Clinical characteristics analysis of 9 Cases COVID- 19 patients receiving integrated Traditional Chinese and Western medicine: a retrospective study

Chengjian Cao (  cccjj2011@163.com ) Zigong First People's Hospital https://orcid.org/0000-0001-5453-4030 Fang Zhang Huaian First People's Hospital Liuying Li Zigong First People's Hospital Maoli Guo Zigong First People's Hospital Minggang Yin Zigong First People's Hospital Huixiu Zhong Zigong First People's Hospital Weiping Liu Zigong First People's Hospital Fuqiang Shao Zigong First People's Hospital Deya Che Zigong First People's Hospital

The above data indicate that if people who are from the epidemic area have the relevant symptoms still need to take relevant measures. And although Case 4 has Type 2 Diabetes Mellitus, but instead he has shortest duration, and the other patients who have underlying diseases were also cured without recurrence, suggest these underlying diseases did not affect the cure of COVID-19. It should also be noted that, except for the relapse in Cases 1, the symptoms of other patients had disappeared one week before discharge. And the virus nucleic acid was tested daily in the hospital to prevent recurrence, and the patients were not discharged until all nucleic acid was negative for 5 consecutive days. Of course, the same measures were taken for Cases 1 before his discharge.

Characteristics Of Clinical Symptoms
As shown in Table 2, except for 2 patients with tachycardia, most of the patients had normal heart rates during the onset(Case 8,Case 9). There was no increase in blood pressure except in two patients with chronic hypertension Case 7,Case 8 . All Respiratory Rates and Oxygen Saturation were normal. All the 9 patients had fever, but most of them had low fever, with the highest body temperature reaching 39.3℃. All the patients had no symptoms such as dizziness rhinobyon rhinorrhoea and headache. 8 out of 9 developed cough symptoms (except Case 1), 3 of them had no phlegm (Case 1, Case 2, Case 4,), and the remaining 6 had phlegm. Only 1 out of 9 patients presented with systemic fatigue symptoms (Case 6), and 2 patients presented with systemic muscle stiffness&myalgia (Case 4, Case 6). In addition, there are 3 patients with Poor Appetite, Nausea, Acid Regurgitation and other gastrointestinal symptoms (Case 6, Case 7, Case 8), 2 patients appeared Chest Stu ness (Case 5, Case 8), and 1 patients appeared nausea and vomiting after taking antiviral drugs. It can be seen that the patients included in this study had fever and cough as the main symptoms, while the symptoms of fatigue and myodynia were less, which was consistent with previous reports by other study [2].   It is worth mentioning that Case 1 has neither cough nor phlegm nor muscle soreness and other symptoms, and has only fever and diarrhea with a maximum temperature of 38.6℃. However, it has also been diagnosed as COVID-19. Besides, he also had relapse.

Examination, Treatment And Outcomes
As mentioned in the Methods part, all patients were underwent routine blood tests, liver biochemical indicators tests, renal biochemical indicators tests, hypersensitive C-Reactive Protein(hs-CRP) tests and Tlymphocyte subsets analysis et al., also in addition to 2019-nCov nucleic acid test and chest CT imaging.
In terms of treatment, as shown in Table 3, we applied the antiviral drugs Lopinavir/Oseltamivir/Ritonavir, also used the Recombinant Human Interferon A2b and Chloroquine Phosphate Tablets, and also used speci c antibiotics for therapy; Drugs such as Tetralogy of viable bi dobacterium tablet and Montmorillonite Powder were also used to improve the gastrointestinal reactions of patients such as diarrhea and diarrhea. Of course, different from some hospitals, we applied Traditional Chinese Medicine (TCM) treatment at the same time of antiviral and supportive treatment. According to the theory of traditional Chinese medicine, according to the different condition of each patient's characteristics, our TCM doctors prescribed formulae that are the most consistent with the symptoms of the patients, thus ensure the curative effect and reduced the incidence of side effects.

Discussion
According to the test results, in all patients, hs-CRP increased and T-lymphocytes decreased at onset, and in the T-cell subsets, the absolute values of CD4 + T cells and CD8 + T cells decreased(as shown in Table 4). Chest CT examination showed that all patients had presentation of the patchy scattered highdensity shadows with the blurred boundary and ground-glass opacity or some consolidation in their bilateral or unilateral lung lobes, the upper lobe or the medial basal segment of the lower lobe, and ground glass opacities and patchy, and streaked shadows were the most common radiologic ndings (as shown in Fig. 1, 2, and Supplementary Materials 1), which is consistent with some results of other studies [10][11].Other laboratory tests showed no speci c changes (data are not listed here). And, after treatment, it can be seen that hs-CRP are reduced, the total number of T lymphocytes is increased, and the absolute values of CD4 + T cells and CD8 + T cells in the T cell subsets are also increased (as shown in Table 4, FIG.3, 4 and Supplementary Materials 2), meanwhile the chest CT examination shows that the in ammation is gradually absorbed and nally disappeared. As of Feb. 27, the last patient had been discharged (Case 1).
Here it is worth mentioning that 1 patient (Case 1) showed relapse. The relapse here means that the chest CT examination of the two patients showed that the in ammation had been absorbed, but the viral nucleic acid test was sometimes negative and sometimes positive. Although it is impossible to completely rule out the errors caused by sample collection, transportation, detection reagent and operation, each inspection process is carried out in strict accordance with standard operating procedures. So Here we speculate that the virus may have a variation to reduce virulence, but unfortunately due to our limited conditions, we were unable to conduct further in-depth studies on the specimens of the two patients.
For now, there is no approved speci c medicine or vaccine for 2019-nCov. Although it has been reported that Remdesivir may have a promising clinical therapeutic effect [6], further Case-Controlled clinical studies are needed to verify its therapeutic e cacy [8].On the other hand, we can say that the control of the epidemic of COVID-19 in China nationwide is not due to the use of Remdesivir, but due to the widespread use of TCM combined with other western medicine. For example, TCM had appeared in the Trial Fourth Edition of the Clinical Guideline Diagnosis and Treatment Protocol for COVID-19 released by National Health Commission of China and National Administration of Traditional Chinese Medicine issued in January 28, 2020 [9], and updated in the subsequent Editions(the newest is Trial Seventh Edition so far) [12]; And National Administration of Traditional Chinese Medicine also issued a speci c TCM formulation QingFeiPaiDuTang(Lung cleansing & detoxifying decoction) to treat COVID-19 [13] to treat COVID-19; Furthermore, out of the 31 provinces in Chinese mainland, health authorities in 23 provinces had o cially issued programs recommending TCM to preventing COVID-19 [14]. And some studies reported that TCM could alleviate symptoms, shorten fever duration, recover radiological changes, and shorten hospital courses [15], Furthermore, the cabin hospitals in Wuhan is the hospitals that mainly treats with TCM, where all the patients in the hospital have been cured and discharged, and the hospital has been closed at March 8. Besides, recently a cohort observational clinical trial on regularity of TCM syndrome and differentiation treatment of COVID-19 has been submitted to the National Library of Medicine (NLM) belonging to National Institutes of Health (NIH), including two groups: Cohort of western medicine and Cohort of integrated TCM and western medicine, and possibly complete on May 2020 [16], which may provide more conclusive proofs for utilizing TCM to COVID-19.
From our experience and results, TCM treatment of COVID-19 does not directly kill the virus, but promote the elimination of the virus by improving the patient's immunity. Our results showed that after treatment, the number of T lymphocytes increased signi cantly, especially CD4 + T cells and CD8 + T cells (Fig. 1).
As we all know that CD4 + T cells are helper T cells that secrete interleukin and interferon, and CD8 + T cells are cytotoxic T cells that play an important role in killing infected cells. Besides, CD4+/ CD8 + ratio also increased in 7 out of 9 patients, which indicated that TCM could improve the patients' immunity, which are also found in SARS treatment [17]. So the application of TCM is like to equip with more powerful weapons and provide more soldiers for the human body to ght the virus, so the mechanism of TCM is different from that of antibiotics and also other antiviral drugs such as Remdesivir. Furthermore, TCM could play roles in every part of COVID-19, including prevention, Health care and treatment, and also including adult, elderly and children [18][19][20].
However, our retrospective study also had major drawbacks, such as the failure to establish a control group due to respect for life. Even so, we believe that from the situation of hospitals in other parts of the country that do not use TCM, as well as the curative effect of China using TCM to control COVID-19, there is also the application of TCM in the treatment of SARS in 2003 [21][22][23][24][25], and in the treatment of H1N1 in 2009 [26][27], TCM could play a signi cant role in the cure of COVID-19.
On the other aspect, according to the experiences of Wuhan, with the development of the epidemic, there will be a shortage of medical resources such as virus detection, diagnosis and treatment [28][29], which could lead to more infections and social panic, and the battle with COVID-19 is still expected to take months globally. Because TCM has the characteristics of symptom-based diagnosis, individual treatment and no need for large detection equipment, so we believe that in this severe situation of the outbreak of a new type of pathogen, spread and can't nd or develop speci c targeted drugs for a while, and even the clinical effects of TCM on COVID-19 is far from conclusive, TCM combined with western medicine treatment may be a good additional candidate for the cure of COVID-19.

Conclusion
In conclusion, through our practical experience and Case analysis, we think that in the process of COVID-19 treatment, the application of western medicine is indispensable, however, if apply TCM at the same time, it can quickly alleviate the disease, accelerate the cure, so, we believe that in the severe situation of the outbreak and diffusion of a new type of pathogen, and can't nd or develop speci c targeted drugs for a while, to some extent the application of TCM should be a rational and even necessary choice for an adjuvant therapy of COVID-19. Our report is expected to provide a meaningful reference for the treatment of COVID-19 worldwide.  Chest CT imaging of patient 6. A: Patchy, ground-glass opacity and mesh shadows were seen in the lower lobe of the right lung, with blurred edges. The interlobular septa were thickened, changed signi cantly in the peripheral belt, and the adjacent pleura was thickened and adhered. B-C: improvement are shown after treatment with integrated traditional Chinese and Western medicine T lymphocyte subsets analysis of patient 3 detected by FCM. A: before treatment. B: after treatment.