BAO Chunmiao,LI Binbin

BAO Chunmiao,Department of Respiratory,Yuyao People's Hospital of Zhejiang Province(the Affiliated Yangming Hospital of Ningbo University),Ningbo 315000,China

LI Binbin,Department of Respiratory,YongJia County People's Hospital,Wenzhou 325000,China

Abstract OBJECTIVE:To study the possible role of traditional Chinese medicine (TCM) of Huangqi (Radix Astragali Mongolici),Gancao(Radix Glycyrrhizae),Jinyinhua(Flos Lonicerae),and Lianqiao(Fructus Forsythiae Suspensae)in absorption of lung lesions in Corona Virus Disease 2019(COVID-19)patients.METHODS:A cohort of COVID-19 cases was recruited.During hospitalization,chest computed tomographic (CT) scan and real time polymerase chain reaction (RT-PCR) test were performed every three days.Comparison was held(Western Medicine,WM vs WM plus TCM) on absorption of lung lesions,time interval from admission to negative test result of RT-PCR(ATN),and medical expense.Multivariate cox regression models were built to identify the possible prognostic factor of delayed absorption of lung lesion.RESULTS:The medical expenditure (1163 ± 379 vs 1137±498,P=0.863)and ATN(13±4 vs 10±4,P=0.055) were comparable between cases treated with WM plus TCM and cases only received WM.Multivariate cox regression model showed that cases receiving extra TCM had lower risk of delayed absorption of lung lesions [Hazard ratio=0.24,95%confidence Interval(0.06,0.96),P=0.043].CONCLUSION:Compared to WM,the treatment of WM plus TCM facilitates the recovery of pulmonary infiltration on COVID-19 cases without significantly increasing medical expense.

Keywords:COVID-19;Traditional Chinese Medicine;Western Medicine;Epidemiology;Computed tomography

INTRODUCTION

Chest computed tomographic(CT)scan was extensively applied in the diagnosis and management of COVID-19 cases.1Conversion to negative test result of real time polymerase chain reaction (RT-PCR) and improvement on chest CT scan predict a recovery from COVID-19.2Previous study reported that over half COVID-19 patients present with typical chest CT development that parallel to the change of RT-PCR test whereas the rest showed a delayed improvement in lung lesions as compared with viral load shedding.3Traditional Chinese medicine(TCM)functioned as an adjunctive option in the management of COVID-19.4The therapeutic role of TCM in this refractory pulmonary infiltration remained unclear.This study was aimed to identify the possible effect of TCM in recovery of COVID-19 in terms of absorption of lung lesions.

METHODS

A cohort of individuals with diagnosis of COVID-19 confirmed by RT-PCR was consecutively recruited.Clinical characteristics of age,gender,comorbidity,smoking status,and time interval from symptom onset to admission(STA)were collected during epidemiological investigation.Diabetes and hypertension were reported as comorbidity while no other disease was found in this study population.STA was used to measure the timing of medical intervention(longer STA indicates a delayed medical intervention).During the hospitalization,chest CT scan and RT-PCR test were performed every three days.Initial CT scan of each patient showed bilateral pulmonary infiltration.Patients with a negative RT-PCR test while CT scan showed nodular or patchy ground glass opacity lesions in multiple areas,with thickening of interlobular and intralobular septa,and halo signs around the nodules were defined as cases with delayed absorption.No medical treatment was provided pre-hospitalisation whereas a combination of IFN α-2b,lopinavir,and umifenovir(western medicine,WM) was initiated on each patient after admission.In addition to WM,computer-aided random selection of patients (n=29) received an extra of TCM (Radix astragali,Radix Glycyrrhizae,Lonicerae JaponicaeFlos,andFructus Forsythia).Baseline laboratory tests (white blood cell,WBC,platelet,Plt,and c-react protein,CRP),time interval from admission to negative RT-PCR (ATN),and medical expense were collected.ATN was used to measure the change of viral load (longer ATN indicated a prolonged coronavirus shedding).The conversion of medical expenditure in Chinese yuan to United States dollars (USD) was made basing on March 18th 2020 (last patient discharged) exchange rate (1 USD=7.03 CNY).This study was approved by the Research Ethics Committee of Yongjia County People's Hospital (approval number:2020-L01),with a waiver of informed consent.

Statistical analysis

Difference between groups (WMvsWM plus TCM)were assessed with independent samplettest,wilcoxon signed rank tests,orChi-square test,depending on the distribution.Survival analyses for time to negative RT-PCR was conducted using two multivariate cox regression models.Age,gender,comorbidity,smoking status,STA were adjusted in the first cox model.In addition to these potential confounders,baseline laboratory test (mean ± standard deviation) was added as a covarite in the second cox model.All analysis was per-formed with STATA 16.0(Stata Corp,College Station,TX,USA),P-value <0.05 was defined as statistically significant.

RESULTS

Without ventilation support,all patients (n=43) were fully recovered from COVID-19 with a mean medical expense of 1154.29 USD.Medical intervention was initiated in early stage of disease (median STA was three days).Mean ATN of our study population was 11.95 d(standard deviation=4.31).Most clinical characteristics had a similar distribution between two groups (29 in WM plus TCM,14 in WM).Baseline laboratory tests found higher level of WBC in WM plus TCM group,as compared with WM only group(7.1 ± 2.7vs5.0 ± 1.1,P=0.014,Table 1).After adjusted for age,gender,comorbidity,smoking status,and STA,multivariate cox regression model presented a pattern of lower risk of delayed absorption of lung lesion in patients treated with WM plus TCM [Hazard ratio=0.47,95%confidence interval(0.21,1.03),P=0.059,Table 2].While adding the laboratory tests in the model,extra TCM in treatment was identified as the prognostic factor of less refractory lung damage[Hazard ratio=0.24,95% confidence interval (0.06,0.96),P=0.043,Table 2].

Table 1 Comparison between WM and WM plus TCM[n(%)]

Table 2 Multivariate cox regression model

DISCUSSION

Chest CT scan plays an important role in early detection of COVID-19,which shows various degrees of pulmonary abnormalities.5Unparalleled progress on CT image and viral load has been reported.6In our study,the combination therapy of WM and TCM was associated with lower risk of delayed absorption of lung lesions,as compared with WM only treatment,without dramatically increasing the medical expenditure.National policy in China rules in full coverage of medical expense by healthcare insurance in treating COVID-19,removing the effect of social-economic status in patients' outcomes.As a measurement for conversion of RT-PCR,ATN was found marginally significant prolongation in WM plus TCM group,suggesting that the disparity in chest CT scan is not only a reflection of presumable later phase of lung tissue repair7but also an indication of different process of viral load shedding.

Better recovery from pulmonary infiltration was found in patients who received treatment of WM plus TCM,which supports a stratified management of COVID-19 patients.There were several studies supported the use of TCM on COVID-19 cases.The empirical use of TCM has been widely applied in treating COVID-19,which was proved to be effective in reducing severe symptoms.8The combination of WM and TCM was reported to be useful in a family case of COVID-19.9Systematic review and Meta-analysis showed that patients with integrated therapy had better outcome without inducing severe adverse drug reactions.10In addition to these studies,we provided radiographic evidence for a trend of disease fades while a combination of TCM and WM was used.For cases only received WM,repeated CT scan may be necessary to identify and evaluate the delayed absorption of lung lesions.

Our study has several limitations.First,only moderate COVID-19 patients (positive RT-PCR and pneumonia) were recruited in this study.So our founding may not apply to severe cases.Another limitation was that we only focused on radiographic outcome in this study.Functional prognosis such as lung capacity test was not performed in the follow up.