Treatment Of COVID-19 In China Research Articles

Hua-Shi-Bai-Du decoction inactivates NLRP3 inflammasome through inhibiting PDE4B in macrophages and ameliorates mouse acute lung injury

BackgroundHua-Shi-Bai-Du decoction (HSBD) exerts significant effects on the prevention and treatment of COVID-19 in China. The activation of the NLRP3 inflammasome of macrophages plays a vital role in COVID-19 pathology. However, no previous studies have focused on this pathological process to explore the effect of HSBD. PurposeOur aim is to uncover the effect of HSBD on NLRP3 inflammasome activation and the underlying mechanisms. MethodsThe NLRP3-activated J774A.1 cells primed by LPS and activated by nigericin/ATP/MSU were used to evaluate NLRP3 activation in vitro. ASC oligomerization and speck formation were assessed by western blot and immunofluorescence imaging. Intracellular K+ levels were determined by the colorimetric assay. Mitochondrial ROS (mtROS) level was detected by the flow cytometry and the fluorescence spectrophotometry. The intracellular cAMP level was determined by chemiluminescence method and ELISA, while phosphodiesterase (PDE) activity was measured using the fluorescent substrate MANT-cAMP. siRNA was applied to knockdown PDE4B. Two in vivo mouse models, MSU-induced peritonitis and LPS-induced acute lung injury (ALI), were used to evaluate the effects of HSBD on IL-1β and other inflammatory cytokines. Pathological changes in lung tissue were observed by histopathological examination. ResultsHSBD not only decreased supernatant IL-1β, caspase-1 p20, and cleaved gasdermin D (GSDMD) in NLRP3-activated J774A.1 cells, but also reduced IL-1β in the peritoneal lavage fluid of mice with MSU-induced peritonitis, demonstrating the suppressive effect on NLRP3 inflammasome activation. The mechanism study showed that HSBD blocked ASC oligomerization and speck formation without affecting K+ efflux or mtROS production. Furthermore, it prevented the decrease of intracellular cAMP by inhibiting PDE4B activity. And in the PDE4B-deficient cells, its suppressive effect on IL-1β release was abolished. In LPS-induced ALI mice, oral administration of HSBD decreased several proinflammatory cytokines (IL-1β, IL-6, TNF-α, and CXCL-1) and attenuated the pathological damage to the lung. ConclusionHSBD suppresses the activation of NLRP3 inflammasome by inhibiting PDE4B activity to counteract the decrease of intracellular cAMP, thereby blocking ASC oligomerization in macrophages. Our findings may provide new insight into the clinical effets of HSBD for the treatment of COVID-19.

Nirmatrelvir and ritonavir for inpatients with severe or critical COVID-19 beyond five days of symptom onset: a propensity score-matched, multicenter, retrospective cohort study

BackgroundThere is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient.MethodsA new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated.ResultsIn the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited.ConclusionsOur study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.

Anti-coronavirus and anti-pulmonary inflammation effects of iridoids, the common component from Chinese herbal medicines for the treatment of COVID-19.

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3μM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1β and IL-8 at 10μM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.

Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching.

Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety. Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded. Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565). Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary.

Effect of Paxlovid on Tacrolimus Concentration in Perioperative Kidney Transplant Patients Infected With COVID-19: A Case Report

Paxlovid, as a new drug, received emergency approval for the treatment of COVID-19 in China; there is very little experience with kidney transplantation patients taking tacrolimus with perioperative COVID-19 infection. We discontinued tacrolimus on the day of using Paxlovid, and we chose to frequently monitor the concentration of tacrolimus and creatinine early in the course of treatment by enzymemultipliedimmunoassaytechnique (EMIT) and liquid chromatography-mass spectrometry (LC-MS/MS). The results show varying degrees of elevation of creatinine levels in 3 patients, and EMIT may overestimate the true concentration of tacrolimus metabolites compared with LC-MS/MS. All the data comply with the Helsinki Congress and the Declaration of Istanbul.

The Levels and Influencing Factors of Compassion Fatigue among New Nurses during the COVID-19 Pandemic

Aim. To investigate the levels and influencing factors of compassion fatigue among new nurses during the COVID-19 pandemic. Background. New nurses are often unable to cope with the escalating nursing problems during the COVID-19 epidemic because of their lack of work experience, which may reduce their level of compassion satisfaction and cause compassion fatigue. However, there is little research on compassion fatigue and compassion satisfaction among new nurses during the COVID-19 epidemic. Methods. This was a cross-sectional study. From June to October 2021, 520 new nurses were selected from eight designated hospital for treatment of COVID-19 in China for electronic survey. Questions elicited social-demographics, work-related information, lifestyle factors, and the Chinese version Professional Quality of Life Scale. Results. The scores of compassion satisfaction, burnout, and secondary traumatic stress of new nurses were 31.85 ± 6.18, 27.94 ± 5.04, and 27.17 ± 4.87, respectively. In addition, regression analysis showed that nurses’ compassion satisfaction, burnout, and secondary traumatic stress were affected by social-demographics, work-related information, and lifestyle factors. Conclusions. During the COVID-19 epidemic, compassion satisfaction, burnout, and secondary traumatic stress of new nurses were at a moderate level, which were relatively affected by work-related information and lifestyle, and had little correlation with social-demographics. Implications for Nursing Management. Hospital administrators can promote new nurses’ compassion satisfaction and alleviate their compassion fatigue by improving job satisfaction, encouraging smoking cessation, arranging work hours reasonably, ensuring sleep hours, reducing workplace violence, and strengthening the reporting of violence incidents.

The Top 100 Cited Articles on Acupuncture in the Last 20 Years: A Bibliometric Analysis

Background: Acupuncture has gained increasing international attention in recent decades. The act of incorporating acupuncture treatment into the routine treatment of COVID-19 in China drove us to review the 100 most influential articles of the last 20 years to learn about the current status and trends of acupuncture. Method: Articles related to acupuncture from January 1, 2001, to July 4, 2022, were searched in the Clarivate Analytics Web of Science Core Collection database. The top 100 most cited publications were selected, and information was extracted. Software such as VOSviewer, GraphPad Prism, Scimago Graphica, and CiteSpace were used to visualize and analyze the extracted data. Result: The 100 most cited articles were identified, with an average of 218 citations (range: 131–625). The majority of the top 100 articles were from the USA (n = 53). The institution that published the most highly cited papers was Harvard University (n = 16). The most influential team was Klaus Linde’s group. Pain was the top-ranked journal in terms of the number of publications. The largest clusters for co-occurrence keyword analysis focused on acupuncture and electroacupuncture analgesia and brain imaging responses to acupuncture stimulation via functional MRI. The two highest strength burst keywords were “randomized controlled trials” and “osteoarthritis,” with “randomized controlled trials” being a consistent burst keyword from 2011 to the present. Conclusion: This study provides insight into articles of historical significance in the field of acupuncture through bibliometric analysis. These data should provide clinicians and researchers with insight into future directions related to acupuncture.

In silico screening of phenylethanoid glycosides, a class of pharmacologically active compounds as natural inhibitors of SARS-CoV-2 proteases

Since the advent of Covid-19, several natural products have been investigated regarding their in silico interactions with SARS-CoV-2 proteases ˗ 3CLpro and PLpro, two of the most important pharmacological targets for antiviral development. Phenylethanoid glycosides (PG) are a class of natural products present in important medicinal plants and a drug containing this group of active ingredients has been successfully used in the treatment of Covid-19 in China. Thus, a dataset with 567 derivatives of this class was built from reviews published between 1994 and 2020, and their interaction against both SARS-CoV-2 proteases was investigated. The virtual screening was performed by filtering the PGs through the evaluation of scores based on the AutoDock Vina, GOLD/ChemPLP, and GOLD/GoldScore evaluation functions. The bRO5 pharmacokinetic parameters of the PGs ranked in the previous step were analyzed and their interaction with key amino acid residues of the 3CLpro and PLpro enzymes was evaluated. Ninety-eight compounds were identified by computational approaches against PLpro and 80 PGs against 3CLpro. Of these, four interacted with key catalytic residues of PLpro, which is an indicative of inhibitory activity, and three compounds interacted with catalytic key residues of 3CLpro. Of these, five PGs occur in plants of the Traditional Chinese Medicine (TCM), while two are components of plants/formulations currently used in the Covid-19 protocols in China. The data presented here show the potential of PGs as selective inhibitors of SARS-CoV-2 3CLpro and PLpro.

The construction and practice of a standardized nursing service system based on the designated hospital for the treatment of COVID-19 in China

The construction and practice of a standardized nursing service system based on the designated hospital for the treatment of COVID-19 in China

An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology

BackgroundThe novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear. PurposeAn integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification. MethodsFirstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB). ResultsAccording to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well. ConclusionIn the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.

Interpretation of the diagnosis and treatment protocol for COVID‐19 (Trial Version 9)

Interpretation of the diagnosis and treatment protocol for COVID‐19 (Trial Version 9)

Amomum tsao-ko essential oil, a novel anti-COVID-19 Omicron spike protein natural products: A computational study.

Since the outbreak of COVID-19, this virus has been constantly mutating. The latest mutant Omicron has been identified as VOC by WHO. The main reason for its concern is the mutation of 46 amino acids in spike protein, which has brought the global epidemic prevention into another difficulty. Herbal aromatic plant Amomum tsao-ko was excavated from formula 1 and 2 for the treatment of COVID-19 in China, and its active components were extracted and identified. Molecular dynamics simulation and Fpocket were applied to find the key sites on RBDOmicron, and molecular docking was also used to reveal the interaction between A. tsao-ko essential oil (AEO) and RBDOmicron. The AEO components were analyzed and identified by GC/Q-TOF MS. There were 20 kinds of AEO with a relative area percentage of more than 1%, and they were related to the three active centres of RBDOmicron. In this study, virtual screening was used to mine the essential oil components of medicinal plants, and it was found that the components could interact with the spike protein RBD in aerosol to block the interaction of RBD and hACE2, thus cutting off the transmission route and protecting the host. This study has certain guiding significance in the modernization of Traditional Chinese medicine and the prevention of COVID-19.

Medication Rule Analysis of the Diagnosis and Treatment Programs of Chinese Medicine for the Prevention and Treatment of COVID-19 in China.

ObjectivesTo summarize the measures and rules of Chinese medicine (CM) and provide reference for clinical application in the prevention and treatment of coronavirus disease (COVID-19).MethodsThe data source was from CM COVID-19 prevention and treatment programs on government websites and official media websites of the different provinces and cities. The search lasted from December 8, 2019 to March 10, 2020. Main variables were medication frequency and combinations of medicines. Cluster analysis and complex network analysis were used by prevention and treatment stage and by area.ResultsAmong 27 CM diagnosis and treatment plans, 203 therapeutic prescriptions were enrolled, of which the top 4 herbs were: Radix glycyrrhizae, Semen armeniacae amarum, Herba ephedrae, and Herba agastachis, respectively. The core combinations were Herba ephedrae and Semen armeniacae amarum. Forty-eight preventive formulae were identified. Ten herbs, including Radix Astragali seu hedysari, Radix glycyrrhizae, Radix saposhnikoviae, Flos lonicerae, etc. were most frequently used. The core prescription of CM compatibility was Radix astragali seu hedysari, Radix glycyrrhizae, and Radix saposhnikoviae, which is the main component of Yu Ping Feng San. There were 45 prevention and treatment prescriptions in East China; the most used CM was Radix glycyrrhizae, Herba agastachis, Pericarpium citri reticulatae, and Gypsum fibrosum. Fifty prescriptions were identified in North China. According to CM analyses, Herba agastachis, Semen armeniacae amarum, Herba ephedrae, and Poria were most frequently used.ConclusionsCM for COVID-19 prevention mainly focuses on improving human immunity; for treatment, prescription focuses on clearing the lungs and removing dampness. Prescriptions vary with regions, perhaps due to climatic and environmental differences, which help clinicians to quickly make CM plans and treat patients according to clinical status, further minimizing resource wastage.Electronic Supplementary MaterialSupplementary materials (Appendices) are available in the online version of this article at 10.1007/s11655-021-2880-1

Efficient discovery of potential inhibitors for SARS-CoV-2 3C-like protease from herbal extracts using a native MS-based affinity-selection method

The 3C-like protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to the virus life cycle and is supposed to be a potential target for the treatment of coronaviral infection. Traditional Chinese medicines (TCMs) have played an impressive role in the treatment of COVID-19 in China. The effectiveness of TCM formulations prompts scientists to take continuous effort on searching for bioactive small molecules from the ancient resources. Herein, we developed a native mass spectrometry-based affinity-selection method for rapid screening of active small molecules from crude herbal extracts applied for COVID-19 therapy. Six common herbs named Lonicera japonica, Scutellaria baicalensis, Forsythia suspensa, Glycyrrhiza uralensis, Cirsium japonicum, and Andrographis paniculata were investigated. After preliminary separation of the crude extracts, the fractions were incubated with 3CLpro. A native MS-based affinity screening assay was then conducted to search for the protein-ligand complexes. A UHPLC-Q/TOF-MS with UNIFI data acquisition and data processing software was applied to identify the hit compounds. Standard compounds were used to verify the outcomes. Among the 16 hits, three flavonoids, baicalein, scutellarein and ganhuangenin, were identified as potential noncovalent inhibitors against 3CLpro with IC50 values of 0.94, 3.02, and 0.84 μM, respectively. Their binding affinities were further characterized by native MS, with Kd values being 1.43, 3.85, and 1.09 μM, respectively. Overall, we established an efficient native MS-based strategy for discovering 3CLpro ligands from crude mixtures, which supplies a potential strategy of small molecule lead discovery from TCMs.

Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway

Ethnopharmacological relevanceXuanfei Baidu Decoction (XFBD), one of the “three medicines and three prescriptions” for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. Aim of the studyThe present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. MethodsWe use TGF-β1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. ResultsThe results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. ConclusionsXuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.

Mechanism of Microbial Metabolite Leupeptin in the Treatment of COVID-19 by Traditional Chinese Medicine Herbs.

ABSTRACTCoronavirus disease 2019 (COVID-19) has caused huge deaths and economic losses worldwide in the current pandemic. The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thought to be an ideal drug target for treating COVID-19. Leupeptin, a broad-spectrum covalent inhibitor of serine, cysteine, and threonine proteases, showed inhibitory activity against Mpro, with a 50% inhibitory concentration (IC50) value of 127.2 μM in vitro in our study here. In addition, leupeptin can also inhibit SARS-CoV-2 in Vero cells, with 50% effective concentration (EC50) values of 42.34 μM. More importantly, various strains of streptomyces that have a broad symbiotic relationship with medicinal plants can produce leupeptin and leupeptin analogs to regulate autogenous proteases. Fingerprinting and structure elucidation using high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS), respectively, further proved that the Qing-Fei-Pai-Du (QFPD) decoction, a traditional Chinese medicine (TCM) formula for the effective treatment of COVID-19 during the period of the Wuhan outbreak, contains leupeptin. All these results indicate that leupeptin at least contributes to the antiviral activity of the QFPD decoction against SARS-CoV-2. This also reminds us to pay attention to the microbiomes in TCM herbs as streptomyces in the soil might produce leupeptin that will later infiltrate the medicinal plant. We propose that plants, microbiome, and microbial metabolites form an ecosystem for the effective components of TCM herbs.

Investigation of Anti-SARS, MERS, and COVID-19 Effect of Jinhua Qinggan Granules Based on a Network Pharmacology and Molecular Docking Approach

Objective Jinhua Qinggan Granules (JQGs) have achieved certain results in the prevention and treatment of COVID-19 in China during this coronavirus storm. In this study, we aimed to analyze the common mechanisms of JQG in the treatment of coronavirus-induced diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 via network pharmacology and molecular docking. Methods The active compounds of JQG were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The common targets associated with these 3 diseases were screened from GeneCards database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of JQG’s core targets were analyzed using The Database for Annotation, Visualization, and Integrated Discovery and KOBAS 3.0 system. Further, the protein-protein interaction network was built using STRING database. The compound-target- signaling pathway network was constructed using Cytoscape 3.7.2. The core components of JQG were docked with core targets, COVID-19 coronavirus 3 Cl hydrolase, and angiotensin-converting enzyme 2 (ACE2) via Discovery Studio 2016 software. Results A total of 139 active compounds, 50 core targets, and 122 signaling pathways were screened out. The results of molecular docking showed that arctiin and linarin had a higher docking score with 3 Cl, ACE2, and core targets of JQH for antiviral effect. Conclusion The potential mechanism of action of JHQ in the treatment of MERS, SARS, and COVID-19 may be associated with the regulation of genes co-expressed with ACE2 and immune- related signaling pathways.

A retrospective analysis of clinical efficacy of ribavirin in adults hospitalized with severe COVID-19

IntroductionCoronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. MethodsA total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. Results68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63–1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. ConclusionsIn hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.

Retrospective Review of Traditional Chinese Medicine Treatment of COVID-19 in China: Clinical Practice and Researches

In the fight against COVID-19 in China, traditional Chinese medicine (TCM) has played an important role in relieving symptoms, preventing deterioration, improving cure rate, reducing death rate, and promoting recovery. Since the third edition of the Diagnosis and Treatment Protocol for COVID-19 (simply referred to as the National Protocol), TCM has been included in the national guidance to tackle the epidemic. In order to make the international medical community fully understand the experience of TCM in the prevention and treatment of COVID-19, we comprehensively reviewed the history, etiology and pathogenesis, prevention and treatment, rehabilitation, and clinical and pharmacological research of TCM used in the endemic. The COVID-19 is under the category of plague or pestilence in TCM. Herbal medicine treatment for COVID-19 is mainly performed based on the syndrome differentiation of three stages and four types. The method also applies to acupuncture and moxibustion treatments. Herbal medicine granules and injections are used flexibly, and Western medicine is adopted to rescue patients in critical conditions. In rehabilitation, the integration of Chinese and Western medicine can be used to improve the respiratory and somatic function of patients. The role TCM has been playing in fighting this epidemic is a further proof of the effect of TCM in preventing and treating infectious diseases, and the relevant experience has been summarized and sublimated.

Development and validation of a rapid and efficient method for simultaneous determination of mycotoxins in coix seed using one-step extraction and UHPLC-HRMS

ABSTRACT Coix seed is an important food and traditional Chinese medicine in China and other Asian countries. Notably, coix seed is currently being used as a traditional medicine for the treatment of COVID-19 in China. However, coix seeds are generally contaminated by mycotoxins, and this risk cannot be ignored. In this paper, we developed a method that involves direct extraction and UHPLC-HRMS analysis for the simultaneous detection of 24 mycotoxins in coix seeds. UHPLC-HRMS instrument and data acquisition parameters, and the sample pretreatment were optimised. One-step extraction showed several advantages compared to the three commercial solid-phase extraction clean-up methods, including ease of use, reduced time of sample preparation, low cost, good recovery, and acceptable matrix effect. The method validation results indicate that all mycotoxins have good linearity and sensitivity. Recoveries were between 74.2–101.1%, and RSD ranged from 0.1–5.8%. The LOQs for 24 mycotoxins were in the range of 0.5–100 µg/kg. To survey the contamination levels of these mycotoxins in commercial coix seeds, more than 70 samples were collected from Chinese markets and were analysed using the newly developed method. Zearalenone (positive ratio: 98.7%, range:1.1–1562 µg/kg), deoxynivalenol (positive ratio: 87%, range: 8.4–382.5 µg/kg), nivalenol (positive ratio: 85.7%, range: 26.8–828.2 µg/kg), fumonisin B1 (positive ratio: 84.4%, range:2.5–314.5 µg/kg), fumonisin B2 (positive ratio: 75.3%, range:1.6–72.8 µg/kg), fumonisin B3 (positive ratio: 48%, range:1.0–203.6 µg/kg), aflatoxin B1 (positive ratio: 29.9%, range: 0.39–14.7 µg/kg), sterigmatocystin (positive ratio: 29.9%, range: 1.4–51.6 µg/kg), and tenuazonic acid (positive ratio: 19.5%, range 36.1–105.7 µg/kg) were the most frequent mycotoxin contaminants. These results highlight the importance of routine monitoring and control of mycotoxins in coix seeds.