Efficacy and safety of chinese herbal medicine for treating mild or moderate COVID-19: A systematic review and meta-analysis of randomized controlled trials and observational studies.

Background: The coronavirus disease 2019 (COVID-19) is still a pandemic globally, about 80% of patients infected with COVID-19 were mild and moderate. Chinese herbal medicine (CHM) has played a positive role in the treatment of COVID-19, with a certain number of primary studies focused on CHM in managing COVID-19 published. This study aims to systematically review the currently published randomized controlled trials (RCTs) and observational studies (OBs), and summarize the effectiveness and safety of CHM in the treatment of mild/moderate COVID-19 patients. Methods: We searched 9 databases up to 19 March 2022. Pairs of reviewers independently screened literature, extracted data and assessed risk of bias. For overall effect, we calculated the absolute risk difference (ARD) of weighted averages of different estimates, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Results: We included 35 RCTs and 24 OBs enrolling 16,580 mild/moderate patients. The certainty of evidence was very low to low. Compared with usual supportive treatments, most effect estimates of CHM treatments were consistent in direction. CHMs presented significant benefits in reducing rate of conversion to severe cases (ARD = 99 less per 1000 patients in RCTs and 131 less per 1000 patients in OBs, baseline risk: 16.52%) and mortality (ARD = 3 less per 1000 patients in RCTs and OBs, baseline risk: 0.40%); shortening time to symptom resolution (3.35 days in RCTs and 2.94 days in OBs), length of hospital stay (2.36 days in RCTs and 2.12 days in OBs) and time to viral clearance (2.64 days in RCTs and 4.46 days in OBs); increasing rate of nucleic acid conversion (ARD = 73 more per 1000 patients in OBs, baseline risk: 16.30%). No serious adverse reactions were found and the differences between CHM and usual supportive care were insignificant. Conclusion: Encouraging evidence showed that CHMs were beneficial in treating mild or moderate patients. CHMs have been proved to possess a safety profile that is comparable to that of usual supportive treatment alone. More rigorously designed clinical trials and mechanism studies are still warranted to further confirm the present findings.

A Novel COVID-19 Image Classification Method Based on the Improved Residual Network

In recent years, chest X-ray (CXR) imaging has become one of the significant tools to assist in the diagnosis and treatment of novel coronavirus pneumonia. However, CXR images have complex-shaped and changing lesion areas, which makes it difficult to identify novel coronavirus pneumonia from the images. To address this problem, a new deep learning network model (BoT-ViTNet) for automatic classification is designed in this study, which is constructed on the basis of ResNet50. First, we introduce multi-headed self-attention (MSA) to the last Bottleneck block of the first three stages in the ResNet50 to enhance the ability to model global information. Then, to further enhance the feature expression performance and the correlation between features, the TRT-ViT blocks, consisting of Transformer and Bottleneck, are used in the final stage of ResNet50, which improves the recognition of complex lesion regions in CXR images. Finally, the extracted features are delivered to the global average pooling layer for global spatial information integration in a concatenated way and used for classification. Experiments conducted on the COVID-19 Radiography database show that the classification accuracy, precision, sensitivity, specificity, and F1-score of the BoT-ViTNet model is 98.91%, 97.80%, 98.76%, 99.13%, and 98.27%, respectively, which outperforms other classification models. The experimental results show that our model can classify CXR images better.

China's challenges in implementing compulsory drug patent licenses and its response in the context of COVID-19

Covid-19 has spread quickly throughout China and the entire world. According to the World Health Organization, there is a public health emergency that is of global significance (WHO). Controlling the drug supply is essential since this hazardous pandemic has seriously jeopardized global public security. This essay starts by looking at the current condition of COVID-19, analyzes the requirements for required drug patent licensing in different countries, points out the problems with mandatory drug patent licensing in China, and finally offers practical suggestions for forced pharma patent licensing. China and the rest of the world have experienced rapid Covid-19 spread. There is an international public health emergency, according to the World Health Organization (WHO). The majority of China's pharmaceutical companies were founded relatively recently, and they are currently producing copycat medications. The government needs to properly understand the value of the compulsory patent licensing system and offer the necessary support to ensure a successful rollout. The government can implement specific policies, add a special fund for drug development, offer loans to pharmaceutical companies, hire qualified staff for drug research and development, and generally strengthen China's pharmaceutical industry. Pharmaceutical companies are the manufacturers of drugs under the obligatory patent licensing system. Pharmaceutical companies should develop their overall strength, increase their ability to produce drugs, and have enough resources to meet social requirements and guarantee public health and safety. To increase the rate of development, it is vital to promote international collaboration and actively introduce foreign innovative systems and industrial facilities.

Efficacy and safety of chinese herbal medicine for treating mild or moderate COVID-19: A systematic review and meta-analysis of randomized controlled trials and observational studies

Background: The coronavirus disease 2019 (COVID-19) is still a pandemic globally, about 80% of patients infected with COVID-19 were mild and moderate. Chinese herbal medicine (CHM) has played a positive role in the treatment of COVID-19, with a certain number of primary studies focused on CHM in managing COVID-19 published. This study aims to systematically review the currently published randomized controlled trials (RCTs) and observational studies (OBs), and summarize the effectiveness and safety of CHM in the treatment of mild/moderate COVID-19 patients. Methods: We searched 9 databases up to 19 March 2022. Pairs of reviewers independently screened literature, extracted data and assessed risk of bias. For overall effect, we calculated the absolute risk difference (ARD) of weighted averages of different estimates, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Results: We included 35 RCTs and 24 OBs enrolling 16,580 mild/moderate patients. The certainty of evidence was very low to low. Compared with usual supportive treatments, most effect estimates of CHM treatments were consistent in direction. CHMs presented significant benefits in reducing rate of conversion to severe cases (ARD = 99 less per 1000 patients in RCTs and 131 less per 1000 patients in OBs, baseline risk: 16.52%) and mortality (ARD = 3 less per 1000 patients in RCTs and OBs, baseline risk: 0.40%);shortening time to symptom resolution (3.35 days in RCTs and 2.94 days in OBs), length of hospital stay (2.36 days in RCTs and 2.12 days in OBs) and time to viral clearance (2.64 days in RCTs and 4.46 days in OBs);increasing rate of nucleic acid conversion (ARD = 73 more per 1000 patients in OBs, baseline risk: 16.30%). No serious adverse reactions were found and the differences between CHM and usual supportive care were insignificant. Conclusion: Encouraging evidence showed that CHMs were beneficial in treating mild or moderate patients. CHMs have been proved to possess a safety profile that is comparable to that of usual supportive treatment alone. More rigorously designed clinical trials and mechanism studies are still warranted to further confirm the present findings.

Changes in HIV Testing Utilization Among Chinese Men Who Have Sex With Men During the COVID-19 Pandemic in Shenzhen, China: An Observational Prospective Cohort Study

Background The Coronavirus Diseases 2019 (COVID-19) directly affects HIV prevention and sexual health services utilization among men who have sex with men (MSM). This study investigated changes in human immunodeficiency virus (HIV) testing utilization among MSM before and after the COVID-19 pandemic received initial control in Shenzhen, China. Methods This study was a sub-analysis of a prospective observational cohort study conducted among MSM in Shenzhen, China between August 2020 and May 2021. Participants were recruited through outreaching in gay venues, online recruitment, and peer referral. Participants completed a baseline online survey between August and September 2020 and a follow-up online survey between April and May 2021. This study was based on 412 MSM who reported to be HIV-negative/unknown sero-status at baseline, 297 (72.1%) of them completed the follow-up online survey. Multilevel logistic regression models (level 1: sources of recruitment;level 2: individual participants) were fitted. Results When comparing follow-up data with baseline data, a significant increase was observed in the uptake of any type of HIV testing (77.9% at Month 6 vs. 59.2% at baseline, p < 0.001). After adjusting for age group, education level, current employment status and monthly personal income, two predisposing factors were associated with higher uptake of HIV testing during the follow-up period. They were: (1) condomless anal intercourse with male non-regular male sex partners at follow-up only (AOR: 5.29, 95%CI: 1.27, 22.01) and (2) sanitizing before and after sex at baseline (AOR: 1.26, 95%CI: 1.02, 1.47). Regarding enabling factors, utilization of HIV testing (AOR: 3.90, 95%CI: 2.27, 6.69) and STI testing (AOR: 2.43, 95%CI: 1.20, 4.93) 6 months prior to the baseline survey was associated with higher uptake of HIV testing during the follow-up period. Having the experience that HIV testing service providers reduced service hours during the follow-up period was also positively associated with the dependent variable (AOR: 3.45, 95%CI: 1.26, 9.41). Conclusions HIV testing utilization among MSM might rebound to the level before the COVID-19 outbreak after the pandemic received initial control in China. This study offered a comprehensive overview to identify potential reasons that can influence the uptake of HIV testing among Chinese MSM.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: a multicenter study.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

COVID-19 CG: Tracking SARS-CoV-2 mutations by locations and dates of interest (preprint)

COVID-19 CG is an open resource for tracking SARS-CoV-2 single-nucleotide variations (SNVs) and lineages while filtering by location, date, gene, and mutation of interest. COVID-19 CG provides significant time, labor, and cost-saving utility to diverse projects on SARS-CoV-2 transmission, evolution, emergence, immune interactions, diagnostics, therapeutics, vaccines, and intervention tracking. Here, we describe case studies in which users can interrogate (1) SNVs in the SARS-CoV-2 Spike receptor binding domain (RBD) across different geographic regions to inform the design and testing of therapeutics, (2) SNVs that may impact the sensitivity of commonly used diagnostic primers, and (3) the recent emergence of a dominant lineage harboring an S477N RBD mutation in Australia. To accelerate COVID-19 research and public health efforts, COVID-19 CG will be continually upgraded with new features for users to quickly and reliably pinpoint mutations as the virus evolves throughout the pandemic and in response to therapeutic and public health interventions.

Erythrocytic ALPHA-synuclein contained in microvesicles regulates astrocytic glutamate homeostasis: a new perspective on Parkinson's disease pathogenesis

Parkinson's disease is a neurodegenerative disorder characterized by the transmission and accumulation of toxic species of &#945;-synuclein (&#945;-syn). Extracellular vesicles (EVs) are believed to play a vital role in the spread of toxic &#945;-syn species. Recently, peripheral &#945;-syn pathology has been investigated, but little attention has been devoted to erythrocytes, which contain abundant &#945;-syn. In this study, we first demonstrated that erythrocyte-derived EVs isolated from Parkinson's disease patients carried elevated levels of oligomeric &#945;-syn, compared to those from healthy controls. Moreover, human erythrocyte-derived EVs, when injected into peripheral blood in a mouse model of Parkinson's disease, were found to readily cross the blood-brain barrier (BBB). These EVs accumulated in astrocyte endfeet, a component of the BBB, where they impaired glutamate uptake, likely via interaction between excitatory amino acid transporter 2 (EAAT2) and oligomeric &#945;-syn. These data suggest that erythrocyte-derived EVs and the oligomeric &#945;-syn carried in them may play critical roles in the progression or even initiation of Parkinson's disease. Additionally, the mechanisms involved are attributable at least in part to dysfunction of astrocytes induced by these EVs. These observations provide new insight into the understanding of the mechanisms involved in Parkinson's disease.

Emergency Responses to Covid-19 Outbreak: Experiences and Lessons from a General Hospital in Nanjing, China.

BACKGROUND: The novel coronavirus 2019 (SARS-CoV-2) has caused wide dissemination across the world. Global health systems are facing the unprecedented challenges. Here we shared the experiences and lessons in emergency responses and management from our hospital, a government-assigned regional anti-Covid-19 general hospital in Nanjing, Jiangsu Province, China. METHODS: Our periodic strategies in dealing with Covid-19 were described in detail. An administrative response including the establishment of Emergency Leadership Committee that was in full charge of management was established. Modifications of infrastructure including the Fever Clinic, inpatient ward, outpatient clinic and operation room were carried out. Special arrangements for outpatient services, hospitalization and surgeries were introduced. Medical personnel training and patient educations were performed. Initiations of Covid-19 researches and application of information technology were introduced. FINDINGS: Since January 16, three cases have been confirmed in our hospital and no healthcare-associated infection was found. During the epidemics, 6.46% staffs suffered depression, 9.87% had anxiety, and 98% were satisfied with the infection control policy. Shortages in staffs and medical consumables, and limitation in space were the obstacles we encountered. INTERPRETATION: As the cost of in-hospital transmission is unbearable, our experiences and lessons suggested that prompt actions should be taken immediately to decrease or eliminate potential in-hospital transmission. Experience shared herein may be useful for those facilities that are and may encounter Covid-19.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: A Multicenter Study (preprint)

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from Jan 17 to Feb 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920 (95% confidence interval : 0.902-0.938; AUROC=0.915, and its standard deviation of 0.028, as evaluated in 5-fold cross-validation). At a value of whether the predicted score >4.0, the model could detect NCP with a specificity of 98.3%; at a cut-off value of < -0.5, the model could rule out NCP with a sensitivity of 97.9%. The study demonstrated that the rapid screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs (preprint)

ABSTRACT Background As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing. Results We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH + fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues. Conclusions The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.

Multiple approaches for massively parallel sequencing of HCoV-19 genomes directly from clinical samples (preprint)

COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.

Prevalence of novel coronavirus pneumonia in the early stage of transmission and responding strategies in Japan / 上海预防医学

Novel coronavirus pneumonia disease (COVID-19) caused by SARS-CoV-2 began to emerge in Wuhan, Hubei, China in December 2019. It is currently spreading globally including Japan. The COVID-19 case in Japan began to appear in middle January 2020 and continued to increase over time. The period from middle January to the end of February is considered to be the initial stage of domestic transmission in Japan. This article described the spread of 935 COVID-19 cases related to Japan by the end of February 2020, including the 15 infected Japanese returned from Wuhan, the 696 infected individuals in the large-scale cruise ship 'Diamond Princess' and the 224 infected individuals in Japan. This paper summarizes the measures to control the spread of SARS-CoV-2 in Japan, such as limiting RT-PCR detection for SARS-CoV-2, reducing the number of patients with mild illness who go to medical institutions unnecessarily, formulating guidelines for SARS-CoV-2 infection consultation, canceling large gatherings and temporarily closing schools. This paper further points out the problems encountered in the prevention and control of the spread of SARS-CoV-2 in Japan, such as the slow detection of RT-PCR, the risk of infection faced by medical staff, the regional differences in the domestic health care service system, the confusion of information disclosure and management. The above introduction as allows us to acquire a better understanding of the new coronavirus pneumonia in Japan and the world and may provide reference for the control the epidemic of COVID-19 in worldwide.