Online Submissions: http://www.journaltcm.com info@journaltcm.com J Tradit Chin Med 2021 December 15; 41(6): 982-984 ISSN 0255-2922 © 2021 JTCM All rights reserved RESEARCH ARTICLE TOPIC Traditional Chinese Medicine enhances absorption of lung lesions in corona virus disease 2019 patients BAO Chunmiao, LI Binbin aa 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 Correspondence to: BAO Chunmiao, Department of Respiratory, Yuyao People's Hospital of Zhejiang Province (the Affiliated Yangming Hospital of Ningbo University), Ningbo 315000, China bcm123qwe@163.com Telephone: +86-15968459836 Doi: 10.19852/j.cnki.jtcm.2021.06.016 Accepted: February 8, 2021 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 © 2021 JTCM All rights reserved Keywords: COVID-19; Traditional Chinese Medicine; Western Medicine; Epidemiology; Computed tomography 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 INTRODUCTION Chest computed tomographic (CT) scan was extensively applied in the diagnosis and management of COVID-19 cases.1 Conversion to negative test result of real time polymerase chain reaction (RT-PCR) and improvement on chest CT scan predict a recovery from COVID-19.2 Previous 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.3 Traditional Chinese medicine (TCM) functioned as an adjunctive option in the management of COVID-19.4 The 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 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 ± vs 10 ± 4, P = 0.055) were comparable between cases treated JTCM | www journaltcm com METHODS A cohort of individuals with diagnosis of COVID-19 982 December 15, 2021 | Volume 41 | Issue | BAO CM et al / Research Article 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 Japonicae Flos, and Fructus Forsythia) Baseline laborato- ry 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 (WM vs WM plus TCM) were assessed with independent sample t test, wilcoxon signed rank tests, or Chi-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- Table Comparison between WM and WM plus TCM [n (%)] Items Total (n = 43) WM plus TCM (n = 29) WM (n = 14) P value Agea 43.6 (14.6) 44.1 (14.7) 42.6 (15.0) 0.768 Maleb 21 (48.8) 13 (44.8) (57.1) 0.449 Delayed absorption of lung lesions 35 (81.4) 23 (79.3) 12 (85.7) 0.613 Comorbidityb (18.6) (24.1) (7.1) 0.240 b Smoker (14.0) (17.2) (7.1) 0.645 WBCa 6.4 (2.5) 7.1 (2.7) 5.0 (1.1) 0.014 212.4 (60.5) 217.5 (56.6) 202.5 (68.9) 0.494 32.0 (35.2) 38.6 (34.6) 29.5 (42.2) 0.878 3.0 (4.0) 3.0 (5.0) 3.0 (3.0) 0.469 12.0 (4.3) 12.8 (4.1) 10.1 (4.4) 0.055 b Plt a CRP c STA (days)c ATN (days) a Medical expense (USD)a 1154.3 (414.2) 1162.6 (378.8) 1137.0 (497.9) 0.863 Notes: WM: western medicine; TCM: traditional Chinese medicine; STA: symptom to admission; ATN: admission to negative real time polymerase chain reaction; USD: United States dollars; WBC: white blood cell; Plt, platelet; CRP: c-react protein a: Mean (standard deviaton); b: n (%); c: Median (IQR) Table Multivariate cox regression model HR P value 95% CI HR P value 95% CI WM plus TCM 0.47 0.059 0.21, 1.03 0.24 0.043 0.06, 0.96 Age 1.02 0.761 0.89, 1.16 0.93 0.026 0.87, 0.99 Male 0.97 0.053 0.93, 1.00 0.61 0.412 0.18, 2.01 Smoker 1.04 0.927 0.48, 2.25 0.86 0.800 0.26, 2.80 Comorbidity 0.84 0.757 0.28, 2.51 3.28 0.206 0.52, 20.77 STA 0.74 0.610 0.23 2.40 1.00 0.965 0.83, 1.20 WBC 1.02 0.916 0.74, 1.39 Plt 1.00 0.742 0.99, 1.01 CRP 0.98 0.082 0.95, 1.00 Notes: WM: Western Medicine; TCM: Traditional Chinese Medicine; STA: symptom to admission; HR: hazard ratio; CI: confidence interval; WBC: white blood cell; Plt: platelet; CRP: c-react protein JTCM | www journaltcm com 983 December 15, 2021 | Volume 41 | Issue | BAO CM et al / Research Article formed with STATA 16.0 (Stata Corp, College Station, TX, USA), P-value < 0.05 was defined as statistically significant reported to be useful in a family case of COVID-19.9 Systematic review and Meta-analysis showed that patients with integrated therapy had better outcome without inducing severe adverse drug reactions.10 In 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 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 ± 2.7 vs 5.0 ± 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] REFERENCES DISCUSSION Chest CT scan plays an important role in early detection of COVID-19, which shows various degrees of pulmonary abnormalities.5 Unparalleled progress on CT image and viral load has been reported.6 In 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 repair but 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.8 The combination of WM and TCM was JTCM | www journaltcm com 10 984 Jalaber C, Lapotre T, Morcet-Delattre T, et al Chest CT in COVID-19 pneumonia: a review of current knowledge Diagn Interv Imaging 2020; 101(7-8): 431-437 Raptis CA, Hammer MM, Short RG, et al Chest CT and coronavirus disease (COVID-19): a critical review of the literature to date AJR Am J Roentgenol 2020; 215(4): 839-842 Ai T, Yang Z, Hou H, et al Correlation of chest CT and RT-PCR testing for coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases Radiology 2020; 296(2): E32-E40 Luo H, Tang QL, Shang YX, et al Can Chinese medicine be used for prevention of corona virus disease 2019 (covid-19)? A review of historical classics, research evidence and current prevention programs Chin J Integr Med 2020; 26(4): 243-250 Wiersinga WJ, Rhodes A, Cheng AC, et al Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review JAMA 2020; 324(8): 782-793 Zhao W, He L, Tang H, et al The relationship between chest imaging findings and the viral load of COVID-19 Front Med (Lausanne) 2020; 7: 558539 Awulachew E, Diriba K, Anja A, et al Computed tomography (CT) imaging features of patients with COVID-19: systematic review and Meta-analysis Radiol Res Pract 2020; 2020: 1023506 Xu J, Zhang Y Traditional Chinese Medicine treatment of COVID-19 Complement Ther Clin Pract 2020; 39: 101165 Ni L, Zhou L, Zhou M, et al Combination of Western Medicine and Chinese traditional patent medicine in treating a family case of COVID-19 Front Med 2020; 14(2): 210-214 Liu M, Gao Y, Yuan Y, et al Efficacy and safety of integrated Traditional Chinese and Western Medicine for corona virus disease 2019 (COVID-19): a systematic review and Meta-analysis Pharmacol Res 2020; 158: 104896 December 15, 2021 | Volume 41 | Issue | ... a family case of COVID-19 Front Med 2020; 14(2): 210-214 Liu M, Gao Y, Yuan Y, et al Efficacy and safety of integrated Traditional Chinese and Western Medicine for corona virus disease 2019 (COVID-19):... for coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases Radiology 2020; 296(2): E32-E40 Luo H, Tang QL, Shang YX, et al Can Chinese medicine be used for prevention of corona virus. .. 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