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195 lines
53 KiB
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<title>27 May, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The Trends of Education after the COVID-19 Situation in Thailand</strong> -
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This research aims to synthesize the views from domestic and international references on the trends of education after COVID-19 situation, then convey the results of the synthesis to the experts from different groups to examine the trends and the feasibility of mix-method research which would be applied in Thai education after COVID-19 situation. The research conducted an in-depth interviewing of 15 experts and used the discussion method with other target groups of 15 experts. The research results defined the proposals of 31 issues for the trends of education after COVID-19 situation in Thailand. These proposals were similar to those of the educational paradigm shift from the 20th to the 21st century. As a result, Thailand is becoming a more digital society and people have to focus on using information and communication technologies (ICT) to gain the maximum benefits to develop the quality of Thai education.
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🖺 Full Text HTML: <a href="https://osf.io/r6msj/" target="_blank">The Trends of Education after the COVID-19 Situation in Thailand</a>
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</div></li>
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<li><strong>In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries</strong> -
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<div>
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The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/sevkf/" target="_blank">In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries</a>
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</div></li>
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<li><strong>How do local-level authorities engage in epidemic and pandemic preparedness activities and coordinate with higher levels of government? Survey results from 33 cities</strong> -
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The COVID-19 pandemic suggests that there are opportunities to improve preparedness for infectious disease outbreaks. While much attention has been given to understanding national-level preparedness, relatively little attention has been given to understanding preparedness at the local-level. We, therefore, aim to describe (1) how local governments were engaged in epidemic preparedness efforts before the COVID-19 pandemic and (2) how they were coordinating with authorities at higher levels of governance before COVID-19. We developed an online survey and distributed it to 50 cities around the world involved in the Partnership for Healthy Cities. The survey included several question formats including free-response, matrices, and multiple-choice questions. RACI matrices, a project management tool that helps explain coordination structures, were used to understand the level of government responsible, accountable, consulted, and informed regarding select preparedness activities. We used descriptive statistics to summarize local-level engagement in epidemic preparedness. Local health authorities from 33 cities completed the survey. Prior to the COVID-19 pandemic, 20 of the cities had completed infectious disease risk assessments, 10 completed all- hazards risk assessments, 11 completed simulation exercises, 10 completed after-action reviews, 19 developed preparedness and response plans, three reported involvement in their country’s Joint External Evaluation of the International Health Regulations, and eight cities reported involvement in the development of their countries’ National Action Plan for Health Security. RACI matrices revealed various models of epidemic preparedness, with responsibility often shared across levels, and national governments accountable for the most activities, compared to other governance levels. In conclusion, national governments maintain the largest role in epidemic and pandemic preparedness but the role of subnational and local governments is not negligible. Local-level actors engage in a variety of preparedness activities and future efforts should strive to better include these actors in preparedness as a means of bolstering local, national, and global health security.
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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/10.1101/2022.05.25.22275614v1" target="_blank">How do local-level authorities engage in epidemic and pandemic preparedness activities and coordinate with higher levels of government? Survey results from 33 cities</a>
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<li><strong>COVID-19 pandemic impact on preterm birth and stillbirth rates associated with socioeconomic disparities: A quasi- experimental study</strong> -
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Background Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES). Methods Using the linked administrative health databases from Manitoba, Canada, we conducted a quasi-experimental study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used interrupted time series analysis using autoregressive integrated moving average models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre- pandemic period data. Finally, we evaluated the lower and higher SES (average annual household income) using subgroup analysis and interaction models. Results We examined 70,931 pregnancies in Manitoba during the study period. Following the implementation of COVID-19 restrictions in March 2020, there were no statistically significant changes in the rates of both PTB (p=0.094) and stillbirths (p=0.958). However, over the pandemic, the PTB rate significantly decreased as a rebound effect by 0.63% per quarter(p=0.005); whereas the stillbirth rate did not change significantly (p=0.878) compared to pre-pandemic period. During the first quarter of 2021, the absolute differences in the observed and expected PTB and stillbirth percentages were 2.05% and 0.04%, respectively. We observed a statistically significant effect modification by SES for PTB rates (p=0.047). Conclusion While the onset of COVID-19 pandemic restrictions was not associated with significant effects on PTB and stillbirth rates, we observed a statistically significant rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.
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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/10.1101/2022.05.25.22275592v1" target="_blank">COVID-19 pandemic impact on preterm birth and stillbirth rates associated with socioeconomic disparities: A quasi-experimental study</a>
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<li><strong>The emergence of variants with increased fitness accelerates the slowdown of genome sequence heterogeneity in the SARS CoV 2 coronavirus</strong> -
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<div>
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Since the outbreak of the COVID-19 pandemic, the SARS-CoV-2 coronavirus has accumulated an important amount of genetic and genomic variability through mutation and recombination events. To test evolutionary trends that could inform us on the adaptive process of the virus to its human host, we summarize all this sequence variability by computing the Sequence Compositional Complexity (SCC) in more than 23,000 high-quality coronavirus genome sequences from across the globe, covering the period spanning from the start of the pandemic in December 2019 to March 2022. In early samples, we found no statistical support for any trend in SCC values over time, although the virus as a whole appears to evolve faster than Brownian Motion expectation. However, in samples taken after the first Variant of Concern (VoC) with higher transmissibility (Alpha) emerges, and controlling for phylogenetic and sampling effects, we were able to detect a statistically significant trend for decreased SCC values over time. SARS-CoV-2 evolution towards lower values of genome heterogeneity is further intensified by the emergence of successive, widespread VoCs. Concomitantly to the temporal reduction in SCC, its absolute evolutionary rate kept increasing toward the present, meaning that the SCC decrease itself accelerated over time. As compared to Alpha or Delta variants, the currently dominant VoC, Omicron, shows much stronger trends in both SCC values and rates over time. These results indicate that the increases in fitness of variant genomes associated to a higher transmissibility leads to a reduction of their genome sequence heterogeneity, thus explaining the general slowdown of SCC along with the pandemic course.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.26.493529v1" target="_blank">The emergence of variants with increased fitness accelerates the slowdown of genome sequence heterogeneity in the SARS CoV 2 coronavirus</a>
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<li><strong>Noninvasive ventilation strategies for patients with severe or critical COVID-19: A rapid review of clinical outcomes</strong> -
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Objectives: To examine whether high flow nasal oxygen (HFNO), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) strategies impact mortality, the need for invasive mechanical ventilation (IMV), or hospital and intensive care unit (ICU) length of stay compared to standard oxygen therapy (SOT) or each other in patients with severe or critical COVID-19 with acute hypoxemic respiratory failure. Methods: A rapid review of randomized controlled trials (RCTs) identified through published systematic and rapid reviews supplemented with a search of bibliographic databases. RCTs were eligible if they compared HFNO, CPAP, or NIV to SOT or another ventilation strategy. Studies were screened, selected, and extracted by a single reviewer and checked by a second reviewer. We assessed risk of bias of included studies using the Cochrane 9Risk of bias9 tool and used the grading of recommendations, assessment, development, and evaluation (GRADE) approach to judge the certainty of the evidence for mortality, need for IMV, and hospital and ICU length of stay. We sought RCT evidence for non-COVID-19 patients with acute hypoxemic respiratory failure and acute respiratory distress to inform additional comparisons and to supplement the available data for COVID-19. Results: A total of 5 RCTs comparing ventilation strategies in patients with severe or critical COVID-19 were included. Patient and study characteristics were extracted and evidence and certainty of evidence assessments were completed for comparisons of HFNO and CPAP to standard oxygen therapy and NIV and CPAP to HFNO. An additional 22 RCTs of non-COVID-19 patients were also included and considered. Results from meta-analysis suggest reductions in mortality and IMV with HFNO (RR mortality 0.87 (0.66-1.13), IMV 0.89 (0.77-1.03); low quality evidence) or CPAP (RR mortality 0.87 (0.64-1.18) low quality evidence, IMV 0.81 (0.67-0.98) moderate quality evidence) compared to SOT. Helmet NIV may reduce IMV (RR 0.69 (0.43-1.09)) and CPAP may reduce IMV (RR 0.69 (0.43-1.09)) and hospital (1.67 days fewer (5.43 fewer-2.09 more) or ICU length of stay (1.02 days fewer (3.97 fewer-1.93 more)) compared to HFNO (low quality evidence). Conclusions: This rapid systematic review highlights the available evidence to support the use of noninvasive ventilation strategies including high flow nasal oxygen, noninvasive ventiltaion (e.g., BiPAP), or CPAP in hospitalized patients with severe or critical COVID-19 and acute hypoxemic respiratory failure who do not need emergent intubation. Findings based on moderate to very low certainty evidence suggest that noninvasive ventilation may be considered as an alternative to standard oxygen therapy to reduce hypoxemia and dyspnea. Additional high quality RCTs are warranted to reduce uncertainty and to fill in important knowledge gaps.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275586v1" target="_blank">Noninvasive ventilation strategies for patients with severe or critical COVID-19: A rapid review of clinical outcomes</a>
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<li><strong>Inhibition of major histocompatibility complex-I antigen presentation by sarbecovirus ORF7a proteins</strong> -
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Viruses employ a variety of strategies to escape or counteract immune responses, including depletion of cell surface major histocompatibility complex class I (MHC-I), that would ordinarily present viral peptides to CD8+ cytotoxic T cells. As part of a screen to elucidate biological activities associated with individual SARS-CoV-2 viral proteins, we found that ORF7a reduced cell surface MHC-I levels by approximately 5-fold. Nevertheless, in cells infected with SARS-CoV-2, surface MHC-I levels were reduced even in the absence of ORF7a, suggesting additional mechanisms of MHC-I downregulation. ORF7a proteins from a sample of sarbecoviruses varied in their ability to induce MHC-I downregulation and, unlike SARS-CoV-2, the ORF7a protein from SARS-CoV lacked MHC-I downregulating activity. A single- amino acid at position 59 (T/F) that is variable among sarbecovirus ORF7a proteins governed the difference in MHC-I downregulating activity. SARS-CoV-2 ORF7a physically associated with the MHC-I heavy chain and inhibited the presentation of expressed antigen to CD8+ T-cells. Speficially, ORF7a prevented the assembly of the MHC-I peptide loading complex and causing retention of MHC-I in the endoplasmic reticulum. The differential ability of ORF7a proteins to function in this way might affect sarbecovirus dissemination and persistence in human populations, particularly those with infection- or vaccine-elicited immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.25.493467v1" target="_blank">Inhibition of major histocompatibility complex-I antigen presentation by sarbecovirus ORF7a proteins</a>
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<li><strong>SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion</strong> -
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The Omicron subvariant BA.2 accounts for a large majority of the SARS-CoV-2 infection worldwide today. However, its recent descendants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively. That these novel Omicron subvariants carry additional mutations in their spike proteins raises concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of our COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. On the other hand, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called Class 2 and Class 3 regions of the receptor-binding domain (RBD). The F486V mutation found in BA.4/5 facilitates escape from certain Class 1 and Class 2 antibodies to the RBD but compromises the spike affinity for the cellular receptor ACE2. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab (LY-COV1404) retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.26.493517v1" target="_blank">SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion</a>
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<li><strong>Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5</strong> -
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After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.26.493539v1" target="_blank">Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5</a>
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<li><strong>Motivation, intention and action: wearing masks to prevent the spread of COVID-19</strong> -
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Governments around the world are seeking to slow the spread of COVID-19 by implementing measures that encourage, or mandate, changes in people’s behaviour. These changes include the wearing of face masks, social distancing, and testing and self-isolating when unwell. The success of these measures depends on (1) the willingness of individuals to change their behaviour and (2) their commitment and capacity to translate that intention into actions. Consequently, understanding and predicting the willingness of individuals to change their behaviour, and their enthusiasm to act on that willingness, is critical in assessing the likely effectiveness of these measures in slowing the spread of the virus. In this paper we analyse responses to two separate regional surveys about people’s intentions and behaviour with respect to preventing the spread of COVID-19 in New Zealand. While motivations and intentions were largely similar across the regions, there was marked difference in action across the regions, specifically with respect to the frequency of wearing face masks. Our analysis suggests that the translation of intention (preventing the spread of COVID-19) into action (as measured by self-reported frequency of face mask use) was strongly associated with perceptions of the risk of infection (as measured by regional case numbers). The results highlight the importance to policy design of distinguishing the factors that might influence the formation of behavioural intentions from those that might influence the implementation of those intentions.
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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/10.1101/2022.05.25.22275599v1" target="_blank">Motivation, intention and action: wearing masks to prevent the spread of COVID-19</a>
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<li><strong>The prevalence of SARS-CoV-2 infection and uptake of COVID-19 antiviral treatments during the BA.2/BA.2.12.1 surge, New York City, April-May 2022</strong> -
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Importance: Routine case surveillance data for SARS-CoV-2 are incomplete, biased, missing key variables of interest, and may be unreliable for both timely surge detection and understanding the burden of infection. Objective: To determine the prevalence of SARS-CoV-2 infection during the Omicron BA.2/BA.2.12.1 surge in relation to official case counts, and to assess the epidemiology of infection and uptake of SARS-CoV-2 antivirals. Design: Cross-sectional survey of a representative sample of New York City (NYC) adult residents, conducted May 7-8, 2022. Setting: NYC, April 23-May 8, 2022, during which the official SARS-CoV-2 case count was 49,253 and BA.2.12.2 comprised 20% of reported cases. Participants: A representative sample of 1,030 NYC adult residents >18 years. Exposure(s): Vulnerability to severe COVID-19, including vaccination/booster status, prior COVID, age, and presence of comorbidities. Main Outcome(s) and Measure(s): Prevalence of SARS-CoV-2 infection during a 14-day period, weighted to represent the NYC adult population. Respondents self-reported on SARS-CoV-2 testing (including at-home rapid antigen tests), testing outcomes, COVID-like symptoms, and contact with confirmed/probable cases. Individuals with SARS-CoV-2 were asked about awareness/use of antiviral medications. Results: An estimated 22.1% (95%CI 17.9%-26.2%) of respondents had SARS-CoV-2 infection during the study period, corresponding to ~1.5 million adults (95%CI 1.3-1.8 million). Prevalence was estimated at 34.9% (95%CI 26.9%- 42.8%) among individuals with co-morbidities, 14.9% (95% CI 11.0%-18.8%) among those 65+ years, and 18.9% (95%CI 10.2%-27.5%) among unvaccinated persons. Hybrid protection against severe disease (i.e., from both vaccination and prior infection) was 66.2% (95%CI 55.7%-76.7%) among those with COVID and 46.3% (95%CI 40.2-52.2) among those without. Among individuals with COVID, 55.9% (95%CI 44.9%- 67.0%) were not aware of the antiviral nirmatrelvir/ritonavir (PaxlovidTM), and 15.1% (95%CI 7.1%-23.1%) reported receiving it. Conclusions and Relevance: The true magnitude of NYCs BA.2/BA.2.12.1 surge was vastly underestimated by routine SARS-CoV-2 surveillance. Until there is more certainty that the impact of future pandemic surges on severe population health outcomes will be diminished, representative surveys are needed for timely surge detection, and to estimate the true burden of infection, hybrid protection, and uptake of time- sensitive treatments.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275603v1" target="_blank">The prevalence of SARS-CoV-2 infection and uptake of COVID-19 antiviral treatments during the BA.2/BA.2.12.1 surge, New York City, April-May 2022</a>
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<li><strong>A repeat pattern of founder events for SARS-CoV-2 variants in Alaska</strong> -
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Alaska is a unique US state because of its large size, geographically disparate population density, and physical distance from the contiguous United States. Here, we describe a pattern of SARS-CoV-2 variant emergence across Alaska reflective of these differences. Using genomic data, we found that in Alaska the Omicron sublineage BA.2.3 overtook BA.1.1 by the week of 2022-02-27, reaching 48.5% of sequenced cases. On the contrary in the contiguous United States, BA.1.1 dominated cases for longer, eventually being displaced by BA.2 sublineages other than BA.2.3. BA.2.3 only reached a prevalence of 10.9% in the contiguous United States. Using phylogenetics, we found evidence of potential origins of the two major clades of BA.2.3 in Alaska and with logistic regression estimated how it emerged and spread throughout the state. The combined evidence is suggestive of founder events in Alaska and is reflective of how Alaska9s unique dynamics influence the emergence of SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275610v1" target="_blank">A repeat pattern of founder events for SARS-CoV-2 variants in Alaska</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Limited induction of lung-resident memory T cell responses against SARS-CoV-2 by mRNA vaccination</strong> -
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Resident memory T cells (TRM) present at the respiratory tract may be essential to enhance early SARS-CoV-2 viral clearance, thus limiting viral infection and disease. While long-term antigen (Ag)-specific TRM are detectable beyond 11 months in the lung of convalescent COVID-19 patients after mild and severe infection1, it is unknown if mRNA vaccination encoding for the SARS-CoV-2 S-protein can induce this frontline protection. We found that the frequency of CD4+ T cells secreting interferon (IFN)g in response to S-peptides was similar in the lung of mRNA-vaccinated patients compared to convalescent-infected patients. However, in vaccinated patients, lung responses presented less frequently a TRM phenotype compared to convalescent infected individuals and polyfunctional TRM were virtually absent. Thus, a robust and wide TRM response established in convalescent-infected individuals may be advantageous in limiting disease if the virus is not block by initial mechanisms of protection, such as neutralization. Still, mRNA vaccines can induce modest responses within the lung parenchyma potentially contributing to the overall disease control.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275300v1" target="_blank">Limited induction of lung-resident memory T cell responses against SARS-CoV-2 by mRNA vaccination</a>
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<li><strong>Overuse in US Medicare during the COVID-19 pandemic</strong> -
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Importance: While the COVID-19 pandemic disrupted regular hospital care and decreased overall volume of hospitalized patients, its impact on low-value care has not been investigated. Objective: To examine the impact of the COVID-19 pandemic on overuse rates. Design: A retrospective cohort study using Medicare fee-for-service claims. Setting: All outpatient and inpatient claims. Participants: Medicare beneficiaries aged 65 and over who met the criteria for one of 10 overuse measures were included, if they had a claim between January 1, 2019 to December 31, 2020. Exposure: Claims meeting overuse measure criteria over various time periods in 2020 were compared to the same period in the previous year: during the initial COVID-19 surge and shutdown (March 15 to May 2, 2020) and periods where states had high (if the mean 7-day case incidence was greater than 175 cases per 100,000 persons) or low COVID-19 incidence. Main Outcomes and Measures: The overuse measures in this study had two components: a denominator encompassing a particular patient cohort and a numerator to capture overuse of each service among patients within this cohort. We report claim volumes for both the denominator cohorts and overuse numerators as well as their rate differences (2020 versus 2019) using incidence rate ratios (IRRs) estimated using Poisson regressions. Results: There were 2,053,792 patients in 2019 and 1,699,807 in 2020 included across all 10 measure cohorts, with 2,112,904 (61.0%) female patients and a mean (SD) age of 76.5 (8.1) years. Across the 10 measures, 302,379 (14.7%) patients had a claim meeting the overuse criteria in 2019 and 234,481 (13.8%) in 2020. The COVID-19 shutdown had a large impact on overall cohort volume; there were 2,341,017 patients during this period, a decrease of 52.3% from 4,912,453 patients in the corresponding 2019 period. Both overuse volume and rates declined in 2020 compared to 2019. In April 2020, there were 3,955 overuse procedure claims (including spinal fusion/laminectomy, carotid endarterectomy, knee arthroscopy, hysterectomy and vertebroplasty) compared to 14,663 in 2019; an IRR of 0.64 (95% CI 0.62 to 0.67; p <0.001). After the COVID-19 shutdown period, 2020 overuse rates were mostly similar to rates in the corresponding 2019 period. Conclusions and Relevance: The COVID-19 shutdown period during March through May in 2020 had a drastic impact on both the overall volume of patients meeting one of 10 measure criteria and the rate of overuse for these patients. Overuse rates, however, returned to 2019 levels shortly after this shutdown period even as COVID incidence rose.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275006v1" target="_blank">Overuse in US Medicare during the COVID-19 pandemic</a>
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<li><strong>Omicron BA.1 and BA.2 Neutralizing Activity Following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab in Vaccinated Solid Organ Transplant Recipients</strong> -
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Neutralizing antibody responses are attenuated in many solid organ transplant recipients (SOTRs) despite SARS- CoV-2 vaccination. Pre-exposure prophylaxis (PrEP) with the monoclonal antibody combination Tixagevimab and Cilgavimab (T+C) might augment immunoprotection, yet activity against Omicron sublineages in vaccinated SOTRs is unknown. Vaccinated SOTRs who received 300+300mg T+C (either single dose or two 150+150mg doses) within a prospective observational cohort submitted pre- and post-injection samples between 1/10/2022-4/4/2022. Binding antibody (anti- receptor binding domain [RBD], Roche) and surrogate neutralization (%ACE2 inhibition; >20% connoting neutralizing inhibition, Meso Scale Discovery) were measured against variants including Omicron sublineages BA.1 and BA.2. Data were analyzed using the Wilcoxon matched-pairs signed-rank test and McNemar9s test. Among 61 participants, median (IQR) anti- RBD increased from 424 (IQR <0.8-2322.5) to 3394.5 (IQR 1403.9-7002.5) U/ml post T+C (p<0.001). The proportion demonstrating vaccine strain neutralizing inhibition increased from 46% to 100% post-T+C (p<0.001). BA.1 neutralization was low and did not increase (8% to 16% of participants post-T+C, p=0.06). In contrast, BA.2 neutralization increased from 7% to 72% of participants post-T+C (p<0.001). T+C increased anti-RBD levels, yet BA.1 neutralizing activity was minimal. Encouragingly, BA.2 neutralization was augmented and in the current variant climate T+C PrEP may serve as a useful complement to vaccination in high-risk SOTRs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.24.22275467v1" target="_blank">Omicron BA.1 and BA.2 Neutralizing Activity Following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab in Vaccinated Solid Organ Transplant Recipients</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-9199; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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Sorrento Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Hymecromone tablets; Other: Placebo<br/><b>Sponsor</b>: Shanghai Zhongshan 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>Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated; Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: <br/>
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China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Hunan Provincial Center for Disease Control and Prevention<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase Ia, Dose-finding Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Prime-2-CoV_Beta<br/><b>Sponsors</b>: <br/>
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University Hospital Tuebingen; FGK Clinical Research GmbH; VisMederi srl; Staburo GmbH; Viedoc Technologies AB<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 Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir; Drug: ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics 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>Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics 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>To Evaluate SSD8432/Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 750mg; Drug: SSD8432 placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical 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 Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: DXP604<br/><b>Sponsor</b>: <br/>
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Wuhan 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>Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Clinical Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 300mg; Drug: SSD8432 750mg; Drug: SSD8432Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical 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>Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd; The University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety of Booster Immunization of COVID-19 Vaccine (Vero Cell), Inactivated (Omicron Variant) in Healthy People Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 Vaccine (Vero cell), Inactivated (Omicron variant); Biological: COVID-19 Vaccine (Vero cell), Inactivated (CZ strain)<br/><b>Sponsor</b>: <br/>
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Sinovac Research and Development 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>Low Versus Moderate-intensity Aerobic Training in Post-discharge COVID-19 Subjects</strong> - <b>Condition</b>: COVID-19; Aerobic Exercises; Elderly<br/><b>Intervention</b>: Other: aerobic exercise<br/><b>Sponsor</b>: University of Hail<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 Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>: Coronavirus Disease 2019 (COVID-19)<br/><b>Intervention</b>: Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])<br/><b>Sponsor</b>: AstraZeneca<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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multifaceted efficacy of caspofungin against fungal infections in COVID-19 patients</strong> - Fungal co-infections of coronavirus disease 2019 (COVID-19) are generally infrequent, but are more common among patients with hematological diseases or severe cases in the intensive care unit (ICU). As fungal infections often carry a high mortality rate, preventing their development is considered important for patients with COVID-19. Caspofungin covers Candida spp. and Aspergillus spp. as causative pathogens of fungal infections associated with COVID-19, and is known to have few side effects…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing of FDA Approved Drugs Against SARS-CoV-2 Papain-Like Protease: Computational, Biochemical, and <em>in vitro</em> Studies</strong> - The pandemic caused by SARS-CoV-2 (SCoV-2) has impacted the world in many ways and the virus continues to evolve and produce novel variants with the ability to cause frequent global outbreaks. Although the advent of the vaccines abated the global burden, they were not effective against all the variants of SCoV-2. This trend warrants shifting the focus on the development of small molecules targeting the crucial proteins of the viral replication machinery as effective therapeutic solutions. The…</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>Insights Into Immunothrombotic Mechanisms in Acute Stroke due to Vaccine-Induced Immune Thrombotic Thrombocytopenia</strong> - During the COVID-19 pandemic, vaccination is the most important countermeasure. Pharmacovigilance concerns however emerged with very rare, but potentially disastrous thrombotic complications following vaccination with ChAdOx1. Platelet factor-4 antibody mediated vaccine-induced immune thrombotic thrombocytopenia (VITT) was described as an underlying mechanism of these thrombotic events. Recent work moreover suggests that mechanisms of immunothrombosis including neutrophil extracellular trap…</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 ORF7a potently inhibits the antiviral effect of the host factor SERINC5</strong> - Serine Incorporator 5 (SERINC5), a cellular multipass transmembrane protein that is involved in sphingolipid and phosphatydilserine biogenesis, potently restricts a number of retroviruses, including Human Immunodeficiency Virus (HIV). SERINC5 is incorporated in the budding virions leading to the inhibition of virus infectivity. In turn, retroviruses, including HIV, encode factors that counteract the antiviral effect of SERINC5. While SERINC5 has been well studied in retroviruses, little is known…</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>Type-I interferons in the immunopathogenesis and treatment of Coronavirus disease 2019</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is currently the major global health problem. Still, it continues to infect people globally and up to the end of February 2022, over 436 million confirmed cases of COVID-19, including 5.95 million deaths, were reported to the world health organization (WHO). No specific treatment is currently available for COVID-19, and the discovery of effective therapeutics requires…</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>Multi-target potential of Indian phytochemicals against SARS-CoV-2: A docking, molecular dynamics and MM-GBSA approach extended to Omicron B.1.1.529</strong> - CONCLUSION: Overall our study imparts the usage of phytochemicals as antiviral agents for SARS-CoV-2 infection. Additional in vitro and in vivo testing of these phytochemicals is required to confirm their potency.</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>Exploring the Spike-hACE 2 Residue-Residue Interaction in Human Coronaviruses SARS-CoV-2, SARS-CoV, and HCoV-NL63</strong> - Coronaviruses (CoVs) have been responsible for three major outbreaks since the beginning of the 21st century, and the emergence of the recent COVID-19 pandemic has resulted in considerable efforts to design new therapies against coronaviruses. Thus, it is crucial to understand the structural features of their major proteins related to the virus- host interaction. Several studies have shown that from the seven known CoV human pathogens, three of them use the human Angiotensin-Converting Enzyme 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>Monoclonal antibody designed for SARS-nCoV-2 spike protein of receptor binding domain on antigenic targeted epitopes for inhibition to prevent viral entry</strong> - SARS, or severe acute respiratory syndrome, is caused by a novel coronavirus (COVID-19). This situation has compelled many pharmaceutical R&D companies and public health research sectors to focus their efforts on developing effective therapeutics. SARS-nCoV-2 was chosen as a protein spike to targeted monoclonal antibodies and therapeutics for prevention and treatment. Deep mutational scanning created a monoclonal antibody to characterize the effects of mutations in a variable antibody fragment…</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>Strategies to Improve Perioperative Communication During the COVID-19 Pandemic</strong> - The coronavirus disease 2019 pandemic has led to a variety of challenges that have necessitated process changes in perioperative environments. Communication failures are a cause of surgical adverse events, and the pandemic has created additional communication concerns. Measures to prevent disease transmission, such as social distancing and wearing personal protective equipment, may inhibit communication. Relational dynamics and the types of collaboration that perioperative health care…</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>Pnictogen-Centered Cascade Exchangers for Thiol-Mediated Uptake: As(III)-, Sb(III)-, and Bi(III)-Expanded Cyclic Disulfides as Inhibitors of Cytosolic Delivery and Viral Entry</strong> - Dynamic covalent exchange cascades with cellular thiols are of interest to deliver substrates to the cytosol and to inhibit the entry of viruses. The best transporters and inhibitors known today are cyclic cascade exchangers (CAXs), producing a new exchanger with every exchange, mostly cyclic oligochalcogenides, particularly disulfides. The objective of this study was to expand the dynamic covalent chalcogen exchange cascades in thiol-mediated uptake by inserting pnictogen relays. A family 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>Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1<em>H</em>-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities</strong> - A series of 26 novel 1-(7-chloroquinolin-4-yl)-4-nitro-1H-pyrazoles bearing a dichloromethyl and an amino or thio moiety at C3 and C5 has been prepared in yields up to 72% from the reaction of 1,1-bisazolyl-, 1-azolyl-1-amino-, and 1-thioperchloro-2-nitrobuta-1,3-dienes with 7-chloro-4-hydrazinylquinoline. A new way for the formation of a pyrazole cycle from 3-methyl-2-(2,3,3-trichloro-1-nitroallylidene)oxazolidine (6) is also described. In addition, the antimalarial activity of the synthesized…</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 conserved subunit vaccine designed against SARS-CoV-2 variants showed evidence in neutralizing the virus</strong> - Novel coronavirus (SARS-CoV-2) leads to coronavirus disease 19 (COVID-19), declared as a pandemic that outbreaks within almost 225 countries worldwide. For the time being, numerous mutations have been reported that led to the generation of numerous variants spread more rapidly. This study aims to establish an efficient multi-epitope subunit vaccine that could elicit both T-cell and B-cell responses sufficient to recognize three confirmed surface proteins of the virus. The sequences of the viral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of oleandrin and PBI-05204 against bovine viruses of importance to commercial cattle health</strong> - CONCLUSIONS: The research demonstrates the potency of oleandrin and PBI-05204 to inhibit infectivity of three important enveloped bovine viruses in vitro. These data showing non-toxic concentrations of oleandrin inhibiting infectivity of three bovine viruses support further investigation of in vivo antiviral efficacy.</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 accessory proteins ORF7a and ORF3a use distinct mechanisms to downregulate MHC-I surface expression</strong> - Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein β (2) -microglobulin (β (2) m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those…</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 Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient</strong> - The syndrome of pulmonary SARS-Cov-2 resulted in significant morbidity and mortality, with new variants spreading rapidly. Vaccines to prevent COVID-19 have been developed to minimize the impact and severity; however, adverse effects of the vaccine have been documented in several studies. In our case, we report a case of a young female who presented to the emergency department with fever, dizziness, headache, vomiting, blurring of vision, numbness, and weakness of left upper and lower limbs….</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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