Timely treatment and higher compliance to traditional Chinese medicine: New influencing factors for reducing severe COVID-19 based on retrospective cohorts in 2020 and 2021.

OBJECTIVE: From the beginning of 2020, our study team formulated a traditional Chinese medicine (TCM) prescription named Sanhanhuashi formula (SHHS) to treat COVID-19 patients. Then we conducted several studies to explore the effectiveness of SHHS formula and other influencing factors on prognosis of disease. The purpose of this study was to describe the trends of patients' characters from 2020 to 2021 based on two separate cohorts, and to explore the influencing factors on incidence of severe COVID-19 conditions, especially the contributions of timely treatment and higher compliance to SHHS formula. METHODS: A retrospective cohort study was conducted in Wuhan, Hubei province and Tonghua, Jilin province. Participants were hospitalized mild to moderate COVID-19 consecutive enrolled patients in Wuhan hospital of traditional Chinese and western medicine (from Feb 13, 2020 to March 8, 2020) and Tonghua central hospital (from Jan 17, 2021 to Feb 5, 2021). Age, sex, time waiting to be hospitalized, medical history, initial symptoms, concomitant medication, and severity of disease were collected. Univariate and multivariate logistic regression were used to explore the associations between various exposures and the outcome, ie. the proportion of patients who were converted to severe status. E-values and its lower control limit (LCL) were calculated for sensitivity analysis. RESULTS: Totally, 176 COVID-19 patients in two hospitals were enrolled. 81 patients were from Wuhan hospital of traditional Chinese and western medicine and 95 from Tonghua central hospital. 42 patients used SHHS formula arrival or exceed 7 days, and 2 (4.8%) progressed to severe condition. Among 134 patients who were exposed SHHS less than 7 days, 18 (13.4%) were converted to severe situation. Compared with those diagnosed in 2020, cases in 2021 were characterized as lower rates of initial symptoms (88.9% vs 35.8%, P < 0.001) and concomitant medications ever widely used, eg. antiviral medicine (71.6% vs 43.2%, P < 0.001), antibiotics (61.7% vs 13.7%, P < 0.001) and Chinese patent medicine (76.5% vs 44.2%, P < 0.001). They also waited less time for hospitalization (median: 12 vs 2 days, P < 0.001). The final multivariate logistic regression model showed that age (> 60 yrs) (OR: 3.943; 95% CI: 1.402-11.086; P = 0.009; E-value = 7.35, LCL:2.15), diagnosis year (OR: 0.165; 95% CI: 0.050-0.551; P = 0.003; E-value=11.6, LCL: 3.03) and SHHS exposure (OR: 0.118; 95% CI: 0.014-0.992; P = 0.049; E-value = 16.43, LCL:1.1) were independent risk factors for predicting severe status. CONCLUSIONS: The profile of COVID-19 patients has changed after one year. In addition to age, diagnosis year and SHHS exposure are two new factors to predict the prognosis of disease. The patients diagnosed in 2021 were mainly benefited from timely treatment. Subsequently, adhere to use SHHS formula a quite longer time reduced the number of severe cases. Therefore, both the current epidemic prevention and control measures and increasing compliance to traditional Chinese medicine are effective ways to reducing severe cases and improving public health.

Efficacy and Safety of Traditional Chinese Medicine in Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis.

Introduction: Until now, there is no clinically approved specific medicine to treat COVID-19. Prior systematic reviews (SRs) have shown that traditional Chinese medicine (TCM) reduces the number of patients with severe disease and time to fever clearance, promotes clinical effectiveness, and improves chest images and the negativity rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test. Few SRs arrived at a definitive conclusion, and more randomized controlled trials (RCTs) were published. We conducted this study to summarize the latest evidence of TCM in COVID-19. Methods: Eight online databases were searched from December 2019 to July 2020, updated to March 2021. Only RCTs evaluating the clinical efficacy and safety of TCM in the treatment of COVID-19 were included. Primary outcomes were clinical cure and the negativity of the SARS-CoV-2 nucleic acid test. Secondary outcomes included clinical deterioration, ARDS, mechanical ventilation, death, time to fever clearance, duration of hospitalization, and chest imaging improvement. Safety outcomes included adverse events and serious adverse events during treatment. Two reviewers selected the included articles, assessed the risk of bias, and extracted data independently and in duplicate. Results: A total of 25 RCTs involving 2222 participants were selected in the systematic review, and seven RCTs were included in the meta-analysis. The results showed that TCM plus routine treatment was significantly better than routine treatment alone in clinical cure (risk ratio [RR] = 1.20, 95% confidence interval (CI) [1.04, 1.38], P = 0.01) and chest image improvement (RR = 1.22, 95% CI [1.07, 1.39], P = 0.01) and could reduce clinical deterioration (RR = 0.39, 95% CI [0.18, 0.86], P = 0.02), ARDS (RR = 0.28, 95% CI [0.11, 0.69], P = 0.01), mechanical ventilation (RR = 0.30, 95% CI [0.12, 0.77], P = 0.01), or death rate (RR = 0.28, 95% CI [0.09, 0.84], P = 0.02). No significant difference between TCM and routine treatment in the negativity of SARS-CoV-2 nucleic acid test (RR = 1.08, 95% CI [0.94, 1.23], P = 0.29) was observed. Finally, there was no overall significant difference in the incidence of adverse events between the two groups. The summary of evidence showed moderate confidence of a benefit of 11.8% in clinical cure and 14.0% in chest image improvement and a reduction of 5.9% in clinical deterioration, 25.4% in ARDS, 18.3% in mechanical ventilation, and 4.5% in death with TCM plus routine treatment compared to routine treatment alone in patients with COVID-19. A low confidence of a benefit of 5.4% in the negativity of SARS-CoV-2 nucleic acid test was also observed. Conclusions: Synethized evidence of 21 outcomes in 8 RCTs showed moderate certainty that TCM treatment plus routine treatment may promote a clinical cure and chest image improvement compared to routine treatment alone while reducing clinical deterioration, development of ARDS, use of mechanical ventilation, and death in patients with COVID-19. TCM treatment plus routine treatment may not promote the negativity of the SARS-CoV-2 nucleic acid test compared to routine treatment alone. TCM treatment was found to be safe for patients with COVID-19.

Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study.

We formulated a traditional Chinese medicine (TCM) prescription, Hanshiyi Formula (HSYF), which was approved and promoted by the Wuhan Municipal Health Commission for treating mild and moderate coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of HSYF on the progression to severe disease in mild and moderate COVID-19 patients. We conducted a retrospective cohort study of patients with mild and moderate COVID-19 in a quarantine station in Wuchang District, Wuhan. Using the real-time Internet information collection application and Centers for Disease Control for the Wuchang District, patient data were collected through patient self-reports and follow-ups. HSYF intervention was defined as the exposure. The primary outcome was the proportion of patients who progressed to a severe disease status, and a stratification analysis was performed. Univariate and multivariate regression analyses were performed to identify influencing factors that may affect the outcome. Further, we used propensity score matching (PSM) to assess the effect of HSYF intervention on the conversion of mild and moderate to a severe disease status. Totally, 721 mild and moderate COVID-19 patients were enrolled, including 430 HSYF users (exposed group) and 291 non-users (control group). No cases in the exposed group and 19 (6.5 %, P < 0.001) cases in the control group progressed to severe disease, and the difference between the two groups (exposed group-control group) was -6.5 % [95 % confidence interval (CI): (-8.87 %, -4.13 %)]. Univariate regression analysis revealed sex (male), age, fever, cough, and fatigue as risk factors for progression to severe disease. After PSM, none of the HSYF users and 7 (4.7 %, P = 0.022) non-users transitioned to severe disease, and the difference between the two groups (exposed group-control group) was -4.7 % [95 % CI: (-8.2 %, -1.2 %)]. Multivariate regression analysis revealed that sex (male) [OR: 3.145; 95 % CI: 1.036-9.545; P = 0.043] and age (> 48 years) [odds ratio (OR): 1.044; 95 % CI: 1.001-1.088; P = 0.044] were independent risk factors for conversion to severe disease. Therefore, HSYF can significantly reduce the progression to severe disease in patients with mild and moderate COVID-19, which may effectively prevent and treat the disease. However, further larger clinical studies are required to verify our results.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

Traditional Chinese Medicine Decoctions Significantly Reduce the Mortality in Severe and Critically Ill Patients with COVID-19: A Retrospective Cohort Study.

Coronavirus disease (COVID-19) is a new infectious disease associated with high mortality, and traditional Chinese medicine decoctions (TCMDs) have been widely used for the treatment of patients with COVID-19 in China; however, the impact of these decoctions on severe and critical COVID-19-related mortality has not been evaluated. Therefore, we aimed to address this gap. In this retrospective cohort study, we included inpatients diagnosed with severe/critical COVID-19 at the Tongren Hospital of Wuhan University and grouped them depending on the recipience of TCMDs (TCMD and non-TCMD groups). We conducted a propensity score-matched analysis to adjust the imbalanced variables and treatments and used logistic regression methods to explore the risk factors associated with in-hospital death. Among 282 patients with COVID-19 who were discharged or died, 186 patients (66.0%) received TCMD treatment (TCMD cohort) and 96 (34.0%) did not (non-TCMD cohort). After propensity score matching at a 1:1 ratio, 94 TCMD users were matched to 94 non-users, and there were no significant differences in baseline clinical variables between the two groups of patients. The all-cause mortality was significantly lower in the TCMD group than in the non-TCMD group, and this trend remained valid even after matching (21.3% [20/94] vs. 39.4% [37/94]). Multivariable logistic regression model showed that disease severity (odds ratio: 0.010; 95% CI: 0.003, 0.037; [Formula: see text]¡ 0.001) was associated with increased odds of death and that TCMD treatment significantly decreased the odds of in-hospital death (odds ratio: 0.115; 95% CI: 0.035, 0.383; [Formula: see text]¡ 0.001), which was related to the duration of TCMD treatment. Our findings show that TCMD treatment may reduce the mortality in patients with severe/critical COVID-19.

Add-On Chinese Medicine for Coronavirus Disease 2019 (ACCORD): A Retrospective Cohort Study of Hospital Registries.

Chinese medicine (CM) was extensively used to treat COVID-19 in China. We aimed to evaluate the real-world effectiveness of add-on semi-individualized CM during the outbreak. A retrospective cohort of 1788 adult confirmed COVID-19 patients were recruited from 2235 consecutive linked records retrieved from five hospitals in Wuhan during 15 January to 13 March 2020. The mortality of add-on semi-individualized CM users and non-users was compared by inverse probability weighted hazard ratio (HR) and by propensity score matching. Change of biomarkers was compared between groups, and the frequency of CMs used was analyzed. Subgroup analysis was performed to stratify disease severity and dose of CM exposure. The crude mortality was 3.8% in the semi-individualized CM user group and 17.0% among the non-users. Add-on CM was associated with a mortality reduction of 58% (HR = 0.42, 95% CI: 0.23 to 0.77, [Formula: see text] = 0.005) among all COVID-19 cases and 66% (HR = 0.34, 95% CI: 0.15 to 0.76, [Formula: see text] = 0.009) among severe/critical COVID-19 cases demonstrating dose-dependent response, after inversely weighted with propensity score. The result was robust in various stratified, weighted, matched, adjusted and sensitivity analyses. Severe/critical patients that received add-on CM had a trend of stabilized D-dimer level after 3-7 days of admission when compared to baseline. Immunomodulating and anti-asthmatic CMs were most used. Add-on semi-individualized CM was associated with significantly reduced mortality, especially among severe/critical cases. Chinese medicine could be considered as an add-on regimen for trial use.

Chinese herbal medicine reduces mortality in patients with severe and critical Coronavirus disease 2019: a retrospective cohort study.

This study aimed to evaluate the efficacy of Chinese herbal medicine (CHM) in patients with severe/critical coronavirus disease 2019 (COVID-19). In this retrospective study, data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20, 2020. All patients were divided into an exposed group (CHM users) and a control group (non-users). After propensity score matching in a 1:1 ratio, 156 CHM users were matched by propensity score to 156 non-users. No significant differences in seven baseline clinical variables were found between the two groups of patients. All-cause mortality was reported in 13 CHM users who died and 36 non-users who died. After multivariate adjustment, the mortality risk of CHM users was reduced by 82.2% (odds ratio 0.178, 95% CI 0.076-0.418; P < 0.001) compared with the non-users. Secondly, age (odds ratio 1.053, 95% CI 1.023-1.084; P < 0.001) and the proportion of severe/critical patients (odds ratio 0.063, 95% CI 0.028-0.143; P < 0.001) were the risk factors of mortality. These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19.

Study on the Knowledge, Attitude, and Practice (KAP) of Nursing Staff and Influencing Factors on COVID-19.

The aim of this study is to investigate the knowledge, attitude, and practice (KAP) on Coronavirus Disease 2019 (COVID-19) care among nursing staff and analyze its influencing factors. The survey was conducted on February 18, 2020, among 7,716 voluntary participants from 143 medical institutions in Zhejiang, China. The findings indicated that KAP of nursing staff scored well. However, the accuracy of psychological nursing knowledge was much lower, 14.3% only. Nursing staff working in isolation wards have higher knowledge (OR = 1.776, 95% CI: 1.491-2.116), attitude (OR = 1.542, 95% CI: 1.298-1.832), and practice (OR = 1.902, 95% CI: 1.590-2.274) scores than those in general wards. In terms of KAP, nursing staff with working experience ≤ 10 years scored lower than those with working experience ≥ 20 years, with OR values of 0.490 (95% CI: 0.412-0.583), 0.654 (95% CI: 0.551-0.775), and 0.747 (95% CI: 0.629-0.886), respectively. It is necessary to take measures to enhance the training on COVID-19, especially for KAP of junior nurses in general wards.

Positive RT-PCR Test Results in 420 Patients Recovered From COVID-19 in Wuhan: An Observational Study.

OBJECTIVE: During the follow-up of patients recovered from coronavirus disease 2019 (COVID-19) in the quarantine and observation period, some of the cured patients showed positive results again. The recurrent positive RT-PCR test results drew widespread concern. We observed a certain number of cured COVID-19 patients with positive RT-PCR test results and try to analyze the factors that caused the phenomenon. METHODS: We conducted an observational study in COVID-19 patients discharged from 6 rehabilitation stations in Wuhan, China. All observed subjects met the criteria for hospital discharge and were in quarantine. Data regarding age, sex, body mass index (BMI), course of disease, comorbidity, smoking status and alcohol consumption, symptoms in and out of quarantine, and intervention were collected from the subjects' medical records and descriptively analyzed. The main outcome of this study was the RT-PCR test result of the observed subjects at the end of quarantine (negative or positive). Logistic regression analysis was used to identify the influencing factors related to recurrent positive RT-PCR test results. RESULTS: In this observational study, 420 observed subjects recovered from COVID-19 were included. The median age was 56 years, 63.6% of the subjects were above 50 years old, and 50.7% (213/420) were female. The most common comorbidities were hypertension [26.4% (111/420)], hyperlipidemia [10.7% (45/420)], and diabetes [10.5% (44/420)]. 54.8% (230/420) manifested one or more symptoms at the beginning of the observation period, the most common symptoms were cough [27.6% (116/420)], shortness of breath 23.8% (100/420)], and fatigue [16.2% (68/420)], with fever rare [2.6% (11/420)]. A total of 325 subjects were exposed to comprehensive intervention; 95 subjects were absence of intervention. The recurrence rate of positive RT-PCR test results with comprehensive intervention was 2.8% (9/325), and that with no intervention was 15.8% (15/95). The results of logistic regression analysis showed that after adjusted for factors such as age, sex, and comorbidity and found out that comprehensive intervention was correlated with the recurrent positive RT-PCR test results. There was appreciably less recurrence in the comprehensive intervention group. CONCLUSIONS: The factors related to positive RT-PCR test results in observed subjects recovered from COVID-19 were age, comorbidity, and comprehensive intervention, among which comprehensive intervention might be a protective factor. CLINICAL TRIAL REGISTRATION: Chictr.org.cn, identifier ChiCTR2000030747.

From the perspective of Traditional Chinese Medicine: Treatment of mental disorders in COVID-19 survivors.

PURPOSE: The aim of this study is to explore the possible benefits of traditional Chinese medicine on the pathogenesis of psychological and mental health of COVID-19 survivors. METHODS: A literature search was conducted to confirm the effects of COVID-19 on psychological and mental health of survivors. In addition to this, on the basis of signs and symptoms, TCM were used on treat mental disorder as per suggested clinical and animal experimental data plus relevant records in classical Chinese medicine books written by Zhang Zhongiing during Han Dynasty. A series of treatment plans were prescribed for COVID-19 survivors with psychological and mental disorders. RESULTS: According to previous extensive studies focusing on effects on mental health of survivors, high incidence was observed in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) survivors. During investigations of mental health of COVID-19 patients and survivors, it is observed that they also had symptoms of mental disorders and immune dysfunction. Furthermore, it was also proposed that depression, anxiety and post-traumatic stress disorder (PTSD) were most common mental disorders requiring special attention after the recovery from COVID-19. The symptoms of COVID-19 were analyzed, and the TCM syndrome of the depression, anxiety and PTSD after recovered from COVID19 was interpreted as internal heat and Yin deficiency. These three mental disorders pertains the category of "Lily disease", "hysteria" and "deficient dysphoria" in TCM. CONCLUSION: Lily Bulb, Rhizoma Anemarrhena Decoction and Ganmai Dazao Decoction were used to treat depression. Suanzaoren Decoction, Huanglian Ejiao Decoction and Zhizi Chi Decoction were suggested for anxiety. Moreover, Lily Bulb, Rehmannia Decoction and Guilu Erxian Decoction were the formula for PTSD.

The role played by traditional Chinese medicine in preventing and treating COVID-19 in China.

Traditional Chinese medicine (TCM), an ancient system of alternative medicine, played an active role in the prevention and control of COVID-19 in China. It improved the clinical symptoms of patients, reduced the mortality rate, improved the recovery rate, and effectively relieved the operating pressure on the national medical system during critical conditions. In light of the current global pandemic, TCM-related measures might open up a new channel in the control of COVID-19 in other countries and regions. Here, we summarize the TCM-related measures that were widely used in China, including TCM guidelines, the Wuchang pattern, mobile cabin hospitals, integrated treatment of TCM and modern medicine for critical patients, and non-medicine therapy for convalescent patients, and describe how TCM effectively treated patients afflicted with the COVID-19. Effective TCM therapies could, therefore, be recommended and practiced based on the existing medical evidence from increased scientific studies.