Retrospective analysis of the efficacy of traditional Chinese medicine Lianhua Qingwen Capsule for the treatment of novel coronavirusinfected pneumonia

Peng Chen,Xiong Gan,Li-Juan Fang,Jie-Xin Lei,Fu-Chao Chen,Yue Wu,Guo-Hong Pan,and Ben-Hong Zhou

Abstract—Objective:The aim of this study was to evaluate the clinical efficacy of traditional Chinese medicine Lianhua Qingwen Capsule (LQC) for the treatment of novel coronavirus-infected pneumonia by a retrospective analysis of confirmed COVID-19 cases,thereby providing a reference for clinical treatment.Methods:We retrospectively analyzed the clinical data of patients with confirmed NCIP treated at the Hanchuan Hospital of People’s Hospital of Wuhan University of China between January 21 and January 30,2020.A total of 32 patients were included in the treatment group,who received routine treatment plus LQC (1 packet,tid),and 32 patients were included in the control group,who received routine treatment alone.The data about response rate of respiratory symptoms were compared and analyzed between the two groups.Results:No significant betweengroup difference was observed in baseline data.The response rates for fever were 84.4% in the treatment group and 56.3%in the control group;for cough,the response rates were 47.8% and 7.4% in the treatment group and the control group,respectively (P <0.05).The response rates for expectoration were 71.4% in the treatment group and 11.8%in the control group;for shortness of breath,the response rates were 78.6% and 0% in the treatment group and the control group,respectively (P <0.05).The average duration of symptoms like fever,cough,fatigue and expectoration in the treatment group were shorter than that in the control group (P <0.05).There was no significant difference in the incidence rate between LQC and control group.Conclusion:Traditional Chinese medicine LQC significantly improved fever,cough,expectoration,and shortness of breath in patients with confirmed COVID-19,thereby providing preliminary evidence for clinical treatment.

Key words—Lianhua Qingwen Capsule,Novel coronavirusinfected pneumonia,COVID-19,Clinical study,Fever,Cough

INTRODUCTION

In December 2019,a number of patients with pneumonia of unknown cause,now confirmed infected with a novel coronavirus were found in Wuhan,China [1].Serval published studies have reported a lot of cases with COVID-19 (now officially named by the World Health Organization as COVID-19) in which most of them traveled to or had contact with people from Wuhan,provides a convenient channel to increase our understanding of epidemiological,clinical,laboratory,and radiological characteristics and treatment and outcomes related to most of the infected patients [2,3].However,no targeted effective antiviral therapy is available for COVID-19,and the main treatments include symptomatic and supportive care and integrative intervention [4,5].Given the important role of integrative traditional Chinese and Western medicine in epidemic prevention and control during the outbreaks of SARS and H1N1a influenza,it is important to investigate the advantage of holistic treatment with traditional Chinese medicine and the efficacy of integrative traditional Chinese and Western medicine for improving COVID-19 clinical symptoms and COVID-19 prevention and control [6].

Lianhua Qingwen Capsule (LQC) is an innovative Chinese patent medicine for the treatment of influenza that is based on the theory of traditional Chinese medicine and meridians and was approved via the accelerated pathway for new drug approval during the SARS outbreak in 2003[7-9].It has broad-spectrum antiviral,antibacterial,antipyretic,and anti-inflammatory properties,eliminates cough and phlegm,and produces immune-modulating effects against viral respiratory infectious diseases [10-12].Specifically,it has significant inhibitory and killing effects on coronaviruses associated with SARS and Middle East Respiratory Syndrome (MERS).The drug has been named 20 times by the National Health Commission and the National Administration of Traditional Chinese Medicine as the recommended drug for the prevention and treatment of respiratory infectious diseases and has become a representative Chinese patent medicine for responding to respiratory public health events [13,14].

Moreover,LQC is one of the recommended drugs inThe Guidelines for the Prevention and Management of Novel Coronavirus-infected Pneumonia(provisional,version 4).Since the outbreak,we have been using integrative traditional Chinese and Western medicine (LQC plus routine treatment) to treat patients with common COVID-19,with good outcomes.Thus,we performed a retrospective analysis of COVID-19 aiming to evaluate the efficacy of LQC and to provide some references for clinical therapy.

MATERIALS AND METHODS

General information

We conducted a retrospective study on the clinical characteristics of laboratory-confirmed cases with COVID-19.Since the outbreak of the epidemic,strict prevention and control measures have been taken in Xiaogan,including the creation of fever clinics to receive and treat patients confirmed or suspected to be infected with the COVID-19 virus,defined as presenting with the main clinical symptoms such as fever,cough,muscle ache,fatigue,expectoration,shortness of breath,headache,sore throat,runny nose,diarrhea,nausea,and vomiting,with special consideration for to those who had prior exposure to infected people or a recent history of a short trip to Wuhan.The data were collected from 64 patients fulfilling the World Health Organization interim guidance criteria for COVID-19 who were selected at the Hanchuan Renmin Hospital of Wuhan University in Xiaogan,China,between January 21 and Ferbary 2,2020.

Exclusion Criteria:patients with 1) Severe or critical COVID-19;2)Non-COVID-19 associated acute respiratory disease;3) Any other chronic respiratory disease or bacterial respiratory infections such as bacterial tonsillitis,acute tracheobronchitis,sinusitis,or otitis media that affect clinical evaluations;4) Asthma requiring daily treatment,underlying pulmonary diseases such as severe interstitial disease and bronchiectasis as per chest X -ray or computed tomography (CT);5) Other underlying diseases such as severe primary immunodeficiency disease,acquired immunodeficiency syndrome,congenital respiratory malformation,congenital heart disease,and pulmonary dysplasia.

Laboratory confirmation and treatment

Nasopharyngeal swabs,oropharyngeal swabs,and/or naso-pharyngeal aspirates were collected from patients to analyze for the presence of COVID-19 through a real time reverse transcription polymerase chain reaction assay (RTPCR).Moreover,paired acute and convalescent sera of the patients were collected and examined.Laboratoryconfirmed cases of COVID-19 were defined as either positive RT-PCR findings or a fourfold or greater increase in antibody titers.

Hospital patients with confirmed COVID-19 received routine treatment (recommended treatment according to The Guidelines for the Prevention and Management of Novel Coronavirus-infected Pneumonia (provisional) from the National Health Commission) or routine treatment plus LQC (1 packet,tid).Patients who received routine treatment plus LQC who met the inclusion and exclusion criteria with body temperature >37.2 °C were included in the treatment group.A logistic regression model was used to calculate the propensity score with age and temperature as covariates,and 32 patients who received routine treatment were selected to match the treatment group 1:1 and were used as the control group.

Data collection

For the present study,the following data were analyzed:demographic data,medical history,exposure history,underlying comorbidities,respiratory symptoms,signs,laboratory findings,chest CT scans.All data were extracted from the electronic medical record (EMR) system by trained research coordinators.The data were reviewed by a trained team of physicians.The incubation period is defined as the time from exposure to the source of transmission to the onset of symptoms.The study was approved by the Ethics Committee of Hanchuan Renmin Hospital of Wuhan University in Xiaogan,China.Patient records were anonymized and deidentified prior to analysis.

Statistical Analysis

For descriptive analysis,count data are expressed as frequency and percent,and measurement data are expressed as the mean and standard deviation.The LQC therapy group was compared with the control group in terms of response rate and average duration of main symptoms (fever,cough,and fatigue) and the response rate of other symptoms (muscle ache,expectoration,nasal congestion,runny nose,sore throat,shortness of breath,chest tightness,difficulty breathing,headache,nausea,vomiting,loss of appetite,and diarrhea).Quantitative data were analyzed with the t-test;categorical data were analyzed with the chi-square test or Fisher’s exact test.SPSS 17.0 (SPSS Inc.,Chicago,IL,USA) software was used to analyze data and was used for statistical analysis.All statistical tests were two-sided.P<0.05 was considered statistically significant.

RESULTS

Characteristics of patients

A total of 64 patients with confirmed common COVID-19 met the entry criteria were admitted during the study period.All the patients were instructed by study investigators to measure their body temperature,to score and record the severity of symptoms,and to administrate study medications by themselves.All the measurements were performed based on the patient’s diary card and recorded on the patient’s card once daily.Of these,the treatment group included 24 men (75.0%) and 8 women(25%),aged 57.2 ± 13.8 years.The control group included 18 men (56.25%) and 14 women (43.75%),aged 62.4 ±12.6 years.There were no significant differences between the groups for the baseline data,such as age,sex,temperature,blood pressure,heart rate,respiratory rate,past history of illness,or time from onset to diagnosis.All patients’ clinical characteristics are shown in Table 1.

Comparison of response rate for respiratory symptoms

Of the 32 patients in the treatment group,32 (100%) had fever,23 (71.9%) had cough,and 17 (53.1%) had fatigue;of the 32 patients in the control group,32 (100%) had fever,27 (84.4%) had cough,and 19 (59.4%) had fatigue.However,these differences were not significant (allP>0.05).And the response rate for fever was 84.4% (n=27)in the treatment group,significantly higher than that in the control group (56.3%;c2=3.100,P=0.032);for cough,the response rate was 47.8% (n=11) in the treatment group,significantly higher than that in the control group(7.4%;P=0.014).No significant between-group differences were observed for the response rate for fatigue(P=0.712) (Table 2).Furthermore,regarding to the other symptoms,the results showed that the response rates were 71.4% for expectoration and 78.6% for shortness of breath in the treatment group,both of which were significantly higher than those in the control group (P<0.05).No significant between-group differences were observed in theresponse rate for other symptoms (Table 2).

Table 1 Baseline characteristics of enrolled patients.(,n=32)

Table 1 Baseline characteristics of enrolled patients.(,n=32)

Note:1 mm Hg ≈ 0.133 kPa;a t-test;b Chi-Square test.

Table 2 Comparison of response rate for main symptoms between treatment group and control group.

Average duration of respiratory symptoms for each individual

The average duration of each individual symptom was shown in Table 3.Significant differences were observed in the average duration of symptoms like fever,cough,fatigue and expectoration (P<0.05).The above data clearly showed that LQC had significantly greater effects on the reduction of the average duration of the above symptoms.

Table 3 The median duration of symptoms.

Safety analysis

There were no significant differences in the baseline data of laboratory test between the groups.There was a total of 11 non-serious adverse events with four from the LQC group and six from the control group,which were assessed as possibly unrelated to medication.The reporting of serious adverse events was in accordance to the relevant regulation of China health authority.There was no significant difference in the incidence rate between LQC and control group.No study medication was discounted due to adverse events in the study.There were no adverse events judged to be related to LQC,while there were four adverse events,nausea and vomiting,judged to be related to control group.

DISCUSSION

Current data show that the main clinical symptoms of COVID-19 are fever,muscle ache,fatigue,expectoration,shortness of breath,headache,sore throat,runny nose,diarrhea,nausea,and vomiting [2-14].According toThe Guidelines for the Diagnosis and Treatment of Novel Coronavirus-infected Pneumonia(provisional,version 5)from the National Health Commission,the disease mainly manifests as fever,fatigue,and dry cough [15].Some patients present nasal congestion,runny nose,sore throat,and diarrhea.In an exclusive interview with Xinhua News Agency,Academician Nanshan Zhong of the Chinese Academy of Engineering commented that fever is still the most important and typical symptom among confirmed COVID-19 cases [16].Therefore,in this study,we evaluated the efficacy of traditional Chinese medicine for the treatment of confirmed cases with fever as the main clinical manifestation.No targeted effective antiviral drugs are available to treat COVID-19.Thus,improving diseaserelated clinical symptoms such as fever,cough,and fatigue has important clinical significance in alleviating disease severity and shortening the disease course.

This disease is considered an“epidemic disease”according to the theory of traditional Chinese medicine.The main cause is epidemic toxin,whose invasion and transformation into heat is the turning point for a more severe condition [17].This is consistent with the main clinical manifestation (fever) of COVID-19.The traditional Chinese medicine LQC is an innovative Chinese patent medicine that is based on the theory of traditional Chinese medicine and meridians and the evolving pattern of viral respiratory infectious diseases and aims to“resolve epidemic toxin and clear the lungs and heat”[9,18].The formula is based on Ephedra apricot kernel gypsum &licorice decoction (Ma Xing Gan Shi Tang) from Treatise on Febrile Diseases by Zhongjing Zhang in the Han Dynasty and on Eu Yan Sang from Differentiation of Warm Diseases by Jutong Wu in the Qing Dynasty,with reference to the use of rhubarb for epidemic diseases from Treatise of Warm Epidemic Diseases by Youke Wu in the Ming Dynasty,and is combined with rhodiola to clear the lungs,remove stasis,and regulate immunity [19].It reflects the experience of traditional Chinese medicine in preventing and treating epidemic diseases for two thousand years.It is clinically indicated for respiratory infectious diseases with fever,chills,cough,and muscle ache.Pharmacological studies have shown that traditional Chinese medicine LQC significantly inhibits the in vitro activity of SARS-CoV,with certain inhibitory effects on the activity of MERS-CoV [12].The formula targets influenza A viruses H1N1 and H3N2 via multiple pathways and significantly suppresses the avian influenza virus H7N9.Moreover,it has antibacterial,antiinflammatory,and antipyretic properties,eliminates cough and phlegm,and produces immune-modulating effects [5-14].These data indicate that LQC enable“holistic and multi-target treatment,”with a sound theoretical and scientific basis.

In this study,we included 64 patients with confirmed COVID-19 and fever,with varying degrees of cough,fatigue,expectoration,muscle ache,shortness of breath,sore throat,nausea,vomiting,loss of appetite,and diarrhea.The results showed that routine treatment plus LQC significantly improved clinical symptoms such as fever,cough,expectoration,and shortness of breath.The integrative treatment significantly shortens the duration of fever,cough,fatigue and expectoration,indicating that LQC were advantageous in improving the duration of these symptoms.Moreover,LQC effectively improved fatigue,muscle ache,nasal congestion,and headache.Given the lack of effective antiviral drugs,it is clinically important to utilize“holistic and multi-target treatment”via traditional Chinese formulas to improve clinical symptoms and patient conditions and shorten the disease course.

In this study,the preliminary results for LQC are consistent with previous literature reports.For example,a randomized,double-blind,multi-center clinical trial that investigated LQC for the treatment of H1N1a in 2009 showed that LQC was comparable to oseltamivir phosphate with respect to time to a negative RNA test and time to alleviation of all influenza symptoms and was superior to oseltamivir phosphate with respect to alleviation of fever,cough,muscle ache,and fatigue [20].Another randomized,controlled clinical study of LQC for the treatment of H1N1a influenza showed similar results [21].In addition,a retrospective analysis of LQC for the treatment of H1N1a influenza at Beijing Ditan Hospital showed that LQC was comparable to oseltamivir with respect to alleviation of fever and time to a negative RNA test [22].This clinical evidence was generated during the H1N1a outbreak in 2009,indicating that LQC played an important role in preventing and treating viral respiratory public health events.This study further demonstrates that LQC has a clinical value for the treatment of COVID-19.

Notably,the current study is a retrospective clinical analysis in patients with confirmed common COVID-19,we did not differentiate traditional Chinese syndromes.Moreover,this study has limitations such as a small sample size and a lack of negative RNA tests and serological data.In the future,large,prospective,randomized,controlled clinical studies are needed to further evaluate the clinical efficacy of the traditional Chinese medicine LQC for the treatment of COVID-19.

ACKNOWLEDGMENT

The authors did not receive any funding for this study.

Author contributions:Peng Chen and Xiong Gan have contributed equally to this study and share first authorship.

Competing interests:The authors declare that they have no conflict of interest.

Citation:Chen P,Gan X,Fang LJ,Lei JX,Chen FC,Wu Y,et al.Retrospective analysis of the efficacy of traditional Chinese medicine Lianhua Qingwen Capsule for the treatment of novel coronavirus-infected pneumonia.Drug Combination Therapy.2021;3(4):20.doi:10.53388/DCT2021110505.

Executive editor:Jin-Feng Liu.

Submitted:23 July 2021,Accepted:15 September 2021,Online:03 November 2021

? 2021 By Authors.Published by TMR Publishing Group Limited.This is an open access article under the CC-BY license (http://creativecommons.org/licenses/BY/4.0/)