key: cord-0938336-lw2yp4ag authors: Zhi, Na; Mo, Qian; Yang, Shuo; Qin, Yuan-xing; Chen, Hao; Wu, Zeng-guang; Lan, Cai-hong; Zhang, Jun; Li, Yin-long title: Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report date: 2020-12-05 journal: J Integr Med DOI: 10.1016/j.joim.2020.11.005 sha: 78d26f74bbdab42d0dc4d594977bcf8987fb2d48 doc_id: 938336 cord_uid: lw2yp4ag After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient’s condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed. The corona virus disease 2019 refers to an acute respiratory infectious disease whose main clinical symptoms include fever, dry cough and fatigue, but can also be accompanied by nasal obstruction, runny nose, sore throat, myalgia and diarrhea, following infection with the sudden acute respiratory syndrome coronavirus-2 [1] . After treatment, which may include improving oxygen supply, antiviral therapy, improving body fluid circulation and enhancing body immunity, the symptoms of most patients can be significantly reduced, and the levels of viral nucleic acids in the body will fall below the limit of detection, finally reaching the clinical cure standard. However, even after reaching the standard of clinical cure, some patients continue to suffer from incomplete absorption of pulmonary exudates and pulmonary fibrosis, symptoms that need to be addressed quickly [2, 3] . Modern medicine recommends the new anti-fibrosis drugs, pirfenidone and nidanib, as the main therapeutic agents for pulmonary fibrosis [4] . Considering that both of these drugs have gastrointestinal tract and photosensitive reactions that include nausea, abdominal pain and diarrhea [5, 6] , and that the spleen and stomach function of convalescent COVID-19 patients are dysregulated, the adverse reactions to pirfenidone and nidanib are poorly tolerated in this population, and there is no safe and reliable specific drug to use in clinical care. Fitting neatly into the category of "plague" in traditional Chinese medicine (TCM) [7] , COVID-19 is a disease that is highly contagious, epidemic-prone, with a sudden onset and critical illness. TCM has a long history of treating diverse diseases that fit the "plague" definition. Relevant studies have shown that TCM can effectively reduce pulmonary exudates and inhibit the release of inflammatory factors [8] ; thus it can play a therapeutic role in convalescent patients with COVID-19. At present, the oral administration of decoctions of Chinese medicines has been widely recommended in the rehabilitation treatment of convalescent patients with COVID-19 [9] . Therefore, this case study selected the oral administration of a decoction of Chinese medicine as the primary treatment method for this convalescent COVID-19 patient. Due to its ease of transmission, COVID-19 has now spread to many countries in the world, seriously threatening the stability of human society, health of populations and quality of life. In order to provide a reference for effective clinical prevention and treatment of COVID-19, this article reports a clinical case of pulmonary inflammatory exudate and fibrosis in a convalescent COVID-19 patient who was treated through the oral administration of a decoction of Chinese medicine. The study followed the Case Reporting Guidelines [10] and "The COVID-19 Diagnosis and Treatment Plan (trial 7th edition)" formulated by the National Health Commission of China [11] , and obtained the informed consent of the patient and the approval of the Ethics Committee of Guizhou Administration of TCM, China. Further, the patient has provided written informed consent for the publication of the case and any accompanying images. The publication has also obtained the approval of the Ethics Committee of Guizhou Provincial Administration of TCM (No. KYH2020-003). A 61-year-old female who had been diagnosed with COVID-19 was placed under inpatient isolation and observation in the designated diagnosis and treatment hospital for COVID-19 in Guizhou Province from February 24, 2020. After initial treatment that included oxygen administration through a nasal catheter, to improve the pulmonary oxygen supply, oral lopinavir, ritonavir and arbido, inhalation of atomized ɑ-interferon were applied to oppose virus infection, and oral thymosin was applied to enhance the body's immunity. The patient had no typical symptoms of COVID-19 such as fever, dry cough, nasal obstruction, runny nose, fatigue, myalgia and diarrhea. However, when she was kept in the hospital for isolation and observation, she had difficulty in falling asleep and poor appetite, accompanied by hunger and thirst without desire to eat or drink, intermittent dry and loose stools, a dark red tongue with yellowish thick and greasy coating in the middle and posterior part, but smooth and uncoated on both sides and the tip of tongue; her pulse was weak and astringent. Table 1 . Additionally, the tongue was reddish, the color and thickness of the tongue coating were basically normal, the pulse was soft and strong, and the pathological sense of astringency had disappeared. The chest CT and tongue imaging results for this patient are shown in Fig. 1 and Fig. 2 , respectively. After the patient was discharged from the hospital, she participated in three follow-up consultations on March 30, 2020, April 6, 2020, and April 13, 2020. The follow-ups mainly included asking the patient whether she had fever, dry cough, stuffy nose, runny nose, fatigue, myalgia, diarrhea, and other typical symptoms related to COVID-19 during the period since her last follow-up. The patient told us that her condition did not relapse or worsen after she was discharged from the hospital, nor did she have any other uncomfortable symptoms. The timeline of this case is shown in Fig. 3 . Regarding yin and yang meridians, yang belongs to excess and yin belongs to deficiency, so the patient is mostly suffering from yin meridian imbalances. Furthermore, in convalescing patients, the pulmonary fibrosis changes into tangible structures, which belongs to the category of "tendon" in the five tissues of TCM and corresponds to liver. The liver meridian of TCM has an internal pathway to the lung, so poor circulation of qi and blood in the liver meridian leads to abnormal physiological function of the lung, which normally has the role of disseminating clear fluids to all meridians. In this case, weakness in lung physiology manifests as incomplete absorption of inflammatory exudate and the development of fibrosis in the lungs. Therefore, liver organ and meridian pathology is one of the causes of disease for this patient. Additional symptoms pointing to liver involvement included the patient's dry and loose stools, which are related to mixed cold and heat and stagnant liver qi. Therefore, the author selected the main prescription "Wume Fructus Pill," and modified its ingredients to offer sour and sweet flavors to nourish yin and blood, regulate cold and heat, and dredge the vessels. From the Western medical perspective, pulmonary fibrosis mainly refers to pulmonary diseases with pathological characteristics, such as alveolar epithelial cell and endothelial cell damage, fibroblast proliferation, excessive collagen deposition, alveolar structure degradation, large accumulation of extracellular matrix and diffuse alveolitis with various causes [15] . Many studies have shown that the pulmonary fibrosis is closely related to some cytokines. Among them, transforming growth factor-β1 (TGF-β1) is the key factor that promotes the activation of fibroblasts and causes irreversible lung injury [16] . Tumor necrosis factor-α (TNF-α) is an active marker of alveolar inflammation, which can promote an inflammatory reaction and the differentiation of interstitial cells, and can also interact with other cytokines, such as TGF-β1, and jointly promote changes in pulmonary fibrosis [17] [18] [19] . Therefore, clinically, pulmonary fibrosis is often inhibited or alleviated by reducing the secretion can also delay and reduce the development of pulmonary interstitial fibrosis [20, 21] . To sum up, under the guidance of TCM theory and modern medical research with a long history and rich clinical experience, it is no accident to select oral treatment of TCM decoction as the main intervention method in this case, which can significantly improve the clinical trials of pulmonary insufficiency and fibrosis changes. It has certain reference value for clinical treatment of convalescent patients in COVID-19. However, it is worth noting that an oral treatment with TCM decoction needs to have the formula adjusted to address the overall symptoms and etiological characteristics of each patient. It is necessary for professional Chinese doctors to make reasonable adjustments to the prescriptions of TCM to meet the individualized treatment needs of other COVID-19 convalescent patients. Targeted oral treatment with TCM decoction was able to effectively promote the absorption of pulmonary inflammatory exudate and to reduce pulmonary fibrosis NZ, QM and SY contributed to the conception of this research; NZ and QM wrote the original paper; YXQ, HC and ZGW contributed to reviewing and editing the manuscript; CHL and JZ were responsible for guiding the application and contacting the patient; YLL was responsible for preparation of herbal medicines. All authors read and approved the final version of the manuscript accepted for publication. National Health Commission of China. New coronavirus pneumonia diagnosis and treatment program (trial version 7) Thinking of the effect of integrated traditional Chinese and Western medicine on the treatment of new coronavirus pneumonia The value of CT imaging combined with tongue diagnosis based on pathology in diagnosis and treatment of new coronary pneumonia Research progress of two novel anti-fibrotic drugs in the treatment of idiopathic pulmonary fibrosis Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label phase Ⅱ study Advances in the research of nintedanib for tumors Thinking of diagnosis and syndrome differentiation treatment of new coronavirus pneumonia Review on the present treatment of COVID-19 with traditional Chinese medicine Expert Guidance on a Comprehensive Intervention Program of Traditional Chinese Medicine for the Recovery of New Coronavirus Pneumonia (Draft) The CARE guidelines consensus-based clinical case reporting guideline development General Office of National Health Commission of the People's Republic of Office of National Administration of Traditional Chinese Medicine. Diagnosis and treatment of corona virus disease-19 Discovery of intervention effect of Chinese herbal formulas on COVID-19 pulmonary fibrosis treated by VEGFR and FGFR inhibitors Study on treatment of "cytokine storm" by anti-2019-nCoV prescriptions based on arachildonic acid metabolic pathway Clinical characteristics of 258 cases of coronavirus disease 2019 in Shenzhen and thinking on the plague name attribute of coronavirus disease The effect of warming the kidney-yang method on the expression of CTGF in the lung of rats with kidney-yang deficiency and pulmonary fibrosis TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease Research progress on the role of tumor necrosis factor-α and transforming growth factor-β1 in the formation of pulmonary fibrosis Significance and expression of cyclooxygenase-2 in rats with pulmonary fibrosis Study on the effect of Polyporus umbellata and Alisma on serum TGF-β1 and TNF-α in rat model of pulmonary fibrosis The effect of Fuling, Yiyiren, and Dongguazi on serum TGF-β1 and TNF-α levels in rats with pulmonary fibrosis Research progress in molecular mechanism of TCM for protection and treatment of pulmonary fibrosis The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.