Properties of the Novel Chinese Herbal Medicine Formula Qu Du Qiang Fei I Hao Fang Warrant Further Research to Determine Its Clinical Efficacy in COVID-19 Treatment

Introduction

Coronaviruses, including severe acute respiratory syndrome-related coronavirus (SARS-CoV)-2, cause acute and chronic respiratory, enteric, and central nervous system diseases in many species, including humans. ¹ Initially tentatively named 2019 novel coronavirus (2019-nCoV), the virus has now been re-named SARS-CoV-2 by the International Committee of Taxonomy of Viruses (ICTV). ² The genome sequences of SARS-CoV-2 shared 79.5% sequence identity with SARS-CoV. ³ SARS-CoV-2 invades the respiratory mucosa and infects other cells, inducing systemic cytokine storms. ⁴ “To date, there is no specific medicine recommended to prevent or treat the novel coronavirus.” ⁵ Due to the rapid spread of SARS-CoV-2 through human-to-human transmission, the number of cases currently continues to rise. Considering the homology of SARS-CoV and SARS-CoV-2, the prior use of Chinese herbal medicine (CHM) in response to SARS-CoV identified naturally occurring compounds with the capacity to inhibit SARS-CoV-2. ⁶

In China, herbal preparations were successfully used in conjunction with modern medical treatment during the 2003 severe acute respiratory syndrome (SARS) outbreak. The use of Sang Ju Yin and Yu Ping Feng San in May of 2003 dramatically reduced the Beijing fatality rate from an initial 52% down to 4% and then 1% within 15 days by modulating T cells and enhancing host defense capacity. ⁷

As these strategies were highly successful, they were repeated in Wuhan, China, at the outset of COVID-19. Due to the absence of specific antiviral therapeutics or a vaccine, the primary treatment strategy for COVID-19 has consisted of supportive care, supplemented by a combination of broad-spectrum antibiotics, antivirals, corticosteroids, convalescent plasma, and CHM ⁶ (Table 1). In controlled clinical studies, supplementary treatment with CHM resulted in marked improvement of symptoms and shortened disease course. As a result of these studies and the obvious success of CHM, more than 85% of patients with COVID-19 in China are receiving CHM treatment. ⁶

Evidence Supporting The Efficacy of CHM

The use of CHM to prevent epidemics of infectious diseases can be traced back to ancient Chinese practices cited in Huang Di's Internal Classic (Huang Di Nei Jing), where its preventive effects were recorded around 2600 BC. ⁸ The famous doctor Sun Si-Miao (541–682 AD) commented on the use of herbal medicines to prevent “pestilence” in his book, Essential Prescriptions Worth a Thousand Gold for Emergencies. He stated that “pestilence comes from nature, so to prevent it, we need to find medicinal herbs that also come from nature. People would not be infected if they know and take preventive medicine.” ⁹ The 2019-20 Chinese National Plan guided the clinical practice of COVID-19 Traditional Chinese Medicine (TCM) treatment in the early stages of the outbreak. A lung cleansing and detoxifying herbal decoction was listed as the first choice among the TCM agents. Liquid herbal decoctions were used to reduce fever, cough, shortness of breath, and gastrointestinal symptoms. ¹⁰ There is often not enough information to determine whether specific herbs or herbal combinations can directly target a virus because herb usage is generally not guided by viral pathology. However, several Chinese medicinal herbs were classified in cited research that confirmed antiviral effects that may directly inhibit the novel coronavirus, SARS-CoV-2. ¹¹ In addition, these herbs play therapeutic roles in suppressing virus and reducing inflammation indirectly through regulating immune system function and modulating cytokine production.

A recent systematic review suggested that “based on historical records and evidence of SARS and H1NI influenza prevention, CHM could be an alternative approach for the prevention of COVID-19 in high-risk populations.” The suggestion is confirmed by 3 SARS prevention studies and 4 H1N1 studies, which concluded that participants who took CHM did not contract SARS and had a lower H1N1 infection rates, respectively. ⁸ Historically in China, at the outset of an outbreak, TCM-recommended approaches included oral administration of preventive herbal formulas, wearing TCM sachets, indoor herbal medicine fumigation, t'ai chi, medical Qigong, acupuncture, tuina, ear acupuncture points, and acupressure for prevention and treatment.^10,12

In the early stages of COVID-19 treatment, CHM was utilized to reduce fever, cough, shortness of breath, and gastrointestinal symptoms. ¹³

The primary TCM treatment principles used to address these symptoms in both the 2003 SARS epidemic and COVID-19 are to tonify qi, protect the organism from external pathogens, disperse wind and discharge heat, and resolve dampness (Table 2).^14–16 According to recent studies, the most frequently used herbs used to tonify qi, disperse wind, discharge heat, and resolve dampness include Radix Glycyrrhizae (Gan Cao), Rhizoma Atractylodis Macrocephalae (Bai Zhu), Lonicerae Japonicae Flos (Jīn Yín Huā), and Fructus forsythia (Lian Qiao). ¹⁷ Astragali Radix (Shēng Huáng Qí) and Saposhnikoviae Radix (Zhì Fáng Fēng) are the key ingredients in Yu Ping Feng powder (YPFP), a formula proven to exert antiviral, anti-inflammatory, and immunoregulatory effects. ¹⁸ YPFP has been shown to have a direct effect on tumor necrosis factor-α (TNF-α), interferon gamma (IFN-γ), interleukin-1β (IL-1β), and IL-4. ¹⁹ Lonicerae Japonicae (Jin Yin Hua) and Forsythiae Fructus (Lian Qiao) are the core components of Yin Qiao powder (YQP), another ancient classical formula used to prevent and treat respiratory infectious diseases. ²⁰ YQP was also found to prevent and treat upper respiratory tract infection due to its antibacterial and antiviral properties. ²¹ An experimental study found that the effect of YQP in preventing and treating upper respiratory tract infection could be explained by its antibacterial and antiviral properties and improvement of the function of upper respiratory mucosal immune system. A multicenter large-scale randomized trial found that YQP combined with another heat-clearing formula could reduce the time to fever resolution in patients with the H1N1 influenza virus infection. ²²

Resistance to bacteria and new emerging microorganisms is an additional problem increasing with a lack of effective antibiotics. ²³ CHM has demonstrated tremendous therapeutic effect with minimal side-effects when used as an antimicrobial and anti-inflammatory. Inflammation is an aspect of the immune response that can prevent infection through production of proinflammatory cytokines and generation of inflammatory mediators in response to microbial products. ²⁴ Currently the treatment of inflammatory disorders involves extensive use of nonsteroidal anti-inflammatory drugs and corticosteroids. As inflammation is the result of various mediators, CHM uniquely exerts anti-inflammatory effects through various mechanisms of action, including inhibition of inflammatory cytokines and mediators, blocking of inflammatory signaling, and interference with chemokines. CHM has also demonstrated antimicrobial effect through inhibition of microbial adherence to mucosal or epithelial surfaces, inhibition of endotoxin shock, and selective inhibition of microbial growth. ²⁵

QŪ DÚ QIÁNG FÈI I HÀO FĀNG

The herbal formula presented for consideration in this article, Qū Dú Qiáng Fèi I Hào Fāng “Eliminating Virus and Strengthening Lung—No.1 Formula,”(QDQF1) is a novel formula from the Institute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine. QDQF1 uses many of the herbs in YPFP and YQP, along with a few key herbs tailored to specific 2019-nCoV symptoms recorded by the World Health Organization (WHO) and the Centers for Disease Control (CDC). QDQF1 contains a variety of ingredients that, when blended, exert synergistic effects on the body due to their individual properties and the combination thereof. This formula contains herbs widely used to tonify qi and protect against external pathogens. The individual properties of each herbal ingredient in the formula QDQF1 are discussed and presented for further study.

ASTRAGALI RADIX (HUÁNG QÍ)

Astragali Radix (Huáng Qí) tonifies qi and blood, raises Yang qi, boosts the protective qi, and secures the exterior, reduces edema, promotes the discharge of pus, and tissue regeneration. ²⁶ Huáng Qí has been shown effective against Japanese encephalitis virus, increases antibody production of spleen cells, and increases IgM antibody production.^27,28 Huáng Qí has been shown to inhibit hepatitis B virus activities. ²⁹ Huáng Qí is an immunoregulator, it exerts immunomodulatory effects by regulating the expression of cytokines such as IL-1, IL-1, IL-6, and inducible nitric oxide synthase (iNOS) as well as the production of nitric oxide (NO). Huáng Qí has been used clinically, medicinally, and traditionally to treat symptoms such as weakness, fever, anemia, loss of appetite, chronic fatigue, chronic phlegmatic disorders, and bleeding. It enhances physical strength and endurance, inhibits liver fibrosis by reducing TNF- and TGF-1 production, and by scavenging active oxidants in activated Kupffer cells. ³⁰

RADIX LEDEBOURIELLAE DIVARICATAE (ZHÌ FÁNG FĒNG)

Radix Ledebouriellae Divaricatae (Zhì Fáng Fēng) is used to treat wind; it can treat all wind patterns, hot or cold, upper or lower body, exterior or interior. ³¹ By expelling wind, it treats cold and damp conditions such as the common cold, headache, body aches, spasms, and stiff neck. Fáng Fēng is commonly used in the treatment of arthralgia, rheumatism, stroke, headaches, fever, cold, and diarrhea. It is also an anticonvulsant, analgesic, anticancer, anticoagulant, anti-inflammatory, and antipyretics. ³² It was determined that one of the major active constituents of Fang Feng has anti-inflammatory potential in lipopolysaccharide (LPS)-activated Raw 264.7 cells through suppressing the activation of JAK2/STAT3 signaling and through inhibiting the expression of iNOS and COX-2. ³³ Fáng Fēng has also been shown to have an effect on the reticuloendothelial system by increasing the phagocytic index. In another study, antimicrobial and antioxidant activities were documented, as well as antifungal, antibacterial, antirheumatoid, and tumor cell growth inhibitory effects. ³⁴

LONICERAE JAPONICAE (JĪN YÍN HUĀ)

Lonicerae Japonicae (Jīn Yín Huā) clears heat and resolves toxicity, for hot painful sores and swelling in various stages of development, especially of the breast, throat, or eyes, and for intestinal abscess. ³⁵ Also for the treatment of infection by exopathogenic wind-heat or epidemic febrile diseases at the early stage, sores, carbuncles, furuncles, and swellings. ³⁶ Lonicerae Japonicae clears heat and toxins and drains pus and promotes healing. Red, sore, swollen, or inflamed eyes and throat, and abscesses of the lung are treated with Jin Yin Hua. ²⁵ Lonicerae Japonicae also promotes sweating in cases of acute wind-heat, cold and flu with fever, chills and fever, sore throat, and headache. Jin Yin Hua nourishes blood and relieves thirst. While this effect is mild, it is useful to acknowledge as it is indicated in heat toxicity with deficiency, a common COVID-19 TCM pattern. ²⁵ It is also effective for acute wind-heat with thirst. Jin Yin Hua possesses biological and pharmaceutical properties such as antioxidant, antiangiogenic, antipyretic, antidiabetic, antibacterial, anti-inflammatory, antitumoral, antiviral, antiangiogenic, hepatoprotective, and antinociceptive activities. ³⁷ Studies have shown its chemical components to have inhibitory actions on viruses including adenovirus, mice influenza virus, respiratory syncytial virus, herpes simplex virus 1 (HSV1), coxsackievirus B3, and parainfluenza. ³⁸

FRUCTUS FORSYTHIAE (QĪNG LIÁN QIÁO)

Fructus Forsythiae (Qīng Lián Qiáo) clears heat and relieves toxicity for externally contracted wind-heat. ³⁵ Its function is to clear heat and detoxify, addressing symptoms of high fever, slight chills, and sore throat. Qing Lian Qiao reduces abscesses and dissipates clumps, sores, swellings, lung abscess, scrofula, and also clears blood heat. Modern pharmacologic studies have confirmed that Forsythiae Fructus possesses anti-inflammatory, antioxidant, antiviral, antivomiting, and antitumor activities, antiemetic, and diuretic effects, as well as choleretic, antipyretic, hepatoprotective, neuroprotective, and cardiovascular protective effects. ³⁹ It also suppresses influenza A virus-induced RANTES secretion by human bronchial epithelial cells to stop accumulation of inflammatory cells in the infective sites, which has been reported to play a crucial role in the progression of chronic inflammation and multiple sclerosis after viral infection. ³⁸

GLEHNIA ROOT (BĚI SHĀ SHĒN)

Glehnia root (Běi Shā Shēn) clears lung heat, nourishes Lung Yin, and generates stomach fluid. ³⁵ It is included for its ability to tonify Yin and affect the lung and the stomach channels. It also nourishes the lungs and stomach, clears lung heat, and generates body fluids. Glehnia root is indicated for treatment of dry nonproductive coughs from heat injuring the Lung Yin. It is used as a traditional herbal medicine for the treatments of cough, phlegm, sore throat, lung abscess, chest pain, dysuria, and dysentery. Běi Shā Shēn is used for its antioxidant, anti-inflammatory, and immunomodulatory properties. Traditionally it has been used for its diaphoretic, antipyretic, antiphlogistic, and analgesic properties. The active components have been identified as quercetin, isoquercetin, rutin, chlorogenic acid, and caffeic acid. ⁴⁰ Studies have shown anticancer, anti-inflammation, and antiviral properties as well as the potential for cardiovascular protective properties.^41,42 In a separate study, antibacterial and antifungal properties were studied. ⁴³ Another study shows the ability to block the protein expression of iNOS and COX-2 in LPS-stimulated RAW265.7 macrophages significantly. Antioxidant, erythrocyte hemolysis inhibition, and lipid peroxidation inhibition were shown in another study.^44,45 Běi Shā Shēn was shown to have neuroprotective effects from ischemic attacks. ⁴⁶

RADIX PLATYCODI, (CHUĀN JIÉ GĚNG)

Radix Platycodi, (Chuān Jié Gěng) opens up and disseminates Lung qi, dispels phlegm, and benefits the throat for coughing and wheezing with profuse sputum, throat pain, and loss of voice. ³⁵ Jie Geng has been shown to reduce allergic airway inflammation by reducing inflammatory cytokine production and inhibited mucin5AC(a gene linked to mucus hypersecretion). ⁴⁷ Other studies have shown the ability to inhibit the excessive production of NO, PGE2, and proinflammatory cytokines, including IL-1β, TNF-α, nuclear factor kappa B (NF-κB) p65, and Phosphorylation of IκBα.^48,49 Jie Geng has also been shown to inhibit platelet aggregation to inhibit thrombosis and hemostasis, which is pertinent to clotting symptoms occurring in COVID-19 cases. ⁵⁰ It is also used in TCM treatment of inflammatory diseases such as bronchitis, asthma, and pulmonary tuberculosis. ⁵¹ Triterpenoids are its main effective constituents, which have antitussive, expectorant, antitumor, antioxidant, and immune enhancement effects. ⁵²

RADIX ISATIDIS (BǍN LÁN GĒN)

Radix Isatidis (Bǎn Lán Gēn) drains heat, resolves fire toxicity, cools the blood, and benefits the throat, for warm heat pathogen diseases, warm epidemic disorders, mumps, and painful swollen throat conditions. ³⁵ Bǎn Lán Gēn contains 4 organic acids demonstrated to suppress Escherichia coli growth, and was prepared in large quantities as an antiviral medicine during the outbreak of SARS coronavirus in many Chinese societies. Besides antimicrobial activities, polysaccharides isolated from Bǎn Lán Gēn have been shown to stimulate the expression of cytokines and thus modulate certain immunologic functions in mice. ⁵³ Bǎn Lán Gēn is used alone or in combination with other herbs to treat a wide variety of infectious and inflammatory diseases, such as influenza, and encephalitis B, to inhibit viral infection, increase spleen weight, and lymphocytes, and antagonize the immunosuppressive actions of hydrocortisone.^54,55 Isatidis Radix has many pharmacologic activities such as antibiotic, antidiabetic, and immune-stimulating effects, and is used to treat encephalitis B and viral infections. It is also found to be clinically effective against infections caused by various subtypes and strains of influenza viruses, including SARS. ²⁵ Previous studies showed that extracts of Bǎn Lán Gēn had diverse biological activities and contained various types of active constituents such as new alkaloids and 54 known compounds. ⁵⁶

RHIZOMA ATRACTYLODIS LANCEAE (CHǍO CĀNG ZHÚ)

Rhizoma Atractylodis Lanceae (Chǎo Cāng Zhú) strongly dries dampness, induces sweating, strengthens the spleen and stomach, and treats atrophy disorders from damp-heat in the lower burner. ³⁵ Chǎo Cāng Zhú is pungent and bitter, and enters the spleen, stomach, and liver meridians. Chǎo Cāng Zhú eliminates dampness, strengthens the spleen, eliminates wind, and disperses cold. According to TCM theory, Chǎo Cāng Zhú was traditionally used to treat influenza. ⁵⁷ Chǎo Cāng Zhú is a traditional medicinal herb, which has antibacterial, antiviral, and anti-inflammatory activities. ⁵⁸ Anticancer activities, nervous and gastrointestinal system activities, antihypertensive, antiplatelet, antiulcer, antimicrobial, and antipyretic activities have been shown in other studies. ⁵⁹ Chǎo Cāng Zhú has also shown to significantly inhibit pulmonary inflammation through cytokine-balancing mechanisms and function as a potential inhibitor of influenza A virus. ⁵⁸ Inhibited expression of iNOS and COX-2 has been shown through the LPS-stimulated Raw246, inhibiting the expression of inflammatory factors, including IL-1, IL-6, and TNF-α. ⁶⁰ It contains sesquiterpenes, sesquiterpenoids, polyethylene alkynes, phytosterols, etc., such as elemol, β-selinene, and atractylone. ⁵⁷

VIOLA YEDOENSIS (ZǏ HUĀ DÌ DĪNG)

Viola Yedoensis (Zǐ Huā Dì Dīng) clears heat and resolves toxicity, for reducing hot swellings especially for red swollen eyes and painful eyes due to liver heat. ³⁵ Zǐ Huā Dì Dīng is used as an antifebrile and detoxifying agent for the treatment of acute pyogenic infections such as boils, furuncles, and carbuncles. ⁶¹ Viola Yedoensis has antibacterial and anti-inflammatory activities, and relieves pain. ⁶² Studies show it is used as a tea to treat toxic heat, swelling, and bronchitis. Extracts of Zǐ Huā Dì Dīng such as flavonol O-glycosides, flavone C-glycosides, and coumarins have been shown to inhibit the growth of human immunodeficiency virus (HIV), hepatitis C virus, and certain bacteria.^63,64 Zǐ Huā Dì Dīng is the most hydrophobic and contains the most potent cycloviolacin Y5 that was found to have HIV inhibitory plant cyclotides.^65,66 Zǐ Huā Dì Dīng was shown to also be effective in suppression of HSV1 and enterovirus 71 in the human neuroblastoma SK-N-SH cell line. ⁵³

GLYCYRRHIZA SP. RAW (SHĒNG GĀN CĂO)

Glycyrrhiza sp. raw (Sheng Gan Cao) tonifies the Spleen qi, moistens the lung, moderates urgency and toxicity, and drains fire. ³⁵ The main bioactive constituents of licorice are triterpene saponins and various types of flavonoids. Pharmacologic activities include antiulceric, anti-inflammatory, antispasmodic, antioxidative, antiallergic, antiviral, antidiabetic, anticancer, antidepressive, hepatoprotective, expectorant, and memory enhancing activities. ⁶⁷ Gan Cao has been shown to be effective against AIDS, herpes zoster, and SARS in many studies. ⁶⁸ Gan Cao attaches itself to the cell membrane, preventing virus attachment and entry. ²³ Furthermore, glycyrrhizin, a major active constituent in Gan Cao, was shown to inhibit replication of SARS clinical isolates. ⁶⁹ Antiviral effects of the component glycyrrhizin in vitro have been effective against Epstein-Barr, herpes simplex, hepatitis A, hepatitis B, hepatitis C, human cytomegalovirus, HIV, influenza, SARS, and Varicella zoster (Tables 3 and 4).^70–73

Discussion

Although the symptoms associated with COVID-19 are continually updated, an analysis of the current symptom consensus of the CDC and WHO outlines 15 potential TCM patterns (Table 4). TCM patterns, and their pathophysiology, can be single patterns, multiple concurrent patterns, or can transform into other patterns as disease progresses or regresses. An overview of the COVID-19 pertinent TCM patterns yields both heat and cold patterns, damp and phlegm syndromes, toxicity, and deficiency patterns. The first 6 patterns (Taiyang Wind Syndrome, Wind-Cold Invading Lung, Taiyang Cold Syndrome, Qi Phase, Pathogenic Lung Heat, and Wind-Heat Lung) are all initial stage patterns of wind, heat, and/or cold exterior. These 6 patterns respond to herbs that “release the exterior” and “expel wind-heat/wind-cold,” such as Fang Feng, Jin Yin Hua, and Lian Qiao.

Combinations of herbs that are both warming and cooling are commonly seen in TCM formulas. This combination of opposite effects is frequently used because the constraint of cold will often transform into heat. With COVID-19, heat often transforms into cold. TCM pathophysiology suggests that this transformation is due to severe oxygen deprivation, which in some patients leads to heat loss and accumulation of cold in the lungs. As given in Table 4, a heat or cold TCM pattern accompanied by fever, pus, or having a clear epidemic nature, is labeled toxicity. Five herbs (Jin Yin Hua, Lian Qiao, Ban Lan Gen, Zi Hua Di Ding, and Gan Cao) that constitute half of the QDQF1 formula have functions that clear heat and relieve toxicity.

Phlegm, Damp-Phlegm, Phlegm-Heat, and Cold Phlegm require herbs that expel or drain damp and phlegm to restore lung function. Jie Geng and Cang Zhu are the primary herbs chosen for this purpose. Bei Sha Shen, Jie Geng, and Gan Cao all have the ability to moisten the lung and stop coughing. Bei Sha Shen nourishes Yin to protect the delicate balance of fluids within the lung. Huang Qi and Gan Cao combined are used to nourish qi to support the overall health of the patient while strengthening Wei and Ying Qi.

Often overlooked symptoms associated with COVID-19 are nausea, vomiting, and diarrhea. Although these symptoms are not associated with the life-threatening pneumonia and hypoxia, case studies from China suggest that people with these symptoms may eventually suffer from more severe respiratory complications. TCM pathophysiology would suggest that the Damp-Heat and Spleen Qi deficiencies commonly associated with these symptoms could transform and complicate each other by leading to increased dampness and phlegm in the body. The obstruction of dampness and phlegm further inhibits the natural movement and production of Qi. Therefore, Huang Qi, Jin Yin Hua, Cang Zhu, and Gan Cao in this combination are used to strengthen the qi and clear damp-heat.

Huang Qi is used here as an immune tonic that protects the body from further infection and reduces edema. Fang Feng is included due to its historical use in infectious diseases and respiratory disorders in TCM. Jin Yin Hua clears and cools early stage epidemic febrile diseases and treats lung abscesses. Lian Qiao relieves heat, toxicity, and is also used in cases of lung abscess. Bei Sha Shen is a lung tonic that protects the yin and fluids from damage due to heat and toxicity. Jie Geng opens the lungs and expels phlegm, discharges pus, and directs the other herbs to the upper part of the body. Ban Lan Gen drains heat and fire toxicity and benefits the throat. Cang Zhu strongly dries dampness while inducing sweating and releasing exterior disorders. Zi Hua Di Ding clears heat and fire toxicity. Gan Cao nourishes the qi, moistens the lungs, stops coughing, clears heat and fire toxicity, and generally harmonizes the formula.

Huang Qi, Fang Feng, Jin Yin Hua, Lian Qiao, Bei Sha Shen, Jie Geng, and Cang Zhu are all credited with the ability to regulate inflammation and/or macrophage production. Huang Qi, Jin Yin Hua, Lian Qiao, Bei Sha Shen, Ban Lan Gen, Cang Zhu, Zi Hua Di Ding, and Gan Cao all have documented antiviral effects. Fang Feng has the ability to increase the phagocytic ability of the reticuloendothelial system, potentially reducing accumulation. Lian Qiao has the ability to reduce chronic bronchial epithelial cell inflammation from viral infections. Bei Sha Shen has neuroprotective effects from ischemic attacks and protects against low oxygen damage. Jie Geng reduces cytokine production and inhibits mucus hypersecretion as well as inhibits thrombosis and hemostasis that complicates many SARS-CoV-2 infections and often leads to death. Ban Lan Gen was clinically effective against SARS, a close genetic match to SARS-CoV-2. Cang Zhu significantly inhibits pulmonary inflammation through cytokine-balancing mechanisms. Gan Cao blocks the ability of the SARS virus to attach to and enter the cell membrane.

Consistent with the research already presented, we conclude that herbs chosen for the QDQF1 formula have been historically paired, and cast a wide net over potential COVID-19 symptomatology. These disparate herbal functions, when combined, have a synergic effect that provides a comprehensive and balanced therapeutic approach from both TCM and Western allopathic viewpoints.

Conclusion

Finding therapeutic solutions for the complex symptomatology of COVID-19 requires the ability to address a wide range of symptoms simultaneously. It is imperative to not only support the immune system, but also maintain immune balance to prevent the life-threatening cytokine storm that frequently presents itself in severe cases. Chinese Medicine has a long history of addressing complex pathologies while also resolving associated symptomatology. The combination and dosage of herbs already listed are used in TCM to treat the common respiratory patterns outlined in Table 4, and reflected in COVID-19 case symptoms identified by WHO and CDC Table 2. The herbs presented in the QDQF1 formula have the capacity, when used together, to address both the viral pathology and symptomology presented by COVID-19.

Utilization of CHM, specifically the novel QDQF1 formula, is a sensible immune supportive strategy validated by the successful historical use of CHM to prevent epidemic spread. This study has revealed that the herbs used in Qu Du Qiang Fei I Hao Fang have a myriad of antiviral, antitumoral, antinociceptive, antioxidant, antiangiogenic, antipyretic, antithrombotic, and anti-inflammatory effects through varied mechanisms of action, including regulation of inflammatory cytokines and mediators.

The intense interest in CHM to prevent and treat COVID-19 stems from its unique ability to resolve symptoms across a wide spectrum of disease presentations, with little or no side-effects when pattern differentiation is applied. Accordingly, further investigation of Qu Du Qiang Fei I Hao Fang in a randomized, double-blind, and placebo-controlled study is recommended to assess its therapeutic efficacy in the early stage treatment of COVID-19.