point for Lung and Spleen (BL 13 and BL 20).
If patients are struggling with an uncontrolled immune system or cytokine storm and excessive production of phlegm, then Spleen treatments can play an important role. From a TCM point of view, phlegm is a form of dampness and treatment of Spleen is very important to help with this issue. In addition, Spleen function is important to nourish the lungs and acts to prevent the excess release of cytokines, histamine and inflammatory mediators from cells (the holding function of Spleen in TCM). Often, if there is an associated sense of pressure or constriction in the chest over the Pericardium Mu point, CV 17, an important addition to Spleen is to add PC 6. This should relieve the pressure pain at CV 17 and the sense of chest tightness. A natural combination of Spleen and Pericardium is to use the coupled extra-ordinary vessel pairs of SP 4 (Command point of Chung Mai) with PC 6 (Command point of Yin Wei Mai). SP 4 is particularly useful to reduce excess production of phlegm. Also adding points such as SP 9 and ST 40 can help with phlegm and dampness. If the patient has the development of vascular issues including clotting, vascular swellings in the extremities, and so on, treatment of Liver and Blood Heat is important. Points such as LV 2 and SP 10 can be helpful from a TCM point of view, LV4 with LV8 can be used from a Japanese point of view (metal/water treatments for fire in meridian).
In the post-COVID state, the goal is to nourish the underlying weakness in Lungs and Kidney Qi and build energy by supporting the digestive function. An important consideration is to also help with tissue oxygenation. In the cases of patients with underlying issues of hypertension (HTN) treatment of this constitutional weakness is vital. Given the discussion above, this may have led to their extreme reaction to the COVID infection with the imbalance between ACE and ACE2. I have had the opportunity to work with Kiiko Matsumoto, a Japanese acupuncture master in the treatment of two severe post-COVID cases. Both had a history of renal hypertension with dysregulation of the renin-angiotensin system.
Both patients manifest tenderness in the Huato Jiaji area at the L1-2 levels, which from the Japanese point of view is a reflection zone of renal hypertension. From an anatomic standpoint, this is the level that the renal artery enters the Kidneys. Treatment focused on releasing that tenderness with HTN points including DU20 and DU19 needled against the flow of the meridian.
In addition, an interesting diagnostic region to determine if tissue level oxygenation is an issue is ST9. This point is at the level of the thyroid cartilage of the neck, medial to the SCM muscle, overlying the carotid artery. This reflex can be considered the carotid body/sinus reflex, which, from a physiological point of view, is involved with blood pressure regulation as well as monitoring blood oxygenation and CO2 levels. If tender, the treatment would be ipsilateral LI 4 and LU 8.
In conclusion, medical acupuncture is a safe and potentially helpful tool to use with patients both during the acute phase of the illness as well those suffering from post-COVID symptoms. More research is needed to demonstrate efficacy, but early data from China and personal experience suggests that this can be a powerful tool to help our patients regain quality of life and rid themselves of lingering effects of the COVID-19 infection.
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