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186 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>11 August, 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>Inhaled Fluticasone for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial</strong> -
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Background: The effectiveness of inhaled corticosteroids to shorten time to symptom resolution or prevent hospitalization or death among outpatients with mild-to-moderate coronavirus 2019 (Covid-19) is unclear. Methods: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged >=30 years, experiencing >=2 symptoms of acute infection for <=7 days were randomized to inhaled fluticasone furoate 200 mcg once daily for 14 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results: Of those eligible for the fluticasone arm, 656 were randomized to and received inhaled fluticasone; 621 received concurrent placebo. There was no evidence of improvement in time to recovery with fluticasone compared with placebo (hazard ratio [HR] 1.01, 95% credible interval [CrI] 0.91-1.12; posterior probability for benefit [HR>1]=0.56). Twenty-four participants (3.7%) in the fluticasone arm had urgent care or emergency department visits or were hospitalized compared with 13 (2.1%) in the pooled, concurrent placebo arm (HR 1.9, 95% CrI 0.8-3.5; posterior probability for benefit [HR<1]=0.03). Three participants in each arm were hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusions: Treatment with inhaled fluticasone furoate for 14 days did not result in improved time to recovery among outpatients with Covid-19 in the United States during the delta and omicron variant surges.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.12.22277548v2" target="_blank">Inhaled Fluticasone for Outpatient Treatment of Covid-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial</a>
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</div></li>
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<li><strong>Ivermectin for Treatment of Mild-to-Moderate COVID-19 in the Outpatient Setting: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial</strong> -
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Background: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the United States with mild-to-moderate symptomatic coronavirus disease 2019 (COVID-19) is unknown. Objective: We evaluated the efficacy of ivermectin 400 mcg/kg daily for 3 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial to evaluate repurposed therapies in outpatients with mild-to-moderate COVID-19. Non-hospitalized adults age >=30 years with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for <=7 days were randomized to receive ivermectin 400 mcg/kg daily for 3 days or placebo. The main outcome measure was time to sustained recovery, defined as achieving at least 3 consecutive days without symptoms. Secondary outcomes included a composite of hospitalization or death by day 28. Results: Of the 3457 participants who consented to be evaluated for inclusion in the ivermectin arm, 1591 were eligible for this study arm, randomized to receive ivermectin 400 mcg/kg (n=817) or placebo (n=774), and received study drug. Of those enrolled, 47% reported receiving at least 2 doses of SARS-CoV-2 vaccination. The posterior probability for any improvement in time to recovery was 0.91 (hazard ratio 1.07, 95% credible interval 0.96 to 1.17). The posterior probability of this benefit exceeding 24 hours was less than 0.01, as measured by the difference in mean time unwell. Hospitalizations or deaths were uncommon (ivermectin [n=10]; placebo [n=9]). Ivermectin at 400 mcg/kg was safe and without serious adverse events as compared with placebo (ivermectin [n=10]; placebo [n=9]). Conclusions: Ivermectin dosed at 400 mcg/kg daily for 3 days resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19 in the United States during the delta and omicron variant time periods. Trial registration: ClinicalTrials.gov Identifier: NCT04885530.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.10.22276252v2" target="_blank">Ivermectin for Treatment of Mild-to-Moderate COVID-19 in the Outpatient Setting: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial</a>
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<li><strong>Leveraging social network topology could improve the efficiency of SARS-CoV-2 epidemic control strategies in resource-limited contexts</strong> -
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Targeted surveillance allows public health authorities to implement testing and isolation strategies when diagnostic resources are limited. When transmission patterns are determined by social contact rates, the consideration of social network topologies in testing schemes is one avenue for targeted surveillance, specifically by prioritizing those individuals likely to contribute disproportionately to onward transmission. Yet, it remains unclear how to implement such surveillance and control when network data is unavailable, as is often the case in resource-limited settings. We evaluated the efficiency of a testing strategy that targeted individuals based on their degree centrality on a social network compared to a random testing strategy in the context of low testing capacity. We simulated SARS-CoV-2 dynamics on two contact networks from rural Madagascar and measured the epidemic duration, infection burden, and tests needed to end the epidemics. In addition, we examined the robustness of this approach when individuals9 true degree centralities were unknown and were instead estimated via readily-available socio-demographic variables (age, gender, marital status, educational attainment, and household size). Targeted testing reduced the infection burden by between 5 - 50% at low testing capacities, while requiring up to 28% fewer tests than random testing. Further, targeted tested remained more efficient when the true network topology was unknown and prioritization was based on socio-demographic characteristics, demonstrating the feasibility of this approach under realistic conditions. Incorporating social network topology into epidemic control strategies is an effective public health strategy for health systems suffering from low testing capacity and can be implemented via socio-demographic proxies when social networks are unknown.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.20.22275359v2" target="_blank">Leveraging social network topology could improve the efficiency of SARS-CoV-2 epidemic control strategies in resource-limited contexts</a>
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</div></li>
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<li><strong>Mental well-being during Covid-19 in adults, mothers and children: behavioral evidence and neural premarkers</strong> -
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We describe data on an extensively characterized group of children and adults (N=69, 41♀, age range=7-51y, including 26 children and mothers) with a total of ~2’500 tests conducted prior to and during the Covid-19 pandemic. Our findings indicate significant effects of Covid-19-related restrictions on mental well-being and psychosocial functioning in children and adults, with changes associated with duration or easing of restrictions. Well-being in mother-child dyads was strongly correlated. For children, time spent outside and friends met were a significant predictor of mood. Additionally, neural correlates of mentalizing in prefrontal regions, assessed prior to Covid-19, preceded later development of fear of illnesses and viruses for all participants, while, among mothers, temporoparietal activation preceded higher perceived burden of care during restrictions.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/pdj7n/" target="_blank">Mental well-being during Covid-19 in adults, mothers and children: behavioral evidence and neural premarkers</a>
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<li><strong>Direct and indirect effects of dorsolateral prefrontal cortex and emotion regulation strategy use on mental health during Covid-19</strong> -
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Background. Covid-19 and associated restrictions have been linked to negative mental health outcomes across the globe. Cognitive emotion regulation strategies constitute means to mitigating negative affect resulting from stressful life events, possibly offering an opportunity to change negative consequences associated with pandemics. Neuronally, emotion regulation is supported by prefrontal and limbic brain regions, but a direct investigation of brain structural characteristics in association with contextual emotion regulation during prolonged stressful events is yet missing. Methods. Variations in cognitive emotion regulation strategy use, anxiety and depression scores were assessed in 43 adults (31♀/12♂, age=35.14±9.20y) during the first months following Covid-19 onset and again at the end of 2020 (seven repeated measures assessments). Pre-pandemic behavioral and neuroimaging measures were available for all participants, allowing the investigation of mediating effects of pre-pandemic emotion regulatory brain structures and use of cognitive emotion regulation strategies during the pandemic on mental well-being at the beginning and end of the first pandemic year. Results. Heightened, but varying levels of anxiety and depression were observed across 2020. While adaptive emotion regulation strategies were most frequently employed, maladaptive strategies explained the highest variation in negative mental health outcomes (i.e., anxiety and depression scores). Adaptive strategies had a positive, maladaptive strategies a negative effect, however, this direction varied when considering long-term mental health effects. Emotion regulation strategy use mediated the association between pre-pandemic emotion regulatory brain structure (i.e., cortical thickness) in right dorsolateral prefrontal cortex and mental health, with prefrontal-amygdala coupling as a possible driving factor. Additionally, early mental health measures impacted later mental well-being. Conclusion. Maladaptive emotion regulation strategies have a negative effect on mental health during prolonged stress as induced by pandemics. Interventions targeting the reduction of maladaptive emotion regulation strategies may provide a way to counteract negative effects, thus offering a window of opportunity for action.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/bmgt9/" target="_blank">Direct and indirect effects of dorsolateral prefrontal cortex and emotion regulation strategy use on mental health during Covid-19</a>
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<li><strong>An observational study on imported COVID-19 cases in Hong Kong during mandatory on-arrival hotel quarantine</strong> -
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Background: Hong Kong has enforced stringent travel restrictions particularly for inbound travellers since the emergence of SARS-CoV-2. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. Methods: We conducted a retrospective cohort study to summarise the characteristics of cases classified as imported cases that were detected on or soon after arrival into Hong Kong from 13 November 2020 through to 31 January 2022, when all arriving persons were required to quarantine in a hotel or a designated quarantine facility. We analysed individual demographics, and clinical information including symptoms and disease severity, virus variants, and Ct values. Results: There were 2269 imported COVID-19 cases aged 0-85 years identified in Hong Kong. Almost half (48.6%) of the imported cases were detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than cases infected with the ancestral strain and other variants (12 days; p<0.001) while lower Ct values at isolation were observed in cases infected with Omicron than the ancestral strain or other variants. No Omicron cases were detected beyond 14 days after arrival, and the cases (n=58, 2.6%) detected after 14 days of quarantine more frequently presented without symptoms at isolation and had a higher RT-PCR Ct-value during isolation. At least some of these cases were post-arrival infections. Conclusions: Testing inbound travellers at arrival and during on-arrival quarantine can detect imported cases early although it may not be sufficient to prevent all introductions of COVID-19 into the community. Public health measures should be adjusted in responses to the emergence of new variants of SARS-CoV-2 based on the epidemiologic evidence from continuous surveillance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.09.22278572v1" target="_blank">An observational study on imported COVID-19 cases in Hong Kong during mandatory on-arrival hotel quarantine</a>
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<li><strong>Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures</strong> -
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Cold-chain environment could extend the survival duration of SARS-CoV-2 and increases the risk of transmission. However, the effect of clod-chain environmental factors and packaging materials on SARS-CoV-2 stability and the efficacy of intervention measures to inactivate SARS-CoV-2 under cold-chain environment remains uncertain. This study aimed to unravel cold-chain environmental factors that preserved the stability of SARS-CoV-2 and disinfection measures against SARS-CoV-2 under the cold-chain environment. The spike gene of SARS-CoV-2 isolated from Wuhan hu-1 was used to construct the SARS-CoV-2 pseudovirus and used as model of the SARS-CoV-2 virus. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, various types of packaging material surfaces i.e., PE plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of LED visible light(wavelength 450 nm-780 nm) and airflow movement on the stability of SARS-CoV-2 pseudovirus at -18{degrees}C were subsequently assessed. The results show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surface compared with the non-porous surfaces including PE plastic, stainless steel and Teflon. Compared with 25{degrees}C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperature. Seawater preserved viral stability both at -18{degrees}C and repeated freeze-thawing cycles compared with deionized water. LED visible light illumination and airflow movement environment at -18{degrees}C reduced the SARS-CoV-2 pseudovirus stability. In conclusion, our results indicate cold-chain temperature and seawater as risk factors for SARS-CoV-2 transmission and LED visible light illumination and airflow movement as possible disinfection measures of SARS-CoV-2 under the cold-chain environment.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.09.503429v1" target="_blank">Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures</a>
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<li><strong>Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages</strong> -
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The SARS-CoV-2 variant, Omicron (B.1.1.529), rapidly swept the world since its emergence. Compared with previous variants, Omicron has a high number of mutations, especially those in its spike glycoprotein that drastically dampen or abolish the efficacy of currently available vaccines and therapeutic antibodies. Several major sublineages of Omicron involved, including BA.1, BA.2, BA.2.12.1, BA.3 and BA.4 BA.5, rapidly changing the global and regional landscape of the pandemic. Although vaccines are available, therapeutic antibodies remain critical for infected and especially hospitalized patients. To address this, we have designed and generated a panel of human/humanized therapeutic bispecific antibodies against Omicron and its sub-lineage variants, with activity spectrum against other lineages. Among these, the top clone CoV2-0213 has broadly potent activities against multiple SARS-CoV-2 ancestral and Omicron lineages, including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3 and BA.4 BA.5. We have solved the cryo-EM structure of the lead bi-specific antibody CoV-0213 and its major Fab arm MB.02. Three-dimensional structural analysis shows distinct epitope of antibody : spike receptor binding domain (RBD) interactions, and demonstrates that both Fab fragments of the same molecule of CoV2-0213 can target the same spike trimer simultaneously, further corroborating its mechanism of action. CoV2-0213 represents a unique and potent broad-spectrum SARS-CoV-2 neutralizing bispecific antibody (nbsAb) against the currently circulating major Omicron variants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3 and BA.4/BA.5), while maintaining activity against certain ancestral lineages (WT/WA-1, Delta), and to some degree other beta-coronavirus species (SARS-CoV). CoV2-0213 is primarily human and ready for translational testing as a countermeasure against the ever-evolving pathogen.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.09.503414v1" target="_blank">Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages</a>
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<li><strong>Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps</strong> -
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The SARS-CoV-2 Omicron variant, with 15 mutations in Spike receptor binding domain (Spike-RBD), renders virtually all clinical monoclonal antibodies against WT SARS-CoV-2 ineffective. We recently engineered the SARS-CoV-2 host entry receptor, ACE2, to tightly bind WT-Spike-RBD and prevent viral entry into host cells (receptor traps). Here we determine cryo-EM structures of our receptor traps in complex with full length Spike. We develop a multi-model pipeline combining Rosetta protein modeling software and cryo-EM to allow interface energy calculations even at limited resolution and identify interface side chains that allow for high affinity interactions between our ACE2 receptor traps and Spike-RBD. Our structural analysis provides a mechanistic rationale for the high affinity (0.53 - 4.2nM) binding of our ACE2 receptor traps to Omicron-RBD confirmed with biolayer interferometry measurements. Finally, we show that ACE2 receptor traps potently neutralize Omicron- and Delta- pseudotyped viruses, providing alternative therapeutic routes to combat this evolving virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.09.503400v1" target="_blank">Computational pipeline provides mechanistic understanding of Omicron variant of concern neutralizing engineered ACE2 receptor traps</a>
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<li><strong>SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference</strong> -
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Background: The reliability of sequence-based inference of SARS-CoV-2 transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. Methods: SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with an RT-PCR cycle threshold less than or equal to 30 underwent whole genome sequencing. Intrahost single nucleotide variants (iSNV) were identified at greater than 5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. Results: There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had greater than 1 consensus that differed by 1-2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and 6 of 11 with distinct ones. Conclusions: In multiple infection households, whole genome consensus sequences differed by 0-1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of sequence-only transmission inference.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.09.22278452v1" target="_blank">SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference</a>
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<li><strong>Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico</strong> -
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Up to November 2021, over 200 different SARS-CoV-2 lineages circulated in Mexico. To investigate lineage replacement dynamics, we applied a phylodynamic approach to explore the evolutionary trajectories of five dominant lineages that circulated during the first year of the local epidemic. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in the country. Lineages B.1.1.222 and B.1.1.519 showed comparable dynamics, represented by clades likely originating in Mexico and persisting for over a year. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. We further explored viral movements across the country, applied within the largest clades identified (belonging to lineage B.1.617.2). Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.05.498834v2" target="_blank">Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico</a>
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<li><strong>How consistent are smartphone application preferences? A descriptive study of mobile application repertoires using behavioral data</strong> -
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Smartphones afford users the ability to select their own mobile application repertoires through the installation of various applications. We report a quantitative descriptive study of the types of applications that people commonly use, the amount of time they spend with these applications, the application combinations that they construct, the consistency of these combinations over time, and the differences in these outcomes by demographic characteristics. Using a longitudinal dataset collected from a U.S. adult sample during the COVID-19 pandemic, the study leverages behavioral data collected via data donations to identify key application adoption patterns and shows that peoples’ mobile application repertoires are concentrated around a set of popular applications that is relatively consistent over time. However, within this set there is considerable diversity between individuals and applications, suggesting that quantifying smartphone usage with a single metric— ‘screentime’ —is unlikely to capture the full extent of media that users engage with.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/jzxun/" target="_blank">How consistent are smartphone application preferences? A descriptive study of mobile application repertoires using behavioral data</a>
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<li><strong>SARS-CoV-2 viral clearance and viral load kinetics in young children (1-6 years) compared to adults: Results of a longitudinal study in Germany</strong> -
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Objective: To investigate SARS-COV-2 viral clearance and viral load kinetics in the course of infection in children aged 1-6 years in comparison with adults. Methods: Prospective cohort study of infected daycare children and staff and their close contacts in households from 11/2020-06/2021, comprising serial (self) sampling of upper respiratory tract specimen and testing for SARS-CoV-2 via PCR. Data on symptoms and exposure were used to determine the date of probable infection for each participant. We determined (a) viral clearance, and (b) viral load dynamics over time. Samples were taken from day 4-6 to day 16-18 after diagnosis of the index case in the respective daycare group (5 samples per participant). Results: We included 40 children (1-6 years) and 67 adults (18-77 years) with SARS-CoV-2 infection. Samples were available at a mean of 4.3 points of time per participant. Among the participants, the 12-day study period fell in different periods within the individual course of infection, ranging from day 5-17 to day 15-26 after assumed infection. Children reached viral clearance at a median of 20 days after assumed infection (95% CI 17-21 days, Kaplan Meier Analysis), adults at 23 days (95% CI 20-25 days, difference not significant). In both children and adults, viral load decreased over time with trajectories of the mean viral load not being statistically different between groups. Only small proportions of those tested positive had a viral load of >1 million copies/ml, which is considered the threshold for infectivity. Kaplan-Meier calculations show that from day 15 (95% CI 13-15), 50% of all participants that had a viral load no longer infectious or were negative. Conclusion: Children aged 1-6 and adults infected with SARS-CoV-2 (wild type and Alpha variant) did not differ significantly in terms of viral load kinetics and time needed to clear the virus. Therefore, containment measures are important also in the daycare settings as long as the pandemic continues.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.09.22278540v1" target="_blank">SARS-CoV-2 viral clearance and viral load kinetics in young children (1-6 years) compared to adults: Results of a longitudinal study in Germany</a>
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<li><strong>Brief Report: Impact of age and SARS-CoV-2 breakthrough infection on humoral immune responses after three doses of COVID-19 mRNA vaccine</strong> -
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Longitudinal immune response data following three-dose COVID-19 mRNA vaccination remain limited, particularly in older adults and those experiencing their first SARS-CoV-2 infection. We quantified wild-type- and Omicron-specific antibody concentrations and virus neutralization activity up to six months post-third-dose in COVID-19-naive adults aged 24-98 years. Among participants who remained COVID-19-naive, antibody concentrations were comparable between age groups over time. Omicron-specific neutralization declined more rapidly in older adults, and at six months was undetectable in 56% and 96% of COVID-19-naive younger and older adults, respectively. Post-vaccine SARS-CoV-2 breakthrough infections increased wild-type- and Omicron-specific responses above three-dose vaccination alone, illustrating beneficial hybrid immunity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.08.22278494v1" target="_blank">Brief Report: Impact of age and SARS-CoV-2 breakthrough infection on humoral immune responses after three doses of COVID-19 mRNA vaccine</a>
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<li><strong>Correcting prevalence estimation for biased sampling with testing errors</strong> -
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Sampling for prevalence estimation of infection is subject to bias by both oversampling of symptomatic individuals and error-prone tests. This results in na"ive estimators that can be very far from the truth. In this work, we present a method of prevalence estimation that removes the effect of testing errors and reduces the effect of oversampling symptomatic individuals. Moreover, this procedure considers stratified errors in which tests have different error rate profiles for symptomatic and asymptomatic individuals. The result is an easily implementable algorithm (for which code is provided) that produces better prevalence estimates than other methods, as demonstrated by simulation and on Covid-19 data from the Israeli Ministry of Health.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.12.21266254v2" target="_blank">Correcting prevalence estimation for biased sampling with testing errors</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>A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07321332 (nirmatrelvir)/ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation in Post-COVID-19 Condition</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Goal Management Training (GMT)<br/><b>Sponsors</b>: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo University Hospital<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>EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)<br/><b>Sponsor</b>: University Vila Velha<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>Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Diagnostic Test: Perfusion brain scintigraphy imaging<br/><b>Sponsor</b>: Brugmann University Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Temelimab 54mg/kg; Drug: Placebo<br/><b>Sponsor</b>: GeNeuro SA<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>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>Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients</strong> - <b>Condition</b>: Post Covid-19 Patients<br/><b>Interventions</b>: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises<br/><b>Sponsor</b>: Riphah International University<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>Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South</strong> - <b>Conditions</b>: COVID-19; Vaccine Uptake<br/><b>Intervention</b>: Behavioral: Tough Talks COVID<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Alabama at Birmingham; National Institute on Minority Health and Health Disparities (NIMHD)<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>rSIFN-co Among Healthy Subjects and Subjects With Mild or Asymptomatic COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Drug: rSIFN-co Nasal Spray; Drug: Placebo Nasal Spray<br/><b>Sponsor</b>: Sichuan Huiyang Life Science and Technology Corporation<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>Evaluation of Safety and Immunogenicity of the Recombinant ZR202-CoV and ZR202a-CoV Vaccines in Adults.</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: ZR202-CoV; Biological: ZR202a-CoV; Biological: Comirnaty®<br/><b>Sponsor</b>: Shanghai Zerun Biotechnology 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>The Effect of Pilates on Biopsychosocial Characteristics in the Covid-19 Pandemic</strong> - <b>Conditions</b>: COVID-19; Healthy; Sedentary; Exercise; Pilates<br/><b>Interventions</b>: Behavioral: Sedantary; Behavioral: Exercise therapy<br/><b>Sponsor</b>: Medipol University<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>Immunogenicity and Safety of BBIBP-Corv Coadministered With PPV23 and IIV4 in Hemodialysis Population</strong> - <b>Conditions</b>: Hemolysis; COVID-19<br/><b>Interventions</b>: Biological: coadministration; Biological: COVID-19 vaccine; Biological: IIV4+PPV23<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Hunan Provincial Center for Disease Control and Prevention; Sichuan Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Xiangya Hospital of Central South University; Beijing Institute of Biological Products Co Ltd.; Chengdu Institute of Biological Products Co.,Ltd.; Shanghai Institute Of Biological Products<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 Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: CV0501 (3 μg); Biological: CV0501 (6 μg); Biological: CV0501 (12 μg); Biological: CV0501 (25 μg); Biological: CV0501 (50 μg); Biological: CV0501 (75 μg); Biological: CV0501 (100 μg); Biological: CV0501 (150 μg); Biological: CV0501 (200 μg)<br/><b>Sponsor</b>: GlaxoSmithKline<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>This Trial is a Clinical Performance Validation Study That Will Evaluate the Clinical Agreement of the Sky Medical™ Rapid Antigen Test Comparing the Antigen Rapid Test to RT-PCR</strong> - <b>Conditions</b>: COVID-19; Sars-CoV-2 Infection<br/><b>Intervention</b>: Diagnostic Test: Sky Medical™ Rapid Antigen Test<br/><b>Sponsor</b>: Sky Medical Supplies & Equipments, LLC<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>The Effect Of Distraction Methods On Fear And Anxiety In Children Before The Covid 19 Test</strong> - <b>Conditions</b>: Anxiety; Fear<br/><b>Interventions</b>: Behavioral: The Kaleidescope; Behavioral: The visual illusion cards<br/><b>Sponsor</b>: Ondokuz Mayıs University<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Author Correction: Structure basis for inhibition of SARS-CoV-2 by the feline drug GC376</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>Single-injection COVID-19 subunit vaccine elicits potent immune responses</strong> - Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein,…</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 Exploration of Resiliency Among Nurse Educators During the COVID-19 Pandemic</strong> - CONCLUSION: Resilience and related characteristics have the potential to assist nurse educators in adapting successfully to stressful circumstances. It is crucial that schools of nursing develop programs to enhance or develop resilience among nurse educators. Support and training in the area of online education are also of paramount importance.</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 long term vaccine-induced anti-SARS-CoV-2 immune response is impaired in quantity and quality under TNFα blockade</strong> - CONCLUSIONS: We show a reduced SARS-CoV-2 neutralising capacity in patients under TNFα blockade. In this cohort, the plasma cell response appears to be less specific and show stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced. This article is protected by copyright. All rights reserved.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial</strong> - CONCLUSION: Administration of zilucoplan to COVID-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function (PaO(2)/FiO(2)) and clinical outcome (mortality and 6-min walk test) suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies.</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>Targeting autophagy regulation in NLRP3 inflammasome-mediated lung inflammation in COVID-19</strong> - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late…</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>Therapeutic drug monitoring and dosage adjustments of immunosuppressive drugs when combined with nirmatrelvir/ritonavir in patients with COVID-19</strong> - Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher…</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>Selective serotonin reuptake inhibitor (SSRI) antidepressants reduce COVID-19 infection: prospects for use</strong> - CONCLUSION: If successful, these drugs can substantially reduce hospitalization and mortality rates, as well as allow for fully outpatient treatment for mild-to-moderate infections. Thus, repositioning SSRIs can provide benefits when faced with a rapidly evolving pandemic such as COVID-19.</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>Targeting Doublecortin-Like Kinase 1 (DCLK1)-Regulated SARS-CoV-2 Pathogenesis in COVID-19</strong> - Host factors play critical roles in SARS-CoV-2 infection-associated pathology and the severity of COVID-19. In this study, we systematically analyzed the roles of SARS-CoV-2-induced host factors, doublecortin-like kinase 1 (DCLK1), and S100A9 in viral pathogenesis. In autopsied subjects with COVID-19 and pre-existing chronic liver disease, we observed high levels of DCLK1 and S100A9 expression and immunosuppressive (DCLK1<sup>(+)S100A9</sup>(+)CD206^(+)) M2-like macrophages and N2-like neutrophils 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>Broad-spectrum antiviral activity of Spatholobus suberectus Dunn against SARS-CoV-2, SARS-CoV-1, H5N1, and other enveloped viruses</strong> - The current COVID-19 pandemic caused by SARS-Cov-2 is responsible for more than 6 million deaths globally. The development of broad-spectrum and cost-effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad-spectrum viral entry inhibitor against SARS-CoV-1/2 and other enveloped…</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>Zinc pyrithione is a potent inhibitor of PL<sup>Pro</sup> and cathepsin L enzymes with <em>ex vivo</em> inhibition of SARS-CoV-2 entry and replication</strong> - Zinc pyrithione (1a), together with its analogues 1b-h and ruthenium pyrithione complex 2a, were synthesised and evaluated for the stability in biologically relevant media and anti-SARS-CoV-2 activity. Zinc pyrithione revealed potent in vitro inhibition of cathepsin L (IC(50)=1.88 ± 0.49 µM) and PL^(Pro) (IC(50)=0.50 ± 0.07 µM), enzymes involved in SARS-CoV-2 entry and replication, respectively, as well as antiviral entry and replication properties in an ex vivo system derived from primary human…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Not “My” crisis: Social identity and followers’ crisis responses to COVID-19</strong> - Operationalizing social group identification as political partisanship, we examine followers’ (i.e., US residents’) affective experiences and behavioral responses during the initial COVID-19 outbreak in the United States (March to May 2020). In Study 1, we conducted content analyses on major news outlets’ coverage of COVID-19 (N = 4319) to examine media polarization and how it plays a role in shaping followers’ perceptions of the pandemic and leadership. News outlets trusted by Republicans…</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>Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease</strong> - Oridonin Inhibits SARS-CoV-2 Oridonin, a natural product extracted from Rabdosia rubescens, possesses a wide range of pharmacological properties, including anti-inflammatory, anti-cancer, anti-microbial, neuroprotection, immunoregulation, etc. In article number 2100124, Baisen Zhong, Litao Sun, and co-workers demonstrate that Oridonin targets the SARS-CoV-2 3CL protease by covalently binding to cysteine145 in its active pocket to exert an anti-SARS-CoV-2 effect, which provides a novel candidate…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>‘In most supermarkets food does not cost £3 per day …’ The impact of the school food voucher scheme during COVID-19</strong> - Households with children eligible for Free School Meals are at risk of food insecurity. This paper reports on a rapid-response study that investigated the impact of the school food voucher scheme during the COVID-19 crisis on young people, families and schools. It pays close attention to the reliance of the state on the goodwill of society and its citizens in feeding those most in need. The Capabilities Approach is used to highlight factors that inhibited and restricted the use of the vouchers…</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>Synthesis, crystal structure elucidation, DFT analysis, drug-likeness and ADMET evaluation and molecular docking studies of triazole derivatives: Binary inhibition of spike protein and ACE2 receptor protein of COVID-19</strong> - The recent incidence of terrible acute respiratory syndrome coronavirus 2 (SARS CoV-2) has presently experienced some noteworthy mutations since its discovery in 2019 in Wuhan, China. The present research work focuses on the synthesis of three triazole derivatives (BMTPP, BMTTP, and BMTIP) and their inhibition activities against SARS-Cov-2 spike and ACE2 receptor proteins. The crystal structure for BMTTP was determined by the SCXRD method and optimized geometrical parameters for the three…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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