Clinical Effectiveness Analysis on 54 NCP Cases with Treatment of Lianhuaqingwen Granules CHENG Dezhong, LI Yi

(The Puren affiliated Hospital of Wuhan University of Science and Technology, Wuhan 430081, China)

Abstract Objective: To analyze the clinical effectiveness of Lianhua Qingwen Granules (LH-C) on novel coronavirus pneumonia (NCP) patients. Methods: The clinical data of 54 ordinary NCP Patients were retrospectively analyzed at the Puren affiliated Hospital to Wuhan University of Science and Technology. Results: After treatment with LH-C for three consecutive days. The rate of symptoms disappearance in fever, asthenia and cough was 47.5%, 35.1%, and 20.0%, respectively. Five days later, the rate of symptoms disappearance in fever, asthenia and cough increased to 62.5%, 59.5%, and 50.0%, respectively. By the seventh day, the rate of symptoms disappearance in fever, asthenia and cough reached at 80.0%, 75.7%, and 76.7%. The days of symptoms disappearance in fever, asthenia, and cough was 3.6±2.14 days, 4.1 ± 2.58 days, and 5.3 ± 2.63 days. As regards the other symptoms disappearance in the chest stuffiness, the dyspnea, and the moist crackles was 84.6%, 100%, and 89.5 %; and the total efficiency was up to 81.6%, without any observed side effects by the seventh day. Conclusion: LH-C could significantly relieve clinical symptoms in ordinary NCP patients by inhibiting fever, asthenia, and couch, and reducing their duration. All these results provided preliminary clinical evidence for LH-C in the NCP treatment.

Keywords: Lianhuaqingwen; SARS-Cov-2; NCP; Clinical efficacy; Retrospective analysis; Typical cases

Chinese classification number: R254.3; R256.19; R512.99

Document identification code: A doi: 10. 3969 / j. Issn. 1673-7202. 2020. 02. 006

Recently, the novel coronavirus pneumonia (Novel Coronavirus Pneumonia, NCP) epidemic has been spreading and it was classified as Class B infectious diseases (managed as a Class A disease) [1]. More than 20 countries and regions in the world have reported confirmed cases, and it is becoming a global public health event [2]. The main symptoms of NCP are fever, asthenia and dry cough. A few patients have symptoms such as nasal obstruction, runny nose, sore throat and diarrhea. It is reported that 15.7% of NCP patients are admitted to the hospital, and the clinical mortality rate is about 1.4% [3]. Some studies also show that 26% of the patients need treatment at the intensive care unit, and the mortality rate of the confirmed patients is 4.3% [4], and delayed the treatment, the therapeutic effect is extremely serious. However, up to now, there is no effective antiviral medicine for NCP, but symptom-based therapiesare mainly used. We used Lianhuaqingwen Granule combined with routine treatment to treat the disease and received good results. Therefore, we here report a retrospective analysis on the clinical data of the 54 NCP patients in our hospital, in order to improve the treatment level of the disease.

  1. 1.        Data and methods

1.1.       General data Research targets are the 54 cases of novel coronavirus pneumonia which were treated with Lianhuaqingwen Granules combined with conventional treatment (according to the surveillance of disease, giving nutritional support, antiviral treatment and antibacterial treatment) from January 1-31, 2020 in Puren Hospital Affiliated to Wuhan University of Science and Technology. The average age of the patients was 60.1 ± 16.98 years, include 29 male (53.7%) and 25 female (46.3%); the average body temperature was (37.93 ± 0.93)℃, the median body temperature was 38.05 ℃, and the maximum body temperature before diagnosis was (38.54) ± 0.60) ℃; average heart rate was 87.9 ± 11.80 beats / min, the median heart rate was 85.5 beats / min, the highest rate was 112 beats / min; the average respiration was 21.1 ± 3.78 breaths / min, the median rate was 20.0 breaths / min, the highest rate was 30.0 breaths / min; those with history of hypertension was 21 cases (38.9%), and those with history of coronary heart disease was 7 cases (13%). There were 10 cases of diabetes mellitus (18.5%), 10 cases of cerebral infarction (18.5%). For laboratory examination: 31 cases (64.6%) of leucocytes in the normal range, 9 cases (18.8%) lower than the normal value, 8 cases (16.7%) higher than the normal value; 25 cases (52.1%) of neutrophils in the normal range, 23 cases (47.9%) were higher than the normal value, 14 cases (29.2%) were in the normal range, 34 cases (70.8%) were lower than the normal value; all patients had C-reactive protein levels higher than normal. All the patients were treated with Lianhuaqingwen Granules for an average of 8.0 ± 4.10 days, with a median of 7.0 days, a minimum of 1.0 days and a maximum of 16.0 days.

Table 1 General Information of NCP Patients

Item

Cases

(count)

Result

Project

Cases

(count)

Result

Age

54

60.10±16.98

Mesenchymal cells (%)

Man (%)

29

53.7

Normal

25

52.1

Body temperature

54

37.93 ±0.93

Low

0

0.0

Heart Rate (beats/min)

54

87.90±11.80

High

23

47.9

Respiration rate (breaths/min)

54

21.10 ±3.78

The lymphocyte (%)

Medical history

Normal

14

29.2

High blood pressure

21

38.9

Low

34

70.8

Coronary heart disease

7

13

High

0

0.0

Diabetes mellitus

10

18.5

C-reactive protein (%)

Cerebral infarction

10

18.5

Normal

0

0.0

White blood cells (%)

Low

0

0.0

Normal

31

64.6

High

44

100.0

Low

9

18.8

Days with treatment  of Lianhuaqingwen Granules

54

8.0 ±4.10

High

8

16.7

1.2.       Diagnostic criteria Patients were diagnosed as NCP positive when they met the diagnostic criteria for novel coronavirus infection (trial version fifth) [5], and showed positive results with the nucleic acid test performed for sputum, throat swab and lower respiratory tract secretions.

1.3.       Inclusion criteria The normal [5] in-patients who are over 18 years old and meet the NCP diagnostic criteria.

1.4.       Exclusion criteria 1) Severe and critical NCP patients; 2) any other chronic respiratory diseases, respiratory bacterial infections such as suppurative tonsillitis, acute tracheobronchial bronchitis, sinusitis, otitis media and other respiratory diseases that affect the clinical trial evaluation; 3) with severe primary immunodeficiency, acquired immunodeficiency syndrome, congenital respiratory malformation congenital heart disease, pulmonary dysplasia and other basic diseases.

1.5.       Treatment Lianhuaqingwen Granule (Beijing Yiling., gyzz20100040) was orally taken, 1 bag/ time, 3times/d; The main therapeutic drugs were intravenous injection of human immunoglobulin (Guizhou Taibang Biological Products Co., Ltd., GJZ s20023034) 2.5g, once a day; ganciclovir injection (Hubei Keyi Pharmaceutical Co., Ltd., GJZ h10980188) 0.5g, once a day; Levofloxacin Hydrochloride Injection (Hu Hu Nanwuzhoutong Pharmaceutical Co., Ltd., gjzz h20083916) 0.4g, once a day; Methylprednisolone Sodium Succinate for injection (Liaoning hisico Pharmaceutical Co., Ltd., gjzz h20133234) 40mg, once a day.

1.6.       Observation index The clinical data of 54 NCP patients were analyzed, including the disappearance rate of main symptoms (fever, asthenia, cough) after 3, 5, 7 days, the disappearance days of fever and other symptoms and signs.

1.7.       Criteria for efficacy evaluation The main symptom “no” is taken as 0 point, and “yes” as 1 point. (before treatment – after treatment) / before treatment is the symptom score reduction rate, when the score is more than 30%, it is regarded as effective treatment, when the score is less than 30%, it is regarded as ineffective treatment, when the score is more than 30%, it is regarded as effective treatment / total number of cases after treatment as effective treatment efficiency, the treatment efficiency of all patients after 3, 5 and 7 days of treatment is analyzed.

1.8.       Statistical method This study uses SAS 9.4 software for descriptive analysis, the counting data is described by the number of cases and the composition ratio, the measurement data is described by the mean ± standard deviation or median, and the baseline data and the efficacy indexes of each visiting point are described and analyzed.

  1. 2.        Result

2.1.       Disappearance rate of main symptoms (fever, asthenia, cough) 1) Before the treatment, there were 40 cases of fever (74.1%), 37 cases of asthenia (68.5%), 30 cases of cough (55.6%); 2) After 3 days of treatment, there were 19 cases of fever (47.5%), 13 cases of asthenia (35.1%), 6 cases of cough (20.0%);  3) After 5 days of treatment, fever disappeared in 25 cases (62.5%), asthenia in 22 cases (59.5%), cough in 15 cases (50.0%); 4) After 7 days of treatment, fever disappeared in 32 cases (80.0%), asthenia in 28 cases (75.0%) The cough symptoms disappeared in 23 cases (76.7%). See Table 2 and Figure 1.

 

 

Table 2 Disappearance rate of main symptoms in NCP patients (%)

Project

Case Number Before treatment

Reduced cases  after 3d treatment

Reduced cases  after 5d treatment

Reduced cases  after 7d treatment

Fever (n=54)

40 (74.1)

19 (47.5)

25 (62.5)

32 (80)

Asthenia (n=54)

37 (68.5)

13 (35.1)

22 (59.5)

28 (75.7)

Cough (n=54)

30 (55.6)

6 (20.0)

15 (50.0)

23 (76.7)

2.2.      
Main symptoms (fever, asthenia, cough) disappeared time 1) The average disappearance time of fever symptoms was (3.6 ± 2.14) days, median disappearance time was 3.0 days, with the shortest time as 1.0 days and the longest time as 8.0 days; 2) the average disappearance time of asthenia symptoms were (4.1 ± 2.58) days, median disappearance time were 4.0 days, the shortest 1.0 days, the longest 12.0 days; 3) the average disappearance of cough symptoms days (5.3 ± 2.63) d, median disappearing days (5.0 d), minimum disappearing days (1.0 d), maximum disappearing days (12.0 d).

71
Figure 1 Disappearance rate of main symptoms in NCP patients

81

Figure 2 Disappearance rate of other symptoms and signs in NCP patients

85

Figure 3 Treatment efficiency of NCP patients

2.3.       Disappearance rate of other symptoms and signs 1) Before treatment: 13 cases (24.1%) had chest distress, 8 cases (14.8%) had dyspnea, 10 cases (18.5%) had anorexia, and 19 cases (35.2%) had moist rales; 2) 7 days after treatment: 2 cases had chest distress, with 11 cases (84.6%) disappeared, 0 cases had dyspnea, with 8 cases disappeared. There were 6 cases of anorexia, with 4 cases odisappeared (40.0%), 2 cases of moist rales, with 17 cases disappeared (89.5%). See Table 3 and Figure 2.

Table 3 Disappearance rate of other symptoms and signs in NCP patients (%)

Project

Case number Before Treatment

Case Reduction After treatment

Chest distress (n=54)

13 (24.1)

11(84.6)

Dyspnea (n=54)

8 (14.8)

8(100.0)

Anorexia (n=54)

10 (18.5)

4(40.0)

Moist rales (n=54)

19 (35.2)

17(89.5)

2.4.       Treatment efficiency Three days after treatment, 23 of 54 NCP patients were effective (46.9%); five days after treatment, 34 were effective (69.4%); seven days after treatment, 40 were effective (81.6%). See Table 4 and Figure 3.

Table 4 effective rate of NCP common type patients [cases (%)]

Project

3d after treatment

5d after treatment

7d after treatment

Effective (n=54)

23 (46.9)

34 (69.4)

40 (81.6)

Futile (n=54)

26 (53.1)

15 (30.6)

9 (18.4)

 

2.5.       Safety analysis After analysis, there was no obvious aggravation in blood routine test, liver and kidney function test in the course of Lianhuaqingwen Granule combined with routine treatment. Compared with previos treatment, all patients except the original symptoms of respiratory tract and digestive tract did not appear new discomfort symptoms or aggravating signs, suggesting that Lianhuaqingwen Granule is safe in clinical application.

3.        Discuss

According to research, coronaviruses found by humans are widely distributed throughout humans and other mammals, some people have mild symptoms after being infected with coronavirus, but some people have severe symptoms and even death.During the past 20 years, two popular β-coronaviruses are Severe Acute Respiratory Syndrome Virus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the infection mortality rates are 10% and 37% respectively. However, the coronavirus found by humans are only the tip of the iceberg. It is likely that more zoonotic diseases and highly infectious coronaviruses would be found in the future [6]. This epidemic was caused by SARS-CoV-2 [7], which is a single-strand RNA positive-strand enveloped β-coronavirus, having a high level sequence similarity with the enzymes of SARS and MERS. In addition, the analysis of protein structure shows that the binding “pocket” of SARS-CoV-2, SARS and MERS virus enzymes with drugs are conservative, so it is speculated that previous anti-SARS and MERS drugs can be used in NCP treatment [8].

Recently, a clinical analysis of 1,099 NCP patients from 31 provinces and cities reported that the proportion of fever and cough in hospitalized patients was 87.9% and 67.7% [3], and another 138 patients with NCP Clinical study found that the main clinical symptoms include fever (98.6%), asthenia (69.6%), cough (59.4%), total mortality rate was 4.3% [4], and a report of 12 patients also reported that main symptoms are cough (46.3%), upper respiratory tract congestion (61.5%), myalgia (23.1%) and headache (23.1%) [9]. “Diagnosis and Treatment Program for Novel Coronavirus Pneumonia (Trial Fifth Edition) [5] issued by National Health Commission” states that the disease main symptoms are fever, asthenia, and cough. Up to now, there isn’t effective antiviral drugs to treat with NCIP, symptom-based supportive therapies and comprehensive intervention are currently used by clinic. Therefore, treatment improving clinical symptoms, such as fever, asthenia, and cough related to the disease, have a great clinical significance for alleviating the severity of the disease and reducing the duration of the disease.

The Previous Basis and Clinical Trials of Lianhuaqingwen Capsule (Granules) indicated that LH-C can obviously inhibit the SARS-CoV viruse exsiting in in vitro culture of cells, and have significant inhibitory effects on H1N1, H3N2, H7N9 influenza virus and so on[11-12], and have no difference with Oseltamivir Phosphate from reducing the duration of viral nucleic acid of H1N1 influenza patients changing to negative and duration of all influenza symptoms, and can remitted fever, relieves cough, muscle ache, asthenia and other symptoms [13,14], Therefore, the clinical data of the combination of Lianhua Qingwen Granules for the treatment of common NCP patients from January 1 to 30, 2020 were summarized and analyzed on the improvement capacity on fever, asthenia, cough and other symptoms retrospectively. It found that under the basis of routine treatment, combination of Lianhuaqingwen Granule for 3 days, the fever disappeared rate is 47.5%; after treating for 5 days, fever, asthenia and cough disappearance rates are 62.5%, 59.5%, and 50.0%; after treating for 7 days, the fever, asthenia, and cough disappearance rates are 80.0%, 75.7%, and 76.7% respectively. The average disappearing period are 3.6 days, 4.1 days, and 5.3 days, which suggests that Lianhuaqingwen Capsule significantly relieves the main symptoms of fever, asthenia, and cough, and also has a significant improvement effect on relieving chest tightness, dyspnea, and moist rales of lung, the effective rate is 81.6%. It indicates that the drug has a good clinical effect on improving clinical symptoms, alleviating the severity of the disease, and reducing the duration of hospital stay. To further analyze clinical data, among the patients diagnosed with NCP common type, a typical case was selected and summarized as follows in order to provide clinical ideas for the treatment of the disease.

A female, 48 years old, native of Hubei, no other disease history. On January 11, 2020, the main symptoms were fever, cough, sputum, sore throat, runny nose, body ache, wheezing, shortness of breath. At the hospital, a chest examination, chest film and a CT of the lungs suggested a lung infection. After treating with Ganciclovir (intravenous injection, 0.5g, 1 time/day) and oseltamivir (oral, 1 capsule, 2 times/day), fever repeated. CT of lungs on January 17 showed “bilateral-lung infection, Viral pneumonia”. On January 18, she was admitted to the hospital with” pulmonary infection”, physical examination: body temperature 39.3 ℃, heart rate 112 beats/min, respiration rate 25 breaths/min, blood pressure 130/70 mm Hg (1 mm Hg = 0.133 kPa), red throat, thick lung sounds, scattered dry and moist rales. Blood routine examination: white blood cell count 3.53 × 109/L, neutrophil ratio 67.2%, lymphocyte ratio 28.4%. Blood biochemical examination: ALT: 35.3 U/L, AST: 42.6U/L, albumin 35.0g/L, lactate dehydrogenase 370 U/L, hydroxybutyrate dehydrogenase 275 U/L, NCP nucleic acid test showed positive.

(1)
Figure 4: Chest CT results

 

After admission, she was given levofloxacin (intravenous injection, 0.4 g, 1 time/day), vitamin C (intravenous injection, 3g, 1 time/day), ambroxol (Intravenous injection, 30mg, 2 times/day), Yanhuning (intravenous injection, 0.4 g, 1 time/day), methylprednisolone (intravenous injection, 40 mg, 1 time/day). On January 21, chest CT showed “infectious lesions in both lungs, compared to previous progress (2020.01.17), bilateral pleural thicker”. Adjusting treatment plan, dose Moxifloxacin (intravenous injection, 0.4 g, 1 time/d), ganciclovir (Intravenous injection, 0.5 g, 1 time/d), dose Lianhua Qingwen Granules (oral, 1 bag, 3 times/d), the body temperature turn into normal the next day. On January 28 and on January 31, The NCP test was negative, and on Feberuary 01, the patient had no fever, cough, sputum, thick breathing sounds of both lungs, a few dry and moist rales, and the chest CT showed absorbination is more obvious than before, as shown in Figure 4, blood routine and blood biochemistry examinations were normal, and the NCPs were negative for 2 consecutive times, comply with the clinical cure standard. They were discharged from the hospital and dose 2 boxes of Lianhua Qingwen granules at home (oral, 1 bag, 3 times/d). The patient feels good after follow-up so far, has no fever, cough, sputum and other symptoms.

In the above-mentioned typical cases, the body temperature returned to normal the next day after the combined application of Lianhuaqingwen Granules, and the symptoms and signs such as cough and moist rales were significantly improved, which was basically consistent with the results of the retrospective clinical analysis of 54 cases, revealing the characteristic advantages of the compound Chinese medicine “overall regulation and multi-target treatment”, suggesting that Lianhuaqingwen Granules has an important clinical application in the treatment of NCP patients. In addition, it should be pointed out that this study is a retrospective clinical study for NCP diagnosed common type patients, the sample size is small, lack of comparison of the efficacy of the control group, some patients failed to perform chest imaging examination in time, and the exact clinical efficacy needs to be evaluated by larger sample, prospective, randomized controlled clinical study.

Conflict of interest: All authors declare that there is no conflict of interest.

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