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<title>29 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>Prosocial motivation for vaccination</strong> -
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<div>
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Both private and public benefits result from vaccination for transmissible diseases, such as seasonal influenza, measles, and COVID-19. To help inform vaccination efforts for such diseases, we ask whether social preferences—concerns for the well-being of other people—influence one’s decision regarding vaccination. We measure these social preferences for 549 online subjects: We give each subject $4 to play a public-good game and make contributions to public welfare. To the extent that one gets vaccinated out of concern for the health of others, contribution in this game is analogous to an individual’s decision to obtain vaccination. We proxy vaccine demand with individuals’ delay to initially vaccinate for COVID-19. We collect COVID-19 vaccination history separately to avoid experimenter-demand effects. We find a strong result: Contribution in the public-good game is associated with greater demand to voluntarily receive a first dose, and thus also to vaccinate earlier. Compared to a subject who contributes nothing, one who contributes the maximum ($4) is 48% more likely to obtain a first dose voluntarily in the four-month period that we study (April through August 2021). People who are more pro-social are indeed more likely to take a voluntary COVID-19 vaccination. We thus recommend further research on the use of pro-social preferences to help motivate individuals to vaccinate for transmissible diseases, such as the flu and HPV.
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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/emj6v/" target="_blank">Prosocial motivation for vaccination</a>
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</div></li>
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<li><strong>Positive Biases and Psychological Functioning During the COVID-19 Pandemic</strong> -
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<div>
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Many individuals have experienced a multitude of chronic stressors and diminished psychological functioning during COVID-19. The current study examined whether cognitive biases towards positive social media or positive autobiographical memories was related to increases in psychological functioning during COVID-19. Participants were 1071 adults (Mage=46.31; 58% female) recruited from CloudResearch/Turk Prime in the spring and summer of 2020. Participants reported on their social media consumption and autobiographical recall, positive and negative affect, and dysphoria symptoms. Results indicated that positively biased social media consumption was related to higher levels of positive affect, and positively biased autobiographical recall was related to lower levels of negative affect and dysphoria symptoms. Relations between positively biased social media consumption and negative affect and dysphoria symptoms differed by racial group; positively biased social media consumption was related to higher levels of negative affect for Black/African American individuals and lower levels of negative affect for Asian American/Pacific Islanders, and to lower levels of dysphoria symptoms for White individuals and Asian American/Pacific Islander individuals. The findings point to potential psychological benefits of positive biases during chronic stressors with some variation across racial groups.
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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/fjnh8/" target="_blank">Positive Biases and Psychological Functioning During the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>Spirituality is associated with Covid-19 vaccination scepticism</strong> -
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<div>
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Vaccine scepticism poses a significant global health risk, which has again become clear during the ongoing Covid-19 pandemic. Previous research has identified spirituality as an important contributor to general vaccine scepticism. In the present manuscript, we assessed whether spirituality similarly contributes to scepticism towards Covid-19 vaccines, including hesitancy in deciding to be vaccinated and vaccine uptake. We conducted two studies online in the UK (N = 585) in late 2020/early 2021. As expected, individuals who strongly identified as spiritual were more sceptical about Covid-19 vaccines. This association was explained by low faith in science, but not by conspiracy beliefs. Importantly, among the vaccinated participants, those who were more spiritual hesitated more in deciding to get a Covid-19 vaccine. Using structural equation modelling (SEM), we further found that spirituality directly predicted lower likelihood of being vaccinated against Covid-19 (Study 3, N = 456). We also identified low science literacy as an additional predictor of Covid-19 scepticism, but not actual vaccine uptake. To conclude, spiritual beliefs are an important factor to consider when aiming to increase understanding of vaccine-related science scepticism and vaccination rejection.
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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/axjnr/" target="_blank">Spirituality is associated with Covid-19 vaccination scepticism</a>
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</div></li>
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<li><strong>Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: A SARS-CoV-2 mRNA vaccine booster elicits sufficient antibody responses that protect against COVID-19, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 two-dose primary series. Spike-specific IgG titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for seven days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (beta=0.305, p<0.001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk: 3.97 [95% confidence interval: 2.48-6.35]); however, the IgG titers after the booster dose were not affected by fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions would not interfere with the elevation of specific IgG titers.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.25.22277569v1" target="_blank">Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication</a>
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</div></li>
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<li><strong>Risk of BA.5 infection in individuals exposed to prior SARS-CoV-2 variants</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The SARS-CoV-2 omicron BA.5 subvariant is progressively displacing earlier subvariants, BA.1 and BA.2, in many countries. One possible explanation is the ability of BA.5 to evade immune responses elicited by prior BA.1 and BA.2 infections. The impact of BA.1 infection on the risk of reinfection with BA.5 is a critical issue because adapted vaccines under current clinical development are based on BA.1. We used the national Portuguese COVID-19 registry to analyze the risk of BA.5 infection in individuals without a documented infection or previously infected during periods of distinct variants9 predominance (Wuhan-Hu-1, alpha, delta, BA.1/BA.2). National predominance periods were established according to the national SARS-CoV-2 genetic surveillance data (when one variant represented >90% of the sample isolates). We found that prior SARS-CoV-2 infection reduced the risk for BA.5 infection. The protection effectiveness, related to the uninfected group, for a first infection with Wuhan-Hu-1 was 52.9% (95% CI, 51.9 - 53.9%), for Alpha 54.9% (51.2 - 58.3%), for Delta 62.3% (61.4 - 63.3%), and for BA.1/BA.2 80.0% (79.7 - 80.2%). The results ought to be interpreted in the context of breakthrough infections within a population with a very high vaccine coverage (>98% of the study population completed the primary vaccination series). In conclusion, infection with BA.1/BA.2 reduces the risk for breakthrough infections with BA.5 in a highly vaccinated population. This finding is critical to appraise the current epidemiological situation and the development of adapted vaccines.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.27.22277602v1" target="_blank">Risk of BA.5 infection in individuals exposed to prior SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>Taxonium: a web-based tool for exploring large phylogenetic trees</strong> -
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<div>
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The COVID-19 pandemic has resulted in a step change in the scale of sequencing data, with more genomes of SARS-CoV-2 having been sequenced than any other organism on earth. Previous web-based tools for phylogenetic exploration were not able to directly scale to this size of tree. We have developed Taxonium, a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes. Taxonium allows visualisation of mutation-annotated trees, where the genotypes at each internal node are indicated, and also links each node to associated metadata. An optional server-side backend permits rapid loading for widely used datasets, while a client-only mode allows the exploration of niche or sensitive data. Taxonium is an open-source tool which can be applied to any large tree. We provide an application for exploring a public tree of more than five million SARS-CoV-2 sequences at http://cov2tree.org, the broader Taxonium tool at http://taxonium.org, and source code at https://github.com/theosanderson/taxonium.
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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/10.1101/2022.06.03.494608v2" target="_blank">Taxonium: a web-based tool for exploring large phylogenetic trees</a>
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</div></li>
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<li><strong>Correlates of protection for booster doses of the BNT162b2 vaccine</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Variants of concern (VOC) of SARS-CoV2 and waning immunity pose a serious global problem. Overall, vaccination and prior infection appear to provide significant protection to the majority of individuals, but some remain susceptible to infection and severe disease. Rigorously identifying a broad spectrum of correlates of protection (COP) is necessary to identify these susceptible populations. The extent to which additional booster doses provide protection is also poorly understood. To address this need, we conducted a multicenter prospective study assessing the association between serological profiles and the risk for SARS-CoV-2 infection, comparing those vaccinated with three to four doses of Pfizer BNT162b2 vaccine. Of 608 healthy adults, 365 received three doses and 243 received four doses. During the first 90 days of followup, 239 (39%) were infected, of whom 165/365 (45%) received 3 doses and 74/243 (30%) four doses. We found that the fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple variants, and reduced the risk of symptomatic infection by 37% [95% I, 15% - 54%]. We identified several parameters based on IgG and IgA binding that were COPs . The strongest association with infection risk was reduced IgG levels to RBD mutants and IgA levels to VOCs, which was a COP in the three-dose group (HR=6.34, p=0.008) and in the four-dose group (HR=8.14, p=0.018). A combination of two commercially available ELISA assays were also associated with protection in both groups (HR = 1.84, p = 0.002; HR = 2.01, p = 0.025, respectively). Most importantly, we identified a subset of individuals with low antibody levels after three doses of vaccine that responded with a significant boost in neutralizing antibody titers after a fourth dose, but were still at significantly increased susceptibility to infection when compared to those who had pre-existing high levels of neutralizing antibodies. Thus, we identify a highly susceptible population that remains susceptible despite apparent responsiveness to vaccines. Further, we develop several specific and sensitive COPs that show dramatic effect sizes and may be utilized to identify individuals most at risk from future exposures.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.16.22277626v2" target="_blank">Correlates of protection for booster doses of the BNT162b2 vaccine</a>
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</div></li>
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<li><strong>Reasons underlying the intention to vaccinate children aged 5-11 against COVID-19: A cross-sectional study of parents in Israel, November 2021</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background Vaccination is a key tool to mitigate the impact of the COVID-19 pandemic. In Israel, COVID-19 vaccines became available to adults in December 2020 and to 5 to 11 year old children in November 2021. Ahead of the vaccine roll-out in children, we aimed to determine whether parents intended to vaccinate their children and describe reasons for their intentions. Methods We recruited parents on social media and collected information on parental socio-demographic characteristics, COVID-19 vaccine history, intention to vaccinate their children against COVID-19, and reasons for parental decisions, using an anonymous online survey. We identified associations between parental characteristics and intention to vaccinate children using a logistic regression model and described reasons for intentions to vaccinate or not using proportions together with 95% confidence intervals (CI). Results 1837 parents participated. Parental non-vaccination and having experienced major vaccination side effects were strongly associated with non-intention to vaccinate their children (OR 0.09 and 0.18 respectively, p<0.001). Compared with others, parents who were younger, lived in the socioeconomically deprived periphery, and belonged to the Arab population had lower intentions to vaccinate their children. Commonly stated reasons for non-intention to vaccinate included vaccine safety and efficacy (53%, 95%CI 50-56) and the belief that COVID-19 was a mild disease (73%, 95%CI 73-79). The most frequently mentioned motives for intending to vaccine children was returning to normal social and educational life (89%, 95%CI 87-91). Conclusion Parental socio-demographic background and their own vaccination experience was associated with intention to vaccinate their children aged 5 to 11. Intention to vaccinate was mainly for social and economic reasons rather than health, whereas non-intention to vaccinate mainly stemmed from health concerns. Understanding rationales for COVID-19 vaccine rejection or acceptance, as well as parental demographic data, can pave the way for intentional educational campaigns to encourage not only vaccination against COVID-19, but also regular childhood vaccine programming.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.03.22271793v3" target="_blank">Reasons underlying the intention to vaccinate children aged 5-11 against COVID-19: A cross-sectional study of parents in Israel, November 2021</a>
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</div></li>
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<li><strong>A Mesoscale Agent Based Modeling Framework For Flow-mediated Infection Transmission In Indoor Occupied Spaces</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The ongoing Covid-19 pandemic, and its associated public health and socioeconomic burden, has reaffirmed the necessity for a comprehensive understanding of flow-mediated infection transmission in occupied indoor spaces. This is an inherently multiscale problem, and suitable investigation approaches that can enable evidence-based decision-making for infection control strategies, interventions, and policies; will need to account for flow physics, and occupant behavior. Here, we present a mesoscale infection transmission model for human occupied indoor spaces, by integrating an agent-based human interaction model with a flow physics model for respiratory droplet dynamics and transport. We outline the mathematical and algorithmic details of the modeling framework, and demonstrate its validity using two simple simulation scenarios that verify each of the major sub-models. We then present a detailed case-study of infection transmission in a model indoor space with 60 human occupants; using a systematic set of simulations representing various flow scenarios. Data from the simulations illustrate the utility and efficacy of the devised mesoscale model in resolving flow-mediated infection transmission; and elucidate key trends in infection transmission dynamics amongst the human occupants.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.20.22275409v2" target="_blank">A Mesoscale Agent Based Modeling Framework For Flow-mediated Infection Transmission In Indoor Occupied Spaces</a>
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</div></li>
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<li><strong>Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Heterologous orally administered adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in individuals who were primed with two-dose CoronaVac (an inactivated SARS-CoV-2 vaccine, by Sinovac) previously, has been reported to be safe and highly immunogenic within 28 days post-boosting. However, antibody persistence and safety up to 6 months of this regimen are not been reported yet. Methods: This is a randomized, open label, single-center trial on safety and immunogenicity of heterologous boost immunization with an orally administered aerosolised Ad5-nCoV vs. homologous boost immunization with CoronaVac after two-dose priming with CoronaVac in Chinese adults aged 18 years and older (NCT05043259). We followed the participants in this trial, including 140 in the low-dose aerosolised Ad5-nCoV group, 139 in the high-dose aerosolised Ad5-nCoV group, and 140 in the CoronaVac group for 6 months. Neutralising antibodies (NAbs) against live wild-type SARS-CoV-2 virus and omicron variant, and receptor-binding domain (RBD)-specific IgG antibodies were detected in serum samples collected at 28 days, 3 months, and 6 months after the booster dose. Serious adverse events (SAEs) were documented till month 6. Results: The low-dose and high-dose heterologous boost immunisation groups had NAb GMTs against live wild-type SARS-CoV-2 of 1937.3 [95% CI 1466.9, 2558.4] and 1350.8 [95% CI 952.6, 1915.3], which were 26.4 folds and 18.4 folds higher than that the CoronaVac group did (73.5 [95%CI 52.3, 103.3]) at 28 days. The low-dose and high-dose heterologous boost immunisation groups had NAb GMTs against live wild-type SARS-CoV-2 of 530.1 (95% CI 412.5, 681.1) and 457.6 (95%CI 349.4, 599.2), which were 26.0 folds and 22.4 folds higher than that the CoronaVac group did (20.4 [95%CI 14.3, 29.1]) at 3 months, respectively. At 6 months, the low-dose and high-dose heterologous booster groups had NAb GMTs against live wild-type SARS-CoV-2 of 312.9 (95%CI 237.7, 411.8) and 251.1 (95%CI 178.2, 354.0), which were 30.1 folds and 24.1 folds higher than the CoronaVac group did (10.4 [95%CI 7.8, 14.0]), respectively. Additionally, the low-dose and high-dose heterologous booster groups had NAb GMTs against live omicron variant of 52.0 (95%CI 37.2, 72.6) and 23.1 (95%CI 15.7, 33.9) at 28 days, 27.9 (95% CI 18.8, 41.3) and 23.3 (95%CI 16.2, 33.3) at 3 months, 16.0 (95%CI 10.9, 23.5) and 12.0 (95%CI 8.5, 16.8) at 6 months, respectively. However, nearly all participants had no detectable NAbs for omicron variant in the CoronaVac group at either 28 days, 3 months, or 6 months. No vaccine-related SAEs were observed. Conclusions: These data suggested that heterologous aerosolised Ad5-nCoV following two-dose CoronaVac priming was safe and persistently more immunogenic than three-dose CoronaVac, although immune responses waned over time.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.26.22278072v1" target="_blank">Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolised Ad5-nCoV in individuals primed with two-dose CoronaVac previously</a>
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</div></li>
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<li><strong>Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2</strong> -
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<div>
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The nonstructural protein 3 (NSP3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a conserved macrodomain enzyme (Mac1) that is critical for pathogenesis and lethality. While small molecule inhibitors of Mac1 have great therapeutic potential, at the outset of the COVID-19 pandemic there were no well-validated inhibitors for this protein nor, indeed, the macrodomain enzyme family, making this target a pharmacological orphan. Here, we report the structure-based discovery and development of several different chemical scaffolds exhibiting low- to sub-micromolar affinity for Mac1 through iterations of computer-aided design, structural characterization by ultra-high resolution protein crystallography, and binding evaluation. Potent scaffolds were designed with in silico fragment linkage and by ultra-large library docking of over 450 million molecules. Both techniques leverage the computational exploration of tangible chemical space and are applicable to other pharmacological orphans. Overall, 160 ligands in 119 different scaffolds were discovered, and 152 Mac1-ligand complex crystal structures were determined, typically to 1 [A] resolution or better. Our analyses discovered selective and cell-permeable molecules, unexpected ligand-mediated protein dynamics within the active site, and key inhibitor motifs that will template future drug development against Mac1.
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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/10.1101/2022.06.27.497816v2" target="_blank">Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2</a>
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</div></li>
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<li><strong>Functional characterization of the RNA interference pathway in A. fumigatus reveals its potential for antifungal therapy</strong> -
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<div>
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RNA-based medicines are an emerging class of drugs that are changing the way we treat infectious diseases. The versatility of this class is clearly on display in the rapid design and adaptation of the mRNA vaccines to SARS-CoV-2. Despite the success of these approaches against viruses, research into RNA-based therapeutics to treat human fungal pathogens, a major source of human morbidity and mortality, is lacking. Here, we provide an improved mechanistic description of the RNA interference pathway in Aspergillus fumigatus and assess this pathway as a potential target for RNA-based medicines. We describe the genetic variation in RNA interference-associated genes in a large collection of environmental and clinical genomes, reveal the proteins regulated by the RNA interference system using advanced proteomics analysis, and define the components essential for hairpin-induced silencing. We then exploit this pathway using a heterologously expressed hairpin RNA construct to silence the pabA gene of A. fumigatus to inhibit growth. The data presented here provide a foundation for a mechanistic description of novel RNA regulatory pathways in A. fumigatus and reaffirm the importance of improved fungal RNA delivery mechanisms for the future design of RNA-based therapeutics against this important human fungal pathogen.
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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/10.1101/2022.07.28.501871v1" target="_blank">Functional characterization of the RNA interference pathway in A. fumigatus reveals its potential for antifungal therapy</a>
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</div></li>
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<li><strong>Effect of Delta and Omicron mutations on the RBD-SD1 do-main of the Spike protein in SARS-CoV-2 and the Omicron mutations on RBD-ACE2 interface complex</strong> -
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<div>
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The receptor-binding domain (RBD) is the essential part in the Spike-protein (S-protein) of SARS-CoV-2 virus that directly binds to the human ACE2 receptor, making it a key target for many vaccines and therapies. Therefore, any mutations at this domain could affect the efficacy of these treatments as well as the viral-cell entry mechanism. We introduce ab initio DFT-based computa-tional study that mainly focuses on two parts: (1) Mutations effects of both Delta and Omicron variants in the RBD-SD1 domain. (2) Impact of Omicron RBD mutations on the structure and properties of the RBD-ACE2 interface system. The in-depth analysis is based on the novel concept of amino acid-amino acid bond pair units (AABPU) that reveal the differences between the Delta and/or Omicron mutations and its corresponding wild-type strain in terms of the role played by non-local amino acid interactions, their 3D shapes and sizes, as well as contribution to hydrogen bonding and partial charge distributions. Our results also show that the interaction of Omicron RBD with ACE2 significantly increased its bonding between amino acids at the interface providing information on the implications of penetration of S-protein into ACE2, and thus offering a possible explanation for its high infectivity. Our findings enable us to present in more conspicuous atomic level detail the effect of specific mutations that may help in predicting and/or mitigating the next variant of concern.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.28.501901v1" target="_blank">Effect of Delta and Omicron mutations on the RBD-SD1 do-main of the Spike protein in SARS-CoV-2 and the Omicron mutations on RBD-ACE2 interface complex</a>
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</div></li>
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<li><strong>Molecular basis for antiviral activity of pediatric neutralizing antibodies targeting SARS-CoV-2 Spike receptor binding domain</strong> -
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Neutralizing antibodies (NAbs) hold great promise for clinical interventions against SARS-CoV-2 variants of concern (VOCs). Understanding NAb epitope-dependent antiviral mechanisms is crucial for developing vaccines and therapeutics against VOCs. Here we characterized two potent NAbs, EH3 and EH8, isolated from an unvaccinated pediatric patient with exceptional plasma neutralization activity. EH3 and EH8 cross-neutralize the early VOCs and mediate strong Fc-dependent effector activity in vitro. Structural analyses of EH3 and EH8 in complex with the receptor-binding domain (RBD) revealed the molecular determinants of the epitope-driven protection and VOC-evasion. While EH3 represents the prevalent IGHV3-53 NAb whose epitope substantially overlaps with the ACE2 binding site, EH8 recognizes a narrow epitope exposed in both RBD-up and RBD-down conformations. When tested in vivo, a single-dose prophylactic administration of EH3 fully protected stringent K18-hACE2 mice from lethal challenge with Delta VOC. Our study demonstrates that protective NAbs responses converge in pediatric and adult SARS-CoV-2 patients.
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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/10.1101/2022.07.27.501708v1" target="_blank">Molecular basis for antiviral activity of pediatric neutralizing antibodies targeting SARS-CoV-2 Spike receptor binding domain</a>
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</div></li>
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<li><strong>P2G3 human monoclonal antibody neutralizes SARS-CoV-2 Omicron subvariants including BA.4 and BA.5 and Bebtelovimab escape mutants</strong> -
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The rapid evolution of SARS-CoV-2 has led to a severe attrition of the pool of monoclonal antibodies still available for COVID-19 prophylaxis or treatment. Omicron subvariants notably escape most antibodies developed so far, with Bebtelovimab last amongst clinically approved therapeutic antibodies to display still good activity against all of them including the currently dominant BA.4/BA.5. We recently described P2G3, a broadly active SARS-CoV-2 monoclonal antibody, which targets a region of Spike partly overlapping with the site recognized by Bebtelovimab. Here, we reveal that P2G3 efficiently neutralizes SARS-CoV-2 omicron subvariants including BA.4/BA.5. We further demonstrate that P2G3 neutralizes Omicron BA.2 and BA.4 mutants escaping Bebtelovimab blockade, whereas the converse is not true.
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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/10.1101/2022.07.28.501852v1" target="_blank">P2G3 human monoclonal antibody neutralizes SARS-CoV-2 Omicron subvariants including BA.4 and BA.5 and Bebtelovimab escape mutants</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Puerto Rico COVID-19 Vaccine Uptake Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Educational intervention<br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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 Learn About a New COVID-19 RNA Vaccine Candidate as a Booster Dose in COVID-19 Vaccine-Experienced Healthy Adults</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: BNT162b5 Bivalent (WT/OMI BA.2); Biological: BNT162b2 Bivalent (WT/OMI BA.1)<br/><b>Sponsors</b>: BioNTech SE; Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Monitoring the Efficacy of a Probiotic Dietary Supplement SmartProbio C in Patients With Severe COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Dietary Supplement: SmartProbio C; Dietary Supplement: Placebo<br/><b>Sponsors</b>: Medi Pharma Vision; Veterinary Research Institute; Brno University Hospital<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>Beta-glucans for Hospitalised Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: MC 3x3; Drug: Placebo<br/><b>Sponsors</b>: Concentra Educacion e Investigación Biomédica; Wohlstand Pharmaceutical<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 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>An Observer-blind, Cohort Randomized, Exploratory Phase 3 Study to Evaluate the Safety and Immunogenicity of Recombinant Covid-19 Vaccine, mRNA Covid-19 Vaccine and Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine as 4th Dose in Individuals Primed/ Boosted With Various Regimens</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth; Biological: Clover SCB-2019<br/><b>Sponsors</b>: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation; University of Oxford<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of Recombinant COVID-19 Vaccine (Sf9 Cell) as a Booster</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: Recombinant COVID-19 Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of Recombinant COVID-19 Variant Vaccine (Sf9 Cell) as a Booster</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: Recombinant COVID-19 variant Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated; Biological: mRNA COVID-19 vaccine (Moderna); Biological: Viral Vector COVID-19 vaccine (AstraZeneca)<br/><b>Sponsor</b>: WestVac Biopharma 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>Effect of Pulmonary Rehabilitation Program on Post Hospitalization Severe COVID- 19 Patients</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Intervention</b>: Combination Product: respiratory exercises - incentive spirometer - walking<br/><b>Sponsor</b>: Fayoum University Hospital<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>Physiotherapy in Post COVID-19 Syndrome Patients</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: Cognitive behavioral principles-based treatment program; Other: Control intervention<br/><b>Sponsor</b>: Universidad de Granada<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>Rehabilitation for People With Post COVID-19 Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: Multidimensional intervention; Other: Control intervention<br/><b>Sponsor</b>: Universidad de Granada<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>Xanthohumol as an Adjuvant Therapy in Critically Ill COVID-19 Patients</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/<br/><b>Sponsor</b>: Medical University of Lublin<br/><b>Suspended</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Trial of Immuno-bridging Between Different Manufacture Scales of Recombinant COVID-19 Vaccine (Sf9 Cell)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Pneumonia<br/><b>Intervention</b>: Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma 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 CHW Intervention to Identify and Decrease Barriers to COVID 19 Testing & Vaccination</strong> - <b>Conditions</b>: Vaccine Hesitancy; COVID-19 Testing; Community Health Workers<br/><b>Intervention</b>: Behavioral: Community Health Worker led curriculum<br/><b>Sponsors</b>: Charles Drew University of Medicine and Science; Los Angeles County Department of Public Health; National Library of Medicine (NLM)<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 to Evaluate Safety and Immunogenicity of COVID-19 Vaccine in Children 6 Months to < 12 Years</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Biological/Vaccine: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Initial Vaccination Period); Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Open Label Crossover Vaccination period); Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Booster Vaccination); Other: Placebo<br/><b>Sponsor</b>: Novavax<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<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>Secondary Immunodeficiency in Rheumatology</strong> - Secondary Immunodeficiency in Rheumatology Abstract. For the treatment of autoimmune and autoinflammatory diseases an immunosuppressive therapy with conventional, small molecule or biological disease modifying anti-rheumatic drugs (DMARDS) plays a key role. This may lead to secondary immunodeficiency with an increased risk for infections, which we discuss in the present article. The risk for reactivation of chronic hepatitis B increases particularly with glucocorticoid dosages of ≥ 20mg/d for…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Pandemic and SMEs Performance Decline: The Mediating Role of Management Innovation and Organizational Resilience</strong> - It is a major practical problem to find out a pathway for firms to quickly recover from the performance decline in the context of the COVID-19 pandemic and other sudden major crisis in the current academic circles. Based on event system theory and structural adjustment to regain fit model, this paper empirically explores the impact of the COVID-19 pandemic on SMEs performance decline and discusses the management innovation response and organizational resilience mechanism of firms by virtue 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>An Efficient Modern Strategy to Screen Drug Candidates Targeting RdRp of SARS-CoV-2 With Potentially High Selectivity and Specificity</strong> - Desired drug candidates should have both a high potential binding chance and high specificity. Recently, many drug screening strategies have been developed to screen compounds with high possible binding chances or high binding affinity. However, there is still no good solution to detect whether those selected compounds possess high specificity. Here, we developed a reverse DFCNN (Dense Fully Connected Neural Network) and a reverse docking protocol to check a given compound’s ability to bind…</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>Addition of Camellia sinensis extract to water to disinfect respiratory viruses accumulated over different surfaces</strong> - New precautions have become part of our daily life since COVID-19 pandemic such as wearing masks, maintaining distance and disinfecting products bought from markets before using them which is exhausting. We aimed to test the inhibitory effect of Camellia sinensis (black tea) water extracts on respiratory viruses and the inhibition of viruses accumulated over different surface types after being soaked in water supplemented with the extracts. Two water extraction methods (extract A: maceration at…</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>Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies</strong> - During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many of the FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro and remarkable efficacy against COVID-19 in clinical trials, no pharmaceutical products have yet been declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes for the treatment…</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>Optimization and evaluation of a live virus SARS-CoV-2 neutralization assay</strong> - Virus neutralization assays provide a means to quantitate functional antibody responses that block virus infection. These assays are instrumental in defining vaccine and therapeutic antibody potency, immune evasion by viral variants, and post-infection immunity. Here we describe the development, optimization and evaluation of a live virus microneutralization assay specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this assay, SARS-CoV-2 clinical isolates are…</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>Urtica dioica Agglutinin: A plant protein candidate for inhibition of SARS-COV-2 receptor-binding domain for control of Covid19 Infection</strong> - Despite using effective drugs and vaccines for Covid 19, due to some limitations of current strategies and the high rate of coronavirus mutation, the development of medicines with effective inhibitory activity against this infection is essential. The SARS-CoV-2 enters the cell by attaching its receptor-binding domain (RBD) of Spike to angiotensin-converting enzyme-2 (ACE2). According to previous studies, the natural peptide Urtica dioica agglutinin (UDA) exhibited an antiviral effect on…</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>DMV biogenesis during β-coronavirus infection requires autophagy proteins VMP1 and TMEM41B</strong> - Upon entering host cells, β-coronaviruses specifically induce generation of replication organelles (ROs) from the endoplasmic reticulum (ER) through their nonstructural protein 3 (nsp3) and nsp4 for viral genome transcription and replication. The most predominant ROs are double-membrane vesicles (DMVs). The ER-resident proteins VMP1 and TMEM41B, which form a complex to regulate autophagosome and lipid droplet (LD) formation, were recently shown to be essential for β-coronavirus infection. Here…</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>An Update on Promising Agents against COVID-19: Secondary Metabolites and Mechanistic Aspects</strong> - CONCLUSION: Prospective treatments targeted at the life cycle stages of the virus may eventuate from research endeavors, and it must not be discounted that therapy originally derived from plant secondary metabolite sources may potentially have a part to play.</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>Propofol directly binds to and inhibits TLR7</strong> - Sedatives/anesthetics are important medical tools to facilitate medical care and increase patients’ comfort. Increasingly, there is recognition that sedatives/anesthetics can modulate immune functions. Toll-like receptors (TLRs) are major pattern recognition receptors involved in the recognition of microbial components. TLR7 recognizes single-strand RNA virus such as influenza and SARS-CoV2 viruses and initiates interferon (IFN) responses. IFN production triggered by TLR7 stimulation is a…</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>Equine Anti-SARS-CoV-2 Serum (ECIG) Binds to Mutated RBDs and N Proteins of Variants of Concern and Inhibits the Binding of RBDs to ACE-2 Receptor</strong> - The COVID-19 pandemic caused by the severe acute syndrome virus 2 (SARS-CoV-2) has been around since November 2019. As of early June 2022, more than 527 million cases were diagnosed, with more than 6.0 million deaths due to this disease. Coronaviruses accumulate mutations and generate greater diversity through recombination when variants with different mutations infect the same host. Consequently, this virus is predisposed to constant and diverse mutations. The SARS-CoV-2 variants 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>Potent and Selective Covalent Inhibition of the Papain-like Protease from SARS-CoV-2</strong> - Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 is essential for viral replication. In addition, PLpro dysregulates the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins. As a result, PLpro is a promising target for inhibition by small-molecule therapeutics….</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>Cellular and Molecular Mechanism of Pulmonary Fibrosis Post-COVID-19: Focus on Galectin-1, -3, -8, -9</strong> - Pulmonary fibrosis is a consequence of the pathological accumulation of extracellular matrix (ECM), which finally leads to lung scarring. Although the pulmonary fibrogenesis is almost known, the last two years of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its post effects added new particularities which need to be explored. Many questions remain about how pulmonary fibrotic changes occur within the lungs of COVID-19 patients, and whether 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>An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding</strong> - CONCLUSION: ARND could be considered as a safe anti-SARS-CoV-2 agent with potential to prevent SARS-CoV-2 coronavirus infection.</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>Protein Scaffold-Based Multimerization of Soluble ACE2 Efficiently Blocks SARS-CoV-2 Infection In Vitro and In Vivo</strong> - Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS-CoV-2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than…</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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