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222 lines
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<title>09 December, 2020</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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>On the Effects of Misclassification in Estimating Efficacy With Application to Recent COVID-19 Vaccine Trials</strong> -
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Understandably, the recent trials for COVID-19 vaccines have garnered a considerable amount of attention and (as of this writing) vaccinations are about to begin. The popular summaries give infection rates in the vaccinated and placebo and estimated efficacy, which for the two trials we focus on (Moderna and Pfizer) are both near 95%. This paper explores the potential effects of possible false positives or false negatives (misclassification) in the COVID-19 diagnosis with specific application to the Moderna and Pfizer trials. The general conclusion, fortunately, is that these potential misclassifications almost always would lead to underestimation of the efficacy and that correcting for false positives or negatives will lead to even higher estimated efficacy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.04.20244244v2" target="_blank">On the Effects of Misclassification in Estimating Efficacy With Application to Recent COVID-19 Vaccine Trials</a>
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</div></li>
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<li><strong>Aging and COVID-19 mortality: A demographic perspective</strong> -
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Demographers have emphasized the importance of age in explaining the spread and impact on mortality of COVID-19. However, the relationship between COVID-19 with age should be contextualized in relation to other causes of death. This study set out to compare the age pattern of COVID-19 mortality with other major causes of death and across countries, and to use these regularities to impute age-specific death counts in countries with partial data. Using US vital Statistics, the COVID-19 mortality doubling time in a Gompertz context was compared with 65 major causes of death. COVID-19 fatality and mortality doubling times were similarly compared within and between 27 countries, using harmonized demographic databases of confirmed COVID-19 cases and deaths. Several findings are supported by the empirical evidence. First, COVID-19 mortality increases exponentially with age at a Gompertz rate near the median of aging-related causes of death, as well as pneumonia and influenza. Second, COVID-19 mortality levels are 2.8 to 8.2 times higher than pneumonia and influenza across the adult age range. Third, the relationship between both COVID-19 fatality and mortality with age varies considerably across countries. Fourth, COVID-19 deaths by age are imputed for Israel as a case in point. In conclusion, the increase in COVID-19 mortality with age resembles the population rate of aging. Country differences in the age pattern of COVID-19 fatality and mortality may point to differences in underlying population health, standards of clinical care, and data quality. This study underscores the need to contextualize the age pattern of COVID-19 mortality in relation to other causes of death.
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</p>
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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/10.1101/2020.10.15.20213454v2" target="_blank">Aging and COVID-19 mortality: A demographic perspective</a>
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</div></li>
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<li><strong>Detection of SARS-CoV-2 by Real-Time PCR under challenging pre-analytical conditions reveals independence of swab media and cooling chain</strong> -
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With global demand for SARS-CoV-2 testing ever rising, shortages in commercially available viral transport media pose a serious problem for laboratories and health care providers. For reliable diagnosis of SARS-CoV-2 and other respiratory viruses, executed by Real-time PCR, the quality of respiratory specimens, predominantly determined by transport and storage conditions, is crucial. Therefore, our aim was to explore the reliability of minimal transport media, comprising saline and the CDC recommended Viral Transport Media (HBSS VTM), for the diagnosis of SARS-CoV-2 and other respiratory viruses (influenza A, respiratory syncytial virus, adenovirus, rhinovirus and human metapneumovirus) compared to commercial products, such as the Universal Transport Media (UTM). We question the assumptions, that the choice of medium and temperature for storage and transport affect the accuracy of viral detection by RT-PCR. Both alternatives to the commercial transport medium (UTM), namely the CDC viral transport media (HBSS VTM) and saline, allow adequate detection of SARS-CoV-2 and other respiratory viruses, regardless of the storage temperature and time. Our study revealed the high resilience of SARS-CoV-2 and other respiratory viruses, enabling proper detection in clinical specimens even after long-time storage at high temperatures, independent of the transport medium9s composition.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.07.21.20158154v2" target="_blank">Detection of SARS-CoV-2 by Real-Time PCR under challenging pre-analytical conditions reveals independence of swab media and cooling chain</a>
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</div></li>
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<li><strong>Belgian Covid-19 Mortality, Excess Deaths, Number of Deaths per Million, and Infection Fatality Rates (8 March - 9 May 2020)</strong> -
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Background: COVID-19 mortality and its relation to excess deaths, the number of Deaths Per Million (DPM), Infection Fatality Rates (IFRs) and Case Fatality Rates (CFRs) are constantly being reported and compared for a large number of countries globally. These measures may appear objective, however they should be interpreted with the necessary care. Objective: Scrutiny of COVID-19 mortality in Belgium over the period 9 March - 28 June 2020 (Weeks 11–26), using the relation between COVID-19 mortality and excess death rates, the number of deaths per million, and infection fatality rates. Methods: The relation between COVID-19 reported mortality and excess death rates is evaluated by comparing publicly available COVID-19 mortality (2020) and the difference of observed and predicted overall mortality. Predictions are based on weekly averages of historical overall mortality data in Belgium (2009-2019). Deaths per million are evaluated using demographic data of the Belgian population (2020). The infection fatality rate is estimated using a delay distribution between infection and death. The number of infections in Belgium is estimated by a stochastic compartmental model, which uses hospitalisation data, serial serological survey data, and COVID-19 mortality data (2020) for calibration. Results: In Belgium, 9621 COVID-19 related deaths are reported between 9 March and 28 June 2020, which is close to the excess mortality estimated by weekly averages of historical mortality data (8985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population in Belgium. Both DPM and IFR increase with age and are substantially larger in the nursing home population. Conclusion: Belgium has virtually no discrepancy between COVID-19 reported mortality and excess mortality. Due to this close agreement it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population dependent. Data comparison of COVID-19 mortality between countries should rather be based on excess mortality than reported mortality.
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</div>
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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/10.1101/2020.06.20.20136234v2" target="_blank">Belgian Covid-19 Mortality, Excess Deaths, Number of Deaths per Million, and Infection Fatality Rates (8 March - 9 May 2020)</a>
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</div></li>
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<li><strong>Containment measures limit environmental effects on COVID-19 early outbreak dynamics</strong> -
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Environmental factors are well known to affect spatio-temporal patterns of infectious disease outbreaks, but whether the recent rapid spread of COVID-19 across the globe is related to local environmental conditions is highly debated. We assessed the impact of environmental factors (temperature, humidity and air pollution) on the global patterns of COVID-19 early outbreak dynamics during January-May 2020, controlling for several key socio-economic factors and airport connections. We showed that during the earliest phase of the global outbreak (January-March), COVID-19 growth rates were non-linearly related to climate, with fastest spread in regions with a mean temperature of ca. 5 degrees, and in the most polluted regions. However, environmental effects faded almost completely when considering later outbreaks, in keeping with the progressive enforcement of containment actions. Accordingly, COVID-19 growth rates consistently decreased with stringent containment actions during both early and late outbreaks. Our findings indicate that environmental drivers may have played a role in explaining the early variation among regions in disease spread. With limited policy interventions, seasonal patterns of disease spread might emerge, with temperate regions of both hemispheres being most at risk of severe outbreaks during colder months. Nevertheless, containment measures play a much stronger role and overwhelm impacts of environmental variation, highlighting the key role for policy interventions in curbing COVID-19 diffusion within a given region. If the disease will become seasonal in the next years, information on environmental drivers of COVID-19 can be integrated with epidemiological models to inform forecasting of future outbreak risks and improve management plans.
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</p>
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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/10.1101/2020.03.23.20040501v4" target="_blank">Containment measures limit environmental effects on COVID-19 early outbreak dynamics</a>
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<li><strong>COVID-19 and Dapsone: Four preventive treatment mechanisms</strong> -
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<div>
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Introduction: 4,4′-Diaminodiphenyl sulfone (Dapsone, DDS) targets COVID-19 as a key to ending the current pandemic. Dapsone is an inflammasome competitor commonly used in combination with clofazimine-rifampicin for the treatment of leprosy. Mechanistic presentation: Dapsone binds to myeloperoxidase and regulates hypochlorite production, thereby reducing the inflammatory response of cells and has a structure that can reduce the sulfur radical production rate by electron charge transfer because they are structurally similar to methionine sulfoxide. Nucleophilic properties of Dapsone compete with ubiquitin by attacking a ubiquitin (Ub)-conjugating enzyme (E2)–Ub thioester linkage. The best-described sites are the amine-containing internal lysine residues and the free amine of the polypeptide backbone’s N-terminus. ORF8b activates NLRP3 through direct interaction of the leucine-rich repeat domain of NLRP3. Nucleophilic properties of DDS compete with NLRP3. Conclusion: Dapsone’s four mechanisms have treated ARDS and prevented SARS-CoV-2 infection.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/jq5tc/" target="_blank">COVID-19 and Dapsone: Four preventive treatment mechanisms</a>
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</div></li>
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<li><strong>Inflated false-negative rates in pooled RT-PCR tests of SARS-CoV-2</strong> -
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Background: Pooling is a popular strategy for increasing SARS-CoV-2 testing throughput. A common pooling scheme is Dorfman pooling: test N individuals simultaneously. If the first test is positive - retest each individual. Methods: Using a probabilistic model, we analyze the false-negative rate (i.e., the probability of a negative result for an infected individual) of Dorfman pooling . Our model is conservative in that it ignores sample dilution effects, which can only worsen pooling performance. Results: We show that one can expect a 60-80% increase in false-negative rates under Dorfman pooling, for reasonable parameter values. Moreover, we show that the false-negative rates under Dorfman pooling increase when the prevalence of infection decreases. Discussion: In most pooling schemes, identifying an infected individual requires positive results in multiple tests and hence substantially deteriorates false-negative rates. Furthermore, this phenomenon is more pronounced when infection prevalence is low - exactly when pooling is most efficient. Thus, pooling presents an inherent trade-off: it is most efficient when it is least accurate. The deterioration of false-negative rates and the aforementioned trade-off are inherent problems of pooling schemes and should be kept in mind by practitioners and policy makers.
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</p>
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</div>
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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/10.1101/2020.12.02.20242651v2" target="_blank">Inflated false-negative rates in pooled RT-PCR tests of SARS-CoV-2</a>
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</div></li>
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<li><strong>Comparison of SARS-COV-2 nasal antigen test to nasopharyngeal RT-PCR in mildly symptomatic patients</strong> -
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Introduction COVID 19 has been vastly spreading since December 2019 and the medical teams worldwide are doing their best to limit its spread. In the absence of a vaccine the best way to fight it is by detecting infected cases early and isolate them to prevent its spread. Therefore, a readily available, rapid, and cost-effective test with high specificity and sensitivity for early detection of COVID 19 is required. In this study, we are testing the diagnostic performance of a rapid antigen detection test in mildly symptomatic cases. (RADT). Methods The study included 4183 male patients who were mildly symptomatic. A nasal sample for the rapid antigen test and a nasopharyngeal sample was taken from each patient. Statistical analysis was conducted to calculate the sensitivity, specificity, positive predictive value, negative predictive value and kappa coefficient of agreement. Results The prevalence of COVID 19 in the study population was 17.5% (733/4183). The calculated sensitivity and specificity were 82.1% and 99.1% respectively. Kappa coefficient of agreement between the rapid antigen test and RT-PCR was 0.859 (p < 0.001). A stratified analysis was performed and it showed that the sensitivity of the test improved significantly with lowering the cutoff Ct value to 24. Conclusion The results of the diagnostic assessment of nasal swabs in the RADT used in our study are promising regarding the potential benefit of using them as a screening tool in mildly symptomatic patients. The diagnostic ability was especially high in cases with high viral load. The rapid antigen test is intended to be used alongside RT-PCR and not replace it. RADT can be of benefit in reducing the use of PCR.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.10.20228973v2" target="_blank">Comparison of SARS-COV-2 nasal antigen test to nasopharyngeal RT-PCR in mildly symptomatic patients</a>
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</div></li>
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<li><strong>Evaluation of high-throughput SARS-CoV-2 serological assays in a longitudinal cohort of mild COVID-19 patients: sensitivity, specificity and association with virus neutralization test</strong> -
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Background: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild COVID-19 patients. Methods: A total of 439 specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The sensitivity (determined weekly) of nine commercial serological assays were evaluated. Correlation, agreement and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at several neutralizing antibody titers. Specificity was assessed using 69 pre-pandemic serum. Results: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMerieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% [CI 95% 21.1-48.3]). The NPA [CI 95%] for other total Ab or IgG assays targeting the S or the RBD was 80.7% [66.7-89.7], 90.3 [78.1-96.1] and 96.8% [86.8-99.3] for Siemens, bioMerieux IgG and DiaSorin, respectively. None of commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC<0.76). Conclusions: Although some assays presented a better agreement with VNT than others, the present findings emphasize that commercialized serological tests including those targeting the RBD cannot substitute a VNT for the assessment of functional antibody response.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.09.30.20194290v3" target="_blank">Evaluation of high-throughput SARS-CoV-2 serological assays in a longitudinal cohort of mild COVID-19 patients: sensitivity, specificity and association with virus neutralization test</a>
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</div></li>
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<li><strong>Epidemic Progression and Vaccination in a Heterogeneous Population. Application to the Covid-19 epidemic</strong> -
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The paper is devoted to a compartmental epidemiological model of infection progression in a heterogeneous population which consists of two groups with high disease transmission (HT) and low disease transmission (LT) potentials. Final size and duration of epidemic, the total and current maximal number of infected individuals are estimated depending on the structure of the population. It is shown that with the same basic reproduction number <i>R</i><sub>0</sub> in the beginning of epidemic, its further progression depends on the ratio between the two groups. Therefore, fitting the data in the beginning of epidemic and the determination of <i>R</i><sub>0</sub> are not sufficient to predict its long time behaviour. Available data on the Covid-19 epidemic allows the estimation of the proportion of the HT and LT groups. Estimated structure of the population is used for the investigation of the influence of vaccination on further epidemic development. The result of vaccination strongly depends on the proportion of vaccinated individuals between the two groups. Vaccination of the HT group acts to stop the epidemic and essentially decreases the total number of infected individuals at the end of epidemic and the current maximal number of infected individuals while vaccination of the LT group only acts to protect vaccinated individuals from further infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.06.20244731v2" target="_blank">Epidemic Progression and Vaccination in a Heterogeneous Population. Application to the Covid-19 epidemic</a>
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<li><strong>Comparable specimen collection from both ends of at-home mid-turbinate swabs</strong> -
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Unsupervised upper respiratory specimen collection is a key factor in the ability to massively scale SARS-CoV-2 testing. But there is concern that unsupervised specimen collection may produce inferior samples. Across two studies that included unsupervised at-home mid-turbinate specimen collection, ~1% of participants used the wrong end of the swab. We found that molecular detection of respiratory pathogens and a human biomarker were comparable between specimens collected from the handle of the swab and those collected correctly. Older participants were more likely to use the swab backwards. Our results suggest that errors made during home-collection of nasal specimens do not preclude molecular detection of pathogens and specialized swabs may be an unnecessary luxury during a pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.05.20244632v1" target="_blank">Comparable specimen collection from both ends of at-home mid-turbinate swabs</a>
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<li><strong>The anti-vaccination infodemic on social media: a behavioral analysis</strong> -
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Vaccinations are without doubt one of the greatest achievements of modern medicine, and there is hope that they can constitute a solution to halt the ongoing COVID-19 pandemic. However, the anti-vaccination movement is currently on the rise, spreading online misinformation about vaccine safety and causing a worrying reduction in vaccination rates worldwide. In this historical time, it is imperative to understand the reasons of vaccine hesitancy, and to find effective strategies to dismantle the rhetoric of anti-vaccination supporters. For this reason, we analyzed the behavior of anti-vaccination supporters on the platform Twitter. Here we identify that anti-vaccination supporters, in comparison to pro-vaccination supporters, share conspiracy theories and make use of emotional language. We demonstrate that anti-vaccination supporters are more engaged in discussions on Twitter and share their content from a pull of strong influencers. We show that the movement9s success relies on a strong sense of community, based on the contents produced by a small fraction of profiles, with the community at large serving as a sounding board for anti-vaccination discourse to circulate online. Surprisingly, our data demonstrate that Donald Trump, together with members of his entourage and his closest supporters, are the main drivers of vaccine misinformation on Twitter. Based on these results, we propose to strategically target the anti-vaccination community online through policies that aim at halting the circulation of false information about vaccines. Based on our data, we also propose solutions to improve the communication strategy of health organizations and build a community of engaged influencers that support the dissemination of scientific insights, including issues related to vaccines and their safety.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.07.20223370v1" target="_blank">The anti-vaccination infodemic on social media: a behavioral analysis</a>
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</div></li>
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<li><strong>Excess deaths associated with the Iranian COVID-19 epidemic: a province-level analysis</strong> -
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Background: The number of publicly reported deaths from COVID-19 may underestimate the true death toll from the epidemic as they rely on provisional data that are often incomplete or omit undocumented deaths from COVID-19. In addition, these reports may be subject to significant under-reporting due to a limited testing capacity of a country to identify suspect cases. This study estimated the number of seasonal excess deaths attributable to the COVID-19 epidemic in 31 provinces of Iran. Methods: We gathered the nationwide and provincial time series of the seasonal all-cause mortality data from spring 2015 to summer 2020 (21 March 2015 to 21 September 2020), in accordance with the Solar Hijri (SH) calendar, from the National Organization for Civil Registration (NOCR). We estimated the expected number of seasonal deaths for each province using a piecewise linear regression model which we established based on the mortality figures for the previous years and considered any significant deviations from the expectation during winter, spring, and summer of 2020 to be directly associated with COVID-19. Results: Our analysis shows that from the start of winter to the end of summer (from 22 December 2019 to 21 September 2020), there were a total of 58.9K (95%CI: 46.9K - 69.5K) excess deaths across all 31 provinces with 27% (95%CI: 20% - 34%) estimated nationwide exposure to SARS-CoV-2. In particular, 2 provinces in the central and northern Iran, namely Qom and Golestan, had the highest level of exposure with 57% (95%CI: 44% - 69%) and 56% (95%CI: 44% - 69%), respectively, while another 27 provinces had significant levels of excess mortality in at least one season with >20% population-level exposure to the virus. We also detected unexpectedly high levels of excess mortality during fall 2019 (from 23 September to 21 December 2019) across 18 provinces. Our findings suggest that this spike cannot be a result of an early cryptic transmission of COVID-19 across the country and is also inconsistent with the molecular phylogenetics estimates for the start of the pandemic and its arrival to Iran. However, in the absence of appropriate surveillance data for detecting severe acute respiratory infections we were unable to make a determination as to what caused the spike in fall 2019.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.07.20245621v1" target="_blank">Excess deaths associated with the Iranian COVID-19 epidemic: a province-level analysis</a>
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<li><strong>Evaluation of SARS-CoV-2 neutralization assays for antibody monitoring in natural infection and vaccine trials</strong> -
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Determinants of protective immunity against SARS-CoV-2 infection require the development of well-standardized, reproducible antibody assays to be utilized in concert with clinical trials to establish correlates of risk and protection. This need has led to the appearance of a variety of neutralization assays used by different laboratories and companies. Using plasma samples from COVID-19 convalescent individuals with mild-to-moderate disease from a localized outbreak in a single region of the western US, we compared three platforms for SARS-CoV-2 neutralization: assay with live SARS-CoV-2, pseudovirus assay utilizing lentiviral (LV) and vesicular stomatitis virus (VSV) packaging, and a surrogate ELISA test. Vero, Vero E6, HEK293T cells expressing human angiotensin converting enzyme 2 (hACE2), and TZM-bl cells expressing hACE2 and transmembrane serine protease 2 (TMPRSS2) were evaluated. Live-virus and LV-pseudovirus assay with HEK293T cells showed similar geometric mean titers (GMTs) ranging 141–178, but VSV-pseudovirus assay yielded significantly higher GMT (310 95%CI 211-454; p < 0.001). Fifty percent neutralizing dilution (ND50) titers from live-virus and all pseudovirus assay readouts were highly correlated (Pearson <i>r</i> = 0.81–0.89). ND50 titers positively correlated with plasma concentration of IgG against SARS-CoV-2 spike and receptor binding domain (RBD) (<i>r </i>= 0.63–0.89), but moderately correlated with nucleoprotein IgG (<i>r</i> = 0.46-0.73). There was a moderate positive correlation between age and spike (Spearman9s rho=0.37, p=0.02), RBD (rho=0.39, p=0.013) and nucleoprotein IgG (rho=0.45, p=0.003). ND80 showed stronger correlation with age than ND50 (ND80 rho=0.51 (p=0.001), ND50 rho=0.28 (p=0.075)). Our data demonstrate high concordance between cell-based assays with live and pseudotyped virions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.07.20245431v1" target="_blank">Evaluation of SARS-CoV-2 neutralization assays for antibody monitoring in natural infection and vaccine trials</a>
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</div></li>
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<li><strong>Integrative analyses identify susceptibility genes underlying COVID-19 hospitalization</strong> -
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Despite rapid progress in characterizing the role of host genetics in SARS-Cov-2 infection, there is limited understanding of genes and pathways that contribute to COVID-19. Here, we integrated a genome-wide association study of COVID-19 hospitalization (7,885 cases and 961,804 controls from COVID-19 Host Genetics Initiative) with mRNA expression, splicing, and protein levels (n=18,502). We identified 27 genes related to inflammation and coagulation pathways whose genetically predicted expression was associated with COVID-19 hospitalization. We functionally characterized the 27 genes using phenome- and laboratory-wide association scans in Vanderbilt Biobank (BioVU; n=85,460) and identified coagulation-related clinical symptoms, immunologic, and blood-cell-related biomarkers. We replicated these findings across trans-ethnic studies and observed consistent effects in individuals of diverse ancestral backgrounds in BioVU, pan-UK Biobank, and Biobank Japan. Our study highlights putative causal genes impacting COVID-19 severity and symptomology through the host inflammatory response.
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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/10.1101/2020.12.07.20245308v1" target="_blank">Integrative analyses identify susceptibility genes underlying COVID-19 hospitalization</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</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>Convalescent Plasma for Treatment of COVID-19: An Open Randomised Controlled Trial</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: SARS-CoV-2 convalescent plasma; Other: Standard of care<br/><b>Sponsors</b>: Joakim Dillner; Karolinska Institutet; Danderyd Hospital; Falu Hospital<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>Phase II / III Study of COVID-19 DNA Vaccine (AG0302-COVID19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Group A (AG0302-COVID19); Biological: Group A (Placebo); Biological: Group B (AG0302-COVID19); Biological: Group B (Placebo)<br/><b>Sponsors</b>: AnGes, Inc.; Japan Agency for Medical Research and Development<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>At-Home Infusion Using Bamlanivimab in Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: bamlanivimab<br/><b>Sponsors</b>: Daniel Griffin, MD PhD; Eli Lilly and Company; Optum, 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>Ivermectin for Severe COVID-19 Management</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Ivermectin<br/><b>Sponsors</b>: Afyonkarahisar Health Sciences University; NeuTec Pharma<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>IFN-beta 1b and Remdesivir for COVID19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Interferon beta-1b; Drug: Remdesivir<br/><b>Sponsor</b>: The University of Hong Kong<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 And Geko Evaluation: The CAGE Study</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Device: geko T3<br/><b>Sponsor</b>: Lawson Health Research Institute<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>LYT-100 in Post-acute COVID-19 Respiratory Disease</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: LYT-100; Other: Placebo<br/><b>Sponsors</b>: PureTech; Clinipace Worldwide; Novotech (Australia) Pty Limited<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>Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids -</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Omegaven®; Drug: Sodium chloride<br/><b>Sponsor</b>: Karolinska University Hospital<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>WHO COVID-19 Solidarity Trial for COVID-19 Treatments</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Remdesivir; Drug: Acalabrutinib; Drug: Interferon beta-1a; Other: Standard of Care<br/><b>Sponsor</b>: The University of The West Indies<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 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Apixaban 2.5 MG; Drug: Placebo<br/><b>Sponsors</b>: Thomas Ortel, M.D., Ph.D.; National Heart, Lung, and Blood Institute (NHLBI)<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>Urine Alkalinisation to Prevent AKI in COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Sodium Bicarbonate 150Meq/L/D5W Inj<br/><b>Sponsor</b>: Guy’s and St Thomas’ NHS Foundation Trust<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>Efficacy and Safety of Ovotransferrin in COVID-19 Patients</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Dietary Supplement: Ovotransferrin<br/><b>Sponsor</b>: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo<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>Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: rNAPc2; Drug: Heparin<br/><b>Sponsors</b>: ARCA Biopharma, Inc.; Colorado Prevention Center<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>Using Travelan to Boost Immune Response in Vitro to COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Other: Travelan OTC<br/><b>Sponsor</b>: Hadassah Medical Organization<br/><b>Active, not 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 Single-Arm Safety and Feasibility Study of Defibrotide for the Treatment of Severe COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Drug: Defibrotide<br/><b>Sponsors</b>: Brigham and Women’s Hospital; Jazz Pharmaceuticals<br/><b>Not yet recruiting</b></p></li>
|
||
</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>Dynamic Chest X-Ray Using a Flat-Panel Detector System: Technique and Applications</strong> - Dynamic X-ray (DXR) is a functional imaging technique that uses sequential images obtained by a flat-panel detector (FPD). This article aims to describe the mechanism of DXR and the analysis methods used as well as review the clinical evidence for its use. DXR analyzes dynamic changes on the basis of X-ray translucency and can be used for analysis of diaphragmatic kinetics, ventilation, and lung perfusion. It offers many advantages such as a high temporal resolution and flexibility in body…</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>Repurposing potential of FDA approved and investigational drugs for COVID-19 targeting SARS-CoV-2 spike and main protease and validation by machine learning algorithm</strong> - The present study aimed to assess the repurposing potential of existing antiviral drug candidates (FDA approved and investigational) against SARS-CoV-2 target proteins that facilitates viral entry and replication into the host body. To evaluate molecular affinities between antiviral drug candidates and SARS-CoV-2 associated target proteins such as spike protein (S) and main protease (M^(pro) ), a molecular interaction simulation was performed using MD software and subsequently the applicability…</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>Tracing the Path of Inhaled Nitric Oxide: Biological Consequences of Protein Nitrosylation</strong> - Nitric oxide (NO) is a comprehensive regulator of vascular and airway tone. Endogenous NO produced by nitric oxide synthases regulates multiple signaling cascades, including activation of soluble guanylate cyclase to generate cGMP, relaxing smooth muscle cells. Inhaled NO is an established therapy for pulmonary hypertension in neonates, and has been recently proposed for treatment of hypoxic respiratory failure and acute respiratory distress syndrome due to COVID-19. In this review, we summarize…</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>Enhancement of the IFN-beta-induced host signature informs repurposed drugs for COVID-19</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent for the outbreak of coronavirus disease 2019 (COVID-19). This global pandemic is now calling for efforts to develop more effective COVID-19 therapies. Here we use a host-directed approach, which focuses on cellular responses to diverse small-molecule treatments, to identify potentially effective drugs for COVID-19. This framework looks at the ability of compounds to elicit a similar transcriptional response to…</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>Geranii Herba as a Potential Inhibitor of SARS-CoV-2 Main 3CL(pro), Spike RBD, and Regulation of Unfolded Protein Response: An In Silico Approach</strong> - CONCLUSIONS: Hence, the compounds present in Geranii Herba could be used as possible drug candidates for the prevention/treatment of SARS-CoV-2 infection.</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 the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge</strong> - The RNA-dependent RNA polymerase (RdRp) is an essential enzyme for the viral replication process, catalyzing the viral RNA synthesis using a metal ion-dependent mechanism. In recent years, RdRp has emerged as an optimal target for the development of antiviral drugs, as demonstrated by recent approvals of sofosbuvir and remdesivir against Hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively. In this work, we overview the main sequence 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>SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II receptor signaling in epithelial cells</strong> - Cytokine storm is suggested as one of the major pathological characteristics of SARS-CoV-2 infection, although the mechanism for initiation of a hyper-inflammatory response, and multi-organ damage from viral infection is poorly understood. In this virus-cell interaction study, we observed that SARS-CoV-2 infection or viral spike protein expression alone inhibited angiotensin converting enzyme-2 (ACE2) receptor protein expression. The spike protein promoted an angiotensin II type 1 receptor (AT1)…</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>Molecular detection of SARS-CoV-2 using a reagent-free approach</strong> - Shortage of reagents and consumables required for the extraction and molecular detection of SARS-CoV-2 RNA in respiratory samples has led many laboratories to investigate alternative approaches for sample preparation. Many groups recently presented results using heat processing method of respiratory samples prior to RT-qPCR as an economical method enabling an extremely fast streamlining of the processes at virtually no cost. Here, we present our results using this method and highlight some major…</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 Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors</strong> - The COVID-19 pathogen, SARS-CoV-2, requires its main protease (SC2M Pro ) to digest two of its translated polypeptides to form a number of mature proteins that are essential for viral replication and pathogenesis. Inhibition of this vital proteolytic process is effective in preventing the virus from replication in infected cells and therefore provides a potential COVID-19 treatment option. Guided by previous medicinal chemistry studies about SARS-CoV-1 main protease (SC1M Pro ), we have designed…</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>SARS-CoV-2 RNA in Wastewater Settled Solids Is Associated with COVID-19 Cases in a Large Urban Sewershed</strong> - Wastewater-based epidemiology may be useful for informing public health response to viral diseases like COVID-19 caused by SARS-CoV-2. We quantified SARS-CoV-2 RNA in wastewater influent and primary settled solids in two wastewater treatment plants to inform the preanalytical and analytical approaches and to assess whether influent or solids harbored more viral targets. The primary settled solids samples resulted in higher SARS-CoV-2 detection frequencies than the corresponding influent samples….</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>Remdesivir Is Effective in Combating COVID-19 because It Is a Better Substrate than ATP for the Viral RNA-Dependent RNA Polymerase</strong> - COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently being treated using Remdesivir, a nucleoside analog that inhibits the RNA-dependent-RNA polymerase (RdRp). However, the enzymatic mechanism and efficiency of Remdesivir have not been determined, and reliable screens for new inhibitors are urgently needed. Here we present our work to optimize expression in E. coli, followed by purification and kinetic analysis of an untagged NSP12/7/8 RdRp…</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>The Need for Ocular Protection for Health Care Workers During SARS-CoV-2 Outbreak and a Hypothesis for a Potential Personal Protective Equipment</strong> - SARS-CoV-2 is a coronavirus with high infectivity and has caused dramatic pressure on health systems all over the world. Appropriate personal protection for medical staffs is critical. For ocular protection, there is ongoing hot debate and concern for potential ocular transmission of SARS-CoV-2. Ocular manifestations and positive detection of viral RNA in ocular samples were only reported in very small number of patients infected with SARS-CoV-2. However, health care workers need to face…</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>Improved protection of filtering facepiece through inactivation of pathogens by hypertonic salt solutions - A possible COVID-19 prevention device</strong> - The filtering facepiece operates through filtration without the ability to kill the viruses. If the filtration might be combined with antiviral agents simultaneously in the masks, this would be much more efficient during the use of these masks and against cross-infection after being discarded. For centuries, sodium chloride (NaCl) contributes to inhibiting pathogens on various occasions. If aerosol with infectious agents reaches the filtering face-piecé surface of the filtering face-piece,…</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>Micro-RNAs in the regulation of immune response against SARS COV-2 and other viral infections</strong> - BACKGROUND: Micro-RNAs (miRNAS) are non-coding, small RNAs that have essential roles in different biological processes through silencing genes, they consist of 18-24 nucleotide length RNA molecules. Recently, miRNAs have been viewed as important modulators of viral infections they can function as suppressors of gene expression by targeting cellular or viral RNAs during infection.</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>Unusual association of COVID-19, pulmonary tuberculosis and human immunodeficiency virus, having progressed favorably under treatment with chloroquine and rifampin</strong> - Infection with the new coronavirus has been declared an international health emergency. Its curative treatment is unknown and is the subject of several clinical trials. In addition, the concomitant association of COVID-19 with tuberculosis and the human immunodeficiency virus, hitherto never described, is potentially fatal. We report the illustrative case of a 32-year-old patient who presented this trifecta of infections and who did well under treatment with chloroquine and anti-mycobacterial…</p></li>
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</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 data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“AYURVEDIC PROPRIETARY MEDICINE FOR TREATMENT OF SEVERWE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2.”</strong> - AbstractAyurvedic Proprietary Medicine for treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)In one of the aspect of the present invention it is provided that Polyherbal combinations called Coufex (syrup) is prepared as Ayurvedic Proprietary Medicine , Aqueous Extracts Mixing with Sugar Syrup form the following herbal aqueous extract coriandrum sativum was used for the formulation of protek.Further another Polyherbal combination protek as syrup is prepared by the combining an aqueous extract of the medicinal herbs including Emblica officinalis, Terminalia chebula, Terminalia belerica, Aegle marmelos, Zingiber officinale, Ocimum sanctum, Adatoda zeylanica, Piper lingum, Andrographis panivulata, Coriandrum sativum, Tinospora cordiofolia, cuminum cyminum,piper nigrum was used for the formulation of Coufex.</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>Haptens, hapten conjugates, compositions thereof and method for their preparation and use</strong> - A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more different targets. The two or more specific binding moieties are conjugated to different haptens, and at least one of the haptens is an oxazole, a pyrazole, a thiazole, a nitroaryl compound other than dinitrophenyl, a benzofurazan, a triterpene, a urea, a thiourea, a rotenoid, a coumarin, a cyclolignan, a heterobiaryl, an azo aryl, or a benzodiazepine. The sample is contacted with two or more different anti-hapten antibodies that can be detected separately. The two or more different anti-hapten antibodies may be conjugated to different detectable labels.</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>疫苗融合蛋白</strong> - 本申请涉及一种融合蛋白，所述融合蛋白包括SARS‑CoV‑2抗原多肽和鞭毛蛋白或其片段。本申请还提供了所述融合蛋白的制备方法和用途。本申请所述的融合蛋白能够诱导机体产生针对SARS‑CoV类病毒的抗原的细胞免疫反应。</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 EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19</strong> -</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>一种SARS-CoV-2假病毒小鼠体内包装系统及其制备方法</strong> - 本发明提供了一种假病毒小鼠体内包装系统的制备方法，包括以下步骤：S1基于慢病毒包装质粒系统和睡美人转座子系统构建SARS‑CoV‑2假病毒包装质粒系统，S2将步骤S1中SARS‑CoV‑2假病毒包装质粒系统与睡美人转座酶表达质粒混合通过水动力注射的方式转染小鼠肝细胞，然后睡美人转座子系统将SARS‑CoV‑2假病毒包装所需序列以剪切粘贴的方式整合到小鼠肝细胞的基因组。本发明可在小鼠体内持续制造分泌SARS‑CoV‑2假病毒，可模拟靶器官被SARS‑CoV‑2病毒持续侵入攻击的过程，从而可模拟出新冠肺炎（COVID‑19）的病理特征。基于SARS‑CoV‑2假病毒小鼠体内包装系统的动物模型安全性高，不需要P3级实验室就能开展研究。利用水动力注射的方式引入SARS‑CoV‑2假病毒包装质粒系统操作简单，成本低。</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>柴胡解毒药物组合物及其制备方法和应用</strong> - 本发明属于中药领域，具体涉及一种柴胡解毒药物组合物及其制备方法和应用，所述柴胡解毒药物组合物以质量份计由如下原料组分制成：柴胡30<sub>60份，黄芩15</sub>30份，法半夏15<sub>30份，生姜15</sub>30份，大枣5<sub>10份，枳实20</sub>40份，大黄10<sub>20份，桃仁10</sub>20份，白芍15~30份。本发明的柴胡解毒药物组合物能够显著改善普通型COVID‑19引起的咳嗽；能改善疫毒闭肺型重型COVID‑19引起的咳嗽，显著改善疫毒闭肺型重型COVID‑19引起的胸闷、气短和乏力等主要症状。另外经大量临床观察，本发明的柴胡解毒药物组合物能够显著改善疫毒闭肺型重型COVID‑19引起的发热面红，咳嗽，痰黄粘少，或痰中带血，喘憋气促，疲乏倦怠，口干苦粘，大便不畅，小便短赤等症状。</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>一种新型冠状病毒RBD核苷酸序列、优化方法与应用</strong> - 本发明公开了一种新型冠状病毒RBD核苷酸序列、优化方法与应用。属于基因工程技术领域。优化步骤：（1）对野生型新型冠状病毒RBD核苷酸序列进行初步优化；（2）将宿主细胞特异性高表达分泌蛋白信号肽序列进行优化；（3）将人IgG1‑Fc核苷酸序列进行优化；（4）将步骤（2）优化后的宿主细胞特异性高表达分泌蛋白信号肽核苷酸序列、步骤（1）得到的初步优化新型冠状病毒RBD核苷酸序列、连接子核苷酸序列和步骤（3）优化后的人IgG1‑Fc核苷酸序列依次连接即可。与现有技术相比，本发明的有益效果：产生的克隆表达效率比野生新型冠状病毒RBD序列提高了约12倍，比中国仓鼠密码子偏性优化序列克隆表达效率提高了2倍。</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>ASSISTING COMPLEX FOR TAKING OF BIOMATERIAL FROM MOUTH IN PANDEMIC CONDITIONS</strong> - FIELD: medicine. SUBSTANCE: invention refers to medicine, namely to methods for contactless taking of biomaterial in tested person. Taking the biomaterial in the tested person is carried out in a room located in a dirty zone and separated by a partition from the clean zone, in which there is a laboratory assistant performing the procedure using a robotic complex. Complex includes digital controller, manipulator with tool unit, small manipulator, camera, monitor, control system of digital controller, manipulator, small manipulator, and complex control system. In the partition there are two holes: one – for installation and passage of the swab, the other – for the test tube installation. In the dirty zone there is a small manipulator having two actuators: one for movement of a test tube with a swab, and the second for positioning and placing a disposable mouthpiece. EFFECT: reduced risk of laboratory assistant and tested person infection by avoiding their direct contact. 17 cl, 1 dwg</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>Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19</strong> -</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></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>Antiinfektive Arzneiform zur Herstellung einer Nasenspülung gegen COVID-19</strong> -</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Einzeldosierte, wasserlösliche oder wassermischbare Arzneiform, umfassend mindestens einen antiinfektiven Arzneistoff, zur Herstellung einer Nasenspülung und/oder zur Verwendung in der lokalen Behandlung des menschlichen Nasenraums.</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p></li>
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</ul>
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