Efficacy and safety of Lianhua Qingwen capsules combined with standard of care in the treatment of adult patients with mild to moderate COVID-19 (FLOSAN): protocol for a randomized, double-blind, international multicenter clinical trial.

Background: Effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are not only the next defense after vaccines but also the key part of establishing a multi-tiered coronavirus disease 2019 (COVID-19) prevention and control system. Previous studies had indicated that Lianhua Qingwen (LHQW) capsules could be an efficacious Chinese patent drug for treating mild to moderate COVID-19. However, pharmacoeconomic evaluations are lacking, and few trials have been conducted in other countries or regions to evaluate the efficacy and safety of LHQW treatment. So, this study aims to explore the clinical efficacy, safety, and economy of LHQW for treating adult patients with mild to moderate COVID-19. Methods: This is a randomized, double-blind, placebo-controlled, international multicenter clinical trial protocol. A total of 860 eligible subjects are randomized at a 1:1 ratio into the LHQW or placebo group to receive two-week treatment and follow-up visits on days 0, 3, 7, 10, and 14. Clinical symptoms, patient compliance, adverse effects, cost scale, and other indicators are recorded. The primary outcomes will be the measured median time to sustained improvement or resolution of the nine major symptoms during the 14-day observation period. Secondary outcomes regarding clinical efficacy will be evaluated in detail on the basis of clinical symptoms (especially body temperature, gastrointestinal symptoms, smell loss, and taste loss), viral nucleic acid, imaging (CT/chest X-ray), the incidence of severe/critical illness, mortality, and inflammatory factors. Moreover, we will assess health care cost, health utility, and incremental cost-effectiveness ratio (ICER) for economic evaluation. Discussion: This is the first international multicenter randomized controlled trial (RCT) of Chinese patent medicine for the treatment of early COVID-19 in accordance with WHO guidelines on COVID-19 management. This study will help clarify the potential efficacy and cost-effectiveness of LHQW in the treatment of mild to moderate COVID-19, facilitating decision-making by healthcare workers. Registration: This study is registered at the Chinese Clinical Trial Registry, with registration number: ChiCTR2200056727 (date of first registration: 11/02/2022).

[Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm].

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Alterations in the gut microbiome and metabolome profiles of septic mice treated with Shen FuHuang formula.

Sepsis has a high mortality rate, and treating sepsis remains a significant challenge worldwide. In former studies, our group found that traditional Chinese medicine, Shen FuHuang formula (SFH), is a promising medicine in treating coronavirus disease 2019 (COVID-19) patients with the septic syndrome. However, the underlying mechanisms remain elusive. In the present study, we first investigated the therapeutic effects of SFH on septic mice. To investigate the mechanisms of SFH-treated sepsis, we identified the gut microbiome profile and exploited untargeted metabolomics analyses. The results demonstrated that SFH significantly enhanced the mice's 7-day survival rate and hindered the release of inflammatory mediators, i.e., TNF-α, IL-6, and IL-1ß. 16S rDNA sequencing further deciphered that SFH decreased the proportion of Campylobacterota and Proteobacteria at the phylum level. LEfSe analysis revealed that the treatment of SFH enriched Blautia while decreased Escherichia_Shigella. Furthermore, serum untargeted metabolomics analysis indicated that SFH could regulate the glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. Finally, we found the relative abundance of Bacteroides, Lachnospiraceae_NK4A136_group, Escherichia_Shigella, Blautia, Ruminococcus, and Prevotella were closely related to the enrichment of the metabolic signaling pathways, including L-tryptophan, uracil, glucuronic acid, protocatechuic acid, and gamma-Glutamylcysteine. In conclusion, our study demonstrated that SFH alleviated sepsis by suppressing the inflammatory response and hence reduced mortality. The mechanism of SFH for treating sepsis may be ascribed to the enrichment of beneficial gut flora and modulation in glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. To sum up, these findings provide a new scientific perspective for the clinical application of SFH in treating sepsis.

Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

Qingfei Jiedu Granules fight influenza by regulating inflammation, immunity, metabolism, and gut microbiota.

Background and aim: Qingfei Jiedu Granules (QFJD) are a new Traditional Chinese Medicine (TCM) which has been clinically used against coronavirus pneumonia in China. In this study, the therapeutic effect and the underlying mechanisms of QFJD against influenza were investigated. Experimental procedure: Pneumonia mice were induced by influenza A virus. Survival rate, weight loss, lung index and lung pathology were measured to evaluate the therapeutic effect of QFJD. The expression of inflammatory factors and lymphocytes was used to assess anti-inflammatory and immunomodulatory effect of QFJD. Gut microbiome analysis was performed to decipher the potential effect of QFJD on intestinal microbiota. Metabolomics approach was conducted to explore the overall metabolic regulation of QFJD. Result and conclusion: QFJD shows a significant therapeutic effect on the treatment of influenza and the expression of many pro-inflammatory cytokines were obviously inhibited. QFJD also markedly modulates the level of T and B lymphocytes. The high-dose QFJD has shown similar therapeutic efficiency compared to positive drugs. QFJD profoundly enriched Verrucomicrobia and maintained the balance between Bacteroides and Firmicutes. QFJD associated with 12 signaling pathways in metabolomics study, 9 of which were the same as the model group and were closely related to citrate cycle and amino acid metabolism.To sum up, QFJD is a novel and promising drug against influenza. It can regulate inflammation, immunity, metabolism, and gut microbiota to fight influenza. Verrucomicrobia shows great potential to improve influenza infection and may be an important target.

Effect of Lianhua Qingwen capsules on the positive rate of COVID-19 close contacts: A retrospective analysis of a large-scale population-based cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is still spreading worldwide. COVID-19 close contact is a key point of this epidemic. However, no medication is now available for close contact. This study aims to evaluate the beneficial effect and safety of the Lianhua Qingwen capsule (LHQW) on COVID-19 close contacts via a large, retrospective cohort study. METHODS: A total of 25,002 close contacts from 199 quarantine sites in Changchun, Jilin, who underwent medical observation, were included. The information about these close contacts were collected for further epidemiological research. Moreover, subjects were divided into an exposure group (LHQW group, oral, 4 capsules/time, t.i.d.; 18,579 subjects) and a non-exposure group (control group; 6,423 subjects). Inverse probability of treatment weighting (IPTW) with propensity score was employed to evaluate the positive rate of the SARS-CoV-2 nucleic acid test in nasal and throat swabs confirmed by polymerase chain reaction (PCR). RESULTS: A total of 22,975 subjects were included in the analysis, 17,286 cases in the LHQW group and 5,689 cases in the control group. The positive rate of nucleic acid testing in the LHQW group was 5.12%, and that in the control group was 9.70% before the adjustment of IPTW of the propensity score; the difference between the two groups was -4.58% (95% CI -5.44- -3.77%, p <  0.001). After adjusting IPTW, the positive rate of nucleic acid testing in the LHQW group and the control group was 5.10% and 9.80%, respectively; the difference between the two groups was -4.70% (95% CI -5.18- -4.23, p < 0.001). The conclusions before and after the IPTW adjustment were consistent. No test drug-related adverse reactions were observed during the study period. CONCLUSION: LHQW has a beneficial effect and safety on the close contacts of SARS-CoV-2 who are under medical observation at the quarantine sites and can be used as an optional drug for those close contacts.

Effect of Lianhua Qingwen Capsules on the Positive Rate of COVID-19 Close Contacts: A Retrospective Analysis of a Large-Scale Population-Based Cohort Study

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Jinhua Qinggan granules for non-hospitalized COVID-19 patients: A double-blind, placebo-controlled, and randomized controlled trial.

Background: Key findings from the World Health Organization Expert Meeting on Evaluation of Traditional Chinese Medicine (TCM) in treating coronavirus disease 2019 (COVID-19) reported that TCMs are beneficial, particularly for mild-to-moderate cases. The efficacy of Jinhua Qinggan granules (JHQG) in COVID-19 patients with mild symptoms has yet to be clearly defined. Methods: We conducted a phase 2/3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with JHQG in mild, non-hospitalized, laboratory-confirmed COVID-19 patients. Participants were randomly assigned to receive 5 g/sacket of JHQG or placebo granules orally thrice daily for 10 days. The primary outcomes were the improvement in clinical symptoms and a proportion tested negative on viral polymerase chain reaction (PCR) after treatment. Secondary outcomes were the time to recover from clinical symptoms and changes in white blood cells (WBC) and acute phase reactants (C-reactive protein (CRP) and ferritin) on the 10th day after treatment initiation. Results: A total of 300 patients were randomly assigned to receive JHQG (150 patients) and placebo (150 patients). Baseline characteristics were similar in the two groups. In the modified intention-to-treat analysis, JHQG showed greater clinical efficacy (82.67%) on the 10th day of the trial compared with the placebo group (10.74%; rate difference: 71.93%; 95% CI 64.09-79.76). The proportion of patients with a negative PCR after treatment was comparable (rate difference: -4.67%; 95% CI -15.76 to 6.42). In contrast, all changes in WBC, ferritin, and CRP levels showed a statistically significant decline in JHQG (P ≤ 0.044) after treatment, but not the latter in placebo (P = 0.077). The median time to recovery of COVID-19-related symptoms including cough, sputum, sore throat, dyspnea, headache, nasal obstruction, fatigue, and myalgia was shorter in the JHQG group compared to the placebo group (P < 0.001 for all). Three patients experienced mild-to-moderate adverse events (AEs) duringthe treatment period in the JHQG group. Findings were similar between the modified intention-to-treat and the per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen. Conclusion: Based on the time to recover from the COVID-19-related symptoms and AEs, it is concluded that JHQG is a safe and effective TCM for symptomatic relief of patients with mild COVID-19. A symptomatic improvement in the JHQG group patients was observed and JHQG use would have important public health implications in such patients. Clinical Trial Registration: The Trial was prospectively registered on www.clinicaltrials.gov with registration number: NCT04723524.

Effectiveness of Lianhua Qingwen Capsule in Treatment of Asymptomatic COVID-19 Patients: A Randomized, Controlled Multicenter Trial.

Background: Asymptomatic patients are unneglected sources in propagating transmission chain due to their high viral loads. However, treatments available based on symptoms seem not applicable to asymptomatic patients. In this study, the authors want to estimate the effectiveness of Lianhua Qingwen (LH) capsule on asymptomatic coronavirus disease 2019 (COVID-19) patients. Methods: A randomized controlled trial (RCT) was performed to explore the effectiveness and safety of LH capsule in treating asymptomatic COVID-19 patients. Patients were randomized to control group (isolated observation) and treatment group (LH, 4 capsules, thrice daily) for 14 days. The primary endpoints were the rate and time of nucleic acid turning negative during the isolation observation. Results: A total of 120 participants were included in the full analysis set (60 each in the control and treatment groups). Data showed that the rate of nucleic acid turning negative during the isolation observation in the treatment group was higher than that in the control group (rate difference: 21.66%, 95% confidence interval [CI]: 4.34 to 37.27, p = 0.0142). Patients in the treatment group have a shorter time of nucleic acid turning negative (7.5 vs. 14.5 days, p = 0.018). Moreover, the rate of clinical symptoms appearance in the treatment group was lower compared with that in the control group (rate difference: -31.67, 95% CI: -46.83 to -13.82, p = 0.0005). The proportion of confirmed mild and common cases in the treatment group was also lower (35.00% vs. 66.67%, p = 0.0005). No serious adverse events were documented. Conclusions: In this study, the authors illustrated that LH capsule is beneficial to asymptomatic COVID-19 patients. Considering the lack of interventions for treating asymptomatic COVID-19 patients at this stage, LH capsule could be considered as a choice. Chinese Clinical Trial Registry: ChiCTR2100042066.

Jinhua Qinggan granules for non-hospitalized COVID-19 patients: A double-blind, placebo-controlled, and randomized controlled trial

Background Key findings from the World Health Organization Expert Meeting on Evaluation of Traditional Chinese Medicine (TCM) in treating coronavirus disease 2019 (COVID-19) reported that TCMs are beneficial, particularly for mild-to-moderate cases. The efficacy of Jinhua Qinggan granules (JHQG) in COVID-19 patients with mild symptoms has yet to be clearly defined. Methods We conducted a phase 2/3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with JHQG in mild, non-hospitalized, laboratory-confirmed COVID-19 patients. Participants were randomly assigned to receive 5 g/sacket of JHQG or placebo granules orally thrice daily for 10 days. The primary outcomes were the improvement in clinical symptoms and a proportion tested negative on viral polymerase chain reaction (PCR) after treatment. Secondary outcomes were the time to recover from clinical symptoms and changes in white blood cells (WBC) and acute phase reactants (C-reactive protein (CRP) and ferritin) on the 10th day after treatment initiation. Results A total of 300 patients were randomly assigned to receive JHQG (150 patients) and placebo (150 patients). Baseline characteristics were similar in the two groups. In the modified intention-to-treat analysis, JHQG showed greater clinical efficacy (82.67%) on the 10th day of the trial compared with the placebo group (10.74%;rate difference: 71.93%;95% CI 64.09–79.76). The proportion of patients with a negative PCR after treatment was comparable (rate difference: −4.67%;95% CI −15.76 to 6.42). In contrast, all changes in WBC, ferritin, and CRP levels showed a statistically significant decline in JHQG (P ≤ 0.044) after treatment, but not the latter in placebo (P = 0.077). The median time to recovery of COVID-19-related symptoms including cough, sputum, sore throat, dyspnea, headache, nasal obstruction, fatigue, and myalgia was shorter in the JHQG group compared to the placebo group (P < 0.001 for all). Three patients experienced mild-to-moderate adverse events (AEs) duringthe treatment period in the JHQG group. Findings were similar between the modified intention-to-treat and the per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen. Conclusion Based on the time to recover from the COVID-19-related symptoms and AEs, it is concluded that JHQG is a safe and effective TCM for symptomatic relief of patients with mild COVID-19. A symptomatic improvement in the JHQG group patients was observed and JHQG use would have important public health implications in such patients. Clinical Trial Registration The Trial was prospectively registered on www.clinicaltrials.gov with registration number: NCT04723524.

[Clinical observation of Xuanfei Baidu Decoction in treatment of severe coronavirus disease 2019 (COVID-19)].

The present study evaluated the effectiveness and safety of Xuanfei Baidu Decoction(XFBD) for severe cases with coronavirus disease 2019(COVID-19).Forty-one patients(diagnosed as severe or critical type) admitted to Hubei Provincial Hospital of Integrated Chinese and Western Medicine and Wuhan Hospital of Traditional Chinese Medicine from February 1 to March 1, 2020, were included.All patients were treated with XFBD based on conventional therapies.Clinical outcomes, length of hospital stay, and lung CT images of patients were observed.Laboratory indicators were compared between admission and the 14 th day of treatment.Traditional Chinese medicine(TCM) symptoms and signs on the 7 th and 14 th days of treatment were also compared with baseline.The differences in clinical characteristics and clinical outcomes between XFBD and western medicine or conventional therapies were analyzed with the published trials on severe COVID-19 cases during the same period as external controls.According to the results, among the 41 cases, 40 were cured and discharged, and 1 died; the median length of hospital stay was 22 days, and the improvement rate of lung CT was 87.2%(34/39).Compared with the conditions on admission, the levels of white blood cells(WBC), C-reactive protein(CRP), fibrinogen(FIB), and lactate dehydrogenase(LDH) were reduced(P<0.05, P<0.01), and levels of procalcitonin(PCT), prothrombin time(PT), creatine kinase(CK), alanine aminotransferase(AST), total bilirubin(TBiL), and other indicators showed a downward trend.Moreover, symptoms like fever, cough, chest tightness/shortness of breath, dyspnea, head and body pain, anorexia, and greasy tongue coating were significantly improved on the 7 th and 14 th days of treatment(P<0.05, P<0.01), and fatigue was improved on the 14 th day of treatment(P<0.01).The mortality, adverse reactions, and major events of the XFBD group were significantly lower than those of the western medicine and conventional treatment groups in the same period, and the usage of antibiotics, hormones, vasopressin, and invasive mechanical ventilation during treatment were generally less than other groups.In conclusion, XFBD has good efficacy and safety in the treatment of severe COVID-19 cases by improving inflammation and clinical symptoms, promoting the absorption of lung inflammation, and reducing mortality.

[Acupuncture as adjuvant therapy for 32 cases of coronavirus disease 2019].

OBJECTIVE: To observe the clinical effect of acupuncture on coronavirus disease 2019 (COVID-19) based on the conventional treatment. METHODS: A total of 35 patients with COVID-19 of mild or ordinary type were involved (3 cases dropped off). Acupuncture was applied on the basis of western medicine and Chinese materia medica treatment. Dazhui (GV 14), Fengchi (GB 20), Kongzui (LU 6), Hegu (LI 4), etc. were selected as the main acupoints, the supplementary acupoints and the reinforcing and reducing manipulations were selected according to syndrome differentiation. Acupuncture treatment was given once a day, 5 times a week. On day 3 and day 7 of acupuncture, relief condition of the main symptoms was observed. Before acupuncture and on day 3 and day 7 of acupuncture, efficacy evaluation scale of TCM on COVID-19 (efficacy evaluation scale) score was recorded. The effects of different intervention time of acupuncture on patients' hospitalization time were compared, the understanding of acupuncture treatment of patients discharged from hospital was recorded, the clinical efficacy and safety of acupuncture treatment were evaluated. RESULTS: On day 3 and day 7 of acupuncture, the symptoms of lung system and non lung system were both relieved; the scores of efficacy evaluation scale were both decreased compared before acupuncture (P<0.05), and the efficacy evaluation scale score of day 7 of acupuncture were lower than day 3 of acupuncture (P<0.05). The average hospitalization time of patients received early acupuncture was shorter than late acupuncture (P<0.05). The total effective rate was 84.4% (27/32) on day 7 of acupuncture, which was higher than 34.4% (11/32) on day 3 of acupuncture (P<0.05). During the acupuncture treatment, there were neither adverse reactions in patients nor occupational exposures in doctors. The patients generally believed that acupuncture could promote the recovery of COVID-19 and recommended acupuncture treatment. CONCLUSION: On the basis of the conventional treatment, acupuncture can effectively relieve the clinical symptoms in patients with COVID-19, early intervention of acupuncture can accelerate the recovery process. Acupuncture has good safety, clinical compliance and recognition of patients.

Qingjin Yiqi granules for post-COVID-19 condition: A randomized clinical trial.

OBJECTIVE: To evaluate the effectiveness and safety of Qingjin Yiqi granules (QJYQ) on post-COVID-19 condition (PCC). METHOD: Patients who met the inclusion criteria were randomly assigned to two groups, the QJYQ group received QJYQ combined with standard rehabilitation treatments (SRTs) and the control group only received SRTs. The treatment course was 14 days. The primary outcomes were modified Medical Research Council (mMRC) scale and Borg scale, while the secondary outcomes included symptoms score and 6-minute walking distance (6MWD). The safety outcome was the incidence of adverse events. RESULTS: A total of 388 patients with PCC were enrolled and randomly assigned to the QJYQ group (n = 194) and the control group (n = 194). Compared to the controls, the mMRC scale was improved in the QJYQ group, which was better than that of the control group [ß (95%CI): -0.626 (-1.101, -0.151), p = 0.010]. A significant improvement in Borg scale was also observed in the QJYQ group compared to the control group [ß (95%CI): -0.395(-0.744, -0.046), p = 0.026]. There was no statistically significant difference in symptoms score and 6MWD between the two groups (p = 0.293, p = 0.724). No treatment-related adverse events were observed in either group. CONCLUSIONS: QJYQ can bring benefits to patients with PCC, mainly in the improvement of breathlessness and fatigue.

Efficacy and Safety of Lianhua Qingke Tablets in the Treatment of Mild and Common-Type COVID-19: A Randomized, Controlled, Multicenter Clinical Study.

BACKGROUND: Lianhua Qingke (LH) tablets is an effective traditional Chinese medicine against various viral infections, especially in relieving coughing. However, its effects on COVID-19 are unknown. METHODS: To examine the therapeutic effectiveness of LH tablets in COVID-19 patients with mild and common types, a randomized, multicenter, controlled study was carried out. COVID-19 cases were randomized to undergo routine treatment with or without LH tablets (4 tablets, three times a day) for 14 days. The primary endpoints were the rate of achieving clinical symptom resolution and the corresponding time. RESULTS: There were 144 participants in the full analysis set (72 each in the LH and control groups). The LH group participants had elevated symptom alleviation rate at 14 days compared with control cases (FAS: 98.61% vs. 84.72%, p = 0.0026). In comparison with control group participants, the LH group participants had reduced median time to clinical symptom alleviation (median: 4 vs. 7 days, p < 0.0001). Higher resolution rates of coughing (98.44% vs. 84.51%, p = 0.0045) and expectoration (100% vs. 82.35%, p = 0.0268) were observed in the LH group. Times to recovery of fever (median: 2 vs. 3 days, p = 0.0007), coughing (median: 4 vs. 7 days, p < 0.0001), and expectoration (median: 3 vs. 6 days, p < 0.0001) were also notably shorter in the LH group. Moreover, the LH group had elevated improvement rates in chest computed tomography signs (FAS: 86.11% vs. 72.22%, p = 0.0402) and clinical cure at day 28 (FAS: 83.33% vs. 68.06%, p = 0.0326). However, no differences were found in the laboratory test and viral assay. Serious adverse events were not detected. CONCLUSION: These preliminary findings indicate LH tablets may be effective in symptomatic COVID-19, especially in relieving coughing. This trial was registered in Chinese Clinical Trial Registry (ChiCTR2100042069).

Cangma Huadu granules, a new drug with great potential to treat coronavirus and influenza infections, exert its efficacy through anti-inflammatory and immune regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Coronavirus and influenza virus infection seriously threaten human health. Cangma Huadu Granules (CMHD) is an in-hospital preparation composed of eight traditional Chinese medicines (TCM), which has been clinically used against COVID-19 in China and may be a promising candidate for the treatment of influenza. However, the role of its treatment urgently needs to be studied. AIM OF THE STUDY: To evaluate the therapeutic effects of CMHD on pneumonia induced by coronavirus (HCoV-229E) and influenza A virus (H1N1/FM1) in mice and explore its mechanism of anti-infection. MATERIALS AND METHODS: Mice were infected with HCoV-229E or H1N1/FM1 virus through the nasal cavity. CMHD (12.1, 6.05 and 3.03 g/kg/d) or the positive control drugs were administered intragastrically. The lung index and histopathological changes were used to evaluate the therapeutic effect of CMHD. The expression of TNF-α, IL-1ß, IL-6 and IL-4 in Serum and the proportion of CD4+ and CD8+ T lymphocytes in peripheral blood were detected to evaluate the anti-inflammatory and immune regulation effects of CMHD, respectively. Furthermore, the levels of p-NF-κBp65/ NF-κB p65, which was the key targets of the NF-κB pathway was analyzed. RESULTS: In HCoV-229E-induced pneumonia, the lung index was markedly reduced, and lung pathology was improved in mice that treated with CMHD (12.1, 6.05 g/kg/d). Meanwhile, the expression of TNF-α, IL-6 were obviously inhibited, but the expression of IL-4 was significantly increased in CMHD groups. Compared with the model group, CMHD could also markedly upregulate the level of CD4+ and CD8+. Furthermore, CMHD has a markedly effect on inhibit the expression of p-NF-κB p65/NF-κB p65 in the lung. In H1N1-induced pneumonia, the lung index of mice in the CMHD (12.1 g/kg/d) treatment group was lower than that in the model group, and less inflammatory infiltration could be seen in the lung pathological. Moreover, CMHD could also obviously decrease the expression of TNF-α, IL-1ß, IL-6, but significantly increase the expression of IL-4. Except for that, CMHD could also markedly downregulate the level of CD4+ and upregulate the level of CD8+ compared with the model group. In addition, CMHD has a markedly effect on inhibit the expression of p-NF-κB p65/NF-κB p65 in the lung. CONCLUSION: CMHD can significantly combats viral infections caused by HCoV-229E and H1N1, and the mechanism may be related to its multiple functions of anti-inflammatory, immunity regulating and inhibiting NF-κB signal transduction pathway.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.