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170 lines
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<title>17 July, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Adolescents with ADHD are at Increased Risk for COVID-19 Vaccine Hesitancy</strong> -
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<div>
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Identifying factors that influence adolescent intentions for COVID-19 vaccination is essential for developing strategic interventions to increase uptake, particularly in subgroups of at-risk adolescents. Attention-deficit/hyperactivity disorder (ADHD) in adolescence is characterized by difficulties regulating attention and behavior, social impairment, and impulsive risk-taking behaviors, which may impact vaccine hesitancy and vaccine uptake. This study examined hesitancy toward COVID-19 vaccines among adolescents with and without ADHD, and explored how ADHD status interacted with malleable social mechanisms and other social determinants of health in predicting vaccine hesitancy. Participants were 196 U.S. adolescents (44.4% male), 45.6% diagnosed with ADHD. Adolescents reported their confidence and willingness toward COVID-19 vaccines from March to May 2021. Adolescents with ADHD reported greater hesitancy and less confidence in COVID-19 vaccine safety compared to adolescents without ADHD (p< .01). Only 61.8% of adolescents with ADHD reported vaccine acceptance, compared to 81.3% of adolescents without ADHD. For all adolescents, those who identified as Black or Latinx and with lower family income had greater hesitancy and reduced confidence, whereas greater COVID-19 concerns, media use, and perceived negative impact on relationships was associated with greater vaccination willingness. Social contextual processes significantly interacted with ADHD status such that for adolescents without ADHD, concerns about COVID- 19 were associated with increased confidence in vaccine safety. Being noncompliant with social distancing guidelines predicted increased risk for vaccine hesitancy, only for adolescents with ADHD. A concerted effort is needed to increase trust, confidence, and social relevance among adolescents, especially those with ADHD and from lower socio-economic backgrounds.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/wc79b/" target="_blank">Adolescents with ADHD are at Increased Risk for COVID-19 Vaccine Hesitancy</a>
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</div></li>
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<li><strong>Relationship difficulties and “technoference” during the COVID-19 pandemic</strong> -
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<div>
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The COVID-19 pandemic has touched many aspects of people’s lives around the world, including their romantic relationships. While media outlets have reported that the pandemic is difficult for couples, empirical evidence is needed to test these claims and understand why this may be. In two highly powered studies (N = 3,271) using repeated measure and longitudinal approaches, we found that people who experienced COVID-19 related challenges (i.e., lockdown, reduced face-to-face interactions, boredom, or worry) also reported greater self and partner phone use (Study 1) and time spent on social media (Study 2), and subsequently experienced more conflict and less satisfaction in their romantic relationship. The findings provide insight into the struggles people faced in their relationships during the pandemic and suggest that the increase in screen time – a rising phenomenon due to the migration of many parts of life online – may be a challenge for couples.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/3cwv7/" target="_blank">Relationship difficulties and “technoference” during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Megatrends in Africa: Implications for food in urban high-density areas with special focus on Nairobi and Cape Town</strong> -
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<div>
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The world is and has been continuously changing and adjusting. Some changes are positive, some are negative. It is important to be aware of emerging changes in order to mitigate negative effects and amplify positive effects. Some of the major current trends are: urbanization, migration, climate change, population growth, biodiversity loss as well as the emergence of pandemics such as COVID 19. All of these trends affect food systems in several ways. A clear understanding of the implications is critical when considering how food systems can be strengthened and made more resilient to withstand the impacts of these trends. Climate change is threatening all aspects of food security. Low- and middle-income countries are projected to be affected to the largest extent. Yield reduction and price increases further increase the incentives to expand production into forest and grasslands which would in turn accelerate climate change. Urban food supply chains will have to adjust to shifting regional supplies and increasingly erratic volumes. Heat and water stress will further amplify the negative human health effects especially in densely populated areas. Biodiversity could be a crucial contributor to improved food system outcomes, yet it is continuously degraded. Many valuable plant species are already threatened and population growth, urbanization, climate change and current market forces increase the pressures on habitats for biodiversity. Direct threats also emerge from current food production systems that contribute to degradation through heavy use of chemical pesticides and fertilizer. Current food systems are already failing to deliver for the poor, contribute to environmental degradation, and fail to withstand disruptions such as the effects of COVID 19. Around 66% of Africans already face food insecurity. The population is projected to double by 2060 and food supply will need to change, diversify and increase drastically in order to overcome the current and emerging challenges. Here, the supply to urban residents will be most critical as urban populations will triple by 2050 and already by 2030, half of the population will reside in cities. With the majority of the population increase likely being absorbed by informal settlements, these areas will require attention to ensure they are made more resilient, to buffer the worst impacts. Food system trends towards more processed, and less nutritious foods are already negatively impacting different segments of populations with the coexistence of multiple forms of malnutrition, and increasing diet associated with non-communicable diseases. Therefore, alternative systems will have to be developed in order to avoid increasing health problems. While focusing on solving or mitigating the acute problems, we need to ensure a clear vision towards a more resilient, sustainable and equitable (food) future that is able to address the needs of all segments of society. The reports of EAT Lancet, the HLPE, the Global Panel on Agriculture and Food Systems for Nutrition and UNICEF are recent examples that highlight the needs and pathways towards this goal. Yet, there remain critical knowledge gaps for action that need to be addressed. Food choice motives are highly complex and interact with other needs and strategies. These are often context specific and generalization remains difficult, with limited evidence in low-and middle-income countries Hence a clear understanding of local contexts, and socio-cultural dynamics remains crucial for understanding, and devising suitable interventions that will respond to consumer needs and behaviour, for better food, nutrition and well-being outcomes. Furthermore, the food system itself and its mechanics have yet to be fully explored when it comes to interventions, particularly the parts which connect rural-producers and urban- consumers, and supporting and enabling food environment. While at the abstract and aggregate level there have been significant advances, the implications for local interventions have to be explored in more detail to avoid negative consequences or spillovers. Overall, clarity on intervention logic, design and monitoring will have to be ensured in order to truly advance the functioning of the food system for all and especially for vulnerable people that are currently ill served.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/uvcb7/" target="_blank">Megatrends in Africa: Implications for food in urban high-density areas with special focus on Nairobi and Cape Town</a>
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</div></li>
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<li><strong>Urban birds’ flight responses were unaffected by the COVID-19 shutdowns</strong> -
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<div>
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The coronavirus disease 2019 (COVID-19) pandemic has dramatically altered human activities, potentially relieving human pressures on urban-dwelling animals. Here, we evaluated whether birds from five cities in five countries (Czech Republic - Prague, Finland - Rovaniemi, Hungary - Budapest, Poland - Poznan, and Australia - Melbourne) changed their tolerance towards human presence (measured as flight initiation distance) during the COVID-19 shutdowns. We collected 6369 flight initiation distance estimates for 147 bird species and found that birds tolerated approaching humans to a similar level before and during the COVID-19 shutdowns. Moreover, during the shutdowns, bird escape behaviour did not consistently change with the level of governmental restrictions (measured as the stringency index). Hence, our results indicate that birds do not flexibly and quickly adjust their escape behaviour to the reduced human presence; in other words, the breeding populations of urban birds examined might already be tolerant of human activity and perceive humans as relatively harmless.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500232v1" target="_blank">Urban birds’ flight responses were unaffected by the COVID-19 shutdowns</a>
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</div></li>
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<li><strong>Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19</strong> -
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<div>
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After more than two years the COVID-19 pandemic continues to burden healthcare systems and economies worldwide, and it is evident that long-term effects of the disease can persist for months post-recovery in some individuals. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to SARS CoV-2 is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed, for 6-7 months, a cohort of COVID-19 patients hospitalized during the early waves of the pandemic. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in PD-L1 expression but increased CD86 expression across almost all cell types examined. Finally, viral load and CRP correlated to the appearance of circulating antibodies and levels of circulating DC and monocyte subsets, respectively. By elucidating some of the long-term effects that SARS-CoV-2 infection has on these key innate myeloid cells, we have shed more light on how the immune landscape remains affected in the months following severe COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500185v1" target="_blank">Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19</a>
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</div></li>
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<li><strong>Understanding public support for COVID-19 pandemic mitigation measures over time: Does it wear out?</strong> -
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<div>
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COVID-19 mitigation measures intend to protect public health, but their adverse psychological, social, and economic effects weaken popular support. Less favorable trade-offs may especially weaken support for more restrictive measures. Support for mitigation measures may also differ between population subgroups who experience different benefits and costs, and decrease over time, a phenomenon termed ‘pandemic fatigue’. We examined self-reported support for COVID-19 mitigation measures in The Netherlands over 12 consecutives waves of data collection between April 2020 – May 2021 in an open population cohort study. Participants were recruited through community panels of the 25 regional public health services, and through links to the online surveys advertised on social media. The 54,010 unique participants in the cohort study on average participated in 4 waves of data collection. Most participants were female (65%), middle-aged (57% 40-69 years), highly educated (57%), not living alone (84%), residing in an urban area (60%), and born in the Netherlands (95%). COVID-19 mitigation measures implemented in the Netherlands remained generally well-supported over time (all scores >3 on 5-point scale ranging 1 (low) – 5 (high)). During the whole period studied, support was highest for personal hygiene measures, quarantine and wearing face masks, high but somewhat lower for not shaking hands, testing and self-isolation, and restricting social contacts, and lowest for limiting visitors at home, and not traveling abroad. Women and higher educated people were more supportive of some mitigation measures than men and lower educated people. Older people were more supportive of more restrictive measures than younger people, and support for more socially restrictive measures decreased most over time in higher educated people or in younger people. This study found no support for pandemic fatigue in terms of a gradual decline in support for all mitigation measures over time. Rather, findings suggest that support for mitigation measures reflects a balancing of benefits and cost, which may change over time, and differ between measures and population subgroups.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/yq2az/" target="_blank">Understanding public support for COVID-19 pandemic mitigation measures over time: Does it wear out?</a>
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</div></li>
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<li><strong>Teladentistry and distance learning :Access to oral health state : systematic Reviews</strong> -
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<div>
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:Covid19 pandemic has changed the vision on how to deal in emergency situations .Advanced technology and spreading growth of internet connection encourage people to use it to obtain helpful advice in critical climate of covid 19 crisis . The aim of this study to through the light on importance of teledentistry in critical emergency situations .
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/p794v/" target="_blank">Teladentistry and distance learning :Access to oral health state : systematic Reviews</a>
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</div></li>
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<li><strong>Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2</strong> -
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<div>
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Some COVID-19 patients are unable to clear their infection or are at risk of severe disease, requiring treatment with neutralising monoclonal antibodies (nmAb) and/or antivirals. The rapid roll-out of novel therapeutics means there is limited understanding of the likely genetic barrier to drug resistance. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to the detection of emerging drug resistance. Here we report the accrual of mutations in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the epitopes of the respective nmAbs. For casirivimab+imdevimab these are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500063v1" target="_blank">Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2</a>
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</div></li>
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<li><strong>Pangenome analysis of SARS-CoV2 strains to Identify Potential vaccine targets by Reverse Vaccinology</strong> -
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<div>
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Background: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) leads to respiratory failure and obstructive alveolar damage, which may be fatal in immunocompromised individuals. COVID-19 pandemic has badly affected every part of the world, and still, the situation in the world is getting worse with the emergence of novel variants. The aim of our study is to explore the genome of SARS-CoV2 followed by in silico reverse vaccinology analysis. This will help to identify the most putative vaccine candidate against the virus in a robust manner and enables cost-effective development of vaccines compared with traditional strategies. Methods: The genomic sequencing data is retrieved from NCBI (Reference Sequence Number NC_045512.2). The sequences are explored through comparative genomics approaches by GENOMICS to find out the core genome. A comprehensive set of proteins obtained was employed in computational vaccinology approaches (names of tools?) for the prediction of the best possible B and T cell epitopes through ABCpred and IEDB Analysis Resource, respectively. The multi-epitopes were further tested against human toll-like receptors and cloned in an E. coli plasmid vector. Findings: The designed Multiepitope Subunit Vaccine was non-allergenic, antigenic (0.6543), & non-toxic, with significant connections with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 84.38%. It has 276 amino acids, consisting of an adjuvant with the aid of an EAAAK linker, AAY linkers used to join the 4 CTL epitopes, and GPGPG linkers used to join the 3 HTL epitopes and KK linkers used to join the 7 B-cell epitopes. MESV docking with human pathogenic toll-like receptors-3 (TLR3) exhibited a stable & high binding affinity. An in-silico codon optimization approach was used in the codon system of E. coli (strain K12) to obtain the GC-Content of Escherichia coli (strain K12): 50.7340272413779 and CAI-Value of the improved sequence: 0.9542834278823386. The multi-epitope vaccine’s optimized gene sequence was cloned in-silico in E. coli plasmid vector pET-30a (+), BamHI, and HindIII restriction sites were added to the N and C-terminals of the sequence, respectively. Conclusion: There is a pressing need to combat Covid-19 and we need quick and reliable approaches to Covid-19. By using In-silico approaches, we acquire an effective vaccine that could trigger adequate immune responses at the cellular and humoral levels. The suggested sequences can be further validated through in vivo and in vitro experimentation. Keywords: Covid-19, SARS Cov-2, Pangenome Analysis, Reverse Vaccinology
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500170v1" target="_blank">Pangenome analysis of SARS-CoV2 strains to Identify Potential vaccine targets by Reverse Vaccinology</a>
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</div></li>
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<li><strong>Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19</strong> -
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<div>
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Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veterans’ experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars, who completed a total of four assessments: one every two months for a total duration of six months. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/xf3zb/" target="_blank">Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19</a>
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<li><strong>Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models</strong> -
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<div>
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ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2’s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified an in vivo ACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.499651v1" target="_blank">Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models</a>
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</div></li>
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<li><strong>Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies</strong> -
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<div>
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Since the end of 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant outcompeted other variants and took over the world. After the emergence of original Omicron BA.1, Omicron BA.2 subvariant emerged and outcompeted BA.1. As of July 2022, some BA.2 subvariants, including BA.2.12.1, BA.4 and BA.5, emerged in multiple countries and begun outcompeting original BA.2. Moreover, a novel BA.2 subvariant, BA.2.75, was detected in eight countries including India at the end of June 2022, and preliminary investigations suggest that BA.2.75 is more transmissible over the other BA.2 subvariants. On July 7, 2022, the WHO classified BA.2.75 as a variant-of-concern lineage under monitoring. We have recently demonstrated that BA.4/5 is highly resistant to a therapeutic monoclonal antibody, cilgavimab, than BA.2. The resistance of SARS-CoV-2 variants to therapeutic antibodies can be attributed to the mutations in the viral spike protein. Compared to the BA.2 spike, BA.2.12.1 and BA.4/5 respectively bear two and four mutations in their spike proteins. On the other hand, the majority of BA.2.75 spike bears nine substitutions. The fact that the mutation number in the BA.2.75 spike is larger than those in the BA.4/5 spike raises the possibility that the BA.2.75 spike significantly reduces sensitivity towards therapeutic monoclonal antibodies than BA.2 and BA.4/5. In this study, we generated pseudoviruses harboring the spike proteins of BA.2.75, BA.4/5 and BA.2 and evaluated the efficacy of ten therapeutic monoclonal antibodies and three antibody cocktails against BA.2.75.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500041v1" target="_blank">Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies</a>
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<li><strong>A zebrafish model of COVID-19-associated cytokine storm syndrome reveals that the Spike protein signals via TLR2</strong> -
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<div>
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Understanding the mechanism of virulence of SARS-CoV-2 and host innate immune responses are essential to develop novel therapies. One of the most studied defense mechanisms against invading pathogens, including viruses, are Toll-like receptors (TLRs). Among them, TLR3, TLR7, TLR8 and TLR9 detect different forms of viral nucleic acids in endosomal compartments, whereas TLR2 and TLR4 recognize viral structural and nonstructural proteins outside the cell. Although many different TLRs have been shown to be involved in SARS-CoV-2 infection and detection of different structural proteins, most studies have been performed in vitro and the results obtained are rather contradictory. In this study, we report using the unique advantages of the zebrafish model for in vivo imaging and gene editing that the S1 domain of the Spike protein from the Wuhan strain (S1WT) induced hyperinflammation in zebrafish larvae via a Tlr2/Myd88 signaling pathway and independently of interleukin-1{beta} production. In addition, S1WT also triggered emergency myelopoiesis, but in this case through a Tlr2/Myd88-independent signaling pathway. These results shed light on the mechanisms involved in the COVID-19-associated cytokine storm syndrome.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500031v1" target="_blank">A zebrafish model of COVID-19-associated cytokine storm syndrome reveals that the Spike protein signals via TLR2</a>
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<li><strong>SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1</strong> -
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SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing antibodies with variable cross-neutralizing capacity. Here we show that unlike SARS-CoV-2 Omicron BA.1, which triggered neutralizing antibodies with limited cross-reactivity, BA.4/5 infection triggers highly cross-reactive neutralizing antibodies. Cross-reactivity was observed both in the absence of prior vaccination and also in breakthrough infections following vaccination. This suggests that next-generation vaccines incorporating BA.4, which is spreading globally, might result in enhanced neutralization breadth.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500039v1" target="_blank">SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1</a>
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<li><strong>Fc effector activity and neutralization against SARS-CoV-2 BA.4 is compromised in convalescent sera, regardless of the infecting variant</strong> -
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The SARS-CoV-2 Omicron BA.1 variant, which exhibits high level neutralization resistance, has since evolved into several sub-lineages including BA.4 and BA.5, which have dominated the fifth wave of infection in South Africa. Here we assessed the sensitivity of BA.4 to neutralization and antibody dependent cellular cytotoxicity (ADCC) in convalescent donors infected with four previous variants of SARS-CoV-2, as well as in post-vaccination breakthrough infections (BTIs) caused by Delta or BA.1. We confirm that BA.4 shows high level resistance to neutralization, regardless of the infecting variant. However, breakthrough infections, which trigger potent neutralization, retained activity against BA.4, albeit at reduced titers. Fold reduction of neutralization in BTIs was lower than that seen in unvaccinated convalescent donors, suggesting maturation of neutralizing responses to become more resilient against VOCs in hybrid immunity. BA.4 sensitivity to ADCC was reduced but remained detectable in both convalescent donors and in BTIs. Overall, the high neutralization resistance of BA.4, even to antibodies from BA.1 infections, provides an immunological mechanism for the rapid spread of BA.4 immediately after a BA.1-dominated wave. Furthermore, although ADCC activity against BA.4 was reduced, residual activity may nonetheless contribute to the protection from disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500042v1" target="_blank">Fc effector activity and neutralization against SARS-CoV-2 BA.4 is compromised in convalescent sera, regardless of the infecting variant</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>Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors<br/><b>Sponsor</b>: Central Hospital, Nancy, France<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>Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients</strong> - <b>Condition</b>: Severe COVID-19<br/><b>Interventions</b>: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)<br/><b>Sponsors</b>: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio<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 Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Molnupiravir 200 mg<br/><b>Sponsors</b>: University of Witwatersrand, South Africa; Bill and Melinda Gates Foundation<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>Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies 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>Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Full Intervention; Other: Enhanced Usual Care<br/><b>Sponsors</b>: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)<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 Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PanCytoVir™ (probenecid); Drug: Placebo<br/><b>Sponsor</b>: TrippBio, 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>Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough</strong> - <b>Condition</b>: Post COVID-19<br/><b>Intervention</b>: Drug: Montelukast Sodium Tablets<br/><b>Sponsor</b>: Assiut University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Topical Antibacterial Agents for Prevention of COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV2 Infection<br/><b>Interventions</b>: Drug: Neosporin; Other: Vaseline<br/><b>Sponsors</b>: Yale University; Bill and Melinda Gates Foundation<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">**NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Drug: Placebo; Drug: Experimental drug<br/><b>Sponsor</b>: Medesis Pharma SA<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>Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study</strong> - <b>Condition</b>: Post-COVID19 Condition<br/><b>Interventions</b>: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure<br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits<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 Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Rehabilitation<br/><b>Interventions</b>: Other: Respiratory training with the use of resistance set on respiratory muscle trainer; Other: Respiratory training without resistance set on respiratory muscle trainer<br/><b>Sponsor</b>: Medical University of Bialystok<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>Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention</strong> - <b>Condition</b>: Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention<br/><b>Sponsor</b>: VA Office of Research and Development<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mineralocorticoid Use in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; ARDS<br/><b>Intervention</b>: Drug: Fludrocortisone Acetate 0.1 MG<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Combination Product: Delcetravir dry powder inhaler<br/><b>Sponsor</b>: Esfam Biotech Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Immunogenicity of Ad5-vector Based Vaccine Against Coronavirus Variants in Adults (≥18 Years) Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: mRNA-based COVID-19 vaccine<br/><b>Sponsor</b>: CanSino Biologics Inc.<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>Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability</strong> - Immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike elicits diverse antibodies, but it is unclear if any of the antibodies can neutralize broadly against other beta-coronaviruses. Here, we report antibody WS6 from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was…</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>Binding adaptation of GS-441524 diversifies macro domains and downregulate SARS-CoV-2 de-MARylation capacity</strong> - Viral infection in cells triggers a cascade of molecular defense mechanisms to maintain host-cell homoeostasis. One of these mechanisms is ADP-ribosylation, a fundamental post-translational modification (PTM) characterized by the addition of ADP-ribose (ADPr) on substrates. Poly(ADP-ribose) polymerases (PARPs) are implicated in this process and they perform ADP-ribosylation on host and pathogen proteins. Some viral families contain structural motifs that can reverse this PTM. These motifs 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>Amelioration of SARS-CoV-2 infection by ANO6 phospholipid scramblase inhibition</strong> - As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the viral and cell membranes. Here, we show that ANO6/TMEM16F-mediated cell surface exposure of phosphatidylserine is critical for SARS-CoV-2 entry and that ANO6-selective inhibitors are effective against SARS-CoV-2 infections. Application of the SARS-CoV-2 Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca^(2+) elevation and ANO6-dependent…</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>Viral E protein neutralizes BET protein-mediated post-entry antagonism of SARS-CoV-2</strong> - Inhibitors of bromodomain and extraterminal domain (BET) proteins are possible anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here we show that BET proteins should not be inactivated therapeutically because they are critical antiviral factors at the post-entry level. Depletion of BRD3 or BRD4 in cells overexpressing ACE2 exacerbates SARS-CoV-2 infection; the same is observed when cells with endogenous…</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 systematic exploration of boceprevir-based main protease inhibitors as SARS-CoV-2 antivirals</strong> - Boceprevir is an HCV NSP3 inhibitor that was explored as a repurposed drug for COVID-19. It inhibits the SARS-CoV-2 main protease (M^(Pro)) and contains an α-ketoamide warhead, a P1 β-cyclobutylalanyl moiety, a P2 dimethylcyclopropylproline, a P3 tert-butylglycine, and a P4 N-terminal tert-butylcarbamide. By introducing modifications at all four positions, we synthesized 20 boceprevir-based M^(Pro) inhibitors including PF-07321332 and characterized their M^(Pro) inhibition potency in test tubes…</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>Inhibition of the lectin pathway of complement ameliorates hypocomplementemia and restores serum bactericidal activity in patients with severe 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>Evaluating the Effects of Curcumin on the Cytokine Storm in COVID-19 Using a Chip-Based Multiplex Analysis</strong> - SARS-CoV-2 can stimulate the expression of various inflammatory cytokines and induce the cytokine storm in COVID-19 patients leading to multiple organ failure and death. Curcumin as a polyphenolic compound has been shown to have anti-inflammatory properties and inhibit the release of numerous pro-inflammatory cytokines. We present multiplex analysis using the Evidence Investigator biochip system to determine the effect of curcumin on serum level of cytokines which are typically elevated in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273</strong> - Background: Patients affected by different types of autoimmune diseases, including common conditions such as Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the SARS-CoV-2 specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants.</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>Analysis of the molecular mechanism of Huangqi herb treating COVID-19 with myocardial injury by pharmacological tools, programming software and molecular docking</strong> - CONCLUSIONS: Huangqi may play a therapeutic role in treating COVID-19 with myocardial injury by the effects of resisting virus and protecting myocardium concurrently.</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>Prolonged NHE Activation may be Both Cause and Outcome of Cytokine Release Syndrome in COVID-19</strong> - The release of cytokines and chemokines such as IL-1β, IL-2, IL-6, IL-7, IL-10, TNF-α, IFN-γ, CCL2, CCL3, and CXCL10 is increased in critically ill patients with COVID-19. Excessive cytokine release during COVID-19 is related to increased morbidity and mortality. Several mechanisms are put forward for cytokine release syndrome during COVID-19. Here we would mention a novel pathways. SARS-CoV-2 increases angiotensin II levels by rendering ACE2 nonfunctional. Angiotensin II causes cytokine release…</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>Beneficial effect of polyphenols in COVID-19 and the ectopic F<sub>1</sub> F<sub>O</sub> -ATP synthase: Is there a link?</strong> - COVID-19 has been proposed to be an endothelial disease, as endothelial damage and oxidative stress contribute to its systemic inflammatory and thrombotic events. Polyphenols, natural antioxidant compounds appear as promising agents to prevent and treat COVID-19. Polyphenols bind and inhibit the F(1) F(o) -ATP synthase rotary catalysis. An early target of polyphenols may be the ectopic F(1) F(o) -ATP synthase expressed on the endothelial plasma membrane. Among the pleiotropic beneficial action…</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>Surface Display of Peptides Corresponding to the Heptad Repeat 2 Domain of the Feline Enteric Coronavirus Spike Protein on <em>Bacillus subtilis</em> Spores Elicits Protective Immune Responses Against Homologous Infection in a Feline Aminopeptidase-N-Transduced Mouse Model</strong> - Although feline coronavirus (FCoV) infection is extremely common in cats, there are currently few effective treatments. A peptide derived from the heptad repeat 2 (HR2) domain of the coronavirus (CoV) spike protein has shown effective for inhibition of various human and animal CoVs in vitro, but further use of FCoV-HR2 in vivo has been limited by lack of practical delivery vectors and small animal infection model. To overcome these technical challenges, we first constructed a recombinant…</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>Corona versus Dengue: Distinct Mechanisms for Inhibition of Polyprotein Processing by Antiviral Drugs</strong> - Inhibitors interfering with processing of the viral polyprotein are used successfully for the control of extremely important viral pathogens, such as HIV and most recently SARS-CoV-2. This Viewpoint provides a mechanistic evaluation of a promising antiviral lead compound against dengue virus, JNJ-A07, 4-(3-((1-(4-chlorophenyl)-2-oxo-2-(6-(trifluoromethoxy)indolin-1-yl)ethyl)amino)-5-methoxyphenoxy)butanoic acid. The antiviral effect of JNJ-A07 appears, in our opinion, to be connected to an…</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 Impact on COVID-19 by Intravenous Bevacizumab Used for Hereditary Hemorrhagic Telangiectasia: A Case Report</strong> - Coronavirus disease 2019 (COVID-19) continues as an infectious pandemic. With emphasis on mitigating its impact globally, strategies have been emphasized on prevention to treatment in severe cases. As for pharmacotherapies, many have been researched, with a few being recommended for patients with COVID-19 depending upon their severity. Bevacizumab, a recombinant monoclonal antibody often used for oncological disease and rare genetic disorders, has gained attention in combatting COVID-19 due to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Clove Phytochemicals as Potential Antiviral Drug Candidates Targeting SARS-CoV-2 Main Protease: Computational Docking, Molecular Dynamics Simulation, and Pharmacokinetic Profiling</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause a sudden respiratory disease spreading with a high mortality rate arising with unknown mechanisms. Still, there is no proper treatment available to overcome the disease, which urges the research community and pharmaceutical industries to screen a novel therapeutic intervention to combat the current pandemic. This current study exploits the natural phytochemicals obtained from clove, a traditional natural therapeutic…</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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