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188 lines
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<title>17 December, 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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<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>Risk of Infection Due to Airborne Virus in Classroom Environments Lacking Mechanical Ventilation</strong> -
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The COVID-19 pandemic highlighted the role of indoor environments on disease transmission. Enclosed spaces where pathogen-laden aerosols accumulate was strongly linked to increased transmission events. Here we employ a surrogate non-pathogenic virus, the bacteriophage phi6, to interrogate aerosol transmission in classroom environments that do not have any natural or mechanical ventilation in order to determine how effectively aerosols facilitate new infections. We find that virus-laden aerosols establish new infections over all distances tested within minutes and that the time of exposure did not change transmission rate. We further find that humidity, but not temperature nor a UV-based disinfection device, significantly impacted transmission rates. Our data suggest that, even without mechanical ventilation, relative humidity remains a highly effective mitigation strategy while UV air treatment did not.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.15.520644v1" target="_blank">Risk of Infection Due to Airborne Virus in Classroom Environments Lacking Mechanical Ventilation</a>
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<li><strong>Cholesterol and ceramide facilitate SARS-CoV-2 Spike protein-mediated membrane fusion</strong> -
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SARS-CoV-2 entry into host cells is mediated by the Spike (S) protein of the viral envelope. The S protein is composed of two subunits: S1 that induces binding to the host cell via its interaction with the ACE2 receptor of the cell surface and S2 that triggers fusion between viral and cellular membranes. Fusion by S2 depends on its heptad repeat domains that bring membranes close together, and its fusion peptide (FP) that interacts with and perturb the membrane structure to trigger fusion. Recent studies suggest that cholesterol and ceramide lipids from the cell surface may facilitate SARS-CoV-2 entry into host cells, but their exact mode of action remains unknown. We have used a combination of in vitro liposome-liposome and in situ cell-cell fusion assays to study the lipid determinants of S-mediated membrane fusion. We found that cholesterol and ceramide both facilitated fusion, suggesting that targeting lipids could be effective against SARS-CoV-2. As proof of concept, we examined the effect of chlorpromazine (CPZ), an antipsychotic drug known to perturb membrane structure. We found that CPZ inhibited S-mediated membrane fusion and thus potentially SARS-CoV-2 entry.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.16.520599v1" target="_blank">Cholesterol and ceramide facilitate SARS-CoV-2 Spike protein-mediated membrane fusion</a>
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<li><strong>Surface-modified measles vaccines encoding oligomeric, fusion-stabilized SARS-CoV-2 spike glycoproteins bypass measles seropositivity, boosting neutralizing antibody responses to omicron and historical variants.</strong> -
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Serum titers of SARS-CoV-2 neutralizing antibodies (nAb) correlate well with protection from symptomatic COVID-19, but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are life-long after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We therefore sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses. Since previous clinical testing of a live measles vaccine encoding a SARS-CoV-2 spike glycoprotein resulted in suboptimal anti-spike antibody titers, our new vectors were designed to encode prefusion-stabilized SARS-CoV-2 spike glycoproteins, trimerized via an inserted peptide domain and displayed on a dodecahedral miniferritin scaffold. Additionally, to circumvent the blunting of vaccine efficacy by preformed anti-measles antibodies, we extensively modified the measles surface glycoproteins. Comprehensive in vivo mouse testing demonstrated potent induction of high titer nAb in measles-immune mice and confirmed the significant incremental contributions to overall potency afforded by prefusion stabilization, trimerization, and miniferritin-display of the SARS-CoV-2 spike glycoprotein, and vaccine resurfacing. In animals primed and boosted with a MeV vaccine encoding the ancestral SARS-CoV-2 spike, high titer nAb responses against ancestral virus strains were only weakly cross-reactive with the omicron variant. However, in primed animals that were boosted with a MeV vaccine encoding the omicron BA.1 spike, antibody titers to both ancestral and omicron strains were robustly elevated and the passive transfer of serum from these animals protected K18-ACE2 mice from infection and morbidity after exposure to BA.1 and WA1/2020 strains. Our results demonstrate that antigen engineering can enable the development of potent measles-based SARS-CoV-2 vaccine candidates.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.16.520799v1" target="_blank">Surface-modified measles vaccines encoding oligomeric, fusion-stabilized SARS-CoV-2 spike glycoproteins bypass measles seropositivity, boosting neutralizing antibody responses to omicron and historical variants.</a>
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<li><strong>The H163A Mutation Unravels an Oxidized Conformation of the SARS-CoV-2 Main Protease and Opens a New Avenue for Anti-Viral Therapeutic Design</strong> -
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The main protease of SARS-CoV-2 (Mpro) is an important target for developing COVID-19 therapeutics. Recent work has highlighted the susceptibility of Mpro to undergo redox-associated conformational changes in response to cellular and immune-system-induced oxidation. Despite structural evidence indicating large-scale rearrangements upon oxidation, the mechanisms of conformational change and its functional consequences are poorly understood. Here, we present the crystal structure of a new Mpro point mutant (H163A) that shows an oxidized conformation with the catalytic cysteine in a disulfide bond. We hypothesize that Mpro adopts this conformation under oxidative stress to protect against over-oxidation. Our metadynamics simulations illustrated a potential mechanism by which H163 modulates this transition and suggest that this equilibrium exists in the wild-type enzyme. We show that other point mutations can also significantly shift the equilibrium towards this state by altering conformational free energies. New therapeutic strategies against SARS-CoV-2 can be explored by understanding how H163 modulates this equilibrium.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.16.520794v1" target="_blank">The H163A Mutation Unravels an Oxidized Conformation of the SARS-CoV-2 Main Protease and Opens a New Avenue for Anti-Viral Therapeutic Design</a>
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<li><strong>A bibliometric analysis of gender in microbiology collaborations</strong> -
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Women are underrepresented in senior academic positions within microbiology globally. Studies show that gender bias affects the progression of women in academia, but there is evidence that improving conscious awareness of bias can improve equity in this regard. Here we carry out a bibliometric analysis of review articles within the microbiology field to investigate the statistical associations with author gender. We analyse the publication data from 1857 review articles published between 2010 and 2022 in three leading microbiology review journals: Nature Reviews Microbiology, Trends in Microbiology, and Annual Review of Microbiology. We find a significant association between the gender of the lead author and the gender of co-authors in multi-author publications. Review articles with men lead authors have a significantly reduced proportion of women co-authors compared to reviews with women lead authors. Given the existing differences in the proportions of men and women in lead author positions, this association may have important consequences for the relative visibility of women in microbiology, along with potential negative impacts on scientific output relating to reduced collaboration diversity. We further probe associations between gender and citation metrics, acknowledgement of contributions, and publishing during the Covid-19 pandemic within microbiology reviews.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.14.520436v1" target="_blank">A bibliometric analysis of gender in microbiology collaborations</a>
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<li><strong>Molecular evolution and structural analyses of spike protein COVID-19 variants in Negeri Sembilan of peninsular Malaysia</strong> -
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The sharing of COVID-19 sequences worldwide has allowed for comprehensive and real-time analyses of COVID-19 genomic diversity at regional levels. Temporal distribution of COVID-19 variants and lineages enables better infection control, surveillance, and facilitates policy making for public health. 417 sequences extracted from all COVID-19 cases in Negeri Sembilan of peninsular Malaysia from July 2021 until May 2022 were used for this study. Phylogenomics revealed a total of 20 circulating lineages, of which seven are still circulating. The majority (60.4%) of viruses in Negeri Sembilan are of GRA lineage with strong representation from the Malaysian lineage BA.1.1 (24.7%). A time series analysis showed a change in the dominating circulating lineage from AY.79 to BA.1.1, which correlated to the relaxing of lockdowns implemented by the Malaysian government. Several Malaysian sub-lineages (BA.2.40.1, BA.2.57 and BA.2.9) have emerged from April 2022 onwards. Evolutionary mutations of the sub-lineages also gave rise to novel single nucleotide polymorphisms (SNPs) in the spike proteins. Out of the 70 SNPs isolated from all samples, in silico prediction revealed five novel SNPs that could cause functional defects to the spike protein, which are S221L, L226S, V826L, C1240F and C1243F. Structural modelling of the V826L showed that the L826 possibly confers an increase in protein flexibility within the S2 region of S protein, which supports our in silico predictions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.15.520679v1" target="_blank">Molecular evolution and structural analyses of spike protein COVID-19 variants in Negeri Sembilan of peninsular Malaysia</a>
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<li><strong>Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection</strong> -
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The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs, including recently circulating BA.4/BA.5, in both pseudovirus-based and live virus assays, and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.15.520606v1" target="_blank">Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection</a>
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<li><strong>Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis</strong> -
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The omicron variant is thought to cause less olfactory dysfunction than previous variants of SARS-CoV-2, but the reported prevalence differs greatly between populations and studies. Our systematic review and meta-analysis provide information about regional differences in prevalence as well as an estimate of the global prevalence of olfactory dysfunction based on 41 studies reporting on nearly 600,000 patients infected with the omicron variant. Our estimate of the omicron-induced prevalence of olfactory dysfunction in populations of European ancestry is 11.6%, while it is significantly lower in all other populations, at 2.9-5.4%. When ethnic differences and population sizes are taken into account, the global prevalence of omicron-induced hyposmia in adults is estimated at 5.2%. Omicron9s effect on olfaction is 3-4fold lower than that of the alpha or delta variant, according to previous meta-analyses and our analysis of studies that directly compared prevalence of olfactory dysfunction between omicron and previous variants. The profile of prevalence differences between ethnicities mirrors the results of a recent genome-wide association study that implicated a gene locus encoding an odorant-metabolizing enzyme, UDP glycosyltransferase, to be linked to the extent of COVID-related loss of smell. Our analysis is consistent with the hypothesis that this enzyme contributes to the observed population differences.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.16.22283582v1" target="_blank">Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis</a>
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<li><strong>Estimating the transmission dynamics of Omicron in Beijing, November to December 2022</strong> -
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We tracked the effective reproduction number Rt of Omicron BF.7 in Beijing in November-December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on November 1-11 (when the zero-covid interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on December 10-14 and self-reported to have been previously test-positive. After the announcement of “20 measures”, we estimated that Rt increased to 3.42 (95% CrI: 2.79-4.17) on November 18. Infection incidence peaked on December 10, and the cumulative infection attack rate was 42.5% (95% CrI: 20.3-63.9) on December 14. Surveillance programmes should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22283522v1" target="_blank">Estimating the transmission dynamics of Omicron in Beijing, November to December 2022</a>
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<li><strong>Streptococcus pneumoniae re-emerges as a cause of community-acquired pneumonia, including frequent co-infection with SARS-CoV-2, in Germany, 2021</strong> -
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<b>Background</b>: The COVID-19 pandemic and the associated containment measures had a substantial impact on pathogens causing pneumonia in adults. The objective of this study was to determine the etiology of hospitalized community-acquired pneumonia (CAP) among adults in Germany in 2021, the second year of the COVID-19 pandemic. <b>Methods</b>: Since January 2021, this on-going, prospective, population-based surveillances study enrolled adult patients with clinically and radiographically confirmed CAP at three hospitals in Thuringia, Germany, serving a population of approximately 280,000. Urine samples were collected from patients and tested for <i>S. pneumoniae</i> using the pneumococcal urinary antigen test (PUAT, BinaxNOW <i>S. pneumoniae</i>) and the proprietary serotype-specific urinary antigen detection (UAD) assays. Nasopharyngeal swabs were tested for 10 respiratory viruses by PCR. <b>Results</b>: A total of 797 patients were enrolled, of whom 760 were included in the analysis. The median age of patients with CAP was 67 years; in-hospital case-fatality rate was 8.4%. A respiratory pathogen was detected in 553 (72.8%) patients. The most common pathogen was SARS-CoV-2 (n=498, 68.2%), followed by <i>S. pneumoniae</i> (n=40, 6.4%). Serotypes contained in the 13-valent, 15-valent and 20-valent pneumococcal conjugate vaccine were detected in 42.5%, 45.0%, and 70.0% of the pneumococcal CAP cases. Between the first and second half of 2021, the proportion of CAP cases associated with <i>S. pneumoniae</i> increased from 1.1% to 5.6% in patients aged 18-59 years and from 2.5% to 12.4% in those aged ≥60 years; coinfection of SARS-CoV-2 and <i>S. pneumoniae</i> among COVID-19 patients increased from 0.7% (2/283 cases) to 6.0% (13/215) in patients aged ≥18 years, and from 1.0% (2/195) to 8.7% (11/127) in those aged ≥60 years. <b>Conclusion</b>: In Germany, the proportion of CAP cases associated with <i>S. pneumoniae</i> rebounded to a near-pandemic level in the second half of 2021 and many pneumococcal infections occurred in patients with COVID-19. Vaccination uptake against respiratory pathogens, including <i>S. pneumoniae</i>, should be strengthened.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22282988v1" target="_blank">Streptococcus pneumoniae re-emerges as a cause of community-acquired pneumonia, including frequent co-infection with SARS-CoV-2, in Germany, 2021</a>
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<li><strong>Prevalence of salivary anti-SARS-CoV-2 IgG antibodies in vaccinated children</strong> -
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Vaccination against COVID-19 has mitigated the impact of SARS-CoV-2 infection, decreasing the probability of progression to severe disease and death in vaccinated people. Parallel to the development and administration of COVID-19 vaccines, the immune response induced by the different vaccine platforms has been investigated, mainly, in the adult population. However, since the approval of the vaccines for use in pediatric individuals was a posteriori, vaccination began later in this population. This, added to the difficulty in obtaining blood samples from pediatric individuals, has led to less knowledge about the humoral immune response following vaccination in children. In this work, we analyzed the humoral response induced by vaccination in children through a non-invasive approach such as the measurement of specific salivary antibodies. Our results showed a high prevalence of specific salivary antibodies (81%), with the highest levels of antibodies being observed in those children who had three doses, a greater number of exposures and a shorter interval time between the last exposure to SARS-CoV-2 antigens and saliva collection. These results agree with those reported for the systemic humoral immune response in vaccinated adults, suggesting the administration of booster doses in children to maintain high antibody levels. Therefore, determination of salivary antibodies against SARS-CoV-2 could be a non-invasive tool for disease surveillance, vaccination follow-up and to assist vaccination strategies against COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22283480v1" target="_blank">Prevalence of salivary anti-SARS-CoV-2 IgG antibodies in vaccinated children</a>
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<li><strong>Depression and its associated factors among COVID-19 survivors in a middle income country</strong> -
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Introduction: COVID-19 survivors who have mental health issues are more likely to have a lower quality of life, reduced work productivity, social troubles, and other health issues. However, information on the mental health of COVID-19 survivors is scarce. Therefore, we aimed to determine the COVID-19 survivors9 mental health status in the form of depression and its associated factors. Methods: This was a cross-sectional study conducted in Malaysia, from July to September 2021, during a nationwide lockdown. Data was collected using an online questionnaire shared on social and news media. Socio-demographic variables, comorbidities, self-perception of health, information on the person’s acute condition during COVID-19 infection, symptoms and duration of symptoms post-COVID, and state of depression were gathered. The Patient Health Questionnaire 9 was used to assess depression. Factors associated with mild to severe depression were analysed using both univariable and multivariable logistic regression analyses. Results: A total of 732 COVID-19 survivors responded to the survey. The respondents were mainly females and of younger age (in their 20s and 30s). Two-thirds perceived themselves to be in good health. One in five reported to have experienced Long COVID. Slightly less than half (47.3%) of the respondents had mild to severe depression (total PHQ-9 score of 5 -27). In the multivariable analysis, being female (aOR: 1.68; 95% CI: 1.08,2.62), of younger age (20s – aOR: 3.26; 95% CI: 1.47, 7.25; 30s – aOR: 2.08; 95% CI: 1.05, 4.15; and 40s – aOR: 2.43; 95% CI: 1.20, 4.90; compared to those in the 50s and above), being overweight/obese (aOR: 1.83; 95% CI: 1.18, 2.83), having Long COVID (aOR: 2.45; 95% CI: 1.45, 4.16) and perceiving to have poorer health (aOR: 4.54; 95% CI: 2.89, 7.13) were associated with mild to severe depression. Conclusion: Females, younger age groups, being overweight/obese, having Long COVID and perceiving to be in poor health were factors associated with higher odds for mild to severe depression.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22283550v1" target="_blank">Depression and its associated factors among COVID-19 survivors in a middle income country</a>
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<li><strong>Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a ‘National Plan’ to reopening</strong> -
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Background In mid-2021, widespread availability of COVID-19 vaccines with demonstrated impacts on transmission promised relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden. We were asked to define vaccine coverage thresholds for transition through the stages of Australia9s 9National Plan9 to easing restrictions and reopening international borders. Methods Using available evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine vaccine coverage targets. The absence of any COVID-19 infections in many sub-national jurisdictions in Australia posed particular methodological challenges for modelling in this setting. We used a novel metric called Transmission Potential (TP) as a proxy measure of the population-level effective reproduction number. We estimated TP of the Delta variant under a range of PHSMs, test-trace-isolate-quarantine (TTIQ) efficiencies, vaccination coverage thresholds, and age-based vaccine allocation strategies. Findings We found that high coverage of vaccination across all age groups (≥ 70) combined with ongoing TTIQ and minimal PHSMs was sufficient to avoid strict lockdowns. At lesser coverage (≤ 60%) rapid case escalation risked overwhelming of the health sector and would prompt a need to reimpose strict restrictions, with substantive economic impacts in order to achieve the goals of the National Plan. Maintaining low case numbers was the most beneficial strategy for health and the economy, and at higher coverage levels (≥ 80%) further easing of restrictions was deemed possible. Interpretation These results reinforced recommendations from other modelling groups that some level of PHSMs should be continued to minimise the burden of the Delta variant following achievement of high population vaccine coverage. They directly informed easing of COVID-19 restrictions in Australia. Funding This study was supported by the Australian Government Department of Health and Ageing, and the National Health and Medical Research Council9s Centre of Research Excellence scheme (GNT1170960).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22282869v1" target="_blank">Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a ‘National Plan’ to reopening</a>
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</div></li>
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<li><strong>The Impact of Freeze-Thaw Cycles on the Integrity of SARS-COV-2 Viral Culture Fluids and Clinical Remnant Samples in Antigen or Nucleic Acid Testing</strong> -
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Preservation at ultra-low temperatures has been a gold standard for long-term storage of many types of clinical specimens including the SARS-CoV-2 virus. The frozen specimens can be easily transported and tested later. In addition, de-identified frozen remnant samples are resources for many preclinical or clinical studies. It is therefore crucial to understand whether freeze and thaw cycles (FTCs) can adversely affect SARS-CoV-2 test performance when frozen samples are tested. Some early studies suggest that the FTCs increased the cycles threshold (Ct) of RT-PCR indicating the potential degradation of the SARS-CoV-2 nucleic acid after FTCs, while the others did not report any significant changes in the SARS-CoV-2 nucleic acids after the FTCs. Moreover, the impact of FTCs on the performance of the SARS-CoV-2 antigen test is scarcely reported. In this study, we performed paired nucleic acid and rapid antigen tests on the same samples to investigate and directly compare how FTCs affect the performance of two types of tests. Both inactivated viral culture fluid samples and clinical remnant samples were studied. Our results showed that FTCs had minimal negative effects on the performance of the rapid SARS-CoV-2 antigen test, and the test results remained largely consistent throughout the FTCs, whereas the Ct values of RT-PCR increased with the increase of the FTC numbers. In addition, our data also demonstrated that the SARS-CoV-2 is preserved better in VTM than PBS during FTCs in regard to nucleic acid testing.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.14.22282041v1" target="_blank">The Impact of Freeze-Thaw Cycles on the Integrity of SARS-COV-2 Viral Culture Fluids and Clinical Remnant Samples in Antigen or Nucleic Acid Testing</a>
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</div></li>
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<li><strong>Synthesizing evidence on the impacts of COVID-19 regulatory changes on methadone treatment for opioid use disorder: Implications for U.S. federal policy</strong> -
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As the U.S. faces a worsening overdose crisis, improving access to evidence-based treatment for opioid use disorder (OUD) remains a central policy priority. Federal regulatory changes in response to the COVID-19 pandemic significantly expanded flexibilities on take-home doses for methadone treatment for OUD. These changes have fueled critical questions about the impact of new regulations on OUD outcomes, and the potential health impact of permanently integrating these flexibilities into treatment policy going forward. To aide US policy makers as they consider implementing permanent methadone regulatory changes, we conducted a review synthesizing peer-reviewed research evidence on the impact of the COVID-19 methadone-take-home flexibilities on methadone program operations, OUD patient and provider experiences, and patient health outcomes. We interpret this evidence in the context of the federal rulemaking process and discuss avenues by which these important findings can be incorporated and implemented into U.S. substance use treatment policy going forward.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22283533v1" target="_blank">Synthesizing evidence on the impacts of COVID-19 regulatory changes on methadone treatment for opioid use disorder: Implications for U.S. federal policy</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study for Immunocompromised Patients for Pre Exposure Prophylaxis of COVID-19 With AZD5156.</strong> - <b>Condition</b>: COVID 19<br/><b>Interventions</b>: Biological: Placebo; Biological: AZD5156; Biological: AZD7442 (EVUSHELD™)<br/><b>Sponsor</b>: AstraZeneca<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Huashi Baidu Formula Clinical Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Huashi Baidu Granule; Drug: Monapiravir<br/><b>Sponsors</b>: Xiyuan Hospital of China Academy of Chinese Medical Sciences; Beijing YouAn Hospital; Kossamak Hospital; Kamuzu University of Health Sciences<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>Shaping Care Home COVID-19 Testing Policy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Lateral Flow Device<br/><b>Sponsor</b>: University College, London<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>Baldachin: Ceiling HEPA-filtration to Prevent Nosocomial Transmission of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Baldachin<br/><b>Sponsor</b>: University Hospital Inselspital, Berne<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>Asunercept for the Treatment of Patients With Moderate to Severe COVID-19 Disease</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Asunercept; Other: Placebo<br/><b>Sponsor</b>: Apogenix AG<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>Study in Adults to Assess the Safety and Efficacy of Inhaled IBIO123, for Post-exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: IBIO123; Other: Placebo<br/><b>Sponsor</b>: Immune Biosolutions 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>A PhaseⅡ Study to Evaluate the Safety & Immunogenicity of SARS-CoV-2 Alpha/Beta/Delta/Omicron Variants COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: SCTV01E; Biological: Placebo (normal saline)<br/><b>Sponsor</b>: Sinocelltech 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>The Efficacy of Azvudine and Paxlovid in High-risk Patients With COVID-19: A Prospective Randomized Controlled Trial</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Paxlovid group<br/><b>Sponsors</b>: Southeast University, China; Hohhot First Hospital, Hohhot, Inner Mongolia, China<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 Supportive Psychotherapy Through Internet-Based Teleconsultation on Psychological and Somatic Symptoms, Neutrophil-Lymphocyte Ratio, and Heart Rate Variability in Post Covid-19 Syndrome Patients</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Supportive Psychotherapy<br/><b>Sponsor</b>: Indonesia 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>Graphene Photothermal Adjuvant Therapy for Mild Corona Virus Disease 2019: A Prospective Randomized Controlled Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Graphene spectrum light wave therapy room<br/><b>Sponsors</b>: Southeast University, China; Hohhot First 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>Post-COVID-19 Chronic Fatigue Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome<br/><b>Intervention</b>: Drug: Synthetic Vitamin B1<br/><b>Sponsors</b>: ClinAmygate; As-Salam Center, Maadi, Cairo, Egypt<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 Efficacy, Safety, and Immunogenicity of SARS-CoV-2 Variant (BA.4 /5) mRNA Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: ABO1020; Biological: Placebo<br/><b>Sponsor</b>: Suzhou Abogen Biosciences Co., Ltd.<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>Prednisolone and Vitamin B1/6/12 in Patients With Post-Covid-Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Prednisolone 20 mg/ 5 mg; Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12); Drug: Placebo for Vitamin B compound; Drug: Placebo for Prednisolon<br/><b>Sponsors</b>: Wuerzburg University Hospital; University Hospital Tuebingen; University Hospital Schleswig-Holstein<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 an Immersive Virtual Reality Intervention</strong> - <b>Conditions</b>: Nurse’s Role; COVID-19 Pandemic; Mental Stress<br/><b>Interventions</b>: Behavioral: Mindfulness-based Stress Reduction by Therapeutic VR; Behavioral: Mindfulness-based Stress Reduction<br/><b>Sponsor</b>: Nanjing University of Traditional Chinese Medicine<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>Communicating Uncertainty - Protocol for Randomized Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Overall uncertainty language<br/><b>Sponsors</b>: Trustees of Dartmouth College; Norwegian Institute of Public Health<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>SARS-CoV-2 viral protein ORF3A injures renal tubules by interacting with TRIM59 to induce STAT3 activation</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>In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea</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>Serum 25-hydroxycholesterol levels are increased in patients with coronavirus disease 2019</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>A leap towards personalised therapy of acute lung injury</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>Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay</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>COVID-19 signalome: Potential therapeutic interventions</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>Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial</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>Prophylactic Administration of the Monoclonal Antibody Adintrevimab Protects against SARS-CoV-2 in Hamster and Non-Human Primate Models of COVID-19</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>Inhibited personality traits, internalizing symptoms, and drinking to cope during the COVID-19 pandemic among emerging adults</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>Pattern enrichment analysis for phage selection of stapled peptide ligands</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>Pea eggplant (<em>Solanum torvum</em> Swartz) is a source of plant food polyphenols with SARS-CoV inhibiting potential</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>Identification of two specific transcriptomic clusters of COVID-19 ARDS patients with different immune profiles and different outcomes</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>Covalent CES2 Inhibitors Protect against Reduced Formation of Intestinal Organoids by the Anticancer Drug Irinotecan</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>Host-directed therapy with 2-Deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2</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>Identification of a pharmacological approach to reduce ACE2 expression and development of an <em>in vitro</em> COVID-19 viral entry model</strong> - No abstract</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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