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1.
Kidney Blood Press Res ; 2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-1962523

ABSTRACT

INTRODUCTION: The angiotensin-converting enzyme 2 (ACE2) as well as the transmembrane protease serine type 2 (TMPRSS2) have been found to play roles in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection risk and severity of COVID-19 might be indicated by the expression of ACE2 and TMPRSS2 in the lung. METHODS: A high salt diet rat model and RAAS blockade were used to test whether these factors affect ACE2 and TMPRSS2 expression of the lung. A normal (0.3% NaCl), a medium (2% NaCl), or a high (8% NaCl) salt diet was fed to rats for 12 weeks, along with enalapril or telmisartan, before examining the lung for histopathological alteration. Using immunofluorescence and qRT-PCR, the localization as well as mRNA expression of ACE2 and TMPRSS2 were investigated. RESULTS: The findings provide evidence that both TMPRSS2 and ACE2 are highly expressed in bronchial epithelial cells as well as ACE2 was also expressed in alveolar type2 (AT2) cells. High salt diet exposure in rats leads to elevated ACE2 expression on protein level. Treatment with RAAS blockers had no effect on lung tissue expression of ACE2 and TMPRSS2. CONCLUSIONS: These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular co-morbidity. High salt intake on the other hand might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.

2.
Int J Infect Dis ; 119: 87-94, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1889471

ABSTRACT

OBJECTIVES: To evaluate the cost-effectiveness of a booster strategy in the United States. METHODS: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of the Pfizer-BioNTech BNT162b2 (administered 6 months after the second dose) among older adults from a healthcare system perspective. RESULTS: Compared with 2 doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million in vaccination cost but save $6.7 million in direct medical cost and gain 3.7 quality-adjusted life-years in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that a booster strategy has a high chance (67%) of being cost-effective. Notably, the cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. If vaccine efficacies reduce by 10%, 30%, and 50%, this threshold will increase to 9.7/100,000, 13.9/100,000, and 21.9/100,000 person-day, respectively. CONCLUSION: Offering the BNT162b2 booster to older adults aged ≥65 years in the United States is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-CoV-2 transmission.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cost-Benefit Analysis , Humans , United States/epidemiology , Vaccination
3.
Frontiers in medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1876654

ABSTRACT

Purpose To investigate the difference in the positive end-expiratory pressure (PEEP) selected with chest electrical impedance tomography (EIT) and with global dynamic respiratory system compliance (Crs) in moderate-to-severe pediatric acute respiratory distress syndrome (pARDS). Methods Patients with moderate-to-severe pARDS (PaO2/FiO2 < 200 mmHg) were retrospectively included. On the day of pARDS diagnosis, two PEEP levels were determined during the decremental PEEP titration for each individual using the best compliance (PEEPC) and EIT-based regional compliance (PEEPEIT) methods. The differences of global and regional compliance (for both gravity-dependent and non-dependent regions) under the two PEEP conditions were compared. In addition, the EIT-based global inhomogeneity index (GI), the center of ventilation (CoV), and standard deviation of regional delayed ventilation (RVDSD) were also calculated and compared. Results A total of 12 children with pARDS (5 with severe and 7 with moderate pARDS) were included. PEEPC and PEEPEIT were identical in 6 patients. In others, the differences were only ± 2 cm H2O (one PEEP step). There were no statistical differences in global compliance at PEEPC and PEEPEIT [28.7 (2.84–33.15) vs. 29.74 (2.84–33.47) ml/cm H2O median (IQR), p = 0.028 (the significant level after adjusted for multiple comparison was 0.017)]. Furthermore, no differences were found in regional compliances and other EIT-based parameters measuring spatial and temporal ventilation distributions. Conclusion Although EIT provided information on ventilation distribution, PEEP selected with the best Crs might be non-inferior to EIT-guided regional ventilation in moderate-to-severe pARDS. Further study with a large sample size is required to confirm the finding.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336854

ABSTRACT

Background Australia implemented an mRNA-based booster vaccination strategy against the COVID-19 Omicron variant in November 2021. We aimed to evaluate the effectiveness and cost-effectiveness of the booster strategy over 180 days. Methods We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy (administered 3 months after 2 nd dose) in those aged ≥16 years in Australia from a healthcare system perspective. The willingness-to-pay threshold was chosen as A$ 50,000. Findings Compared with 2-doses of COVID-19 vaccines without a booster, Australia’s booster strategy would incur an additional cost of A$0.88 billion but save A$1.28 billion in direct medical cost and gain 670 quality-adjusted life years (QALYs) in 180 days of its implementation. This suggested the booster strategy is cost-saving, corresponding to a benefit-cost ratio of 1.45 and a net monetary benefit of A$0.43 billion. The strategy would prevent 1.32 million new infections, 65,170 hospitalisations, 6,927 ICU admissions and 1,348 deaths from COVID-19 in 180 days. Further, a universal booster strategy of having all individuals vaccinated with the booster shot immediately once their eligibility is met would have resulted in a gain of 1,599 QALYs, a net monetary benefit of A$1.46 billion and a benefit-cost ratio of 1.95 in 180 days. Interpretation The COVID-19 booster strategy implemented in Australia is likely to be effective and cost-effective for the Omicron epidemic. Universal booster vaccination would have further improved its effectiveness and cost-effectiveness. Funding National Natural Science Foundation of China. Bill and Melinda Gates Foundation

5.
Front Cell Infect Microbiol ; 11: 778808, 2021.
Article in English | MEDLINE | ID: covidwho-1789350

ABSTRACT

Objectives: Overuse of antibiotics and antibiotic resistance are global healthcare problems. In pediatric patients with respiratory infections, viral and bacterial etiologies are challenging to distinguish, leading to irrational antibiotic use. Rapid and accurate molecular diagnostic testing methods for respiratory pathogens has been shown to facilitate effective clinical decision-making and guide antibiotic stewardship interventions in the developed regions, but its impacts on pediatric patient care in the developing countries remain unclear. Methods: In this single-center, retrospective case-control study, we compared demographics, clinical characteristics, especially microbiological findings, and antibiotic usage between pediatric patients with respiratory infection receiving FilmArray Respiratory Panel (FilmArray RP) testing and a matched routine testing control group. Our primary outcome was the duration of intravenous antibiotics treatment (DOT) during hospitalization. Results: Each group consisted of 346 children with a respiratory infection. In the FilmArray RP testing group, the DOT was shorter than that in the routine testing group (6.41 ± 3.67 days versus 7.23 ± 4.27 days; p = 0.006). More patients in the FilmArray RP testing group de-escalated antibiotic treatments within 72 hours of hospitalization (7.80%, 27/346 versus 2.60%, 9/346; p = 0.002). By contrast, fewer patients in the FilmArray RP testing group had escalated antibiotic treatments between 72 hours and seven days (7.80% versus 14.16%; p = 0.007). The cost of hospitalization was significantly lower in the FilmArray RP testing group ($ 1413.51 ± 1438.01 versus $ 1759.37 ± 1929.22; p = 0.008). Notably, the subgroup analyses revealed that the FilmArray RP test could shorten the DOT, improve early de-escalation of intravenous antibiotics within 72 hours of hospitalization, decline the escalation of intravenous antibiotics between 72 hours and seven days, and reduce the cost of hospitalization for both patient populations with or without underlying diseases. Conclusions: Molecular point-of-care testing for respiratory pathogens could help to reduce intravenous antibiotic use and health care costs of pediatric patients with respiratory infections in developing countries.


Subject(s)
Respiratory Tract Infections , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Child , Humans , Molecular Diagnostic Techniques , Point-of-Care Testing , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Retrospective Studies
6.
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1755869

ABSTRACT

Objectives: To evaluate the cost-effectiveness of a booster strategy in the US. Methods: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of Pfizer-BioNTech BNT162b2 (administered 6 months after 2nd dose) among older adults, from a healthcare system perspective. Results: Compared with 2-doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million in vaccination cost, but save $6.7 million in direct medical cost and gain 3.7 QALYs in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that a booster strategy has a high chance (67%) of being cost-effective. Notably, the cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. If vaccine efficacies reduce by 10%, 30%, and 50%, this threshold will increase to 9.7/100,000, 13.9/100,000, and 21.9/100,000 person-day, respectively. Conclusion: Offering BNT162b2 booster to older adults aged ≥65 years in the US is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-COV-2 transmission.

7.
Biochem Genet ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1718783

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is an enveloped single-stranded RNA virus that can lead to respiratory symptoms and damage many organs such as heart, kidney, intestine, brain and liver. It has not been clearly documented whether myocardial injury is caused by direct infection of cardiomyocytes, lung injury, or other unknown mechanisms. The gene expression profile of GSE150392 was obtained from the Gene Expression Omnibus (GEO) database. The processing of high-throughput sequencing data and the screening of differentially expressed genes (DEGs) were implemented by R software. The R software was employed to analyze the Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was constructed by the STRING website. The Cytoscape software was applied for the visualization of PPI network and the identification of hub genes. The statistical analysis was performed by the GraphPad Prism software to verify the hub genes. A total of 516 up-regulated genes and 191 down-regulated genes were screened out. The top 1 enrichment items of GO in biological process (BP), Cellular Component (CC), and Molecular Function (MF) were type I interferon signaling pathway, sarcomere, and receptor ligand activity, respectively. The top 10 enrichment pathways, including TNF signaling pathway, were identified by KEGG enrichment analysis. A PPI network was established, consisting of 613 nodes and 3,993 edges. The 12 hub genes were confirmed as statistically significant, which was verified by GSE151879 dataset. In conclusion, the hub genes of human iPSC-cardiomyocytes infected with SARS-CoV-2 were identified through bioinformatics analysis, which may be used as biomarkers for further research.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294352

ABSTRACT

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning, to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) problem in statistical machine learning. Here, we have implemented Portal Learning to predict chemicalprotein interactions on a genome-wide scale. Systematic studies demonstrate that Portal Learning can effectively assign ligands to unexplored gene families (unknown functions), versus existing state-of-the-art methods. Compared with AlphaFold2-based protein-ligand docking, Portal Learning significantly improved the performance by 79% in PR-AUC and 27% in ROC-AUC, respectively. The superior performance of Portal Learning allowed us to target previously “undruggable” proteins and design novel polypharmacological agents for disrupting interactions between SARS-CoV-2 and human proteins. Portal Learning is general-purpose and can be further applied to other areas of scientific inquiry.

9.
Tecnologia En Marcha ; 34(SP):38-45, 2021.
Article in English | Web of Science | ID: covidwho-1551978

ABSTRACT

The Covid-19 pandemic has forced us to change the way we used to handle education in our homes, through sanitary restrictions that seek to prohibit or reduce physical contact, moving from the traditional way to a virtual methodology;reason for which we must look for new solutions to adapt to this new teaching strategy. In addition, the pandemic has accelerated the arrival of the 4.0 revolution or technological revolution, where new challenges arise for society. The above reasons serve to justify and encourage that STEM education cannot stop. However, given the crisis we are experiencing and the solutions provided, the excessive use of virtual environments can affect areas such as psychological, social, etc. Through this project, a learning model implemented through volunteers is proposed, based on an interactive semi-virtual environment, where the participant can interact synchronously with a volunteering model provided by the volunteer tutor, and the learning process is supported through workshops and the use of virtual tools.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293237

ABSTRACT

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning, to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) problem in statistical machine learning. Here, we have implemented Portal Learning to predict chemicalprotein interactions on a genome-wide scale. Systematic studies demonstrate that Portal Learning can effectively assign ligands to unexplored gene families (unknown functions), versus existing state-of-the-art methods. Compared with AlphaFold2-based protein-ligand docking, Portal Learning significantly improved the performance by 79% in PR-AUC and 27% in ROC-AUC, respectively. The superior performance of Portal Learning allowed us to target previously “undruggable” proteins and design novel polypharmacological agents for disrupting interactions between SARS-CoV-2 and human proteins. Portal Learning is general-purpose and can be further applied to other areas of scientific inquiry.

11.
Front Cardiovasc Med ; 8: 698923, 2021.
Article in English | MEDLINE | ID: covidwho-1348469

ABSTRACT

Objective: The COVID-19 pandemic placed heavy burdens on emergency care and posed severe challenges to ST-segment-elevation myocardial infarction (STEMI) treatment. This study aimed to investigate the impact of COVID-19 pandemic on mechanical reperfusion characteristics in STEMI undergoing primary percutaneous coronary intervention (PPCI) in a non-epicenter region. Methods: STEMI cases undergoing PPCI from January 23 to March 29 between 2019 and 2020 were retrospectively compared. PPCI parameters mainly included total ischemic time (TIT), the period from symptom onset to first medical contact (S-to-FMC), the period from FMC to wire (FMC-to-W) and the period from door to wire (D-to-W). Furthermore, the association of COVID-19 pandemic with delayed PPCI risk was further analyzed. Results: A total of 14 PPCI centers were included, with 100 and 220 STEMI cases undergoing PPCI in 2020 and 2019, respectively. As compared to 2019, significant prolongations occurred in reperfusion procedures (P < 0.001) including TIT (420 vs. 264 min), S-to-FMC (5 vs. 3 h), FMC-to-W (113 vs. 95 min) and D-to-W (83 vs. 65 min). Consistently, delayed reperfusion surged including TIT ≥ 12 h (22.0 vs.3.6%), FMC-to-W ≥ 120 min (34.0 vs. 6.8%) and D-to-W ≥ 90 min (19.0 vs. 4.1%). During the pandemic, the patients with FMC-to-W ≥ 120 min had longer durations in FMC to ECG completed (6 vs. 5 min, P = 0.007), FMC to DAPT (24 vs. 21 min, P = 0.001), catheter arrival to wire (54 vs. 43 min, P < 0.001) and D-to-W (91 vs. 78 min, P < 0.001). The pandemic was significantly associated with high risk of delayed PPCI (OR = 7.040, 95% CI 3.610-13.729, P < 0.001). Conclusions: Even in a non-epicenter region, the risk of delayed STEMI reperfusion significantly increased due to cumulative impact of multiple procedures prolongation.

12.
Thorax ; 2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1318208

ABSTRACT

BACKGROUND: As the epidemic of COVID-19 is gradually controlled in China, a summary of epidemiological characteristics and interventions may help control its global spread. METHODS: Data for COVID-19 cases in Hubei Province (capital, Wuhan) was extracted until 7 March 2020. The spatiotemporal distribution of the epidemic in four periods (before 10 January, 10-22 January, 23 January-6 February and 7 February-7 March) was evaluated, and the impacts of interventions were observed. RESULTS: Among 67 706 COVID-19 cases, 52 111 (76.97%) were aged 30-69 years old, and 34 680 (51.22%) were women. The average daily attack rates (95% CI) were 0.5 (0.3 to 0.7), 14.2 (13.2 to 15.1), 45.7 (44.0 to 47.5) and 8.6 (7.8 to 9.3) cases per 106 people in four periods, and the harmonic means (95% CI) of doubling times were 4.28 (4.01 to 4.55), 3.87 (3.78 to 3.98), 5.40 (4.83 to 6.05) and 45.56 (39.70 to 52.80) days. Compared with the first period, daily attack rates rose rapidly in the second period. In the third period, 14 days after 23 January, the daily average attack rate in and outside Wuhan declined by 33.8% and 48.0%; the doubling times increased by 95.0% and 133.2%. In the four periods, 14 days after 7 February, the daily average attack rate in and outside Wuhan decreased by 79.1% and 95.2%; the doubling times increased by 79.2% and 152.0%. CONCLUSIONS: The public health interventions were associated with a reduction in COVID-19 cases in Hubei Province, especially in districts outside of Wuhan.

13.
Transl Pediatr ; 10(3): 560-568, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1184108

ABSTRACT

BACKGROUND: Telemedicine is becoming an emerging innovative supplement to the traditional medical system in China. In the present study, we described the rapid implementation of the telemedicine in pediatrics during the coronavirus disease 2019 (COVID-19) outbreak and explored its value in response to the demand for pediatric medical services during the epidemic. METHODS: An Internet-based platform for multidisciplinary online medical consultation was established on February 8, 2020, by a national children's medical center in China. The medical data of the traditional hospital visits and novel online visits from the first two months (February 8 to March 31) after the establishment of the platform were collected and analyzed. The demographic features, changes in the disease spectrum and characteristics of online medical services were described. RESULTS: The total number of visits was significantly lower (by 75.3%) than that of in the same period in the previous year. The disease spectrum was different with a significant decrease of >95% in the number of patients with infectious or contagious diseases. The online visits accounted for 14.7% of all visits. Online patients came from all over the country, covering 91% of the administrative regions of China, and the largest proportion of inquiries were for infants (33.7%) (P<0.01). The response rate of experts to requests for online consultations was 100%. During the study period, 266 experts from 25 pediatric specialties completed 12,318 effective consultations, proving different degrees of online supplementation for various specialties (4.3-168.4%). Online consultations mainly addressed two types of problems: (I) accessibility of the traditional hospital visits and (II) consultations regarding an illness. Data from pediatric nephrology showed that 96% of the patients with stable chronic kidney disease successfully received follow-up medication adjustment guidance through the online platform. CONCLUSIONS: The traditional hospital medical services have been affected by the COVID-19 outbreak. The multidisciplinary online medical consultation system is a strategy to actively respond to the medical needs of children during unique periods.

14.
Thorax ; 2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1088297

ABSTRACT

BACKGROUND: As the epidemic of COVID-19 is gradually controlled in China, a summary of epidemiological characteristics and interventions may help control its global spread. METHODS: Data for COVID-19 cases in Hubei Province (capital, Wuhan) was extracted until 7 March 2020. The spatiotemporal distribution of the epidemic in four periods (before 10 January, 10-22 January, 23 January-6 February and 7 February-7 March) was evaluated, and the impacts of interventions were observed. RESULTS: Among 67 706 COVID-19 cases, 52 111 (76.97%) were aged 30-69 years old, and 34 680 (51.22%) were women. The average daily attack rates (95% CI) were 0.5 (0.3 to 0.7), 14.2 (13.2 to 15.1), 45.7 (44.0 to 47.5) and 8.6 (7.8 to 9.3) cases per 106 people in four periods, and the harmonic means (95% CI) of doubling times were 4.28 (4.01 to 4.55), 3.87 (3.78 to 3.98), 5.40 (4.83 to 6.05) and 45.56 (39.70 to 52.80) days. Compared with the first period, daily attack rates rose rapidly in the second period. In the third period, 14 days after 23 January, the daily average attack rate in and outside Wuhan declined by 33.8% and 48.0%; the doubling times increased by 95.0% and 133.2%. In the four periods, 14 days after 7 February, the daily average attack rate in and outside Wuhan decreased by 79.1% and 95.2%; the doubling times increased by 79.2% and 152.0%. CONCLUSIONS: The public health interventions were associated with a reduction in COVID-19 cases in Hubei Province, especially in districts outside of Wuhan.

15.
Medicine (Baltimore) ; 100(1): e24120, 2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1024161

ABSTRACT

BACKGROUND: Evaluating the effectiveness and safety of external treatment of traditional Chinese medicine therapy for COVID-19 with diarrhea is the primary purpose of this systematic evaluation program. METHODS: We will search the randomized controlled trials from inception to November 2020. The following database is our focus area: Cochrane Central Register of Controlled Trials, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), VIP database for Chinese technical Periodicals, and Wanfang Database. We will choose articles published both in Chinese and English. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be carried out using Review Manager Software V.5.3. RESULTS: The results will provide high-quality synthesis of current evidence for researchers in this subject area. CONCLUSION: This studys decision will provide evidence of whether external treatment of traditional Chinese medicine is an effective and safe intervention for coronavirus disease 2019 with diarrhea. REGISTRATION NUMBER: INPLASY2020110095 (DOI number: 10.37766/inplasy2020.11.0095).


Subject(s)
COVID-19/therapy , Diarrhea/therapy , Diarrhea/virology , Medicine, Chinese Traditional , Research Design , Humans , SARS-CoV-2
16.
Stem Cells Int ; 2020: 8836372, 2020.
Article in English | MEDLINE | ID: covidwho-939928

ABSTRACT

BACKGROUND: Clinical trials are at the cornerstone of evidence-based stem cell therapies, but the quality assessment for designing and conduct these sometimes-complex studies are scarce of evidence. This study is aimed at developing a handy quality assessment tool for stem cell clinical trials, enhancing capacity of the self-regulate overall quality, and participating protection. METHODS: The framework of quality assessment tool was based on the PQRS (progress-quality-regulation-scientific) quality assessment tool, and detailed quality indicators were developed by leader group discussion, expert consulting, and literature review. Stem cell clinical trials were retrieved from the International Clinical Trials Registry Platform, and corresponding quality indicators were assessed and extracted. The validity and feasibility of conceptual quality assessment tool were further evaluated by using structural equation modeling. RESULTS: The quality assessment tool for stem cell clinical trials contains four critical quality attributes, including participant protection, scientific value, quality control, and stem cell products, and 9 observed quality indicators. From 11 primary clinical trial registries in the International Clinical Trials Registry Platform, 9410 stem cell trial registrations were identified, and 1036 studies were eligible for publications and protocols screening. After reviewed full text, 37 studies were included in the validity and feasibility evaluation: 32 studies were completed, and 3 studies terminated early. Most of the studies (83.79%) were in the early phase, and 63.16% of the studies were investigator-initiated trial. To further tested for validity, the critical quality attributes and quality indicators (QIs) between expertise further validated by the SEM method, which showed a good fit for the model (chi - square = 26.008; P = 0.353; TLI = 0.967; CFI = 0.978; RMSEA = 0.048). Compared with exploratory trials, evaluating using the quality assessment tool, confirmatory trials performed similarly in participant protection, scientific value, and quality control, but lower in stem cell products. CONCLUSIONS: The results of critical quality attributes and quality indicators between expertise and confirmatory validation analysis are basically consistent, indicating the feasibility and validity of applying this quality assessment tool for overall quality evaluation of stem cell trials.

17.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1088

ABSTRACT

Background: As the epidemic of coronavirus disease 2019 (COVID-19) in China is gradually becoming under control, a summary of the epidemiological characteristic

18.
EClinicalMedicine ; 26: 100529, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-773737
19.
Chin. Trad. Herbal Drugs ; 12(51): 3211-3222, 20200628.
Article in Chinese | WHO COVID, ELSEVIER | ID: covidwho-684027

ABSTRACT

Objective: To explore the active compounds, targets and signaling pathways of Xingnaojing Injection (XNJI) for the treatment of neurological damage caused by SARS-CoV-2, so as to explore its mechanism. Methods: Using TCMSP, BATMAN, Swiss Target Prediction, and other databases, the chemical compounds and targets of XNJI were retrieved. Cytoscape software was used to construct XNJI efficacy network of "drug-compounds-targets" for coronavirus and neuroprotection, and the action mechanism was predicted by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then core compounds were verified by molecular docking with 3CL Mpro, ACE2, and 2019-nCoV RBD/ACE2-B0AT1 complex. Results: A total of 105 active compounds of XNJI, 928 drug targets, 741 targets of coronavirus, 611 targets of neuroprotection, 83 drug-disease common targets, 12 core compounds, and seven key targets were obtained. The function enrichment analysis of GO yielded 204 entries, KEGG pathway enrichment screened 120 signaling pathways, which included Hepatitis B, pathways in cancer, TNF, HIF-1, and VEGF signaling pathway, and so on. The results of molecular docking showed that core compounds of XNJI had a good bonding activity with 3CL Mpro, ACE2 and complex. The chlorogenin and kaempferol had the lowest binding energy with three proteins and might play an important role in treatment. Conclusion: The core compounds in XNJI including chlorogenin, kaempferol, 5-hydroxy- 6,7,3',4',5'-pentamethoxyflavone, 3-methylkempferol, morin, gardenin, quercetin, artemisetin, genistein, dryobalanone, curcumin, and elemicin, which might interfere with various signaling pathways by acting on key targets like PARP1, PTGS2, MMP9, CDK2, ADORA2A, ALOX5, GSK3B, and regulate the inflammatory response, apoptosis, oxidative stress, angiogenesis, and other processes to improve the neurological damage caused by SARS-CoV-2, and inhibit virus replication and prevent infection of the host cell by binding with 3CL Mpro, ACE2 and complex, which suggest that XNJI may have a positive therapeutic effect on the neurological damage caused by SARS-CoV-2.

20.
J Allergy Clin Immunol Pract ; 8(8): 2585-2591.e1, 2020 09.
Article in English | MEDLINE | ID: covidwho-609222

ABSTRACT

BACKGROUND: The clinical management of coronavirus disease 2019 (COVID-19) is dependent on understanding the underlying factors that contribute to the disease severity. In the absence of effective antiviral therapies, other host immunomodulatory therapies such as targeting inflammatory response are currently being used without clear evidence of their effectiveness. Because inflammation is an essential component of host antiviral mechanisms, therapies targeting inflammation may adversely affect viral clearance and disease outcome. OBJECTIVE: To understand whether the persistent presence of the virus is a key determinant in the disease severity during COVID-19 and to determine whether the viral reactivation in some patients is associated with infectious viral particles. METHODS: The data for patients were available including the onset of the disease, duration of viral persistence, measurements of inflammatory markers such as IL-6 and C-reactive protein, chest imaging, disease symptoms, and their durations among others. Follow-up tests were performed to determine whether the viral negative status persists after their recovery. RESULTS: Our data show that patients with persistent viral presence (>16 days) have more severe disease outcomes including extensive lung involvement and requirement of respiratory support. Two patients who died of COVID-19 were virus-positive at the time of their death. Four patients demonstrated virus-positive status on the follow-up tests, and these patient samples were sent to viral culture facility where virus culture could not be established. CONCLUSIONS: These data suggest that viral persistence is the key determining factor of the disease severity. Therapies that may impair the viral clearance may impair the host recovery from COVID-19.


Subject(s)
Coronavirus Infections/physiopathology , Inflammation/physiopathology , Pneumonia, Viral/physiopathology , Adolescent , Adult , Aged , Betacoronavirus , C-Reactive Protein/immunology , COVID-19 , Child , Child, Preschool , Comorbidity , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Female , Glucocorticoids/therapeutic use , Humans , Infant , Inflammation/epidemiology , Inflammation/immunology , Inflammation Mediators/immunology , Interleukin-6/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Real-Time Polymerase Chain Reaction , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index , Young Adult
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