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<title>26 May, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The widening of inequalities in COVID-19 years of life lost from 2020 to 2021: a Scottish Burden of Disease study</strong> -
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<div>
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Background: Previous studies have highlighted the large extent of inequality in adverse COVID-19 health outcomes. Our aim was to monitor changes in the overall, and inequalities in COVID-19 years of life lost to premature mortality (YLL) in Scotland from 2020 and 2021. Methods: Cause-specific COVID-19 mortality counts were derived at age-group and area-deprivation level using Scottish death registrations for 2020 and 2021. YLL was estimated by multiplying mortality counts by age-conditional life expectancy from the Global Burden of Disease 2019 reference life table. Various measures of absolute and relative inequality were estimated for triangulation purposes. Results: There were marked inequalities in COVID-19 YLL by area deprivation in 2020, which were further exacerbated in 2021; confirmed across all measures of absolute and relative inequality. Half (51%) of COVID-19 YLL was attributable to inequalities in area deprivation in 2021, an increase from 41% in 2020. Conclusion: Despite a highly impactful vaccination programme in preventing mortality, COVID-19 continues to represent a substantial area of fatal population health loss for which inequalities have widened. Tackling systemic inequalities with effective interventions are required to mitigate further unjust health loss in the Scottish population from COVID-19 and other causes of ill-health and mortality.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/mhu6r/" target="_blank">The widening of inequalities in COVID-19 years of life lost from 2020 to 2021: a Scottish Burden of Disease study</a>
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<li><strong>Toward more realistic social distancing policies via advanced feedback control</strong> -
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A continuously time-varying transmission rate is suggested by many control-theoretic investigations on non- pharmaceutical interventions for mitigating the COVID-19 pandemic. However, such a continuously varying rate is impossible to implement in any human society. Here, we significantly extend a preliminary work (M. Fliess, C. Join, A. d9Onofrio, Feedback control of social distancing for COVID-19 via elementary formulae, MATHMOD, Vienna, 2022), based on the combination of flatness-based and model-free controls of the classic SIR model. Indeed, to take into account severe uncertainties and perturbations, we propose a feedback control where the transmission rate, i.e., the control variable, is piecewise constant. More precisely, the transmission rate remains constant during an appreciable time interval. Strict extended lockdowns may therefore be avoided. The poor knowledge of fundamental quantities such as the rate of infection hinders a precise calibration of the transmission rate. Thus, the results of our approach ought therefore not to be regarded as rules of action to follow accurately but as a guideline for a wise behavior.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.25.22275562v1" target="_blank">Toward more realistic social distancing policies via advanced feedback control</a>
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</div></li>
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<li><strong>Population-weighted greenspace exposure tied to lower COVID-19 mortality rates: A nationwide dose-response study</strong> -
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The COVID-19 outbreak has caused enormous deaths and profound social and economic disruption globally. Accumulating evidence suggests exposure to greenspace may reduce the risk of COVID-19 mortality. Greenspace exposure enhances immune functioning, reduces inflammation, and replenishes gut microbiota may protect against the risk of mortality among those with COVID-19. However, previous studies often fail to distinguish the health effect of different types of greenspace, explore the dose-response association and optimal buffer distance, and consider the spatial dynamics of population distribution and geographic locations of greenspace. This study examined the associations among ratio of different types of greenspaces, population-weighted exposure to different types of greenspaces, and COVID-19 mortality rates using a negative binomial generalized linear mixed effects model across 3,025 counties, adjusted for socioeconomic, demographic, pre-existing chronic disease, policy and regulation, behavioral, and environmental factors. The population-weighted measure gave proportionally greater weight to greenspace near areas of higher population density. Exposure to forest and pasture was negatively associated with COVID-19 mortality rates, while developed open space has insignificant or positive associations with mortality rates. Forest outside park has the largest effect size across all buffer distances, followed by forest inside park. The optimal exposure buffer distance is 1km for forest outside park, with 1 unit of increase in exposure associated with a 9.9% decrease in mortality rates (95% confidence interval: 6.9% -12.8%). The optimal exposure buffer distance of forest inside park is 400m, with 1 unit of increase in exposure, associated with a 4.7% decrease in mortality rates (95% confidence interval: 2.4% - 6.9%). Greenspaces, especially nearby forest, may be effective at lowering the mortality risk of COVID-19 patients. Our findings suggest that policymakers and planners should prioritize forestry within walking distance of residential clusters to mitigate mortality rates during current and future respiratory pandemics.
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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/10.1101/2022.05.24.22275549v1" target="_blank">Population- weighted greenspace exposure tied to lower COVID-19 mortality rates: A nationwide dose-response study</a>
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</div></li>
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<li><strong>Atovaquone for Treatment of COVID-19: A Prospective Randomized, Double-Blind, Placebo-Controlled Clinical Trial</strong> -
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Background: An in-silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log- transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples. Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho -0.45, p=0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho -0.54, p= 0.005). Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients. clincialtrials.gov (NCT04456153).
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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/10.1101/2022.05.24.22275411v1" target="_blank">Atovaquone for Treatment of COVID-19: A Prospective Randomized, Double-Blind, Placebo-Controlled Clinical Trial</a>
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</div></li>
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<li><strong>Health workers’ Perspective on the Feasibility and Acceptability of the Introduction of AgRDT for COVID-19 in Kisumu County, Western Kenya</strong> -
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COVID-19 pandemic remains a major global public health challenge also in Low- and Middle-Income Countries (LMIC), due to fragile health systems, limited resources and personnel, low testing and counseling capacity, community perceptions, among others. In Kisumu County of Western Kenya, a unique Public Private Partnership (PPP) was rolled-out to increase testing and capacity building by linking private facilities to the ongoing public sector efforts in combating COVID-19. It became increasingly clear that centralized PCR testing for COVID-19 was too labor-intensive, expensive, prone to machine breakdowns and stock-outs of essential reagents, resulting in long turn-around times and sometimes even adaptations of patient selection criteria. A clear need was identified for rapid point-of-care COVID-19 testing (AgRDT). After successful field evaluation, RDT for COVID-19 was offered through the PPP. This paper aimed to understand the health workers perspective on the feasibility and acceptability of the introduction of the AgRDT in Kisumu County. In-Depth Interviews were conducted with selected health workers (n=23) from the participating facilities and analyzed using Nvivo 11 The health workers accepted the use of AgRDT as it enabled the strengthening of the existing health system, increased testing capacity and provided capacity building opportunities. Challenges included poor management of results discrepant with PCR gold standard. The health workers applauded the introduction of AgRDT with the Kisumu County Department of Health as a more realistic and user-friendly approach, leading to fast turn-around times and increased personal safety experience.
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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/10.1101/2022.05.24.22275498v1" target="_blank">Health workers’ Perspective on the Feasibility and Acceptability of the Introduction of AgRDT for COVID-19 in Kisumu County, Western Kenya</a>
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<li><strong>Clearing the Fog: A Systematic Review on Cognitive Dysfunction in COVID-19</strong> -
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Objective: The systematic review aims to examine the association between COVID-19 and cognitive dysfunction, including the link between the severity of COVID-19 and the occurrence of cognitive impairment and the potential pathophysiological mechanisms related to brain fog among COVID-19 patients. Methods: PubMed, Oxford University Press, ProQuest Health and Medical Complete, ScienceDirect, Ovid, HERDIN, Google Scholar, and Cochrane Library databases were accessed to retrieve literature using the PRISMA guidelines. Results: After critical appraisal, thirteen full journal articles were included in the study. The studies showed the most frequent cognitive impairment are attention, memory, and executive function in COVID-19 patients. Compared with healthy controls (HC) in 3 out of 4 studies, cognitive impairment was only evident in COVID-19 patients. Furthermore, two studies showed no correlation between brain fog and depression, and five studies showed a link between the severity of COVID-19 infection and cognitive impairment. Cases ranging from mild to severe illness presented manifestations of brain fog. However, a disparity in the evidence of the pathophysiology of COVID-19 and cognitive dysfunction exists, prompting the need to investigate further. Additionally, recent studies provide insufficient evidence for direct central nervous system invasion, and there are emerging studies that contrast the presumed pathogenesis of neurological complications from neuroinflammation. Conclusion: There is an association between COVID-19 and cognitive dysfunction. Manifestation of cognitive dysfunction is present regardless of illness severity. Moreover, there are existing pathophysiological mechanisms of the Coronavirus that lead to cognitive dysfunction in COVID-19 patients; however, additional studies are required to substantiate such mechanisms further.
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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/10.1101/2022.05.24.22275552v1" target="_blank">Clearing the Fog: A Systematic Review on Cognitive Dysfunction in COVID-19</a>
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</div></li>
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<li><strong>Increasing computational protein design literacy through cohort-based learning for undergraduate students</strong> -
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Undergraduate research experiences can improve student success in graduate education and STEM careers. During the COVID-19 pandemic, undergraduate researchers at our institution and many others lost their work-study research positions due to interruption of in-person research activities. This imposed a financial burden on the students and eliminated an important learning opportunity. To address these challenges, we created a paid, fully-remote, cohort-based research curriculum in computational protein design. Our curriculum used existing protein design methods as a platform to first educate and train undergraduate students and then to test research hypotheses. In the first phase, students learned computational methods to assess the stability of designed protein assemblies. In the second phase, students used a larger dataset to identify factors that could improve the accuracy of current protein design algorithms. This cohort- based program created valuable new research opportunities for undergraduates at our institute and enhanced the undergraduates’ feeling of connection with the lab. Students learned transferable and useful skills such as literature review, programming basics, data analysis, hypothesis testing, and scientific communication. Our program provides a model of structured computational research training opportunities for undergraduate researchers in any field for organizations looking to expand educational access.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.24.493341v1" target="_blank">Increasing computational protein design literacy through cohort-based learning for undergraduate students</a>
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</div></li>
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<li><strong>Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot</strong> -
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<div>
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Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.24.493347v1" target="_blank">Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot</a>
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<li><strong>Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States</strong> -
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Covid-19 has caused more than 1 million deaths in the US, including at least 1,433 deaths among children and young people (CYP) aged 0-19 years. Deaths among US CYP are rare in general, and so we argue here that the mortality burden of Covid-19 in CYP is best understood in the context of all other causes of CYP death. Using publicly available data from the National Center for Health Statistics, and comparing to mortality in 2019, the immediate pre-pandemic period, we find that Covid-19 is a leading cause of death in CYP aged 0-19 years in the US, ranking #9 among all causes of deaths, #5 in disease related causes of deaths (excluding accidents, assault and suicide), and #1 in deaths caused by infectious / respiratory diseases. Due to the impact of mitigations such as social distancing and our comparison of a single disease (Covid-19) to groups of causes such as deaths from pneumonia and influenza, these rankings are likely conservative lower bounds. Our findings underscore the importance of continued vaccination campaigns for CYP over 5 years of age in the US and for effective Covid-19 vaccines for under 5 year olds.
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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/10.1101/2022.05.23.22275458v1" target="_blank">Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States</a>
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<li><strong>A Monte Carlo Estimation of the Narrow-Sense Heritability of COVID-19 Infection and Severity from AncestryDNA Survey Data</strong> -
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Respiratory infectious diseases, such as COVID-19, demonstrate a host genetic component that contributes to inter-individual differences of susceptibility and infection. At present, the relative effect of environmental and genetic factors of COVID-19 is unknown. This research presents a Monte Carlo (MC) estimation of the genetic narrow-sense heritability of COVID-19 infection and severity from AncestryDNA survey data. The results suggest a moderate genetic contribution to COVID-19 infection and a low genetic contribution for COVID-19 severity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.23.22275364v1" target="_blank">A Monte Carlo Estimation of the Narrow-Sense Heritability of COVID-19 Infection and Severity from AncestryDNA Survey Data</a>
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<li><strong>Hemin shows antiviral activity in vitro, possibly through suppression of viral entry mediators.</strong> -
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Heme oxygenase-1 (HO-1) is a stress-induced enzyme that catalyzes the breakdown of heme into biliverdin, carbon monoxide, and iron. Targeting HO-1 to treat severe COVID-19 has been suggested by several groups, yet the role of HO-1 in SARS-CoV-2 infection remains unclear. Based on this, we aimed to investigate the antiviral activity of Hemin, an activator of HO-1. Infectivity of SARS-CoV-2 was decreased in Vero E6 cells treated with Hemin. Hemin also decreased TMPRSS2 and ACE2 mRNA levels in non-infected cells, possibly explaining the observed decrease in infectivity. TMPRSS2 protein expression and proteolytic activity were decreased in Vero E6 cells treated with Hemin. Besides that, experimental studies supported with in silico calculations. Overall, our study supports further exploration of Hemin as a potential antiviral and inflammatory drug for the treatment of COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.24.493187v1" target="_blank">Hemin shows antiviral activity in vitro, possibly through suppression of viral entry mediators.</a>
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<li><strong>Intranasal vaccination induced cross-protective secretory IgA antibodies against SARS-CoV-2 variants with reducing the potential risk of lung eosinophilic immunopathology</strong> -
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To control the coronavirus disease 2019 (COVID-19) pandemic, there is a need to develop vaccines to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. One candidate is a nasal vaccine capable of inducing secretory IgA antibodies in the mucosa of the upper respiratory tract, the initial site of infection. However, regarding the development of COVID-19 vaccines, there is concern about the potential risk of inducing lung eosinophilic immunopathology as a vaccine-associated enhanced respiratory disease as a result of the T helper 2 (Th2)-dominant adaptive immune response. In this study, we investigated the protective effect against virus infection induced by intranasal vaccination of recombinant trimeric spike protein derived from SARS-CoV-2 adjuvanted with CpG oligonucleotides, ODN2006, in mouse model. The intranasal vaccine combined with ODN2006 successfully induced not only systemic spike-specific IgG antibodies, but also secretory IgA antibodies in the nasal mucosa. Secretory IgA antibodies showed high protective ability against SARS-CoV-2 variants (Alpha, Beta and Gamma variants) compared to IgG antibodies in the serum. The nasal vaccine of this formulation induced a high number of IFN-{gamma}-secreting cells in the draining cervical lymph nodes and a lower spike-specific IgG1/IgG2a ratio compared to that of subcutaneous vaccination with alum as a typical Th2 adjuvant. These features are consistent with the induction of the Th1 adaptive immune response. In addition, mice intranasally vaccinated with ODN2006 showed less lung eosinophilic immunopathology after viral challenge than mice subcutaneously vaccinated with alum adjuvant. Our findings indicate that intranasal vaccine adjuvanted with ODN2006 could be a candidate that can prevent the infection of antigenically different variant viruses, reducing the risk of vaccine-associated enhanced respiratory disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.24.493348v1" target="_blank">Intranasal vaccination induced cross-protective secretory IgA antibodies against SARS-CoV-2 variants with reducing the potential risk of lung eosinophilic immunopathology</a>
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<li><strong>Humoral Immunity to SARS-CoV-2 and Inferred Protection from Infection in a French Longitudinal Community Cohort</strong> -
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Population-level immunity to SARS-CoV-2 is growing through vaccination as well as ongoing circulation. Given waning immunity and emergence of new variants, it is important to dynamically determine the risk of re-infection in the population. For estimating immune protection, neutralization titers are most informative, but these assays are difficult to conduct at a population level. Measurement of antibody levels can be implemented at high throughput, but has not been robustly validated as a correlate of protection. Here, we have developed a method that predicts neutralization and protection based on variant-specific antibody measurements to SARS-CoV-2 antigens. This approach allowed us to estimate population-immunity in a longitudinal cohort from France followed for up to 2 years. Participants with a single vaccination or immunity caused by infection only are especially vulnerable to COVID-19 or hospitalization due to SARS- CoV-2. While the median reduced risk to COVID-19 in participants with 3 vaccinations was 96%, the median reduced risk among participants with infection-acquired immunity only was 42%. The results presented here are consistent with data from vaccine-effectiveness studies indicating robustness of our approach. Our multiplex serological assay can be readily optimized and employed to study any new variant and provides a framework for development of an assay that would include protection estimates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.23.22275460v1" target="_blank">Humoral Immunity to SARS-CoV-2 and Inferred Protection from Infection in a French Longitudinal Community Cohort</a>
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<li><strong>Diagnostic accuracy of the Panbio COVID-19 Antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation</strong> -
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Background: Accurate and timely diagnosis is essential in limiting the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Real-time reverse transcription-polymerase chain reaction (rRT-PCR), the reference standard, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen rapid diagnostic tests (Ag RDTs) provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%. Methods: This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention9s (CDC) rRT-PCR test. Results: We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms >7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30. Conclusion: The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool for only symptomatic patients in high-risk settings with limited access to RT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.23.22275439v1" target="_blank">Diagnostic accuracy of the Panbio COVID-19 Antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation</a>
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<li><strong>Initial protection against Omicron in children and adolescents by BNT162b2</strong> -
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BACKGROUND The BNT162b2 (Pfizer-BioNTech) 2-dose vaccine for children and the BNT162b2 3rd dose for adolescents were approved shortly before the Omicron outbreak in Israel. The effects of these vaccines on the rates of Omicron confirmed infection are not yet clear. METHODS We extracted data for the Omicron-dominated (sub-lineage BA.1) period December 26, 2021 through January 8, 2022. We compared rates of confirmed Covid-19 infection between children 5-10 years old 14-35 days after receiving the 2nd dose to an internal control group of children 3-7 days after receiving the 1st dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents 12-15 years old 14-60 days after receiving a booster dose to an internal control group of adolescents 3-7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure. RESULTS In the 5-10 age group, the estimated rate of confirmed infection was 2.3 fold (95% CI, 2.0 to 2.5) lower in the 2nd dose group than in the internal control group. In adolescents, the third dose decreased confirmed infection rates by 3.3-fold (95% CI, 2.8 to 4.0). CONCLUSIONS A recent 2-dose BNT162b2 vaccination in children and a recent booster dose in adolescents reduced the rate of confirmed infection compared to the respective internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as PIMS and long-COVID.
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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/10.1101/2022.05.22.22275323v1" target="_blank">Initial protection against Omicron in children and adolescents by BNT162b2</a>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)<br/><b>Sponsors</b>: University of California, Irvine; Hudson Valley Healing Arts Center<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>Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-9199; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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Sorrento Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Hymecromone tablets; Other: Placebo<br/><b>Sponsor</b>: Shanghai Zhongshan Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated; Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: <br/>
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China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Hunan Provincial Center for Disease Control and Prevention<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase Ia, Dose-finding Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Prime-2-CoV_Beta<br/><b>Sponsors</b>: <br/>
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University Hospital Tuebingen; FGK Clinical Research GmbH; VisMederi srl; Staburo GmbH; Viedoc Technologies AB<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Radiation: [18F]DPA-714 positron emission tomography (PET) scan<br/><b>Sponsors</b>: Amsterdam UMC, location VUmc; ZonMw: The Netherlands Organisation for Health Research and Development<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Palbociclib<br/><b>Sponsor</b>: biotx.ai GmbH<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About the Study Medicine (Called Nirmatrelvir/Ritonavir) in Pregnant Women With Mild or Moderate COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir; Drug: ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<br/><b>Sponsor</b>: CanSino Biologics Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate SSD8432/Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 750mg; Drug: SSD8432 placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: DXP604<br/><b>Sponsor</b>: <br/>
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Wuhan Institute of Biological Products Co., Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Clinical Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 300mg; Drug: SSD8432 750mg; Drug: SSD8432Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd; The University of Hong Kong<br/><b>Not yet recruiting</b></p></li>
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</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>Pnictogen-Centered Cascade Exchangers for Thiol-Mediated Uptake: As(III)-, Sb(III)-, and Bi(III)-Expanded Cyclic Disulfides as Inhibitors of Cytosolic Delivery and Viral Entry</strong> - Dynamic covalent exchange cascades with cellular thiols are of interest to deliver substrates to the cytosol and to inhibit the entry of viruses. The best transporters and inhibitors known today are cyclic cascade exchangers (CAXs), producing a new exchanger with every exchange, mostly cyclic oligochalcogenides, particularly disulfides. The objective of this study was to expand the dynamic covalent chalcogen exchange cascades in thiol-mediated uptake by inserting pnictogen relays. A family of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1<em>H</em>-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities</strong> - A series of 26 novel 1-(7-chloroquinolin-4-yl)-4-nitro-1H-pyrazoles bearing a dichloromethyl and an amino or thio moiety at C3 and C5 has been prepared in yields up to 72% from the reaction of 1,1-bisazolyl-, 1-azolyl-1-amino-, and 1-thioperchloro-2-nitrobuta-1,3-dienes with 7-chloro-4-hydrazinylquinoline. A new way for the formation of a pyrazole cycle from 3-methyl-2-(2,3,3-trichloro-1-nitroallylidene)oxazolidine (6) is also described. In addition, the antimalarial activity of the synthesized…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A conserved subunit vaccine designed against SARS-CoV-2 variants showed evidence in neutralizing the virus</strong> - Novel coronavirus (SARS-CoV-2) leads to coronavirus disease 19 (COVID-19), declared as a pandemic that outbreaks within almost 225 countries worldwide. For the time being, numerous mutations have been reported that led to the generation of numerous variants spread more rapidly. This study aims to establish an efficient multi-epitope subunit vaccine that could elicit both T-cell and B-cell responses sufficient to recognize three confirmed surface proteins of the virus. The sequences of the viral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of oleandrin and PBI-05204 against bovine viruses of importance to commercial cattle health</strong> - CONCLUSIONS: The research demonstrates the potency of oleandrin and PBI-05204 to inhibit infectivity of three important enveloped bovine viruses in vitro. These data showing non-toxic concentrations of oleandrin inhibiting infectivity of three bovine viruses support further investigation of in vivo antiviral efficacy.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to downregulate MHC-I surface expression</strong> - Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein β (2) -microglobulin (β (2) m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Rare Case of COVID-19 Vaccine-Induced Thrombotic Thrombocytopenia in a Young Patient</strong> - The syndrome of pulmonary SARS-Cov-2 resulted in significant morbidity and mortality, with new variants spreading rapidly. Vaccines to prevent COVID-19 have been developed to minimize the impact and severity; however, adverse effects of the vaccine have been documented in several studies. In our case, we report a case of a young female who presented to the emergency department with fever, dizziness, headache, vomiting, blurring of vision, numbness, and weakness of left upper and lower limbs….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neutralizing antibody and T cell responses against SARS-CoV-2 variants of concern following ChAdOx-1 or BNT162b2 boosting in the elderly previously immunized with CoronaVac vaccine</strong> - CONCLUSION: Boosting with either ChAdOx-1 or BNT162b2 in CoronaVac-primed healthy elderly individuals induced high NAb production against all examined VOCs except Omicron. BNT162b2 stimulated higher NAb and some T-cell responses than ChAdOx-1. Vaccine boosting is, therefore, recommended for elderly individuals previously immunized with CoronaVac.</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>Red blood cell distribution width as a marker of hyperinflammation and mortality in COVID-19</strong> - CONCLUSIONS: RDW predicts COVID-19-associated ARDS mortality and reflects the hyperinflammatory background and the effects of cytokines such as IL-6, irrespective of tocilizumab 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>Antiviral Activity of Medicinal Plants against Human Coronavirus: a systematic scoping review of and experimentations</strong> - CONCLUSION: This review shows that complementary medicine have the potential for new drug discovery against coronavirus. Further research is needed before definitive conclusions can be made concerning the safety and efficacy of the use of these medicinal plants.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents</strong> - Cyclophilin A (CypA) is linked to diverse human diseases including viral infections. With the worldwide emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2), drug repurposing has been highlighted as a strategy with the potential to speed up antiviral development. Because CypA acts as a proviral component in hepatitis C virus, coronavirus and HIV, its inhibitors have been suggested as potential treatments for these infections. Here, we review the structure of cyclosporin A and…</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>Pyronaridine Protects against SARS-CoV-2 Infection in Mouse</strong> - There are currently relatively few small-molecule antiviral drugs that are either approved or emergency-approved for use against severe acute respiratory coronavirus 2 (SARS-CoV-2). One of these is remdesivir, which was originally repurposed from its use against Ebola. We evaluated three molecules we had previously identified computationally with antiviral activity against Ebola and Marburg and identified pyronaridine, which inhibited the SARS-CoV-2 replication in A549-ACE2 cells. The in vivo…</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 treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism</strong> - Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given…</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>Gelatin Stabilizes Nebulized Proteins in Pulmonary Drug Delivery against COVID-19</strong> - Delivering medication to the lungs via nebulization of pharmaceuticals is a noninvasive and efficient therapy route, particularly for respiratory diseases. The recent worldwide severe acute respiratory syndrome coronavirus type 2 (SARS- CoV-2) pandemic urges the development of such therapies as an effective alternative to vaccines. The main difficulties in using inhalation therapy are the development of effective medicine and methods to stabilize the biological molecules and transfer them to 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>A novel property of hexokinase inhibition by Favipiravir and proposed advantages over Molnupiravir and 2 Deoxy D glucose in treating COVID-19</strong> - CONCLUSION: Favipiravir could continue to be part of the COVID-19 treatment regimen due to its resistance to host esterases, hexokinase inhibition potential and proven safety through human trials.</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>Thiazole-based SARS-CoV-2 protease (COV M<sup>pro</sup> ) inhibitors: Design, synthesis, enzyme inhibition, and molecular modeling simulations</strong> - As an attempt to contribute to the efforts of combating the pandemic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19, new analogs of the repurposed drug nitazoxanide which showed promising inhibitory efficacy on a viral protease enzyme were designed, synthesized and evaluated for their inhibitory activity on the main protease of the SARS-CoV-2 virus, using the COV2-3CL protease inhibition assay. The obtained results showed that the…</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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