Based on network pharmacology and molecular mechanism of action of Ganlu Yin in the treatment of COVID-19

Objectives: This study was conducted to explore the mechanism of Ganlu Yin in the treatment of COVID-19 based on network pharmacology and molecular docking technology. Methods: TCMSP, ETCM and TCMID databases were used to dig out the chemical components in the compound ingredients of Ganlu Yin. Swiss ADME platform was used for ADME screening and Swiss Target Prediction server was used to predict potential targets of chemical components. The COVID-19 related genes were obtained from GeneCards database and Drugbank website, and the intersection targets between Ganlu Yin and COVID-19 were obtained by Venn analysis. The targets were imported into String analysis platform to construct a protein interaction network, and Cytoscape 3.9.0 software was used for visualization processing. GO enrichment and KEGG pathway analysis were performed on the intersection targets through David database. The core components, clinical antiviral drugs, core targets and novel Coronavirus (SARS-COV-2) hydrolase 3CLpro (Mpro), omicron B. 1.1.529 spike protein and angiotensin converting enzyme 2(ACE2) were tested by molecular docking. Results: A total of 213 effective chemical components and 1 023 drug targets in Ganlu Yin were screened out, including 4 620 COVID-19 related genes and 328 intersection targets. The core components mainly included p-sitosterol, quercetin, and kaherol. The key core targets involved GAPDH, AKT1, TNF, ALB, and EGFR, etc. A total of 241 items were screened by GO functional enrichment, including inflammatory response, protein phosphorylation, positive regulation of gene expression and other biological processes. A total of 85 KEGG pathways were screened out, which were mainly enriched in influenza A, HIF-1 signaling pathway, hepatitis C and other pathways. The results of molecular docking showed that the core chemical components in Ganlu Yin had good binding ability with core targets and disease targets ACE2, 3CLpro and spike protein, especially kahenol with ACE2, 13-sitosterol with 3CLpro, and quercetin with spike protein. Conclusions: Prescription Ganlu Yin has the characteristics of multi-component and multi-target action, and can treat COVID-19 through multiple signaling pathways.

Treatment Effect of Qingfei Paidu Decoction Combined With Conventional Treatment on COVID-19 Patients and Other Respiratory Diseases: A Multi-Center Retrospective Case Series.

Background: Qingfei Paidu decoction (QFPDD) has been widely used in treating coronavirus disease 2019 (COVID-19) in China. However, studies on the treatment effect of COVID-19 patients and other respiratory diseases have not been well demonstrated. Our study aims to determine the treatment effect of QFPDD in combination with conventional treatment on COVID-19 patients and other respiratory diseases. Methods: This retrospective study recruited COVID-19 patients who were treated with QFPDD for at least two courses (6 days) from seven hospitals in five provinces from January 21 to March 18 2020. Demographic, epidemiological, clinical, laboratory, computed tomography characteristics, treatment, and outcome data were collected and analyzed. The improvements in clinical symptoms before and after QFPDD treatment were compared. Results: Eight COVID-19 patients were included in this study. Of them, six were males (75.0%). The median age of the patients was 66 (60-82) years. Four patients were classified as mild and moderate cases (50.0%); there were two severe cases (25.0%) and critical cases (25.0%). The most common symptom was cough (7 [87.5%]), followed by fever (6 [75.0%]), fatigue (4 [50.0%]), asthma (4 [50.0%]), and anorexia (3 [37.5%]). Abnormal findings included decrease in neutrophils (3 [37.5%]), lymphocytes (2 [25.0%]), alkaline phosphatase (3 [37.5%]), lactic dehydrogenase (4 [50.0%]), erythrocyte sedimentation rate (2 [25.0%]), and C-reactive protein (5 [83.3%]) at admission. After one course (3 days) of QFPDD, nasal obstruction and sore throat completely disappeared, and fever (5 [83.3%]), fatigue (2 [50.0%]), and cough (2 [28.6%]) were improved. After two courses (6 days), the fever disappeared completely in all patients, and the other symptoms showed a tendency to improve. In non-severe patients, 87.5% baseline symptoms completely disappeared. In severe patients, 61.1% of the baseline symptoms completely disappeared after patients were administered QFPDD for two courses. Of the abnormal indicators, 55.6% returned to normal levels. The median duration to complete fever recovery was 1.0 day. The median durations of viral shedding and hospitalization were 10.5 and 21.5 days, respectively. None of the patients worsened and died, and no serious adverse events occurred related to QFPDD during hospitalization. Conclusion: QFPDD combined with conventional treatment improved clinical symptoms in COVID-19 patients with other respiratory diseases, and no serious adverse reactions associated with QFPDD were observed. Larger sample studies confirm our findings in the future.

Effect of Qingfei Paidu decoction combined with Western medicine treatments for COVID-19: A systematic review and meta-analysis.

BACKGROUND: Qingfei Paidu decoction (QFPDD) showed to be beneficial for the treatment of coronavirus disease 2019 (COVID-19) in China. PURPOSE: This study aimed to systematically assemble the evidence on the efficacy and safety of QFPDD combined with Western medicine treatments (WMT) for COVID-19. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, CSTJ, CBM, Wanfang Data for clinical trials with a control arm until January 13, 2022. Studies matched the selection criteria were included. Data extraction and quality assessment of the included studies were independently conducted by two reviewers. Review Manager 5.4 was used for meta-analysis. RESULTS: A total of 9 trials including 1108 COVID-19 patients met the selection criteria. Meta-analysis demonstrated that QFPDD combined with WMT reduced aggravation rate (AR) by 71% [risk ratio (RR) = 0.29, 95% confidence intervals (CI) (0.17, 0.51)], increased effective rate (ER) by 13% [RR = 1.13, 95%CI (1.04, 1.22)], shortened 4.78 days of viral shedding [95%CI (-5.79, -3.77)] and 4.45 days of hospital stay [95%CI (-6.05, -2.86)], also decreased the incidence of adverse events (AE) by 56% [RR = 0.44, 95%CI (0.22, 0.89)]. CONCLUSION: QFPDD combined with WMT might reduce the proportion of severe cases and the incidence of AE, shorten the duration of viral shedding and length of hospital stay. More randomized controlled trials (RCTs) are required to confirm our findings in the future.

Reflections on development of rapid and living evidence-based Chinese medicine guidelines for Coronavirus disease 2019

As evidence is rapidly accumulated and updated during the coronavirus disease 2019 (COVID-19) pandemic, rapid and living guidelines are needed to guide the clinical practice of Chinese medicine (CM), for which the WHO handbook of rapid guideline development should be referred to, and the characteristics of CM should be addressed. When constructing the body of evidence, we need to systematically search the studies related to COVID-19 (direct) and indirect diseases, and to collect the experience evidence from ancient documents and expert consensus, thereby maximumly presenting the advantages of CM. When the recommendations are developed, the co-existing direct and indirect evidence, as well as the co-existing research and experience evidence should be fully considered and synthesized by taking priority on whichever higher level evidence it is. The development of the rapid and living CM guidelines meets the ever-changing clinical needs during COVID-19 pandemic, and can provide CM evidence supports for decision making during public health emergencies.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study.

OBJECTIVE: Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. METHODS: A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. RESULTS: A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. CONCLUSION: COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable.

Traditional Chinese Medicine guidelines for coronavirus disease 2019.

OBJECTIVE: To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of coronavirus disease 2019 (COVID-19) and provide timely clinical practice guidance. METHODS: The guidelines were developed in accordance with the World Health Organization rapid guideline process. The evidence on TCM for COVID-19 from published guidelines, direct and indirect published clinical evidence, first hand clinical data, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation (GRADE) method was used to grade the evidence and make the recommendations. RESULTS: Based on the available evidence, the guidelines recommended 17 Chinese medicines for COVID-19: 2 Chinese herbal granules, 7 Chinese patent medicines, and 8 Chinese herbal injections. CONCLUSION: As the literature search was conducted on March, any subsequent versions of these guidelines require an up-to-date literature review. We hope that the evidence summary in these will be helpful in global efforts to address COVID-19.

Development of Rapid Advice Guidelines for the Treatment of Coronavirus Disease 2019 with Traditional Chinese Medicine.

The worldwide spread of the 2019 novel coronavirus has become a profound threat to human health. As the use of medication without established effectiveness may result in adverse health consequences, the development of evidence-based guidelines is of critical importance for the clinical management of coronavirus disease (COVID-19). This research presents methods used to develop rapid advice guidelines on treating COVID-19 with traditional Chinese medicine (TCM). We have followed the basic approach for developing WHO rapid guidelines, including preparing, developing, disseminating and updating each process. Compared with general guidelines, this rapid advice guideline is unique in formulating the body of evidence, as the available evidence for the treatment of COVID-19 with TCM is from either indirect or observational studies, clinical first-hand data together with expert experience in patients with COVID-19. Therefore, our search of evidence not only focuses on clinical studies of treating COVID-19 with TCM but also of similar diseases, such as pneumonia and influenza. Grading of recommendations assessment, development and evaluation (GRADE) methodology was adopted to rate the quality of evidence and distinguish the strength of recommendations. The overall certainty of the evidence is graded as either high, moderate, low or very low, and to give either "strong" or "weak" recommendations of each TCM therapy. The output of this paper will produce the guideline on TCM for COVID-19 and will also provide some ideas for evidence collection and synthesis in the future development of rapid guidelines for COVID-19 in TCM as well as other areas.