Risk assessment and analysis of Traditional Chinese Medicine intervention in coronavirus disease

ZHAO Yufeng,PANG Huaxin,Lü Lanting,ZHOU Pei,WANG Kaining,CAI Shengxing,ZHANG Huifeng,LI Kun

ZHAO Yufeng,ZHOU Pei,ZHANG Huifeng,Data Center of Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China

PANG Huaxin,School of Computer and Information Technology,Beijing Jiaotong University,Bejing 100044,China

Lü Lanting,School of Public Administration and Policy,Renmin University of China,Bejing 100872,China

WANG Kaining,CAI Shengxing,Data Center of Traditional Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China

LI Kun,Vice President,China Academy of Chinese Medical Sciences,Beijing 100700,China

Abstract OBJECTIVE:To explore the advantages of Traditional Chinese Medicine (TCM) in "prevention" and "control" of coronavirus disease 2019 (COVID-19) pandemic.METHODS:In this paper,we wish to estimate the effect on the virus transmission of scenarios assuming TCM were used to build the first defense line at the very early stage of the spread in Wuhan.We therefore first developed a classic susceptible infected removed(susceptible infected removed,SIR) transmission model based on the national data in China and then updated it to a TCM-SIR model to assess the potential impact of such assumptions,i.e.the underlying risk of lives lost and social economy loss.RESULTS:(a) With the nationwide community lockdown,the risk value was from 90 000 to 250 000 without TCM intervention and the risk value was from 70 000 to 220 000 with TCM intervention;(b) Based the risk assessment method,we forecasted that the infections peak would be 58016 without TCM intervention,which happened on February 17 2020.However,the infections peak would be 45713 with TCM intervention,which happened on 16 February 2020.CONCLUSIONS:The adoption of nationwide community lockdown is conducive to timely control the epidemic and protect people's lives and safety.At the same time,we can get lower infections if TCM intervention can be considered.We can also get the benefits from TCM prevention of COVID-19 pandemic by the basic number of infections.

Keywords:COVID-19;medicine,Chinese traditional;risk assessment;public health

1.INTRODUCTION

Sudden major infectious diseases are the one of the biggest threats to health in China and in the world.With the development of social economy,countries have a deeper understanding of infectious diseases and the focus of prevention and control,and have reached certain global consensus.1,2How to improve the prevention,response and management system of major public health emergencies has always been a worldwide problem.In this“war of coronavirus disease 2019 (COVID-19)”,China has successfully controlled COVID-19 after paying countless sacrifices,and avoided its extensive outbreak.It also showed many highlights and advantages worthy of promoting globally,including the effective and rapid response of TCM in the prevention and control.3-6As a fact,it is difficult to achieve the vaccines or effective specific drugs to guide the emergency prevention and control of a sudden major infectious disease outbreak because of the limitations of clinical trial researches.Therefore,it is significantly important to establish a risk assessment model for TCM to participate in the prevention and control of major infectious diseases.The rich and effective clinical experience of plague by TCM accumulated in thousands of years and the representative“Theory of Febrile Diseases”once again showed its outstanding advantages and values,that is,to quickly discover the core pathogenesis,evolution rules and form the general treatment of TCM,all of which have shown positive effects in both "prevention" and“control”.In this paper,we propose a prediction model to assess the potential impact and effectiveness of TCM in the COVID-19 epidemic.

For many prediction models,7-10there are two main problems of the prediction models of COVID-19 which mainly focuses on the trend of the epidemic:one is the great limitations in the integrity and systematization of the data;two is the lack of risk assessment variable for TCM which has the potential to greatly speed up the decision making and enhance the ability of prevention and control.Therefore,based on COVID-19 data in China and the classic SIR model of infectious disease transmission,the TCM-SIR model of major communicable diseases transmission under the framework of Chinese medicine prevention and control was first established.The error caused by the lack of data in the early stage of epidemic was overcome by double prediction.Mastering the law temporal and spatial variation of COVID-19 under different medical resources settings,prevention schemes and isolation levels,we aim to realize the rapid assessment of different epidemic risks under different risk plans based on the spatio-temporal change rule of the epidemic spread.Meanwhile,we proposed to build a new national level Internet plus Chinese medicine to quickly respond to epidemic prevention and control,so as to bring Chinese medicine into full play.To optimize the rapid risk assessment,decision support and response mechanism of major public health emergencies in China.

2.DATA SOURCE

The COVID-19 diagnosis number comes from the official website of the National Health Commission.TCM number comes from the official number of the State Administration of TCM.

3.ANALYSIS METHODS

Based on the classic infectious disease transmission model SIR,the TCM intervention mode is transformed into super parameter to dynamically adjust the infection coefficient and recovery coefficient,in order to explore the changes of the number of infections under the TCM intervention.

3.1.Solving strategy of SIR model

First,SIR model8-10divides the population in the epidemic area into susceptible group S (t),infected group I (t) and removed group R (t).At the same time,we assume that:(a) the number of people affected by infectious diseases is relatively stable without intensive flow of cross-regional population in large scale;(b) the population will all be potential for infection regardless of physical differences.In unit time,the number of S (t)who can be infected by I (t) is directly proportional to the total number of I (t);(c) In unit time,R (t) is directly proportional to I (t),and there is no secondary infection in R (t).Based on the above definitions and assumptions,the differential equation of SIR model is as follows:

β and γ represented the infection coefficient and recovery coefficient of the disease in the process of transmission.Equation (1) is obtained by solving the differential equation as a whole.S0andI0are the initial values of susceptible population and infected population respectively.

In order to get the accurate dynamic change law of I (t),the most important is to estimate the infection coefficient and recovery coefficient during the epidemic.We use exponential smoothing method and least square method to fit and estimate the infection coefficient.The advantage of exponential smoothing method is that it is generally used as a statistical algorithm for local prediction of time series prediction which is characterized by strengthening the role of recent observations on the predicted value in the observation period,giving unequal weights to observations at different times,thus increasing the weights of recent observations,so that the predicted value can quickly reflect the actual changes.The least square method is a mathematical optimization technique.It finds the best function match of data by minimizing the square sum of error.By using it,the unknown data can be easily obtained,and the square sum of the error between the obtained data and the actual data can be minimized.According to the above assumptions,as for the recovery coefficient which is proportional to the number of days the patient treated in hospital,it is estimated by the combination of the results of the recovery length of general viral pneumonia (2-3 weeks) and that of SARS(about 22 d) as well as the days in hospital of patients with COVID-19 reported in medical record data.

3.2.Solution strategy of TCM-SIR model

Traditional Chinese medicine has certain direct antiviral effect,11-17and because of its multi-component and multitarget characteristics,it can effectively inhibit the conversion of viral pneumonia from mild to severe,quickly improve the symptoms of patients,with definite clinical effect.Xiaet al18found that the proportion of patients treated with the combination of TCM and Western medicine from common type to severe type was 5.9%,less than 33.3% in the western medicine group.Therefore,we assume that the intervention of TCM can affect the infection coefficient and recovery coefficient of infectious diseases.The impact rate of change is as follows:

C in the formula is the infection factors of TCM intervention.According to relevant literature and data,TCM intervention reduces the probability of patients from ordinary type to critical type by 28.4%.The probability of light to ordinary type is correspondingly reduced.To this end,through analogy verification,we comprehensively considered the probability mean of different phenotypes,and took its derivative as the infection factor C of TCM intervention.According to the analysis above,C is assumed to be 3.5.By dynamically adjusting the infection coefficient and recovery coefficient,we can predict the changes of I (t) under the intervention of TCM and evaluate the development trend of the epidemic.

3.3.Estimation of basic number of infections

The basic infection number R is one of the core indicators to evaluate the harm degree of infectious diseases.A reasonable estimate of R will help people understand the risk of the epidemic,and help decision makers to make plans and take measures reasonably to prevent and control the epidemic,preventing its spread.Meanwhile,it will help suspected people to understand its impact on themselves and their life so as to avoid unnecessary panic and out-of-control behaviors.We estimate R by mathematical derivation.According to the results of Zhao et al,19,20the basic infection number is calculated as follows:

In the formula,ris the growth rate of the infected.Based on SIR model we can predict the number of the infected people.With the results,we can calculate the change of the growth rate of the number of infected people in the past and in the future.According to the change trend of the epidemic,we can get the growth rate r and the confidence interval.

For L and I,they both come from observations of current situation.L is the average length of incubation period of the infected.I=S-L,while S is the interval between the time one person who gets infected and the time he/she infected the next person.In the early stage of the epidemic,L and S are difficult to obtain,or with errors because of small samples.Therefore,it is often assumed that S follows the exponential distribution on the premise of recognizing the incubation period.Then we can think that L and I are independent and identically distributed,that is,they account for each half in S,then SI actually obeys gamma distribution (exponential distribution is a special case of gamma distribution).Next,L and I can be estimated according to the gamma distribution characteristics and the actual situation of the event,and the confidence interval is given.In this COVID-19,the basic infection number R is predicted to be1.57-2.6.In addition,the confidence interval is calculated by:

For the basic infection number R,200 independent experiments were conducted,and the average results were reported in this paper.In Equation (6),RmeanandRstdrepresent the mean and the variance of the results of 200 experiments,whereN=200.

3.4.Quarantine measures

According to the past experience of epidemic prevention and control,the proportion of infected people hospitalized,the proportion of intensive care in hospital and the mortality rate are different in different age groups.The main feature of the change is that the risk of infection is higher in children,and the youth and middle-aged children is the strongest to defense the diseases,but with the increase of age,these proportions are on the rise.Therefore,children and people over 70 years old need special attention and care.According to the situation above,five isolation modes are specified in our project:(a) quarantine of infected patients at home;(b)quarantine of infected patients' families;(c) isolation of children at home after school closure;(d) isolation of the senior over 70 years old;(e) regional or national communities’ lockdown.The strictness of quarantine measures shows the severity of the epidemic,and the degree of negative impact on social economy.

4.ANALYSIS RESULTS OF INFECTION RISK ASSESSMENT UNDER MULTIPLE INTERVENTIONS

Due to the significant effect of TCM in improving people's immunity,relevant research shows that it can reduce the risk of infection by 40% in susceptible people.If TCM could be added in the early prevention and control measures,combined with certain quarantine measures,the risk level might be reduced.Therefore,we introduced isolation measures and TCM Prevention and control as super parameters into SIR model to build TCM-SIR model,and predicted the change of infection number and basic infection number.Taking the COVID-19 data in Wuhan as example,we calculated theRin Wuhan was 2.2.The preliminary calculation results under the combination of different level of quarantine measures and TCM intervention are shown in Table 1.As shown in Table 1,as COVID-19 is of high infectious rate,serious incidence,serious risk assessment,so the adoption of nationwide community lockdown is conducive to timely control the epidemic and protect people's lives and safety.At the same time,the promotion of TCM intervention as prevention method,the selection of appropriate prescription of TCM prescription to the most susceptible population could increase the immunity of isolated population and reduce the risk of infection.As a result,the number of infected and the morality rate of COVID-19 would have been further reduced.In addition,for the infectious diseases with low risk and low degree of harm,the effect of TCM prevention with low-level quarantine measures is better than that of only mediumlevel isolation measures,and with less negative impact.Therefore,the results have shown that implementing the intervention of TCM would have brought down the infectious rate and therefore better outcomes in terms of lives saved,as well as less economic impact.

Table 1 Epidemic risk assessment with the combination of multiple quarantine measures and Traditional Chinese Medicine intervention

Combining Figure 1,due to the complexity of the epidemic and incompleteness of data in early stages of the outbreak,we use the existing number of confirmed diagnoses across the country to estimate the number of infected people.Before January 23,no proper intervention was initiated in the country,and test for the new virus stream were not even available,which as a result led to a false face-fact that the number of diagnoses in hospitals grew relatively slowly.With the implementation of a series of epidemic prevention and control measures and the national isolation strategy,hospital testing and community inspections have been strengthened.More and more people were diagnosed,and the number of confirmed diagnoses continued to rise.On February 11,Wuhan began to implement parallel examinations of clinical diagnosis and accounting detection,which led to an increase in the number of confirmed cases.On February 17,the number of infections (existing confirmed diagnoses) reached a peak nationwide,at 58 016,afterwards it began to decline slowly.If the prevention and control of TCM and measures are taken in the early stage,based on the estimated trends of the number of infected people,it is fairly clear that early intervention could reduce the risk of infection in susceptible people,and the increase in the number of early infected people could be slowed down.Our estimation shows that with TCM prevention,the value could have reached peak on February 16 at 45 713(a day earlier and much less infected).Compared with the actual situation,the peak number of infected decreased by 12 303 (Figure 1).This could have alleviated hospital pressure,protected people's lives and reduced social and economic losses.

Wuhan was hit the hardest in China.In the early stage,due to the insufficient quantity of testing materials,there was a big gap between the number of infected that were confirmed by the test and the number of people actually infected.With the improvement of testing efficiency,and the use of clinical symptoms diagnosis on February 11,the number of confirmed cases rapidly increased.Shortly after that,universal testing was implemented in the Wuhan area,and the gap between number of confirmed cases and that of actual infected cases continued todecrease.On February 18,the number of infections reached its peak,at 38 020.The simulation scenario implementing the intervention of TCM shows that on February 17,the average number of infections predicted by the model reached a peak of 29 103 cases,which was 8917 fewer cases than the actual situation.It can be seen that in Figure 2,if intervention of TCM could be applied in the early stage of the outbreak,anti-infection ability of susceptible groups and healthy groups (especially this group) could be improved.Moreover,in the course of hospital treatment,the combination of TCM and Western medicine could effectively reduce the probability of patients moving from mild to severe conditions,and help patients recover speed.This would not only reduce the operating load of hospitals,but also save treatment costs and all over losses.

Figure 1 Comparison of confirmed cases with or without Traditional Chinese Medicine interventions in China

Figure 2 Comparison of confirmed cases with or without Traditional Chinese Medicine interventions in Wuhan

In order to better assess the scale of the epidemic across China,we have broken down the data into 4 regional categories according to Table 2:the whole country(China),Wuhan alone (Wuhan),and the whole country except Hubei Province (Ot-Pro) and Hubei Province except Wuhan (Ot-City),according to the impact and spread of COVID-19.Because the peak number of actual infections occurred around February 18,we took February 18 as the central point and selected 53 d of infections from January 23 to March 15 to calculate the average R and Standard deviation.During this 53-days,the overall basic infection number R in China is 2.27 [95%CI(1.96,2.57)].As the epidemic center in China,Wuhan,the capital of Hubei Province,has the largest R average of 2.43 [95%CI(1.85,3.01)].This also caused Hubei to be more severely affected by radiation than other provinces and cities;the average number of basic infections was 2.19 [95%CI(1.85,2.53)].Although the Spring Festival home-coming Movement caused the spread of COVID-19 from Wuhan to other provinces and cities,the timely national strategy of isolation of all people had been able to contain the risk of community transitions to a minimum.Thanks to that,the average R of other provinces and cities nationwide (except Hubei Province) is below 2,which is about 1.79 [95%CI(1.55,2.03)].We conduct multiple experiments for different N set in (100,500,1000,2000),The experiments are shown as follows in Table 3:

Table 2 Number of basic infections in different areas

Table 3 Change of R with different N in China

5.DISCUSSION

Due to the insufficient understanding of the epidemic in the early stage and the relative errors of the data collected,the prediction of SIR model would deviate in the process of infectious power assessment.In order to reduce the deviation problem,we creatively combined the exponential smoothing method and the least square method to estimate the infection coefficient in SIR model,so as to make it conform to the real epidemic development trend as much as possible,and to ensure the reasonable and effective prediction of the number of infected people as well as the accurate evaluation of the basic infection number which could be the data support.According to the risk assessment of epidemic based on the infectious power assessment model,a reasonable decision-making and deployment can be made.In this study,the innovative combination of TCM with the isolation measures allow TCM showed its advantages in prevention and treatment.The TCM intervention was transformed into super parameters,and the infection coefficient and recovery coefficient of SIR model were adjusted,thus the TCM-SIR model was constructed to predict the change of infection number after TCM Intervention and to assist further decision-making.The new mode of Isolation &Protection could reduce the contact probability,improve the immunity,and greatly reduce the risk of infection,and keep the epidemic under control at time.

Based on the most comprehensive data of COVID-19 in China,we constructed and improved the classic SIR of infectious disease transmission model to systematically predict the trend of spread,assess the risk and estimates the marginal effect.Based on the theory of "prevention and control of epidemic diseases" of TCM and the analysis of the home page medical data nationwide collected by the National Data Center of Chinese Medicine,along with the feedback of TCM experts from the forefront of the fight against COVID-19,the innovate TCM-SIR model was built to discuss the temporal and spatial variation of the epidemic in China under different medical resources settings,different prevention programs and different isolation levels.The aim was to provide scientific basis to formulate appropriate strategies for prevention and control,optimize resource allocation,evaluate cost-effectiveness of intervention measures,and bring into play the characteristics of TCM,optimize and improve risk quick-assessment,decision support and response mechanism of the major public health emergencies in China.According to the experience of Wuhan and the whole country,in the early stage of COVID-19 when there is no vaccine or special drugs,it is particularly important for the victory of the whole to build the first line of defense at community level by using TCM which is easy,cheap but useful.The core of“Wuchang Mode”was“TCM general prescription+community+Internet”which made full use of Internet and dug the advantages of community health services,has relieved the pressure of diagnosis and treatment in large hospitals,and provided good treatment and medical service for people under different conditions,and was the effective way to timely control COVID-19 in the early stage in China.

In conclusion,according to the analysis of the experimental simulating results,it seems that:first,the combination of exponential smoothing method and least square method can avoid the prediction bias in the proposed TCM-SIR model and therefore improve the accuracy in estimating the infection coefficient;second,since we innovatively transformed the prevention and control intervention of traditional Chinese medicine into super parameters in the model,the effects of TCM are captured and the estimated infection coefficient and recovery coefficient are corrected,and then the marginal impact of each and every scenarios of different prevention and control measure packages are accurately estimated.It is clearly shown that when it is still early to guide effective treatment for the COVID-19 pandemic based on large-scale standardized clinical trials,the new mode of isolation plus protection by TCM in prevention and control can improve the immunity of the population on top of the basis of reducing crowd contact probability,and to achieve the goal of further lowering the risk of infection,and control the pandemic at an earlier stage.

6.REFERENCES

1.WHO.Cumulative number of reported probable cases of severe acute respiratory syndrome (SARS).2020-02-23.https://www.who.int/csr/sars/country/en/.

2.The Asian Development Bank.SARS:economic impacts and implications.2020-02-23.https://www.adb.org/publications/sarseconomic-impacts-and-implications.

3.Ren PH,Li ZQ,Zhu HP,Wang P,Qiu ZN,Zhang ZM.The rule of TCM treatment for Corona Virus Disease 2019 based on the theory of pestilence.Jinan Da Xue Xue Bao (Zi Ran Ke Xue Yu Yi Xue Ban) 2020;41:144-50+162.

4.Shi ZF,Dai QG,Zhong CM,Zhang XY,Zhao C,Shang HC.The qualitative research of the prevention and treatment of traditional Chinese medicines on Corona Virus Disease 2019 using software Nvivo.Jinan Da Xue Xue Bao (Zi Ran Ke Xue Yu Yi Xue Ban)2020;41:163-74.

5.Zou L,Yu X,Wu YQ,Sun D,Wu YG,Fang H.Analysis and thinking on Traditional Chinese Medicine in preventing and treating severe cases of novel coronavirus pneumonia.Shanghai Zhong Yi Yao Da Xue Xue Bao 2020;34:11-6.

6.Zhang LL,Li C,Li J,et al.Experience in Treating COVID-19 by Stages.Zhong Yi Yao Xin Xi 2020;37:17-20.

7.Kumar A,Goel K,Nilam.A deterministic time-delayed SIR epidemic model:mathematical modeling and analysis.Theor Biosci 2020;139:67-76.

8.Qun L,Daqing J,Tasawar H,Ahmed A,Bashir A.A stochastic SIRS epidemic model with logistic growth and general nonlinear incidence rate.Physica A 2020;551.

9.Elazzouzi A,Lamrani Alaoui A,Tilioua M,Tridane A.Global stability analysis for a generalized delayed SIR model with vaccination and treatment.Adv Differ Equ 2019;2019:532.

10.Kermack WO,Mckendrick A GA.A contribution to the mathematical theory of epidemics.P Roy Soc A-Math phy 1927;115:700-21.

11.Liu WL,Li XC,Zhang Y,et al.Thoughts on Traditional Chinese Medicine treatment of COVID-19 in Liao Shen area.Shanghai Zhong Yi Yao Za Zhi 2020;54:27-9+35.

12.Yu XY,Xu YL,Li XJ,Yang PY,Zhang X,Jia YJ.Analysis of TCM prevention and control measures for lung cancer patients under novel coronavirus epidemic situation.Tianjin Zhong Yi Yao 2020;37:1213-6.

13.Ni GH,Wang YG,Shaanxi plays the role of traditional Chinese medicine in epidemic prevention and control.Zhong Yi Yao Guan Li Za Zhi 2020;28:86.

14.Zhang BL.What role has Chinese medicine played in the prevention and treatment of the new crown pneumonia epidemic.Study Times,2020-03-18.cited 2021-05-30;9:34 screens.Available from URL:http://www.satcm.gov.cn/xinxifabu/meitibaodao/2020-03-18/14043.html.

15.Yang FG,Huang M,Zhang JH.Advantages of the treatment with Traditional Chinese Medicine on novel coronavirus neumonia outbreak:academician Zhang Boli answered authoritatively.Tianjin Zhong Yi Yao 2020;37:363-4.

16.Dean of Santai County Hospital of Traditional Chinese Medicine,Mianyang City,Sichuan Province LU Wenhua.Traditional Chinese Medicine to Build“Firewall”to Fight Epidemic in Online Domain.Health Newspaper,2020(005).

17.Qin YH.Give Full Play to the characteristic advantages of Traditional Chinese Medicine and firmly win the fight against epidemic situation.Hunan Daily,2020-02-20.cited 2021-05-30;9:50 screens.Available from URL:https://news.hnucm.edu.cn/info/1018/9737.htm.

18.Xia WG,An CQ,Zheng CJ,et al.Clinical Observation on 34 Patients with Novel Coronavirus Pneumonia (COVID-19) Treated with Intergrated Traditional Chinese and Western Medicine.Zhong Yi Za Zhi 2020;61:375-82.

19.Zhao S,Lin Q,Ran J,et al.Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China,from 2019 to 2020:a data-driven analysis in the early phase of the outbreak.Int J Infect Dis 2020;92:214-7.

20.Wu JT,Kathy L,Leung GM.Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan,China:a modelling study.Lancet 2020;395:689-97.