Screening For Severe Early Warning Indicators Of COVID-19 And A Real-world Study Of Intervention With Angong Niuhuang Wan

Objective1.Observe key elements of Chinese medicine symptoms in patients with COVID-19.Explore characteristics of disease nature,location and mechanism.Analyze the early warning value of ying-xue differentiation for serious cases.2.To screen the early warning indicators of severe cases of COVID-19 with focus on elements of Chinese medicine.3.To analyze the correlation between Angong Niuhuang Wan and outcome of severe cases of COVID-19,and to explore the importance of treating with prior evidence.4.To study the appropriate timing and application of Angong Niuhuang Wan in the treatment of COVID-19.Methods1.Analyze the TCM syndrome characteristics of COVID-19 in Guangzhou and Xiamen by using retrospective research methods.Patients with COVID-19 infection were admitted by Guangdong Guangzhou designated hospital from May to June 2021 and Fujian Xiamen designated hospital from September to October 2021.Basic information,clinical symptoms,tongue picture data were collected for western typing and ying-xue syndrome differentiation.Frequency and percentage statistics of symptoms on the 2nd,4th,6th,8th,12th,and 14th days of disease course were performed.Factor analysis was used to explore the core pathogenesis of symptoms and tongue images throughout entire course.System clustering method was applied to analyze the evolution of pathogenesis in five stages of traditional Chinese medicine syndromes,including 1-3 days,4-6 days,7-11 days,12-20 days,and 20 days later.Compare the typing of severe cases during the high-risk period(4-11 days)with ying-xue syndrome differentiation by chi square analysis.2.Screening severe early-warning factors of COVID-19 by using retrospective research methods.409 patients with COVID-19 were admitted by Guangzhou and Xiamen designated hospital,and divided into severe group and non severe group.The severe group collected pre severe data,while the non severe group collected data for 7-11 days of disease course.Including basic information(age,gender,BMI,underlying diseases,vaccines,etc.a total of 15 items),symptom information(fever,cough,sore throat,etc.a total of 17 items),tongue image information(tongue color,tongue shape,coating color,coating texture,etc.a total of 29 items),and test data(white blood cells,C-reactive protein,interleukin-6,etc.a total of 22 items).Using SPSS statistical analysis,the first step is chi square univariate analysis,and the positive results are obtained using binary logistic regression to obtain severe warning indicators.Calculate the area under the ROC curve of the measurement data to obtain the corresponding value of the maximum Jordan index.3.Analyze the correlation between Angong Niuhuang Wan and its medication time and severe outcome of COVID-19 by using retrospective research methods.Cases originated from 409 patients in Guangzhou and Xiamen.Study on correlation between Angong Niuhuang Wan and severe outcome included patients diagnosed with ying-xue syndrome differentiation and with fever symptoms during course of the disease.Patients who took the pill after being diagnosed as severe were excluded,and were divided into medication group and non-medication group based on whether they took Angong Niuhuang Wan.SPSS statistical software conducted a propensity score,with age and fever days as indicators,a ratio of 1:1,and a caliper of 0.03 for matching.Paired cases were analyzed using binary unconditional stepwise logistic regression with severity as the outcome and administration of Angong Niuhuang Wan as the covariate.A study on the correlation between different medication times and severe outcomes of Angong Niuhuang Wan include patients who took medication.Those who took medication after the diagnosis of severe cases were excluded.According to the medication time before or after the progression of the condition to ying-xue syndrome,they were divided into pre medication group and post medication group.Based on whether the condition ultimately progresses to severe illness,after single factor screening of basic information and treatment information,binary unconditional stepwise logistic regression analysis was performed to analyze the correlation.4.To analyze the appropriate time and application key points of Angong NiuhuWan in treating non severe patients with COVID-19.359 patients with COVID-19 infection were admitted by Guangdong Guangzhou designated hospital from May to June 2021 and Fujian Xiamen designated hospital from September to October 2021.They were grouped by whether used Angong Niuhuang Wan and matched with factors obtained in Study 2(age,obesity,thickness,PCT,fever).R language Matchit instruction package were used to give propensity score.Nucleic acid turning negative as outcome state,number of turning days as outcome time,using of Angong Niuhuang Wan as influencing factor,PS stratification as control factor,SPSS survival analysis Kaplan Meier method is used for efficacy evaluation.Results1.Analysis of TCM syndrome characteristics of COVID-19 in Guangzhou and Xiamen.A total of 409 cases were successfully admitted.There were 189 males(46.21%)and 220 females(53.79%),with a median age of 42(31,53).Disease classification:79 cases were mild,280 cases were moderate,34 cases were severe,and 16 cases were critically severe.Clinical classification adjusted to severe cases is 8.5(7,11)days of disease course.There were 202 cases in ying-xue syndrome group,89 cases in the non-ying-xue syndrome group,and 118 cases with missing diagnostic data.More than 10%of the respiratory support methods used were oxygen therapy in 145 cases(35.45%)and nasal high flow in 69 cases(16.87%).Western medicine accounted for more than 10%of the cases:128 cases(31.30%)of ibuprofen,111 cases(27.14%)of high-flow nasal cannula oxygen therapy,78 cases(19.07%)of thymosin,64 cases(15.65%)of neutralizing antibodies,and 61 cases(14.91%)of ambroxol hydrochloride tablets.The application of traditional Chinese patent medicines and simple preparations accounted for more than 10%:82 cases of Angong Niuhuang Wan(20.05%),68 cases of antelope horn powder(16.63%).401 cases(98.04%)were treated with traditional Chinese medicine decoction.A total of 7012 daily symptom records were obtained,including 16 clinical symptoms.The top three most common symptoms were cough(36.84%,2583times),expectoration(21.29%,1493times),and fever(12.25%,859times).Out of 409 patients,10 cases were excluded from the analysis of factors,and 399 cases were included.Common factors with a load coefficient of ≥0.4 were selected for presentation.Disease location was lung and spleen and conformed to wei-qi ying-xue syndrome differentiation.The core pathogenesis is heat,dampness,toxin,blood stasis,and deficiency.System clustering analysis shows that 1-3 days syndrome type is mainly characterized by cold dampness and damp heat invading the lungs.Patients with damp heat syndrome are more likely to have symptoms of yin injury and qi consumption.4-6 days syndrome is mainly characterized by cold dampness and dampness heat stagnation in the lungs,which may be accompanied by a tendency to enter the camp and spleen deficiency.For severe cases ranging from 7 to 11 days,the main symptoms are the closing of the lungs with epidemic virus,heat entering the blood circulation,and the transformation of dryness to yin.For non-critical cases,symptoms are cold dampness or dampness heat accumulation.For those who recover,the main symptoms are qi deficiency.Severe cases of Yin deficiency,spleen deficiency,phlegm stasis,and dampness toxin worsen after 12 to 20 days.There is a significant difference between the total differentiation of ying-xue syndrome differentiation and the classification of severe cases.On the 9th day(P=0.043)and 10th day(P=0.049),coverage rate of ying-xue syndrome group for severe cases was 100%and 80%,respectively;and coverage rates of heavy group for ying-xue syndrome group were 15.0%and 19.0%,respectively.2.Analysis of severe early-warning indicators of COVID-19.A total of 409 cases were successfully included.50 cases in the severe group and 359 cases in the non severe group.84 early warning indicators preliminary included.Univariate analysis,excluding indicators with a severe positive rate of<3%,used P<0.05 as inclusion criteria for positive indicators.Four indicators including age,BMI,hypertension,and vaccine were included in the basic information.In the symptom information,6 indicators including fever,cough,expectoration,shortness of breath,fatigue and fatigue,and poor appetite were included.Among the tongue features,purple,fat,tooth marks,thick,and greasy are included.Nine indicators including NE,LY,PLT,IL-6,PCT,D-dimer,CK,AST,and LDH were included.Binary logistic regression analysis,with severity as the outcome indicator,Chinese medicine severe warning analysis obtained four factors:age(P<0.001),fever(P<0.001),obesity(P<0.001),and thickness(P<0.001).Western medicine severe warning analysis obtained three factors:age(P<0.001),fever(P<0.001),and PCT(P<0.001).The overall severe warning analysis received five factors:age(P<0.001),fever(P<0.001),PCT(P<0.001),thickness(P=0.003),and obesity(P=0.002).The area under the ROC curve of the measurement data is:PCT:0.901,age:0.814.PCT value corresponding to the highest climb index is 0.0675ng/ml,with age corresponding to 49.5 years old.3.Study on the correlation between Angong Niuhuang Wan and severe outcome in COVID-19.A study on the correlation between Angong Niuhuang Wan and severe outcome:156 cases diagnosed as ying-xue syndrome and with fever symptoms were included;20 cases(12.82%)became severe cases,and 136 cases(87.18%)did not become severe cases.70 cases were matched with propensity scores,including 35 cases in the medication group and 35 cases in the non medication group.After matching,both groups reached a balance in age(P=0.664)and fever days(P=0.981).The results of binary unconditional stepwise logistic analysis showed that there was no correlation between the use of Angong Niuhuang Wan and severe outcomes(P=0.330).A study on the correlation between different medication times and severe outcomes of Angong Niuhuang Wan:60 patients(27 males(45.00%)and 33 females(55.00%)were included.The medication was used in 36 cases(60.00%)before ying-xue syndrome and 24 cases(40.00%)after ying-xue syndrome.There were 14 severe cases and 46 non-severe cases.Binary unconditional stepwise logistic regression shows that the duration of medication(P=0.002)may have an impact on the outcome of severe outcome.Among them,the risk of developing severe illness in patients treated after ying-xue syndrome is 9.308 times higher than those treated before ying-xue syndrome.There were 2 cases of adverse reactions,1 case was mild,and 1 case was moderate,all of which were cured.It is considered that it may not be related to Angong Niuhuang Wan.4.Study treating of Angong Niuhuang Wan before evidence on COVID-19There were 359 patients in the non-critical group.147 patients with missing data were excluded,212 patients last.28 were in the treatment group,and 184 in the control group.After propensity score matching,74 cases were obtained,including 26 in the medication group and 48 in the unused group.After matching,five screening indicators of age,PCT,fever,thickness,and obesity all reached a balance.Kaplan Meier regression analysis indicated that second group showed statistical significance in three test methods:Log Rank(P=0.014),Tarone Ware(P=0.022),and Breslow(P=0.017).Medication group had a higher probability of negative nucleic acid conversion before discharge and could benefit more from taking Angong Niuhuang Wan.The main characteristics of the second group of tongue images are thick,dry or cracked fur,yellow fur color,and red,crimson,purple,and dark tongue texture.Indicating the suitable timing of Angong Niuhuang Wan:Epidemic toxins enter the body,causing excessive heat and qi distribution,forcing evil to enter the ying,and containing phlegm and blood stasis.When treating with prior evidence for epidemic diseases,attention should be paid to:mastering the nature,location,and mechanism of the disease,paying attention to the speed of transmission.If the disease stops,it should not be used for a long time.Cooperate with other treatment methods and use medication flexibly.ConclusionThe TCM syndrome elements of COVID-19 conform to the pathogenic characteristics of damp toxin.The disease is located in the lung.involving the middle energizer and multiple viscera.The core pathogenesis is "heat,toxin,dampness,stasis,and deficiency".The combination of traditional Chinese and Western medicine with severe warning indicators(age,fever,PCT,tongue fat,and thick coating)can provide an entry point for"treating with prior evidence".Early application of Angong Niuhuang Wan may reduce the risk of severe outcome.For non severe cases patients with high early-warning index scores,there is a greater likelihood of benefit,and the appropriate timing is when the epidemic virus enters the body,transforms heat,has a tendency to enter the ying,and is accompanied by phlegm and blood stasis.Mastering the pathogenesis,flexible medication,and stopping the disease in clinical practice are the key application points of "treating with prior evidence".