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198 lines
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<title>14 February, 2021</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Correlates of Financial Concerns and Symptoms of Depression and Posttraumatic Stress Disorder in Impoverished Urban-dwelling Individuals in Bangladesh During the COVID-19 Pandemic: Face-to-face Interview Findings</strong> -
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Background: The COVID-19 pandemic has impacted the physical, mental and financial health of many individuals. How substantially marginalized groups like impoverished urban-dwelling individuals are specifically impacted amid this pandemic is poorly understood. The present study aimed to investigate correlates of financial concerns and symptoms of depression and posttraumatic stress disorder (PTSD) during the COVID-19 pandemic among impoverished urban-dwelling individuals residing in Dhaka, Bangladesh. Methods: A cross-sectional survey was conducted between August and September 2020 using face-to-face interviews in six disadvantaged neighborhoods (“slums”) in Dhaka. Individuals were interviewed using a structured questionnaire consisting of questions assessing socio-demographics, lifestyle, financial well-being relating to the COVID-19 pandemic, depression, and PTSD. Results: A total of 435 individuals (male=54.7%; mean age=45.0±12.0 years; age range=18-85 years) participated. Most (96.3%) reported that their household income decreased due to the COVID-19 pandemic. Associated factors included female gender, primary education, jobless, food scarcity, and depression. Depression symptoms were linked to female gender, being jobless, being divorced, living in a joint family, excessive sleep, and smoking. Low incomes, excessive sleep, joblessness, and food scarcity were positively associated with PTSD symptoms. In contrast, less sleep appeared protective against PTSD. Limitations: Potential limitations included cross-sectional study design and limited sample size. Conclusions: Public health initiatives, in particular mental health services, should be introduced to mitigate against psychological and financial effects of the pandemic on impoverished urban-dwelling individuals in Bangladesh.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/nfr5m/" target="_blank">Correlates of Financial Concerns and Symptoms of Depression and Posttraumatic Stress Disorder in Impoverished Urban-dwelling Individuals in Bangladesh During the COVID-19 Pandemic: Face-to-face Interview Findings</a>
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<li><strong>COVID-19-related symptoms 6 months after the infection - Update on a prospective cohort study in Germany</strong> -
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Objective Many anecdotal reports indicate the presence of ′long COVID′ - COVID-19-related symptoms weeks to months after the acute illness. However, frequency and symptom-pattern of ′long COVID′ in relation to acute disease severity are uncertain. As part of an ongoing, prospective cohort study we therefore conducted an online survey among adults 6 months after acute COVID-19. Methods The prospective online study Life&Covid is ongoing in Germany since May 2020. Participants were recruited 0 to 4 months after their SARS-CoV-2 infection und followed up by subsequent surveys. The survey 6 months after the infection was completed by 127 out of 148 individuals invited by email (86%). All grades of acute disease severity were included and 91% of the participants had been treated as outpatients during their acute illness. Results Six months after the infection, 67% of the study participants reported at least one symptom as a consequence of COVID-19. Exertional dyspnea (30% of participants), fatigue (25%) and diminished sense of taste/smell (19%) were the most common individual symptoms. At least one symptom, exertional dyspnea, and fatigue were reported more often after a severe acute illness, but diminished sense of taste/smell was unrelated to acute severity. Age group and sex did not associate with the frequency of symptoms at 6 months. Conclusions Based on this study, the prevalence of COVID-19-related symptoms 6 months after the infection is high. Some bias for overestimation may have affected this result. Nevertheless, ′long COVID′ requires attention in medical care and a better scientific understanding.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.12.21251619v1" target="_blank">COVID-19-related symptoms 6 months after the infection - Update on a prospective cohort study in Germany</a>
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<li><strong>Risk of Corona virus disease 2019 (COVID-19) among spectacles wearing population of Northern India</strong> -
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Introduction- Severe Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2) spread mainly through respiratory droplets and contact routes. Long term use of spectacles may prevent repeated touching and rubbing of the eyes. Aim of the study is to compare the risk of COVID-19 in long term spectacles wearers with the risk in persons not using spectacles. Objectives- To know the association between infection with SARSCoV-2 and wearing of spectacles. Materials and methods- In this study, 304 patients of Corona virus disease 2019 (COVID-19) were selected. Their spectacles wearing behaviour was assessed through a questionnaire. Spectacles wearing behaviour of general population was obtained from older studies (for comparison). Risk of COVID-19 was calculated in long term spectacles wearers as well as in persons not using spectacles. Chi- Square test was used for statistical analysis. Results- In this study, total 58 patients showed the behavior of using spectacles continuously during day time and always on outdoor activities. The risk of COVID-19 was found 0.48 in spectacles wearing population as compared to 1.35 in population not using spectacles. The calculated risk ratio was 0.36. The protective effectiveness of the spectacles was found statistically significant (p- value .00113). Conclusion- The present study showed that the risk of Covid-19 was about 2- 3 times less in spectacles wearing population than the population not wearing those. The nasolacrimal duct may be a route of virus transmission from conjunctival sac to the nasopharynx.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.12.21249710v1" target="_blank">Risk of Corona virus disease 2019 (COVID-19) among spectacles wearing population of Northern India</a>
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</div></li>
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<li><strong>Performance of SARS-CoV-2 rapid antigen test compared with real-time RT-PCR in asymptomatic individuals</strong> -
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Screening, testing and contact tracing plays a pivotal role in the control of COVID-19 pandemic. To carry out this strategy it is necessary to increase the testing capacity. Here, we compared a SARS CoV-2 rapid antigen test (RAT) and RT-PCR in 842 asymptomatic individuals from Tarapaca, Chile. We report a sensibility of 69.86%, a specificity of 99.61%, PPV of 94.44% and NPP of 97.22% with Ct values (Ct > 27) that were significantly higher among individuals with false-negative RAT. These results support the fact that RAT might have a significant impact in the identification of asymptomatic carriers in areas that lack well-equipped laboratories to perform SARS-CoV-2 real -time RT-PCR diagnostics or the results take more than 24-48 hours, as well as zones with high traffic of individuals, such as border/customs, airports, interregional bus, train stations or in any mass testing campaign requiring rapid results.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.12.21251643v1" target="_blank">Performance of SARS-CoV-2 rapid antigen test compared with real-time RT-PCR in asymptomatic individuals</a>
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<li><strong>Disease-economy trade-offs under alternative pandemic control strategies</strong> -
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Public policy and academic debates regarding mitigation strategies frequently note potential disease-economy trade-offs, and advocate for prioritizing one outcome over the other. Using a calibrated coupled epi-economic model of individual behavior embedded within the broader economy during COVID-19, we show that targeted isolation strategies can avert up to 91% of individual economic losses relative to voluntary isolation strategies. Notably, the economic savings from targeted isolation strategies do not impose an additional disease burden, avoiding disease-economy trade-offs. In contrast, widely-used blanket lockdowns do create sharp disease-economy trade-offs and impose substantial economic costs per marginal case avoided. These results highlight the benefits of targeted isolation strategies for disease control, as they address the fundamental coordination failure between infectious and susceptible individuals which drives the recession. Our coupled-systems framework uses a novel data-driven approach to map economic activities to contacts, which facilitates developing effective mitigation strategies for future novel pathogens. Application of this framework can help control disease spread and avert trillions of dollars in losses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.12.21251599v1" target="_blank">Disease-economy trade-offs under alternative pandemic control strategies</a>
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<li><strong>An alternative approach for bioanalytical assay development for wastewater-based epidemiology of SARS-CoV-2</strong> -
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Wastewater-based epidemiology could be applied to track down SARS-CoV-2 outbreaks at high spatio-temporal resolution and could potentially be used as an early-warning for emergence of SARS-CoV-2 circulation in the general population. Epidemiological surveillance of SARS-CoV-2 could play a role in monitoring the spread of the virus in the population and controlling possible outbreaks. However, sensitive sample preparation and detection methods are necessary to detect trace levels of SARS-CoV-2 RNA in influent wastewater (IWW). Unlike predecessors, method development of a SARS-CoV-2 RNA concentration and detection procedure was performed with IWW samples with high viral SARS-CoV-2 loads (in combination with seeding IWW with a surrogate coronavirus). This is of importance since the SARS-CoV-2 genome in IWW might have already been subject to in-sewer degradation into smaller genome fragments or might be present in a different form (e.g. cell debris,etc). Centricon Plus-70 (100 kDa) centrifugal filter devices resulted in the lowest and most reproducible Ct-values for SARS-CoV-2 RNA. Lowering pore sizes did not improve our limit of detection and quantification. Real-time polymerase chain reaction (qPCR) was employed for the amplification of the N1, N2, N3 and E_Sarbeco-gene. This is one of the first studies to apply digital polymerase chain reaction (dPCR) for the detection of SARS-CoV-2 RNA in IWW. Interestingly, qPCR results were comparable with dPCR results suggesting that qPCR is a valid method. In this study, dPCR was also used as a proxy to assess the precision of qPCR. In this light, dPCR showed high variability at low concentration levels (100 copies/microliter), indicating that variability in bioanalytical assays for SARS-CoV-2 RNA might be substantial. On average, the N2-gene showed high in-sample stability in IWW for 10 days of storage at 4 degrees. Between-sample variability was substantial due to the low native concentrations in IWW. Additionally, the E-gene proved to be less stable compared to the N2-gene and showed higher variability. Freezing the IWW samples resulted in a 10-fold decay of loads of the N2- and E-gene in IWW. Although WBE can already aid in filling some knowledge gaps in the epidemiological surveillance of SARS-CoV-2, future WBE studies should aim to further validate and standardize bioanalytical assays, especially with regards to methodological limitations.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.12.21251626v1" target="_blank">An alternative approach for bioanalytical assay development for wastewater-based epidemiology of SARS-CoV-2</a>
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<li><strong>Viroselect: A novel SARS-CoV-2 detection assay to resolve inconclusive samples</strong> -
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Background: India bears the second largest burden of SARS-CoV-2 infection. A multitude of RT-PCR detection assays with disparate gene targets including automated high throughput platforms are available. Varying concordance and interpretation of diagnostic results in this setting can result in significant reporting delays leading to suboptimal disease management. Here, we report the development of a novel ORF-1a based SARS-CoV-2 RT-PCR assay, Viroselect, showing high concordance with conventional assays and the ability to resolve inconclusive results generated during the peak of the epidemic in Mumbai, India. Methods: We identified a unique target region within SARS-CoV-2 ORF1a, non-structural protein (nsp3), that was used to design and develop our assay. This hypervariable region (1933-3956) between SARS-CoV-2, SARS-CoV, and MERS-COV was utilized to design our primers and probe for RT-PCR assay. We further evaluated concordance of our assay with commonly used EUA (USFDA) manual kits as well as an automated high throughput testing platform. Further, a retrospective analysis using Viroselect on samples reported as inconclusive during April-October 2020 was carried out. Results: A total of 701 samples were tested. Concordance analysis of 477 samples demonstrated high overall agreement of Viroselect assay with both manual (87.6%; 95% CI) as well as automated (84.7%; 95% CI) testing assays. Also, in the retrospective analysis of 224 additional samples reported as inconclusive, Viroselect was able to resolve 100% (19/19) and 93.7% (192/205) samples which were termed inconclusive by manual and automated high throughput platform respectively. Conclusion: We show that Viroselect had high concordance with conventional assays, both manual and automated, as well as highlight its potential in resolving inconclusive samples.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.11.21251605v1" target="_blank">Viroselect: A novel SARS-CoV-2 detection assay to resolve inconclusive samples</a>
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<li><strong>Deep learning models for COVID-19 chest x-ray classification: Preventing shortcut learning using feature disentanglement</strong> -
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In response to the COVID-19 global pandemic, recent research has proposed creating deep learning based models that use chest radiographs (CXRs) in a variety of clinical tasks to help manage the crisis. However, the size of existing datasets of CXRs from COVID-19+ patients are relatively small, and researchers often pool CXR data from multiple sources, for example, using different x-ray machines in various patient populations under different clinical scenarios. Deep learning models trained on such datasets have been shown to overfit to erroneous features instead of learning pulmonary characteristics – a phenomenon known as shortcut learning. We propose adding feature disentanglement to the training process, forcing the models to identify pulmonary features from the images while penalizing them for learning features that can discriminate between the original datasets that the images come from. We find that models trained in this way indeed have better generalization performance on unseen data; in the best case we found that it improved AUC by 0.13 on held out data. We further find that this outperforms masking out non-lung parts of the CXRs and performing histogram equalization, both of which are recently proposed methods for removing biases in CXR datasets.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.11.20196766v1" target="_blank">Deep learning models for COVID-19 chest x-ray classification: Preventing shortcut learning using feature disentanglement</a>
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<li><strong>Natural Mucosal Barriers and COVID-19 in Children</strong> -
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COVID-19 is more benign in children compared to adults for unknown reasons. This contrasts with viruses such as influenza where disease manifestations are often more severe in children1. We hypothesized that a more robust early innate immune response to SARS-CoV-2 may protect against severe disease and compared clinical outcomes, viral copies and cellular gene and protein expression in nasopharyngeal swabs from 12 children and 27 adults upon presentation to the Emergency Department. SARS-CoV-2 copies were similar, but compared to adults, children displayed higher expression of genes associated with interferon signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-alpha2, IFN-gamma, IP-10, IL-8, and IL-1beta were detected in nasal fluid in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected in nasal fluid from both groups and correlated negatively with mucosal IL-18. These findings suggest that a more robust innate immune response in children compared to adults contributes to favorable clinical outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.12.21251310v1" target="_blank">Natural Mucosal Barriers and COVID-19 in Children</a>
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<li><strong>Replicating the “Asian Disease” Framing Paradigm During the 2020 COVID-19 Pandemic: A Study of Stress, Worry, Trust, and Choice Under Risk</strong> -
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The Asian disease problem has been widely used to demonstrate the framing effect, whereby different wording of the same options leads to predictably different choices. Notably, it is highly evocative of the COVID-19 pandemic. Accordingly, we investigated how participants would respond to the problem as part of a large-scale international survey (Nincluded = 88,181) conducted from March to May 2020. As predicted by the appraisal-tendency framework, we found larger risk aversion and a larger framing effect than under typical circumstances. Also consistent with the appraisal-tendency framework, we found that perceived stress and concerns over coronavirus were positively associated with the framing effect, while lower levels of trust in the government’s efforts to handle the pandemic were negatively associated with the framing effect. However, the findings did not support predictions regarding the associations between distress, concerns, and trust, and risk aversion in general. Our findings showed that the framing effect is magnified under conditions of high distress and concern, and mitigated under conditions of high distrust. This work might also provide important practical implications regarding the optimal way of framing public messages involving risk, and the possible cross-national variability of the perception of these messages.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/rbfwp/" target="_blank">Replicating the “Asian Disease” Framing Paradigm During the 2020 COVID-19 Pandemic: A Study of Stress, Worry, Trust, and Choice Under Risk</a>
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<li><strong>Do social norms influence young people’s willingness to take the COVID-19 vaccine?</strong> -
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Although young adults are not at great risk of becoming severely ill with COVID-19, their willingness to get vaccinated affects the whole community. Vaccine hesitancy has increased during recent years, and more research is needed on its situational determinants. This paper reports a preregistered experiment (N = 654) that examined whether communicating descriptive social norms – information about what most people do – is an effective way of influencing young people’s intentions and reducing their hesitancy to take the COVID-19 vaccine. We found weak support for our main hypothesis that conveying strong (compared to weak) norms leads to reduced hesitancy and stronger intentions. Furthermore, norms did not produce significantly different effects compared to standard vaccine information from the authorities. Moreover, no support was found for the hypothesis that young people are more strongly influenced by norms when the norm reference group consists of other young individuals rather than people in general. These findings suggest that the practical usefulness of signaling descriptive norms is rather limited, and may not be more effective than standard appeals in the quest of encouraging young adults to trust and accept a new vaccine.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/sybta/" target="_blank">Do social norms influence young people’s willingness to take the COVID-19 vaccine?</a>
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<li><strong>The pandemic fallacy: Inaccuracy of social scientists’ and lay judgments about COVID-19’s societal consequences in America</strong> -
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Effective management of global crises relies on expert judgment of their societal effects. How accurate are such judgments? In the spring of 2020, we asked social scientists (N = 717) and lay Americans (N = 394) to make predictions about COVID-19 pandemic-related societal change across social and psychological domains. Six months later we obtained retrospective assessments for the same domains (Nscientists = 270; NlayP = 411) and compared these judgments to objective data to assess estimation accuracy. Social scientists were no more accurate than lay people, neither in prospective nor retrospective judgments. Across studies and samples, estimates of the magnitude of change were off by more than 20% and less than half of participants accurately predicted the direction of changes. Taken together, we find that experts and lay people fared poorly at predicting social and psychological consequences of the pandemic and misperceive what effects it may have already had.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/g8f9s/" target="_blank">The pandemic fallacy: Inaccuracy of social scientists’ and lay judgments about COVID-19’s societal consequences in America</a>
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<li><strong>Stage 2 registered report: Changing health compliance through message repetition based on the extended parallel process model in the COVID-19 pandemic</strong> -
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When people are confronted with health proposals during the coronavirus disease 2019 (COVID-19) pandemic, it has been suggested that fear of COVID-19 can serve protective functions and ensure public health compliance. However, health proposal repetition and its perceived efficacy also influence the behavior intention toward the proposal, which has not yet been confirmed in the COVID-19 context. The present study examined whether the extended parallel process model (EPPM) could be generalized to a naturalistic context like the COVID-19 pandemic. Additionally, we explored how repetition of a health proposal is involved with the EPPM. In this study, two groups of participants were exposed to the same health proposal related to COVID-19, where one group was exposed once and another group twice. They then filled out a questionnaire consisting of items concerning behavior intention and adapted from the Risk Behavior Diagnosis Scale. Structural equation modeling was used to determine the multivariate associations between the variables. Although the results showed that behavior intention is predicted by perceived efficacy, no significant influence of perceived threat was detected. Furthermore, no significant effect of repetition was found toward either response efficacy or perceived susceptibility. These findings indicate that to promote health compliance during the COVID-19 pandemic, it is more efficient to focus on the perceived efficacy of effective health proposals rather than on the perceived threat of the disease. For future health communication research, the present study suggests improved methods for analysis strategies and repeated manipulation of messages.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/4j93s/" target="_blank">Stage 2 registered report: Changing health compliance through message repetition based on the extended parallel process model in the COVID-19 pandemic</a>
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<li><strong>Worker well-being before and during the COVID-19 restrictions: A longitudinal study in the UK</strong> -
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The potential impact of COVID-19 restrictions on worker well-being is currently unknown. In this study we examine 15 well-being outcomes collected from 621 full-time workers assessed before (November, 2019 - February, 2020) and during (May-June, 2020) the COVID-19 pandemic. Fixed effects analyses are used to investigate how the COVID-19 restrictions and involuntary homeworking affect well-being and job performance. The majority of worker well-being measures are not adversely affected. Homeworkers feel more engaged and autonomous, experience fewer negative emotions and feel more connected to their organisations. However, these improvements come at the expense of reduced homelife satisfaction and job performance.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/659yd/" target="_blank">Worker well-being before and during the COVID-19 restrictions: A longitudinal study in the UK</a>
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<li><strong>Moral Injury and Light Triad traits: anxiety and depression in health-care personnel during the COVID-19 pandemic</strong> -
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During the COVID-19 pandemic, health workers are facing morally challenging, stressful, and life-threatening decisions while working with limited human and medical resources. The purpose of the current study was to determine the influence of Moral Injury and Light Triad (LT) personality traits on anxiety and depression symptoms of health-care personnel during the COVID-19 pandemic. A quantitative, cross-sectional research design was used, the study included a sample of 169 health-care workers. Data was gathered through the Moral Injury Symptom Scale for Health Professionals (MISS-HP), Light Triad Scale (LTS), the Generalized Anxiety Disorder- 7 (GAD-7), and the Patient-Health Questionnaire-9 (PHQ-9). Results suggest that almost 9 out of 10 respondents experienced at least one potentially morally injurious event, 45.6% were at significant risk of impairment related to Moral Injury. Working with limited staff and resources, and the implications of it, were among the most common potentially morally injurious situations reported by the respondents. Results suggest that MISS-HP Mistrust subscale has significant negative correlations with Light Triad traits. A hierarchical regression model determined that Moral Injury, but not Light Triad traits, significantly affected depression symptoms. The overall model accounted for 42.6% of the variance in depression scores. On the other hand, anxiety symptoms were significantly predicted by Moral Injury, as did LTS-Humanism. The model accounted for 38.2% of the variance in anxiety scores. Control variables included respondents’ sex, years of experience, profession, and prior COVID-19 diagnosis. The results were discussed according to their implications to public health.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/42a3p/" target="_blank">Moral Injury and Light Triad traits: anxiety and depression in health-care personnel during the COVID-19 pandemic</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Safety and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) to Treat COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: COVI-AMG; Drug: Placebo<br/><b>Sponsor</b>: Sorrento Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate a Single Dose of STI-2020 (COVI-AMG™) in Adults With Mild COVID-19 Symptoms</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: COVI-AMG; Drug: Placebo<br/><b>Sponsor</b>: Sorrento Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An Effectiveness Study of the Sinovac’s Adsorbed COVID-19 (Inactivated) Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: Adsorbed COVID-19 (Inactivated) Vaccine<br/><b>Sponsor</b>: Butantan Institute<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of the Kinetics of COVID-19 Antibodies for 24 Months in Patients With Confirmed SARS-CoV-2 Infection</strong> - <b>Conditions</b>: Covid19; SARS-CoV 2<br/><b>Intervention</b>: Other: Sampling by venipuncture<br/><b>Sponsor</b>: Centre Hospitalier Régional d’Orléans<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy and Safety of VB-201 in Patients With COVID-19</strong> - <b>Condition</b>: Severe COVID-19<br/><b>Interventions</b>: Drug: VB-201 + Standard of care; Drug: Standard of care<br/><b>Sponsor</b>: Vascular Biogenics Ltd. operating as VBL Therapeutics<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Convalescent Plasma Therapy</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19 Infection<br/><b>Intervention</b>: Biological: Convalescent plasma<br/><b>Sponsors</b>: Angelica Samudio; Consejo Nacional de Ciencias y Tecnología, Paraguay; Ministerio de Salud Pública y Bienestar Social, Paraguay; Centro de información y recursos para el desarrollo, Paraguay<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Ivermectin<br/><b>Sponsor</b>: FMH College of Medicine and Dentistry<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telerehabilitation in Covid-19 After Hospital Discharge</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: Standard Physiotherapy program; Other: Telerehabilitation<br/><b>Sponsor</b>: Universidad de Granada<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Assess Efficacy and Safety of Inhaled Interferon-β Therapy for COVID-19</strong> - <b>Conditions</b>: Severe Acute Respiratory Syndrome Coronavirus 2; COVID-19<br/><b>Interventions</b>: Drug: SNG001; Drug: Placebo<br/><b>Sponsor</b>: Synairgen Research Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AGILE (Early Phase Platform Trial for COVID-19)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: CST-2: EIDD-2801; Drug: CST-2: Placebo<br/><b>Sponsors</b>: University of Liverpool; University of Southampton; Liverpool School of Tropical Medicine; Lancaster University; Liverpool University Hospitals NHS Foundation Trust<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pulmonary Rehabilitation of Patients With a History of COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Procedure: Pulmonary rehabilitation<br/><b>Sponsor</b>: University of Rzeszow<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy and Safety of Prothione™ Capsules for Mild to Moderate Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: Coronavirus Disease 2019 (COVID-19)<br/><b>Interventions</b>: Drug: Placebo; Drug: Prothione™ (6g)<br/><b>Sponsor</b>: Prothione, LLC<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Enriched Heparin Anti COVID-19 Trial</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Heparin sodium; Drug: Placebo<br/><b>Sponsor</b>: UPECLIN HC FM Botucatu Unesp<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community Network-driven COVID-19 Testing of Vulnerable Populations in the Central US</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Social Network Strategy + COVID-19 messaging<br/><b>Sponsor</b>: University of Chicago<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Oral and Subcutaneous Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenovirus Platform in Healthy Volunteers in USA</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD (Suspension for injection); Drug: hAd5-SFusion+ N-ETSD (Oral capsule)<br/><b>Sponsor</b>: ImmunityBio, Inc.<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three Salvianolic acids inhibit 2019-nCoV spike pseudovirus viropexis by binding to both its RBD and receptor ACE2</strong> - Since December 2019, the new coronavirus [also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV)]- induced disease, COVID-19, has spread rapidly worldwide. Studies have reported that the traditional Chinese medicine Salvia miltiorrhiza possesses remarkable antiviral properties; however, the anti-coronaviral activity of its main components, salvianolic acid A (SAA), salvianolic acid B (SAB), and salvianolic acid C (SAC) is still debated. In this study, we used Cell…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications</strong> - The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors</strong> - Currently, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected people among all countries and is a pandemic as declared by the World Health Organization (WHO). SARS-CoVID-2 main protease is one of the therapeutic drug targets that has been shown to reduce virus replication, and its high-resolution 3D structures in complex with inhibitors have been solved. Previously, we had demonstrated the potential of natural compounds such as serine protease inhibitors eventually leading…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Early detection of neutralizing antibodies against SARS-CoV-2 in COVID-19 patients in Thailand</strong> - CONCLUSION: The sVNT is a practical and robust serological test for SARS-CoV-2 infection and does not require specialized biosafety containment. It can be used clinically to aid diagnosis in both early and late infection especially in cases when the real-time RT-PCR results in weakly negative or weakly positive, and to determine the protective immune response from SARS-CoV-2 infection in patients.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19</strong> - In the search for inhibitors of COVID-19, we have targeted the interaction between the human angiotensin-converting enzyme 2 (ACE2) receptor and the spike receptor binding domain (S1-RBD) of SARS-CoV-2. Virtual screening of a library of natural compounds identified Kobophenol A as a potential inhibitor. Kobophenol A was then found to block the interaction between the ACE2 receptor and S1-RBD in vitro with an IC(50) of 1.81 ± 0.04 μM and inhibit SARS-CoV-2 viral infection in cells with an EC(50)…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2</strong> - Heterologous polyclonal antibodies might represent an alternative to the use of convalescent plasma (CP) or monoclonal antibodies (mAbs) in COVID-19 by targeting multiple antigen epitopes. However, heterologous antibodies trigger human natural xenogeneic antibody responses particularly directed against animal-type carbohydrates, mainly the N-glycolyl form of the neuraminic acid (Neu5Gc) and the Gal α1,3-galactose (αGal), potentially leading to serum sickness or allergy. Here, we immunized…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>P2Y14 Receptor as a Target for Neutrophilia Attenuation in Severe COVID-19 Cases: From Hematopoietic Stem Cell Recruitment and Chemotaxis to Thrombo-inflammation</strong> - The global SARS-CoV-2 pandemic starting in 2019 has already reached more than 2.3 million deaths. Despite the scientific community’s efforts to investigate the COVID-19 disease, a drug for effectively treating or curing patients yet needs to be discovered. Hematopoietic stem cells (HSC) differentiating into immune cells for defense express COVID-19 entry receptors, and COVID-19 infection hinders their differentiation. The importance of purinergic signaling in HSC differentiation and innate…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting Endolysosomal Two-Pore Channels to Treat Cardiovascular Disorders in the Novel COronaVIrus Disease 2019</strong> - Emerging evidence hints in favor of a life-threatening link between severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and the cardiovascular system. SARS-CoV-2 may result in dramatic cardiovascular complications, whereas the severity of COronaVIrus Disease 2019 (COVID-19) and the incidence of fatalities tend to increase in patients with pre-existing cardiovascular complications. SARS-CoV-2 is internalized into the host cells by endocytosis and may then escape the endolysosomal…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2</strong> - An efficient treatment against a COVID-19 disease, caused by the novel coronavirus SARS-CoV-2 (CoV2), remains a challenge. The papain-like protease (PL^(pro)) from the human coronavirus is a protease that plays a critical role in virus replication. Moreover, CoV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. We used Approximate Bayesian Computation tools, molecular modelling and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pseudo-Dipeptide Bearing α,α-Difluoromethyl Ketone Moiety as Electrophilic Warhead with Activity against Coronaviruses</strong> - The synthesis of α-fluorinated methyl ketones has always been challenging. New methods based on the homologation chemistry via nucleophilic halocarbenoid transfer, carried out recently in our labs, allowed us to design and synthesize a target-directed dipeptidyl α,α-difluoromethyl ketone (DFMK) 8 as a potential antiviral agent with activity against human coronaviruses. The ability of the newly synthesized compound to inhibit viral replication was evaluated by a viral cytopathic effect…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture</strong> - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the newly emergent causative agent of coronavirus disease-19 (COVID-19), has resulted in more than two million deaths worldwide since it was first detected in 2019. There is a critical global need for therapeutic intervention strategies that can be deployed to safely treat COVID-19 disease and reduce associated morbidity and mortality. Increasing evidence shows that both natural and synthetic antimicrobial peptides (AMPs), also…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics</strong> - Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has become a worldwide pandemic. Symptoms range from mild fever to cough, fatigue, severe pneumonia, acute respiratory distress syndrome (ARDS), and organ failure, with a mortality rate of 2.2%. However, there are no licensed drugs or definitive treatment strategies for patients with severe COVID-19. Only antiviral or anti-inflammatory drugs are used as symptomatic treatments based on clinician experience. Basic medical…</p></li>
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||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fluoxetine Can Inhibit SARS-CoV-2 In Vitro</strong> - An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease pandemic, drastically affecting global health and economy. Though the understanding of the disease has improved, fighting the virus remains challenging. One of the strategies is repurposing existing drugs as inhibitors of SARS-CoV-2. Fluoxetine (FLX), a selective serotonin reuptake inhibitor, reportedly inhibits the replication of RNA viruses, especially Coxsackieviruses B (CVB), such…</p></li>
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||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro</strong> - The current COVID-19 pandemic requires urgent development of effective therapeutics. 5-amino levulinic acid (5-ALA) is a naturally synthesized amino acid and has been used for multiple purposes including as an anticancer therapy and as a dietary supplement due to its high bioavailability. In this study, we demonstrated that 5-ALA treatment potently inhibited infection of SARS-CoV-2, a causative agent of COVID-19, in cell culture. The antiviral effects could be detected in both human and…</p></li>
|
||
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review</strong> - Leflunomide (LF) represents the prototype member of dihydroorotate dehydrogenase (DHODH) enzyme inhibitors. DHODH is a mitochondrial inner membrane enzyme responsible for catalytic conversion of dihydroorotate into orotate, a rate-limiting step in the de novo synthesis of the pyrimidine nucleotides. LF produces cellular depletion of pyrimidine nucleotides required for cell growth and proliferation. Based on the affected cells the outcome can be attainable as immunosuppression, antiproliferative,…</p></li>
|
||
</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
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<ul>
|
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Compositions and methods for detecting SARS-CoV-2 spike protein</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU317343760">link</a></p></li>
|
||
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU315792577">link</a></p></li>
|
||
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU315792579">link</a></p></li>
|
||
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用</strong> - 本发明涉及病毒检测领域，特别涉及病毒核酸提取或保存试剂、引物探针组合、病毒扩增试剂、试剂盒及其应用。本发明病毒检测装置提供了一种简单易行的病毒核酸提取方法，整个过程大约5‑15分钟，回收纯化的核酸，可用于病毒核酸的检测。包括PCR、NASBA、LAMP、RPA等。相比较于传统的病毒提取方法，本方法病毒核酸回收率高、用时少、操作方便、易于临床推广。本发明涉及单管同时检测新型冠状病毒COVID‑19 N和ORF基因以及人源内参基因的等温扩增引物、探针组合序列和反应缓冲液，该体系特异性好，灵敏度高（50 cp/mL），特异性高，只需20 min的检测时间，最快可在10 min左右报阳性。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317398766">link</a></p></li>
|
||
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种侧链修饰的聚氨基酸及其制备方法和用途</strong> - 本发明提供了一种侧链修饰的聚氨基酸及其制备方法，所述侧链修饰的聚氨基酸具有如下优势：（1）主链和侧链结构及其连接方式都可以灵活选取，使制得的聚合物胶束具有良好生物相容性和靶向递送效率，（2）聚氨基酸主链的电荷极性为电正性，对主链的电荷调节促进胶束的pH值响应，帮助RNA从“溶酶体陷阱”中逃离进入胞浆，（3）通过量化侧链修饰脂肪链的链长、饱和度和脂肪链数量来控制侧链的疏水性部分，精确调节疏水部分的体积和缔合作用强度，（4）由于RNA和DNA在结构和负电性上的相似性，高效构建包裹和递送体，（5）通过双亲性功能高分子的侧链修饰引入不同的生物功能基团，实现递送体系对靶点组织和部位的特异性结合，提高靶向递送效果。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317398760">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>靶向SARS-CoV-2冠状病毒的抗体及其诊断和检测用途</strong> - 本发明涉及靶向SARS‑CoV‑2冠状病毒的抗体及其诊断和检测用途。具体涉及特异性结合冠状病毒S蛋白的抗体或其抗原结合片段和抗体对以及包含所述抗体或其抗原结合片段和抗体对的检测产品。本发明还涉及编码所述抗体或抗原结合片段的核酸及包含其的宿主细胞，以及制备所述抗体或抗原结合片段的方法。此外，本发明涉及所述抗体或其抗原结合片段、抗体对的预防、治疗或诊断用途。相较于常规的IgG/IgM检测，该检测方法直接检测样本中病毒的RBD蛋白，可以有效避免可能的样本中无关IgG/IgM对于检测的干扰，有效提高检测的灵敏度。所述抗体或抗体对可用于诊断和/或检测冠状病毒。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317346928">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A PHARMACEUTICAL COMPOSITION OF NITAZOXANIDE AND MEFLOQUINE AND METHOD THEREOF</strong> - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of a nitazoxanide or its pharmaceutically acceptable salts thereof and an mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the nitazoxanide in the ratio of 0.05% to 66% w/v and the mefloquine in the ratio of 0.05% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of nitazoxanide and mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN316412781">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>TREATMENT OF COVID-19 WITH REBAMIPIDE</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU315792482">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>METHOD AND APPARATUS FOR ACQUIRING POWER CONSUMPTION IMPACT BASED ON IMPACT OF COVID-19 EPIDEMIC</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU314745621">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种新冠肺炎CT检测识别定位系统及计算设备</strong> - 本发明涉及图像处理领域，公开了一种新冠肺炎CT检测识别定位系统及计算设备，包括图像采集单元、模块建立单元、新冠肺炎病灶识别单元和新冠肺炎病灶定位单元；图像采集单元采集待识别检测新冠肺炎的CT图像、新冠肺炎CT影像病灶分割训练数据集和新冠CT图像识别训练集；模块建立单元建立U_Net卷积神经网络模型、加入注意力机制的InceptionV3网络和目标检测模型；新冠肺炎病灶识别单元对已分割出病灶的轮廓特征图像进行识别；新冠肺炎病灶定位单元确定病灶在人体肺部的位置。本发明利用U_Net卷积神经网络模型对新冠病灶检测分割，并通过加入注意力机制的网络进行新冠肺炎识别，通过目标检测模型定位病灶在肺部的位置，识别准确率高，计算速度快。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN317076812">link</a></p></li>
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</ul>
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