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186 lines
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<title>11 April, 2023</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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<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>Natural Environments, Psychosocial Health, and Health Behaviors in a Crisis – A Scoping Review of the Literature in the COVID-19 Context</strong> -
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The COVID-19 outbreak has led to major restrictions globally, affecting people’s psychosocial health and their health behaviors. Thus, the purpose of this scoping review was to summarize the available research regarding the nature-health-association in the COVID-19 context. Keywords related to natural environments and COVID-19 were combined to conduct a systematic online search in six major databases. Eligibility criteria were a) published since 2020 with data collected in the COVID-19 context b) peer-reviewed, c) original empirical data collected on human participants, d) investigated the association between natural environments and psychosocial health or health behavior, and e) English, German, or Scandinavian language. Out of 8,568 articles being obtained, we identified 82 relevant articles representing 80 unique studies. Most studies focused on adults in the general population and were predominantly conducted in the USA and Europe. Overall, the findings tentatively indicate that nature mitigates the impact of COVID-19 on psychological health and physical activity. Through thematic analysis of the extracted data, three primary themes were identified: 1) type of nature assessed, 2) psychosocial health and health behaviors investigated, and 3) heterogeneity in the nature-health relationship. Research gaps in the COVID-19 context were identified regarding I) nature characteristics that promote psychosocial health and health behaviors, II) investigations of digital and virtual nature, III) psychological constructs relating to mental health promotion, IV) health behaviors other than physical activity, V) underlying mechanisms regarding heterogeneity in the nature-health relationship based on human, nature, and geographic characteristics, and VI) research focusing on vulnerable groups. Overall, natural environments demonstrate considerable potential in buffering the impact of stressful events on a population level on mental health. However, future research is warranted to fill the mentioned research gaps and to examine the long-term effects of nature exposure during COVID-19.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/a9unf/" target="_blank">Natural Environments, Psychosocial Health, and Health Behaviors in a Crisis – A Scoping Review of the Literature in the COVID-19 Context</a>
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</div></li>
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<li><strong>NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing</strong> -
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<div>
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The blood proteome holds great promise for precision medicine but poses daunting challenges due to the low abundance of the majority of plasma proteins and the vast dynamic range across the proteome. We report the development and validation of a novel proteomic analysis technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA) - that incorporates a dual capture and release mechanism to suppress the assay background to the minimum, thus drastically improving the signal-to-noise ratio. NULISA improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level, which is enabled by antibody-conjugated DNA sequences that mediate the purification of immunocomplexes and contain target- and sample-specific barcodes for next-generation sequencing-based, highly multiplexed analysis. To demonstrate its performance and utility, we developed a 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins that demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultra-high sensitivity enabled the detection of previously difficult-to-detect but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA uniquely addresses longstanding challenges in the proteomic analysis of liquid biopsy samples and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.09.536130v1" target="_blank">NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing</a>
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</div></li>
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<li><strong>SARS-CoV-2’s evolutionary capacity is mostly driven by host antiviral molecules</strong> -
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The COVID-19 pandemic has been characterised by sequential variant-specific waves shaped by viral, individual human and population factors. SARS-CoV-2 variants are defined by their unique combinations of mutations and there has been a clear adaptation to human infection since its emergence in 2019. Here we use machine learning models to identify shared signatures, i.e., common underlying mutational processes, and link these to the subset of mutations that define the variants of concern (VOCs). First, we examined the global SARS-CoV-2 genomes and associated metadata to determine how viral properties and public health measures have influenced the magnitude of waves, as measured by the number of infection cases, in different geographic locations using regression models. This analysis showed that, as expected, both public health measures and not virus properties alone are associated with the rise and fall of regional SARS-CoV-2 reported infection numbers. This impact varies geographically. We attribute this to intrinsic differences such as vaccine coverage, testing and sequencing capacity, and the effectiveness of government stringency. In terms of underlying evolutionary change, we used non-negative matrix factorisation to observe three distinct mutational signatures, unique in their substitution patterns and exposures from the SARS-CoV-2 genomes. Signatures 0, 1 and 3 were biased to C->T, T->C/A->G and G->T point mutations as would be expected of host antiviral molecules APOBEC, ADAR and ROS effects, respectively. We also observe a shift amidst the pandemic in relative mutational signature activity from predominantly APOBEC-like changes to an increasingly high proportion of changes consistent with ADAR editing. This could represent changes in how the virus and the host immune response interact, and indicates how SARS-CoV-2 may continue to accumulate mutations in the future. Linkage of the detected mutational signatures to the VOC defining amino acids substitutions indicates the majority of SARS-CoV-2’s evolutionary capacity is likely to be associated with the action of host antiviral molecules rather than virus replication errors.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.07.536037v1" target="_blank">SARS-CoV-2’s evolutionary capacity is mostly driven by host antiviral molecules</a>
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<li><strong>Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking</strong> -
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SARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.08.536123v1" target="_blank">Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking</a>
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<li><strong>Unbiased spectral cytometry immunome characterization predicts COVID-19 mRNA vaccine failure in older adults and patients with lymphoid malignancies.</strong> -
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COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, NK cells, monocytes and CD45RA+CCR7- Tγδ cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note up to 7 subsets were found within the CD45RA+CCR7- Tγδ population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV-2 mRNA vaccines.
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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/10.1101/2023.04.10.23288350v1" target="_blank">Unbiased spectral cytometry immunome characterization predicts COVID-19 mRNA vaccine failure in older adults and patients with lymphoid malignancies.</a>
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<li><strong>Global surveillance of novel SARS-CoV-2 variants</strong> -
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Earlier global detection of novel SARS-CoV-2 variants gives governments more time to respond. However, few countries can implement timely national surveillance resulting in gaps in monitoring. The UK implemented large-scale community and hospital surveillance, but experience suggests it may be faster to detect new variants through testing UK arrivals for surveillance. We developed simulations of the emergence and importation of novel variants with a range of infection hospitalisation rates (IHR) to the UK. We compared time taken to detect the variant though testing arrivals at UK borders, hospital admissions, and the general community. We found that sampling 10 to 50% of arrivals at UK borders could confer a speed advantage of 3.5 to 6 weeks over existing community surveillance, and 1.5 to 5 weeks (depending on IHR) over hospital testing. We conclude that directing limited global capacity for surveillance to highly connected ports could speed up global detection of novel SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.10.23288358v1" target="_blank">Global surveillance of novel SARS-CoV-2 variants</a>
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<li><strong>A cross-sectional study of the association between COVID-19 infection and psychological distress in Japanese workers</strong> -
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The COVID-19 pandemic infected many people worldwide with SARS-CoV2. Psychological distress is one of the sequelae reported to occur in many of those infected (Choutka et al., 2022). We investigated the association between personal experience of COVID-19 infection and psychological distress in Japan. A total of 18,560 persons participated in the original survey, conducted in December 2020. After excluding unreliable responses, data from 14,901 persons who participated in a follow-up survey in December 2022-were included in the analysis. Odds ratios (ORs) were estimated by univariate and multiple logistic regression analysis with history of COVID-19 infection as the independent variable and presence of psychological distress as the dependent variable. This results showed that the experience of COVID-19 infection is associated with psychological distress. Moreover, most cases of mental distress among those who experienced COVID-19 infection can be at least partly explained by a perception of unfair treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.08.23288312v1" target="_blank">A cross-sectional study of the association between COVID-19 infection and psychological distress in Japanese workers</a>
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</div></li>
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<li><strong>Data-driven control of airborne infection risk and energy use in buildings</strong> -
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The global devastation of the COVID-19 pandemic has led to calls for a revolution in heating, ventilation, and air conditioning (HVAC) systems to improve indoor air quality (IAQ), due to the dominant role of airborne transmission in disease spread. While simple guidelines have recently been suggested to improve IAQ mainly by increasing ventilation and filtration, this goal must be achieved in an energy-efficient and economical manner and include all air cleaning mechanisms. Here, we develop a simple protocol to directly, quantitatively, and optimally control transmission risk while minimizing energy cost. We collect a large dataset of HVAC and IAQ measurements in buildings and show how models of infectious aerosol dynamics and HVAC operation can be combined with sensor data to predict transmission risk and energy consumption. Using this data, we also verify that a simple safety guideline is able to limit transmission risk in full data-driven simulations and thus may be used to guide public health policy. Our results provide a comprehensive framework for quantitative control of transmission risk using all available air cleaning mechanisms in an indoor space while minimizing energy costs to aid in the design and automated operation of healthy, energy-efficient buildings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.19.23287460v2" target="_blank">Data-driven control of airborne infection risk and energy use in buildings</a>
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<li><strong>Pre-pandemic humoral immunity to SARS-CoV-2 in Africa: systematic review and meta-analysis</strong> -
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Objective: To assess the evidence on the presence of antibodies that are cross-reactive with SARS-CoV-2 antigens in pre-pandemic samples from African populations. Methods: We performed a systematic review and meta-analysis of studies evaluating pre-pandemic African samples for anti-SARS-CoV-2 cross-reactive antibodies using pre-set assay-specific thresholds for seropositivity. Results: 24 articles with 146 datasets were eligible, including 3,194 positives among 27,269 measurements (11.7%) with large between-dataset heterogeneity. Positivity was similar for anti-N and anti-S antibodies (14% and 11%, respectively) and it was higher for anti-S1 (23%) and lower for anti-RBD antibodies (7%). Positivity was non-significantly higher for IgM than for IgG antibodies. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% CI, 13-17%) versus 2%, 95% CI 1-3% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (15% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in countries and cohorts of high HIV seroprevalence, but this association was not validated in individual samples. Conclusions: Pre-pandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. Levels of cross-reactivity tracks especially with malaria prevalence.
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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/10.1101/2022.10.07.22280814v2" target="_blank">Pre-pandemic humoral immunity to SARS-CoV-2 in Africa: systematic review and meta-analysis</a>
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<li><strong>Accurately Estimating Total COVID-19 Infections using Information Theory</strong> -
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Abstract One of the most significant challenges in the early combat against COVID-19 was the dif- ficulty in estimating the true magnitude of infections. Unreported infections drove up disease spread in numerous regions, made it very hard to accurately estimate the infectivity of the pathogen, therewith hampering our ability to react effectively. Despite the use of surveillance- based methods such as serological studies, identifying the true magnitude is still challenging today. This paper proposes an information theoretic approach for accurately estimating the number of total infections. Our approach is built on top of Ordinary Differential Equations (ODE) based models, which are commonly used in epidemiology and for estimating such infec- tions. We show how we can help such models to better compute the number of total infections and identify the parameterization by which we need the fewest bits to describe the observed dynamics of reported infections. Our experiments show that our approach leads to not only substantially better estimates of the number of total infections but also better forecasts of infec- tions than standard model calibration based methods. We additionally show how our learned parameterization helps in modeling more accurate what-if scenarios with non-pharmaceutical interventions. Our results support earlier findings that most COVID-19 infections were un- reported and non-pharmaceutical interventions indeed helped to mitigate the spread of the outbreak. Our approach provides a general method for improving epidemic modeling which is applicable broadly.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.09.14.21263467v3" target="_blank">Accurately Estimating Total COVID-19 Infections using Information Theory</a>
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<li><strong>Childcare burden and changes in fertility desires of mothers during the COVID-19 pandemic</strong> -
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Background: Previous studies have documented a decline in fertility desires following the COVID-19 outbreak, but reasons for this decline are not well understood. This study examined whether greater childcare burden on mothers during the lockdowns and quarantines, COVID-related stress and COVID-19 exposure were associated with a change in desired number of children. Methods: The survey was conducted in Poland in April–July 2021 and completed by 622 non-pregnant mothers without diagnosed infertility. Women were asked whether the COVID-19 pandemic has changed their reproductive plans. Childcare burden was reported during lockdown and quarantines. Results: Almost 30% of mothers reported decrease in their fertility desires because of the pandemic. Associations were observed between childcare responsibilities during the quarantine (but not lockdown) and fertility desires: mothers who solely or mainly took care of their children during the quarantine(s) were more likely to decrease their desired number of children ([adjusted] aOR = 1.91, 95% CI = 1.16–3.15). Mothers with higher levels of COVID-related stress (aOR = 1.81, 95% CI = 1.48–2.22) and greater COVID exposure index (aOR = 1.39, 95% CI = 1.12–1.72) were more likely to decrease their fertility desires. Conclusions: Mothers who bare more childcare responsibilities during quarantine had lower desire to have more children. At the same time, both greater COVID-related stress and exposure were associated with a decreased wish to have children, regardless of the childcare responsibilities during the pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3m9zs/" target="_blank">Childcare burden and changes in fertility desires of mothers during the COVID-19 pandemic</a>
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<li><strong>COVID-19 Vaccine Uptake And Its Associated Factors among general population In Basmaia City in Baghdad 2022</strong> -
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Objective: Vaccination is a vital cornerstone of public health, which has saved countless lives throughout history. Therefore, achieving high vaccination uptake rates is essential for successful vaccination programs. Unfortunately, vaccine uptake has been hindered by deferent factors and challenges. The objective of this study is to assess COVID-19 vaccine uptake and associated factors among the general population. Methods: This study is a descriptive cross-sectional study conducted in Basmaia city, Baghdad from June to October 2022. Data were collected through a semi-structured questionnaire using multi-stage random sampling. Statistical analysis was performed using descriptive statistics, chi-square analysis, Mann-Whitney test, and binary and multivariable logistic regression. Results: the prevalence of COVID-19 vaccine uptake was 70.4%. The most common reason for getting vaccinated was protection from the disease, while fear of side effects and not needing the vaccine were the main reasons for refusal. The study found that gender, age, education level, job title, risk perception, knowledge, and attitude towards the vaccine were significantly associated with COVID-19 vaccine uptake. Males were 2.273 times more likely to get vaccinated than females, and older age groups had higher odds of vaccination than younger age groups. Those with higher education levels were also more likely to receive the vaccine. Participants with higher risk perception, knowledge, and positive attitude towards the vaccine were more likely to get vaccinated. And found that mandatory vaccination policies may negatively impact uptake of subsequent vaccine doses. Conclusion: the study found a high prevalence of COVID-19 vaccine uptake, with gender, age, education level, and job title being significant factors associated with vaccine uptake. Additionally, mandatory vaccination policies may have a negative impact on the uptake of subsequent vaccine doses. Public health efforts should prioritize addressing these factors to increase vaccine uptake.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.07.23288262v1" target="_blank">COVID-19 Vaccine Uptake And Its Associated Factors among general population In Basmaia City in Baghdad 2022</a>
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<li><strong>Spatial and Temporal Origin of The Third SARS-Cov-2 Outbreak in Taiwan</strong> -
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Since the first report of SARS-CoV-2 in December 2019, Taiwan has gone through three local outbreaks. Unlike the first two outbreaks, the spatial and temporal origin of the third outbreak (April 20 to November 5, 2021) is still unclear. We assembled and analyzed a data set of more than 6,000 SARS-CoV-2 genomes, including 300 from Taiwan and 5812 related sequences downloaded from GISAID as of 2021/12/08. We found that the third outbreak in Taiwan was caused by a single virus lineage belonging to Alpha (B.1.1.7) strain. This lineage, T-III (the third outbreak in Taiwan), carries a distinct genetic fingerprint, consisting of spike M1237I (S-M1237I) and three silent mutations, C5812T, C15895T, and T27869C. The T-III is closest to the sequences derived from Turkey on February 8, 2021. The estimated age of the most recent common ancestor (TMRCA) of T-III is March 23, 2021 (95% highest posterior density [HPD] February 24 - April 13, 2021), almost one month before the first three confirmed cases on April 20, 2021. The effective population size of the T-III showed approximately 20-fold increase after the onset of the outbreak and reached a plateau in early June 2021. Our results reconcile several unresolved observations, including the occurrence of two infection clusters at the same time without traceable connection and several airline pilots who were PCR negative but serum IgM-/IgG+ for SARS-CoV-2 in late April. Therefore, in contrast to the general notion that the third SARS-CoV-2 outbreak in Taiwan was sparked by two imported cases from USA on April 20, 2021, which, in turn, was caused by the partial relaxation of entry quarantine measures in early April 2021, our comprehensive analyses demonstrated that the outbreak was most likely originated from Europe in February 2021.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.04.498645v3" target="_blank">Spatial and Temporal Origin of The Third SARS-Cov-2 Outbreak in Taiwan</a>
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<li><strong>A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases</strong> -
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Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAM) to pulmonary diseases remains poorly understood due to difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, i.e., Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (GM-CSF, TGF-{beta}, and IL-10) that facilitate the conversion of blood-obtained monocytes to an AM-Like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function, and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.05.535806v1" target="_blank">A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases</a>
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<li><strong>The Rous sarcoma virus Gag polyprotein forms biomolecular condensates driven by intrinsically-disordered regions</strong> -
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Biomolecular condensates (BMCs) play important roles in cellular structures including transcription factories, splicing speckles, and nucleoli. BMCs bring together proteins and other macromolecules, selectively concentrating them so that specific reactions can occur without interference from the surrounding environment. BMCs are often made up of proteins that contain intrinsically disordered regions (IDRs), form phase-separated spherical puncta, form liquid-like droplets that undergo fusion and fission, contain molecules that are mobile, and are disrupted with phase-dissolving drugs such as 1,6-hexanediol. In addition to cellular proteins, many viruses, including influenza A, SARS-CoV-2, and human immunodeficiency virus type 1 (HIV-1) encode proteins that undergo phase separation and rely on BMC formation for replication. In prior studies of the retrovirus Rous sarcoma virus (RSV), we observed that the Gag protein forms discrete spherical puncta in the nucleus, cytoplasm, and at the plasma membrane that co-localize with viral RNA and host factors, raising the possibility that RSV Gag forms BMCs that participate in the virion intracellular assembly pathway. In our current studies, we found that Gag contains IDRs in the N-terminal (MAp2p10) and C-terminal (NC) regions of the protein and fulfills many criteria of BMCs. Although the role of BMC formation in RSV assembly requires further study, our results suggest the biophysical properties of condensates are required for the formation of Gag complexes in the nucleus and the cohesion of these complexes as they traffic through the nuclear pore, into the cytoplasm, and to the plasma membrane, where the final assembly and release of virus particles occurs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.07.536043v1" target="_blank">The Rous sarcoma virus Gag polyprotein forms biomolecular condensates driven by intrinsically-disordered regions</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>A Nasal Treatment for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Optate; Drug: Placebo<br/><b>Sponsor</b>: Indiana University<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>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Chinese Herb; Diagnostic Test: Placebo<br/><b>Sponsor</b>: Chinese University of Hong Kong<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>Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants</strong> - <b>Condition</b>: COVID19 Testing<br/><b>Interventions</b>: Behavioral: FABI tailored COVID-19 testing pamphlet; Behavioral: Standard COVID-19 home-based test kit<br/><b>Sponsors</b>: Texas Woman’s University; National Institutes of Health (NIH)<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>Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Complementary self-help strategies in addition to treatment as usual; Other: Treatment as usual<br/><b>Sponsor</b>: Universität Duisburg-Essen<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>A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: PF-07817883; Drug: Placebo<br/><b>Sponsor</b>: Pfizer<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>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: usual care and follow-up by a nurse; Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>: Centre Hospitalier Universitaire de Saint Etienne<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>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: conventional western medicine treatment; Drug: Dexamethasone oral tablet; Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>: China-Japan Friendship 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>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsors</b>: First Affiliated Hospital of Wenzhou Medical University; REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., 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>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>: COVID-19; Diagnostic Test<br/><b>Intervention</b>: Device: Lollipop<br/><b>Sponsor</b>: University of Wisconsin, Madison<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>Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial</strong> - <b>Conditions</b>: Healthy; COVID-19; Distress, Emotional<br/><b>Interventions</b>: Behavioral: RASMUS Resilience Training; Behavioral: Progressive Muscle Relaxation<br/><b>Sponsor</b>: Medical University Innsbruck<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>Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms</strong> - <b>Condition</b>: Long Covid19<br/><b>Interventions</b>: Drug: Testofen; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: RDC Clinical Pty Ltd<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>Care for Veterans Post-COVID</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Concordant Care Training; Behavioral: Education Packet Training<br/><b>Sponsor</b>: VA Office of Research and Development<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>Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals</strong> - <b>Conditions</b>: Infectious Disease; COVID-19<br/><b>Interventions</b>: Biological: RVM-V001 30 µg; Biological: RVM-V002 30 µg; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration<br/><b>Sponsor</b>: RVAC Medicines (US), Inc.<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>HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 Nasal Spray; Drug: Placebo<br/><b>Sponsor</b>: Huahui Health<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>Addressing Vaccine Acceptance in Carceral Settings Through Community Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: ADVANCE Steering Committee interventions<br/><b>Sponsors</b>: Yale University; National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>L-Tartaric Acid Inhibits Diminazene-induced Vasorelaxation in Isolated Rat Aorta</strong> - CONCLUSION: This investigation provides important experimental evidence of the efficacy of L-tartaric acid in inhibiting diminazene-induced vasorelaxation.</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>Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19</strong> - Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice. 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were predicted, which were…</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>Discovery and characterization of the covalent SARS-CoV-2 3CL<sup>pro</sup> inhibitors from Ginkgo biloba extract via integrating chemoproteomic and biochemical approaches</strong> - CONCLUSION: Collectively, GBE50 and some constituents in this herbal product could strongly inhibit SARS-CoV-2 3CL^(pro) in dose- and time-dependent manner. Gallocatechin and sciadopitysin were identified as potent SARS-CoV-2 3CL^(pro) inhibitors, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.</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>Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral…</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>Neurological damages in COVID-19 patients: Mechanisms and preventive interventions</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19) which led to neurological damage and increased mortality worldwide in its second and third waves. It is associated with systemic inflammation, myocardial infarction, neurological illness including ischemic strokes (e.g., cardiac and cerebral ischemia), and even death through multi-organ failure. At the early stage, the virus infects the lung epithelial cells and is slowly…</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 Unexpected Protective Role of Thrombosis in Sepsis-Induced Inflammatory Lung Injury Via Endothelial Alox15</strong> - CONCLUSION: We have demonstrated that moderate levels of thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of Alox5 inhibits severe pulmonary thrombosis-induced increase of ALI. Thus, activation of ALOX15 signaling represents a promising therapeutic strategy for treatment of ARDS, especially in sub-populations of patients with thrombocytopenia and/or severe pulmonary thrombosis.</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>Massively Parallel Profiling of RNA-targeting CRISPR-Cas13d</strong> - Type VI CRISPR enzymes cleave target RNAs and are widely used for gene regulation, RNA tracking, and diagnostics. However, a systematic understanding of their RNA binding specificity and cleavage activation is lacking. Here, we describe RNA c hip- h ybridized a ssociation- m apping p latform (RNA-CHAMP), a massively parallel platform that repurposes next-generation DNA sequencing chips to measure the binding affinity for over 10,000 RNA targets containing structural perturbations, mismatches,…</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>Immune and ionic mechanisms mediating the effect of dexamethasone in severe COVID-19</strong> - CONCLUSION: Our findings suggest that dexamethasone attenuates inflammatory cytokine release via Kv1.3 suppression, and this mechanism contributes to dexamethasone-mediated immunosuppression in severe COVID-19.</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>Transporter Inhibition Profile for the Antivirals Tilorone, Quinacrine and Pyronaridine</strong> - Pyronaridine, tilorone and quinacrine are cationic molecules that have in vitro activity against Ebola, SARS-CoV-2 and other viruses. All three molecules have also demonstrated in vivo activity against Ebola in mice, while pyronaridine showed in vivo efficacy against SARS-CoV-2 in mice. We have recently tested these molecules and other antivirals against human organic cation transporters (OCTs) and apical multidrug and toxin extruders (MATEs). Quinacrine was found to be an inhibitor of OCT2,…</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 therapeutic effect and mechanism of parthenolide in skeletal disease, cancers, and cytokine storm</strong> - Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic…</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>Immune-mediated liver injury following COVID-19 vaccination</strong> - Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like…</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>Happily Distant or Bitter Medicine? The Impact of Social Distancing Preferences, Behavior, and Emotional Costs on Subjective Wellbeing During the Epidemic</strong> - To inhibit the spread of COVID-19 Public health officials stress, and governments often require, restrictions on social interaction (“social distancing”). While the medical benefits are clear, important questions remain about these measures’ downsides: How bitter is this medicine? Ten large non-probability internet-based surveys between April and November 2020, weighted statistically to reflect the US population in age, education, and religious background and excluding respondents who even…</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-alpha reductase inhibitors use in prostatic disease and beyond</strong> - 5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology…</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>Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions</strong> - SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant…</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>Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection</strong> - Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards…</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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