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188 lines
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<title>05 November, 2022</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>Managing Information and Planning for Health Charities’ Participation</strong> -
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<div>
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This research aims to investigate managing information and planning for the participation of health charities. With the Covid-19 outbreak, it was important to use information systems to optimize health management. The correct processing of information is the basis for better use of health charities’ participation. Using the snowball technique, and semi-structured interviews, 47 experts and non-experts in Fars province were asked for their opinions. Next, based on the fuzzy network analysis, important factors were prioritized. Four categories and 8 important criteria were identified. To prioritize the effective aspects of the participation of health charities in Fars province, a network analysis technique was used via MATLAB software. Strategy and programs with a normal weight of 0.34 showed the highest priority. Research and education with a normal weight of 0.26 received the second priority. Laws and regulations with a normal weight of 0.24 were placed as the third priority. Based on the obtained results, creating strategy and planning, training and building cultural in this field, ease of rules and regulations as well as planning of financial resources play an important role in managing the participation of health donors. With precise planning of health programs, donors see the transparency of decisions. They check the part that needs financing and equipment completion. Because the quality of plans and programs, effectiveness and efficiency of strategies, and the quality of results depend on the decisions made by donors.
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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://osf.io/kd39r/" target="_blank">Managing Information and Planning for Health Charities’ Participation</a>
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</div></li>
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<li><strong>Screening COVID-19 by Swaasa AI Platform using cough sounds: A cross-sectional study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The Advent of Artificial Intelligence (AI) has led to the use of auditory data for detecting various diseases, including COVID-19. SARS-CoV-2 infection has claimed more than 6 million lives till date and hence, needs a robust screening technique to control the disease spread. In the present study we developed and validated the Swaasa AI platform for screening and prioritizing COVID-19 patients based on the signature cough sound and the symptoms presented by the subjects. The cough data records collected from 234 COVID-19 suspects were subjected to validate the convolutional neural network (CNN) architecture and tabular features-based algorithm. The likelihood of the disease was predicted by combining the final output obtained from both the models. In the clinical validation phase, Swaasa was found to be 75.54% accurate in detecting the likely presence of COVID-19 with 95.45% sensitivity and 73.46% specificity. The pilot testing of Swaasa was carried out on 183 presumptive COVID subjects, out of which 82 subjects were found to be positive for the disease by Swaasa. Among them, 58 subjects were truly COVID-19 positive, which corresponds to a Positive Predictive Value of 70.73%. The currently available rapid screening methods are very costly and require technical expertise, therefore a cost effective, remote monitoring tool would be very beneficial for preliminary screening of the potential COVID-19 subject.
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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/10.1101/2022.11.02.22281821v1" target="_blank">Screening COVID-19 by Swaasa AI Platform using cough sounds: A cross-sectional study</a>
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</div></li>
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<li><strong>Rapid onset of chronic urticaria after Moderna COVID-19 booster vaccine</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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A substantial number of patients with newly onset of chronic urticaria was observed rapidly after the booster vaccine against COVID-19. This observation was unprecedented compared to the primary series of vaccination. To address this concern, we initiated an online observational study with the help of local allergists. We found a striking association between the booster dose, the Moderna vaccine, and the new onset of chronic urticaria within the following 10 days. These data were confirmed when reviewing all cases of CSU related to COVID-19 vaccination reported to Swissmedic, the Swiss regulatory agency. These data should not discourage patients from being vaccinated, as this vaccination campaign has been instrumental in reducing COVID-19 burden and preventing millions of deaths. Yet, there is an urgent need to establish appropriate guidelines and monitor this adverse event more closely, considering that a fourth dose is currently being administered.
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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/10.1101/2022.11.03.22281730v1" target="_blank">Rapid onset of chronic urticaria after Moderna COVID-19 booster vaccine</a>
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</div></li>
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<li><strong>Emotion and Anxiety Interact to Bias Spatial Attention</strong> -
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<div>
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Emotional expressions are an evolutionarily conserved means of social communication and are essential for social interactions. It is important to understand how anxious individuals perceive their social environments, including emotional expressions, especially with the rising prevalence of anxiety during the COVID-19 pandemic. Anxiety is often associated with an attentional bias for threat-related stimuli, such as angry faces. Yet the mechanisms by which anxiety enhances or impairs two key components of spatial attention—attentional capture and attentional disengagement—to emotional expressions are still unclear. Moreover, positive valence is often ignored in studies of threat-related attention and anxiety, despite high occurrence of happy faces during everyday social interaction. Here, we investigated the relationship between anxiety, emotional valence, and spatial attention in 574 participants across two preregistered studies. We found that happy faces capture attention more quickly than angry faces during the visual search experiment and found delayed disengagement from both angry and happy faces over neutral faces during the spatial cueing experiment. We also show that anxiety has a distinct impact on both attentional capture and disengagement of emotional faces. Together our findings highlight the role of positively valenced stimuli in attracting and holding attention and suggest that anxiety is a critical factor modulating spatial attention to emotional stimuli.
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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://osf.io/qcp34/" target="_blank">Emotion and Anxiety Interact to Bias Spatial Attention</a>
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</div></li>
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<li><strong>Unsupervised clustering of SARS-CoV-2 positive hospitalized patients identifies six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Defining the molecular mechanisms of novel emerging diseases like COVID-19 is crucial to identify treatable traits to improve patient care. To circumvent a priori bias and the lack of in-depth knowledge of a new disease, we opted for an unsupervised approach, using the detailed circulating proteome, as measured by 4985 aptamers (SOMAmers), of 731 SARS-CoV-2 PCR-positive hospitalized participants to Biobanque québécoise de la COVID-19 (BQC19). The consensus clustering identified six endophenotypes (EPs) present in this cohort, with varying degrees of disease severity. One endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death. Clinical features of this endophenotype, showed increased levels of C-reactive protein, D-dimers, elevated neutrophils, and depleted lymphocytes. Moreover, metabolomic analysis supported a role for immunothrombosis in severe COVID-19 ARDS. Furthermore, the approach enabled the identification of Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling as features of the molecular pathways associated with severe COVID-19. Finally, this information was sufficient to train an accurate predictive model solely based on clinical laboratory measurements, suggesting the use of blood markers as surrogates for generalizing these EPs to new patients and automating identification of high-risk groups in the clinic.
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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/10.1101/2022.11.02.22281834v1" target="_blank">Unsupervised clustering of SARS-CoV-2 positive hospitalized patients identifies six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome</a>
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</div></li>
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<li><strong>Prior infections and effectiveness of SARS-CoV-2 vaccine in test-negative study: A systematic review and meta-analysis</strong> -
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<div>
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Background: Prior infection with SARS-CoV-2 can provide protection against infection and severe COVID-19. In settings with high pre-existing immunity, vaccine effectiveness (VE) should decrease with higher levels of immunity among unvaccinated individuals. Here, we conducted a systematic review and meta-analysis to understand the influence of prior infection on VE. Methods: We included test-negative design (TND) studies that examined VE against infection or severe disease (hospitalization, ICU admission, or death) for primary vaccination series. To determine the impact of prior infections on VE estimates, we compared studies that excluded or included people with prior COVID-19 infection. We also compared VE estimates by the cumulative incidence of cases before the start of and incidence rates during each study in the study locations, as further measures of prior infections in the community. Findings: We identified 67 studies that met inclusion criteria. Pooled VE among studies that included people with prior COVID-19 infection was lower against infection (pooled VE: 77%; 95% confidence interval (CI): 72%, 81%) and severe disease (pooled VE: 86%; 95% CI: 83%, 89%), compared with studies that excluded people with prior COVID-19 infection (pooled VE against infection: 87%; 95% CI: 85%, 89%; pooled VE against severe disease: 93%; 95% CI: 91%, 95%). There was a negative correlation between the cumulative incidence of cases before the start of the study and VE estimates against infection (spearman correlation (ρ) = -0.32; 95% CI: -0.45, -0.18) and severe disease (ρ = -0.49; 95% CI: -0.64, -0.30). There was also a negative correlation between the incidence rates of cases during the study period and VE estimates against infection (ρ = -0.48; 95% CI: -0.59, -0.34) and severe disease (ρ = -0.42; 95% CI: -0.58, -0.23). Interpretation: Based on a review of published VE estimates we found clear empirical evidence that higher levels of pre-existing immunity in a population were associated with lower VE estimates. Excluding previously infected individuals from VE studies may result in higher VE estimates with limited generalisability to the wider population. Prior infections should be treated as confounder and effect modificatory when the policies were targeted to whole population or stratified by infection history, respectively.
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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/10.1101/2022.11.03.22281925v1" target="_blank">Prior infections and effectiveness of SARS-CoV-2 vaccine in test-negative study: A systematic review and meta-analysis</a>
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</div></li>
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<li><strong>Estimating the gendered impact of COVID-19</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The extent of gendered COVID-19 impact remains undetermined for the lack of sex-disaggregated data. The prevailing view puts males nearly twice as impacted as females. Globally, access to resources and their usage are gendered- mostly favoring males. Gender gaps widen during natural/man-made calamities and pandemics. Modeling estimates of impact for top 70 countries reporting >300 sex-disaggregated COVID-19 deaths (>80% of total), indicates average mortality sex (male:female) ratio (COVID-MSR) of 1.37±0.30 (95% confidence interval:1.30-1.44; range:0.85-2.47) against prevalent pre-pandemic MSR of 1.79±0.41 (1.70-1.89; range:0.93-2.99). Contrary to the prevailing view, widened gender gaps globally increased female mortality by 19.57±21.16% (14.62%-24.88%; range: -22.46 to +68.50%) causing an estimated 22.03% excess deaths (360 thousand by 30 December 2021). Identification of factors favoring gendered impacts is needed for equitable pandemic management.
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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/10.1101/2022.11.02.22276012v1" target="_blank">Estimating the gendered impact of COVID-19</a>
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</div></li>
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<li><strong>Evaluation of antibody kinetics and durability in health subjects vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China</strong> -
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<div>
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Background: Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed. Methods: We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests. Results: Our results revealed that binding antibody IgM peaked 14-28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The NAb inhibition rate subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89) to 17.8% (16/90). Conclusions: Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The homologous booster slightly increased antibody responses to the Delta and Omicron variants; therefore, the optimization of booster procedures is vital. Funding: Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation.
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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.biorxiv.org/content/10.1101/2022.11.03.515011v1" target="_blank">Evaluation of antibody kinetics and durability in health subjects vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China</a>
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<li><strong>The COVID-19 pandemic sparked off a large-scale outbreak of carbapenem-resistant Acinetobacter baumannii from the endemic strains of an Italian hospital</strong> -
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<i>Acinetobacter baumannii</i> is an insidious nosocomial pathogen that poses a serious threat due to the rise of incidence of multidrug resistant (MDR) strains. During the COVID-19 pandemic, MDR <i>A. baumannii</i> clones have caused several outbreaks worldwide. Here we describe a detailed investigation of an MDR <i>A. baumannii</i> outbreak that occurred at Fondazione IRCCS Policlinico San Matteo (Pavia, Italy). A total of 96 <i>A. baumannii</i> strains, isolated between January and July 2020 from 41 inpatients (both SARS-CoV-2 positive and negative) in different wards, were characterized by phenotypic and genomic analyses combining Illumina and Nanopore sequencing. Antibiotic susceptibility testing revealed that all isolates were resistant to carbapenems and the sequence analysis attributed this to the carbapenemase gene <i>bla</i><sub>OXA-23</sub>. Screening of virulence factors unveiled that all strains carried determinants for biofilm formation, while plasmid analysis revealed the presence of two plasmids, one of which was a ∼100kbp long and encoded a phage sequence. A core genome-based phylogeny was inferred to integrate outbreak strain genomes with background genomes from public databases and the local surveillance program. All strains belonged to the globally disseminated ST2 clone and were divided into two main clades. Strains from the outbreak clustered with surveillance isolates from 2019, suggesting that the outbreak was caused by two strains that were already circulating in the hospital before the start of the pandemic. The intensive spread of <i>A. baumannii</i> in the hospital was enhanced by the extreme emergency situation of the first COVID-19 pandemic wave that resulted in minor attention to infection prevention and control practices.
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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/10.1101/2022.06.28.22276851v2" target="_blank">The COVID-19 pandemic sparked off a large-scale outbreak of carbapenem-resistant Acinetobacter baumannii from the endemic strains of an Italian hospital</a>
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</div></li>
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<li><strong>Population-based sero-epidemiological estimates of real-world vaccine effectiveness against Omicron infection in an infection-naive population, Hong Kong, January to July 2022</strong> -
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The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. While current vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections (i.e. irrespective of symptoms) remains sparse. We addressed this knowledge-gap using a community-wide serosurvey with 5,310 subjects by estimating how vaccination histories modulated risk of infection in Hong Kong (which was largely infection naive) during a large wave of Omicron epidemic during January-July 2022. We estimated that Omicron infected 45% (41-48%) of the Hong Kong population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection (VE of 47% (95% credible interval 34-68%) and 70% (43-99%) for three and four doses of BNT162b2 respectively; VE of 31% (1-73%) and 59% (10-99%) for three and four doses of CoronaVac respectively) seven days after vaccination, but protection waned with half-lives of 15 (3-47) weeks for BNT162b2 and 5 (1-37) weeks for CoronaVac. Our findings suggest that booster vaccination can temporarily enhance population immunity ahead of anticipated waves of infections.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.01.22281746v1" target="_blank">Population-based sero-epidemiological estimates of real-world vaccine effectiveness against Omicron infection in an infection-naive population, Hong Kong, January to July 2022</a>
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</div></li>
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<li><strong>Antiviral effect of candies containing persimmon-derived tannin against SARS-CoV-2 delta strain</strong> -
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<div>
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Inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the mouth has the potential to reduce the spread of coronavirus disease 2019 (COVID-19) because the virus is readily transmitted by dispersed saliva. Persimmon-derived tannin has strong antioxidant and antimicrobial activity owing to its strong adhesiveness to proteins, and it also exhibited antiviral effects against non-variant and alpha variant SARS-CoV-2 in our previous study. In this report, we first demonstrated the antiviral effects of persimmon-derived tannin against the delta variant of SARS-CoV-2 in vitro via the plaque assay method. We then examined the effects of candy containing persimmon-derived tannin. Our plaque assay results show that saliva samples provided by healthy volunteers while they were eating tannin-containing candy remarkably suppressed the virus titers of the SARS-CoV-2 delta variant. In addition, we found that the SARS-CoV-2 viral load in saliva from patients with COVID-19 that was collected immediately after they had eaten the tannin-containing candy was below the level of detection by PCR for SARS-CoV-2. These data suggest that adding persimmon-derived tannin to candy and holding such candy in the mouth is an effective method by which to inactivate the SARS-CoV-2 in saliva, and the application of this approach has potential for inhibiting the transmission of COVID-19.
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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.biorxiv.org/content/10.1101/2022.10.31.513793v1" target="_blank">Antiviral effect of candies containing persimmon-derived tannin against SARS-CoV-2 delta strain</a>
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<li><strong>SOCIAL COMMUNICATION PATHWAYS TO COVID-19 VACCINE SIDE-EFFECT EXPECTATIONS AND EXPERIENCE</strong> -
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<div>
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Objective: Negative beliefs about medication and vaccine side-effects can spread rapidly through social communication. This has been recently documented with the potential side-effects from the COVID-19 vaccines. We tested if pre-vaccination social communications about side-effects from personal acquaintances, news reports, and social media predict post-vaccination side-effect experiences. Further, as previous research suggests that side-effects can be exacerbated by negative expectations, we assessed if personal expectations mediate the relationships between social communication and side-effect experience. Method: In a prospective longitudinal survey (N=551), COVID-19 vaccine side-effect information from three sources—social media posts, news reports, and first-hand accounts from personal acquaintances—as well as side-effect expectations, were self-reported pre-vaccination. Vaccination side-effect experience was assessed post-vaccination. Results: In multivariate regression analyses, the number of pre-vaccination social media post views (β = .17) and impressions of severity conveyed from personal acquaintances (β = .42) significantly predicted an increase in pre-vaccination side-effect expectations, and the same variables (βs = .11, .14, respectively) predicted post-vaccination side-effect experiences. Moreover, pre-vaccination side-effect expectations fully mediated the relationship between both sources of social communication and experienced side-effects from a COVID-19 vaccination. Conclusions: This study identifies links between personal acquaintance and social media communications and vaccine side-effect experiences and provides evidence that pre-vaccination expectations account for these relationships. The results suggest that modifying side-effect expectations through these channels may change the side-effects following a COVID-19 vaccination as well as other publicly discussed vaccinations and medications.
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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://psyarxiv.com/e2bfv/" target="_blank">SOCIAL COMMUNICATION PATHWAYS TO COVID-19 VACCINE SIDE-EFFECT EXPECTATIONS AND EXPERIENCE</a>
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<li><strong>Spatial Optimization to Improve COVID-19 Vaccine Allocation</strong> -
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Early distribution of COVID-19 vaccines was largely driven by population size and did not account for COVID-19 prevalence nor location characteristics. In this study, we applied an optimization framework to identify distribution strategies that would have lowered COVID-19 related morbidity and mortality. Optimized vaccine allocation would have decreased case incidence by 8% with 5,926 fewer COVID-19 cases, 106 fewer deaths, and 4.5 million dollars in healthcare cost saved during the first half of 2021. As COVID-19 variants continue to be identified, and the likelihood of future pandemics remains high, application of resource optimization should be a priority for policy makers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.30.22281737v1" target="_blank">Spatial Optimization to Improve COVID-19 Vaccine Allocation</a>
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</div></li>
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<li><strong>Distinct phenotype of SARS-CoV-2 Omicron BA.1 in human primary cells but no increased host range in cell lines of putative mammalian reservoir species</strong> -
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<div>
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SARS-CoV-2’s genetic plasticity has led to several variants of concern (VOCs). Here we studied replicative capacity for seven SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, and Omicron BA.1) in primary reconstituted airway epithelia (HAE) and lung-derived cell lines. Furthermore, to investigate the host range of Delta and Omicron compared to ancestral SARS-CoV-2, we assessed replication in 17 cell lines from 11 non-primate mammalian species, including bats, rodents, insectivores and carnivores. Only Omicron’s phenotype differed in vitro, with rapid but short replication and efficient production of infectious virus in nasal HAEs, in contrast to other VOCs, but not in lung cell lines. No increased infection efficiency for other species was observed, but Delta and Omicron infection efficiency was increased in A549 cells. Notably replication in A549 and Calu3 cells was lower than in nasal HAE. Our results suggest better adaptation of VOCs towards humans, without an extended host range.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.04.510352v2" target="_blank">Distinct phenotype of SARS-CoV-2 Omicron BA.1 in human primary cells but no increased host range in cell lines of putative mammalian reservoir species</a>
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<li><strong>Reversal of increases in methadone distribution for opioid use disorder in the US during the COVID-19 pandemic</strong> -
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Introduction: This study aimed to investigate US patterns of distribution of methadone for OUD from 2010 to 2021 in order to identify potential obstacles in the mitigation of the opioid epidemic. Methods: The number of Opioid Treatment Programs (OTP) per state, and the weight of methadone in grams distributed to OTPs per state, were obtained from the US Drug Enforcement Administration9s Automated Reports and Consolidated Ordering System. Methadone was adjusted for state population and compared across all fifty states and Washington DC from 2010 to 2021. Medicaid9s State Drug Utilization Data database was utilized to determine methadone prescriptions for all fifty states and DC. This was corrected for the number of Medicaid enrollees in each state. Results: The overall distribution of methadone to OTPs significantly increased from 2010 to 2020 (+61.00%) and from 2015 to 2020 (+26.22%) (P < 0.0001). The states with the highest percent change from 2010 to 2020 were Montana (+897.02%), Alaska (+421.11%), and Vermont (+353.67%). In contrast to 2010 and 2015, 2019 (pre-COVID-19 pandemic) to 2021 (post-pandemic) showed no significant change in the US distribution of methadone to OTPs (-5.15%). From 2019 to 2021, methadone distribution in Ohio (+47.53%) significantly increased while it significantly decreased in Florida (-54.61%), New Hampshire (-52.99%), Nebraska (-47.96%), and Alabama (-44.27%) relative to the national mean. Twenty states (MD, VT, NM, ME, GA, NC, NY, NH, UT, OK, SC, MT, WA, AL, TX, MN, FL, SD, NE and MS) had fewer OTPs in 2021 relative to prior years. In 2020, 89.23% of methadone covered by Medicaid was distributed among three states (VA, MT, IA), and seven states (VA, MT, IA, WI, TN, OR, VT) distributed 98.47%. Conclusions: This investigation revealed three patterns for methadone distribution in the US: 1) increased utilization over the past decade, 2) a decline from 2019 to 2021, and 3) pronounced state level variation with some states (e.g. Wyoming) having no OTPs or Medicaid coverage. New policies are urgently needed to remove access barriers to methadone treatment in order to reduce the worsening overdose crisis in the US.
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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/10.1101/2022.03.09.22272154v2" target="_blank">Reversal of increases in methadone distribution for opioid use disorder in the US during the COVID-19 pandemic</a>
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</div></li>
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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>Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>Safety and Efficacy of Medications COVID-19</strong> - <b>Condition</b>: Severe Covid-19<br/><b>Intervention</b>: Drug: Oral bedtime melatonin<br/><b>Sponsor</b>: Hospital San Carlos, Madrid<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>Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma<br/><b>Sponsors</b>: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá<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>Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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 Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: EuCorVac-19; Biological: ChAdOx1<br/><b>Sponsor</b>: EuBiologics 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>Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Molnupiravir (Esperavir); Drug: Standard of care<br/><b>Sponsor</b>: Promomed, LLC<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>Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir/ritonavir; Drug: Standard of care<br/><b>Sponsors</b>: Promomed, LLC; Sponsor GmbH<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>Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<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>Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms</strong> - <b>Conditions</b>: Covid19; Post-acute COVID-19 Syndrome<br/><b>Interventions</b>: Other: Inspiratory + expiratory muscle training group; Other: Inspiratory + expiratory muscle training sham group; Other: Exercise training program<br/><b>Sponsors</b>: Universidad Complutense de Madrid; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid<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>Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial</strong> - <b>Conditions</b>: COVID-19; Coronavirus Infections<br/><b>Interventions</b>: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co 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>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza</strong> - <b>Conditions</b>: Influenza, Human; COVID-19<br/><b>Interventions</b>: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV<br/><b>Sponsors</b>: BioNTech SE; 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>Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Drug: ASC10; Drug: Placebo<br/><b>Sponsor</b>: Ascletis Pharmaceuticals Co., 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>A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®<br/><b>Sponsor</b>: GreenLight Biosciences, 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>Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Avacc 10; Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle; Other: Placebo<br/><b>Sponsors</b>: Intravacc B.V.; 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>The Phase Ⅱ/Ⅲ Trial of LYB001</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB001; Biological: Placebo<br/><b>Sponsor</b>: Yantai Patronus Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Recent advances in understanding spleen tyrosine kinase (SYK) in human biology and disease, with a focus on fostamatinib</strong> - Spleen tyrosine kinase (SYK) is an important regulatory molecule of signal transduction pathways involved in the pathogenesis of autoimmune diseases such as immune thrombocytopenia (ITP), and the SYK-signaling pathway has emerged as a potential target for the treatment of numerous diseases. The aim of this narrative review is to summarize the biological properties of SYK and its involvement in disease pathways, provide an update on SYK inhibitors in the treatment of ITP, and consider other…</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>Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics</strong> - CONCLUSION: The mechanism of N-0385 treatment COVID-19 was investigated by molecular docking and molecular dynamics simulation. We speculated that N-0385 may not only inhibit SARS-CoV-2 invasion directly by acting on TMPRSS2, ACE2 and DPP4, but also inhibit the immune recognition process and inflammatory response by regulating TLR7, NLRP3 and IL-10 to prevent SARS-CoV-2 invasion. Therefore, these results suggested that N-0385 may act through multiple targets to reduce SARS-CoV-2 infection 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>Bovine lactoferrin inhibits SARS-CoV-2 and SARS-CoV-1 by targeting the RdRp complex and alleviates viral infection in the hamster model</strong> - Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed to determine the components that contribute to the antiviral effects of breastmilk and explore their potential mechanism. Lactoferrin (Lf) and milk fat globule membrane (MFGM) inhibit SARS-CoV-2 related coronavirus GX_P2V and SARS-CoV-2 trVLP in vitro and block viral entry into cells. We confirmed that bovine lactoferrin (bLf) blocked the binding between human…</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>Constructing Janus Microsphere Membranes for Particulate Matter Filtration, Directional Water Vapor Transfer, and High-Efficiency Broad-Spectrum Sterilization</strong> - Commercial masks have significant drawbacks, including low water vapor transmission efficiency and limited ability to inhibit harmful microorganisms, whereas in this contribution, a series of Janus microsphere membranes are developed with hierarchical structures by quenching and crystallizing 12-hydroxystearic acid and halicin layer-by-layer on a polypropylene non-woven fabric, laminating them with hydrophilic cotton fibers in a one-pot process, and further demonstrate the potential of this…</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>Management of Severe and Critical COVID-19 Infection with Immunotherapies</strong> - Following the reduction in mortality demonstrated by dexamethasone treatment in severe COVID-19, many targeted immunotherapies have been investigated. Thus far, inhibition of IL-6 and JAK pathways have the most robust data and have been granted Emergency Use Authorization for treatment of severe disease. However, it must be noted that critically ill patients comprised a relatively small proportion of most of the trials of COVID-19 therapeutics, despite bearing a disproportionate burden of…</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>Topoisomerase 3b is dispensable for replication of a positive-sense RNA virus–murine coronavirus</strong> - A recent study demonstrated that a DNA-RNA dual-activity topoisomerase complex, TOP3B-TDRD3, is required for normal replication of positive-sense RNA viruses, including several human flaviviruses and coronaviruses; and the authors proposed that TOP3B is a target of antiviral drugs. Here we examined this hypothesis by investigating whether inactivation of Top3b can inhibit the replication of a mouse coronavirus, MHV, using cell lines and mice that are inactivated of Top3b or Tdrd3. We found that…</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 urgency of strengthening health information to support public perception and involvement in the COVID-19 vaccine</strong> - CONCLUSIONS: Strengthening positive information can alter the sense of community vulnerability, making it a driving force for participation in the COVID-19 vaccine campaign. This finding is an appropriate strategy to expand the reach and resolve public doubts about accepting the vaccine.</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>S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters</strong> - In parallel with vaccination, oral antiviral agents are highly anticipated to act as countermeasures for the treatment of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oral antiviral medication demands not only high antiviral activity, but also target specificity, favorable oral bioavailability, and high metabolic stability. Although a large number of compounds have been identified as potential inhibitors of SARS-CoV-2…</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 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir</strong> - The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was rapidly declared a pandemic by the World Health Organization (WHO). Early clinical symptomatology focused mainly on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are now well-documented. To experimentally determine whether SARS-CoV-2 could replicate in and affect human brain cells, we infected iPSC-derived…</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>Ubiquitination of SARS-CoV-2 ORF7a Prevents Cell Death Induced by Recruiting BclXL To Activate ER Stress</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has emerged in the last 2 years. The accessory protein ORF7a has been proposed as an immunomodulating factor that can cause dramatic inflammatory responses, but it is unknown how ORF7a interacts with host cells. We show that ORF7a induces cell apoptosis by recruiting the prosurvival factor BclXL to the endoplasmic reticulum (ER) via the exposed C-terminal residues…</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><em>In silico</em> approaches and <em>in vitro</em> assays identify a coumarin derivative as antiviral potential against SARS-CoV-2</strong> - COVID-19, a disease caused by SARS-CoV-2, was declared a pandemic in 2020 and created a global crisis in health systems, with more than 545 million confirmed cases and 6.33 million deaths. In this sense, this work aims to identify possible inhibitors of the SARS-CoV-2 RdRp enzyme using in silico approaches. RdRp is a crucial enzyme in the replication and assembly cycle of new viral particles and a critical pharmacological target in the treatment of COVID-19. We performed a virtual screening…</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>Elucidating Design Principles for Engineering Cell-Derived Vesicles to Inhibit SARS-CoV-2 Infection</strong> - No abstract</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>Inhalation of Low Molecular Weight Heparins as Prophylaxis against SARS-CoV-2</strong> - New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple prophylactic agent to prevent infection. Low molecular weight heparins (LMWH) are potent inhibitors of SARS-CoV-2 binding and infection in vitro. The airways are a major route for infection and therefore inhaled LMWH could be a prophylactic treatment against SARS-CoV-2. We investigated the efficacy of in vivo inhalation of LMWH in humans to prevent SARS-CoV-2 attachment to nasal epithelial cells in…</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>Lupus anticoagulant-hypoprothrombinemia syndrome with severe bleeding diathesis after coronavirus disease 2019: a case report</strong> - Acquired antibodies against factor II (prothrombin) are rare and most commonly associated with severe liver disease or vitamin K antagonist treatment. In very rare cases, these antibodies and associated hypoprothrombinemia are found in patients with lupus anticoagulant (LAC), an antiphospholipid antibody that inhibits phospholipid-dependent coagulation tests. This uncommon entity, called lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), may cause both severe, life-threatening bleeding…</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><em>HLA-C</em> dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections</strong> - One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients’ upper airways cells, the first barrier against respiratory infections and the first cells…</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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