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188 lines
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<title>22 December, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Parental contributions to language development during the COVID-19</strong> -
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The COVID-19 pandemic caused temporary yet significant changes in young children’s learning environments around the world. In Turkey and many other countries where young children are commonly taken care of at home, a notable pandemic-related change was the increased presence of the father at home. This study utilized this unusual situation to examine the contributions of mothers and fathers in language learning. A two-part online survey was administered to the parents of an 8- to 36- month-old, and we analyzed data from 128 families at Time 1 (Mage = 21.91) and 52 families at Time 2 (Mage = 25.09). As a proxy of the parental language input, we asked the parents to write a story about a picture as if they were telling a bedtime story to their child. The number of words used in the mother’s story, but not the father’s story, predicted the vocabulary level of children. We also report socio-economic status (SES), use of digital devices, and book reading to examine the possible indirect influence of parents. Overall, our results suggest parental input is the key to healthy language development during the global crisis, but the generalizability of the finding should be tested in the future.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/wvbjd/" target="_blank">Parental contributions to language development during the COVID-19</a>
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<li><strong>Digital Omicron Detection using Unscripted Voice Samples from Social Media</strong> -
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The success of artificial intelligence in clinical environments relies upon the diversity and availability of training data. In some cases, social media data may be used to counterbalance the limited amount of accessible, well-curated clinical data, but this possibility remains largely unexplored. In this study, we mined YouTube to collect voice data from individuals with self- declared positive COVID-19 tests during time periods in which Omicron was the predominant variant, while also sampling non-Omicron COVID-19 variants, other upper respiratory infections (URI), and healthy subjects. The resulting dataset was used to train a DenseNet model to detect the Omicron variant from voice changes. Our model achieved 0.85/0.80 sensitivity/specificity in separating Omicron samples from healthy samples and 0.76/0.70 sensitivity/specificity in separating Omicron samples from symptomatic non-COVID samples. In comparison with past studies, which used scripted voice samples, we showed that leveraging the intra-sample variance inherent to unscripted speech enhanced generalization. Our work introduced novel design paradigms for audio-based diagnostic tools and established the potential of social media data to train digital diagnostic models suitable for real-world deployment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.13.22279673v3" target="_blank">Digital Omicron Detection using Unscripted Voice Samples from Social Media</a>
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<li><strong>SARS-CoV-2 vaccine and increased myocarditis mortality risk: A population based comparative study in Japan</strong> -
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ABSTRACT Objective: To investigate the association between SARS-CoV-2 vaccination and myocarditis death Design: Population based comparative mortality study Setting: Japan Participants: Vaccinated population was 99 834 543 individuals aged 12 years and older who have been received SARS-CoV-2 vaccine once or twice by 14 February 2022. Reference population was defined persons aged 10 years and older from 2017 to 2019. Main outcome measures: The primary outcome was myocarditis death, defined as the case with “myocarditis” for primary cause of death and with onset 28 days or less after vaccination disclosed on 11 November 2022. Myocarditis mortality rate ratio (MMRR) of the SARS-CoV-2 vaccinated to the reference population by 10-year age group and standardised mortality ratio (SMR) were calculated. Mortality odds ratios (MORs) by 10-year age group were also calculated for supplementary analysis. Healthy vaccine effect-adjusted MMRRs (adMMRRs) or adjusted SMR (adSMR) were calculated by dividing MMRRs or SMR by 0.24 respectively. Results: Number of myocarditis death which met the inclusion criteria were 32 cases. MMRR (95% confidence interval) was 4.03 (0.77 to 13.60) in 20s, 7.80 (2.85 to 18.56) in 30s, respectively. SMR of myocarditis was 1.69 (1.18 to 2.42) for overall vaccinated population, 1.35 (0.84 to 2.55) for those 60 years or older. Estimated adMMRRs and adSMR were about 4 times higher than the MMRRs and SMR. Pooled MOR for myocarditis were 148.49 (89.18 to 247.25). Conclusion: SARS-CoV-2 vaccination was associated with higher risk of myocarditis death, not only in young adults but also in all age groups including the elderly. Considering healthy vaccinee effect, the risk may be 4 times or higher than the apparent risk of myocarditis death. Underreporting should also be considered. Based on this study, risk of myocarditis following SARS-CoV-2 vaccination may be more serious than that reported previously.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.13.22281036v2" target="_blank">SARS-CoV-2 vaccine and increased myocarditis mortality risk: A population based comparative study in Japan</a>
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<li><strong>The facilitators and barriers to improving functional activity and wellbeing in people with dementia: A qualitative study from the Process Evaluation of Promoting Activity, Independence and Stability in Early Dementia</strong> -
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Background. The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with dementia. A Randomised Controlled Trial (RCT) showed no measurable benefits in activities of daily living, physical activity or quality of life. Objective. To explore participant responses to PrAISED and explain the mechanisms behind a complex intervention that did not lead to expected health gains. Methods. A process evaluation using qualitative methods, comprising interviews and researcher notes Setting. Data were collected in the homes of participants or remotely by telephone or videoconferencing. Sample. Eighty-eight interviews were conducted with 44 participants living with dementia (n = 32 intervention group; n = 12 control group) and 39 caregivers. Sixty-nine interviews were conducted with 26 therapists. Results. Participants valued the intervention as proactively addressing health issues that were of concern to them, and as sources of social contact, interaction, information, and advice. Facilitators to achieving positive outcomes included perceiving progress toward desired goals, positive expectations, therapist skills and rapport with participants, and caregiver support. Barriers included: cognitive impairment, which prevented independent engagement and carryover between sessions; chronic physical health problems and intercurrent acute illness and injury; tapering (progressively infrequent supervision intended to help develop habits and independent activity); and the COVID-19 pandemic. Conclusions. Interventions aiming to maintain activity, independence and stability may not be appropriate in the context of dementia even in the mild stages of the condition. Various factors affected outcomes including caregiver support, rapport with therapists, availability of supervision, motivational factors, and the limitations of remote delivery. The effects of cognitive impairment, multimorbidity and frailty overwhelmed any positive impact of the intervention. Maintenance of functional ability is valued, but in the face of inevitable progression of disease, other less tangible outcomes become important, challenging how we frame health gain and trial outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.20.22283555v1" target="_blank">The facilitators and barriers to improving functional activity and wellbeing in people with dementia: A qualitative study from the Process Evaluation of Promoting Activity, Independence and Stability in Early Dementia</a>
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<li><strong>SARS-CoV-2 variant-specific differences in inhibiting the effects of the PKR-activated integrated stress response</strong> -
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The integrated stress response (ISR) is a eukaryotic cell pathway that triggers translational arrest and the formation of stress granules (SGs) in response to various stress signals, including those caused by viral infections. The SARS-CoV-2 nucleocapsid protein has been shown to disrupt SGs, but SARS-CoV-2 interactions with other components of the pathway remains poorly characterized. Here, we show that SARS-CoV-2 infection triggers the ISR through activation of the eIF2-kinase PKR while inhibiting a variety of downstream effects. In line with previous studies, SG formation was efficiently inhibited and the induced eIF2 phosphorylation only minimally contributed to the translational arrest observed in infected cells. Despite ISR activation and translational arrest, expression of the stress-responsive transcripts ATF4 and CHOP was not induced in SARS-CoV-2 infected cells. Finally, we found variant-specific differences in the activation of the ISR between ancestral SARS-CoV-2 and the Delta and Omicron BA.1 variants in that Delta infection induced weaker PKR activation while Omicron infection induced higher levels of p-eIF2 and greatly increased SG formation compared to the other variants. Our results suggest that different SARS-CoV-2 variants can affect normal cell functions differently, which can have an impact on pathogenesis and treatment strategies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.21.521388v1" target="_blank">SARS-CoV-2 variant-specific differences in inhibiting the effects of the PKR-activated integrated stress response</a>
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<li><strong>Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19</strong> -
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Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus formation. This hyperinflammation is dependent on high levels of anti-spike IgG with aberrant Fc tail glycosylation, leading to Fc{gamma} receptor hyperactivation. For development of immune-regulatory therapeutics, drug specificity is crucial to counteract excessive inflammation while simultaneously minimizing inhibition of antiviral immunity. We here developed an in vitro activation assay to screen for small molecule drugs that specifically counteract antibody-induced pathology. We identified that anti-spike induced inflammation is specifically blocked by small molecule inhibitors against SYK and PI3K. We identified SYK inhibitor entospletinib as the most promising candidate drug, which also counteracted anti-spike-induced endothelial dysfunction and thrombus formation. Moreover, entospletinib blocked inflammation by different SARS-CoV-2 variants of concern. Combined, these data identify entospletinib as a promising treatment for severe COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.20.521247v1" target="_blank">Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19</a>
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<li><strong>Mechanism of LLPS of SARS-CoV-2 N protein</strong> -
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SARS-CoV-2 nucleocapsid (N) protein with low mutation rate is the only structural protein not only functioning to package viral genomic RNA, but also manipulating the host-cell machineries, thus representing a key target for drug development. Recent discovery of its liquid-liquid phase separation (LLPS) not only sheds light on previously-unknown mechanisms underlying the host-SARS-CoV-2 interaction and viral life cycle, but most importantly opens up a new direction for developing anti-SARS-CoV-2 strategies/drugs. However, so far the high-resolution mechanism of LLPS of N protein still remains unknown because it is not amenable for high-resolution biophysical investigations. Here we systematically dissected N protein into differential combinations of domains followed by DIC and NMR characterization. We successfully identified N (1-249), which not only gives high-quality NMR spectra, but phase separates as the full-length N protein. The results together decode for the first time: 1) nucleic acid modulates LLPS by dynamic but specific interactions multivalently over both folded NTD/CTD and Arg/Lys residues within IDRs. 2) ATP, mysteriously with concentrations >mM in all living cells but absent in viruses, not only specifically binds NTD/CTD, but also Arg residues within IDRs with Kd of 2.8 mM. 3) ATP dissolves LLPS by competitively displacing nucleic acid from binding the protein. Therefore, ATP and nucleic acid interplay in modulating LLPS by specific competitions for binding over the highly overlapped binding sites. Our study deciphers the mechanism of LLPS of N protein, which is targetable by small molecules. ATP is not only emerging as a cellular factor controlling the host-SARS-CoV-2 interaction, but also provides a lead for developing anti-SARS-CoV-2 drugs efficient for different variants of SARS-CoV-2. Fundamentally, our results imply that the mechanisms of LLPS of IDR-containing proteins mediated by ATP and nucleic acids appear to be highly conserved from human to virus.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.21.521431v1" target="_blank">Mechanism of LLPS of SARS-CoV-2 N protein</a>
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<li><strong>Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity</strong> -
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The success of the human body in fighting SARS-CoV-2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance. We report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV-2 compared with uninfected controls. In contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients. These features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.20.521139v1" target="_blank">Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity</a>
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<li><strong>Structure adaptation in Omicron SARS-CoV-2/hACE2:Biophysical origins of evolutionary driving forces</strong> -
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Since its emergence, the Covid19 pandemic has been sustained by a series of transmission waves initiated by new variants of the SARS-CoV-2 virus. Some of these arise with higher transmissivity and/or increased disease severity. Here we use molecular dynamics simulations to examine the modulation of the fundamental interactions between the receptor binding domain (RBD) of the spike glycoprotein and the host cell receptor (human angiotensin-converting enzyme 2: hACE2) arising from Omicron variant mutations (BA.1 and BA.2) relative to the original wild type strain. We find significant structural differences in the complexes which overall bring the spike protein and its receptor into closer proximity. These are consistent with and attributed to the higher positive charge on the RBD conferred by BA.1 and BA.2 mutations relative to the wild type. However, further differences between sub-variants BA.1 and BA.2 (which have equivalent RBD charges) are also evident: Mutations affect interdomain interactions between the up-chain and its clockwise neighbor chain, resulting in enhanced flexibility for BA.2. Consequently, additional close contacts arise in BA.2 which include binding to hACE2 by a second spike protein monomer, in addition to the up-chain - a motif not found in BA.1. Finally, the mechanism by which the glycans stabilize the up state of the Spike protein differs for the wild type and the Omicrons. We also found the glycan on N90 of hACE2 turns from inhibiting, to facilitating the binding to Omicron spike protein. These structural and electrostatic differences offer further insight into the mechanisms by which viral mutations modulate host cell binding and provide a biophysical basis for evolutionary driving forces.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.20.521221v1" target="_blank">Structure adaptation in Omicron SARS-CoV-2/hACE2:Biophysical origins of evolutionary driving forces</a>
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<li><strong>Stratification of hypertensive COVID-19 patients by quantitative NMR spectroscopy of serum metabolites, lipoproteins and inflammation markers</strong> -
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Background: The exact pathophysiology of humans suffering from the multifaceted SARS-CoV-2 infection is not yet conclusively understood and risk stratification is needed. Novel diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, important confounders such as age, sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider gender, as well as arterial hypertension (AHT) which affects more than 1.2 billion people worldwide, when investigating COVID-19-positive serum samples in a large age-matched cohort. As AHT is a risk factor for severe COVID-19 disease, this study focuses on comparing metabolomic characteristics of COVID-19 patients with and without AHT. Methods and Findings: NMR serum data from 329 COVID-19 patients were compared with 305 individuals from a healthy age and sex-matched control cohort. 134 of the 329 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Statistical comparison of the COVID-19 cohort with the control cohort reproduced results of previous studies. However, several differences emerged when AHT was considered. Especially, the previously described triglyceride-rich lipoprotein profile was no longer observed in COVID-19 patients, nor was an increase in ketone bodies. Typical metabolic changes that were apparent in COVID-19 patients in both sexes and with AHT were an increase in C- reactive protein (CRP) and the ratio of total glycoprotein (Glyc) to supramolecular phospholipids composite (SPC) which is an inflammatory NMR parameter. Further alterations were a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Typical metabolic cardiovascular risk markers could be detected in hypertensive COVID-19 patients, as well as higher inflammatory NMR parameters than in normotensive COVID-19 patients. Conclusion: We could show that a more precise picture of COVID-19 blood serum parameters emerge when AHT is considered which accordingly should be included in future studies and would help for a refined patient stratification.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.20.22283729v1" target="_blank">Stratification of hypertensive COVID-19 patients by quantitative NMR spectroscopy of serum metabolites, lipoproteins and inflammation markers</a>
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<li><strong>Designing epitope-focused vaccines via antigen reorientation</strong> -
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A major challenge in vaccine development, especially against rapidly evolving viruses, is the ability to focus the immune response toward evolutionarily conserved antigenic regions to confer broad protection. For example, while many broadly neutralizing antibodies against influenza have been found to target the highly conserved stem region of hemagglutinin (HA-stem), the immune response to seasonal influenza vaccines is predominantly directed to the immunodominant but variable head region (HA-head), leading to narrow-spectrum efficacy. Here, we first introduce an approach to controlling antigen orientation based on the site-specific insertion of short stretches of aspartate residues (oligoD) that facilitates antigen-binding to alum adjuvants. We demonstrate the generalizability of this approach to antigens from the Ebola virus, SARS-CoV-2, and influenza and observe enhanced antibody responses following immunization in all cases. Next, we use this approach to reorient HA in an ‘upside down’ configuration, which we envision increases HA-stem exposure, therefore also improving its immunogenicity compared to HA-head. When applied to HA of H2N2 A/Japan/305/1957, the reoriented H2 HA (reoH2HA) on alum induced a stem-directed antibody response that cross-reacted with both group 1 and 2 influenza A HAs. Our results demonstrate the possibility and benefits of antigen reorientation via oligoD insertion, which represents a generalizable immunofocusing approach readily applicable for designing epitope-focused vaccine candidates.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.20.521291v1" target="_blank">Designing epitope-focused vaccines via antigen reorientation</a>
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<li><strong>Number of COVID-19 hospitalisations averted by vaccination: Estimates for the Netherlands, January 6, 2021 through August 30, 2022</strong> -
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Background Vaccines against COVID-19 have proven effective in preventing COVID-19 hospitalisation. In this study, we aimed to quantify one aspect of the public health impact of COVID-19 vaccination by estimating the number of averted hospitalisations. We present results from the beginning of the vaccination campaign (period 1, January 6, 2021) and a period starting at August 2, 2021 (period 2) when all adults had the opportunity to complete their primary series, until August 30, 2022. Methods Using calendar-time specific vaccine effectiveness (VE) estimates and vaccine coverage (VC) by round (primary series, first booster and second booster) and the observed number of COVID-19 associated hospitalisations, we estimated the number of averted hospitalisations per age group for the two study periods. From January 25, 2022, when the indication of hospitalisation was registered, hospitalisations not causally related to COVID-19 were excluded. Results In period 1, there were an estimated 98,170 (95% confidence interval (CI) 96,123-99,928) averted hospitalisations, of which 90,753 (95% CI 88,790-92,531) in period 2, equalling 57.0% and 67.9% of all hospital admissions. Estimated averted hospitalisations were lowest for 12-49-year-olds and highest for 70-79-year-olds. More admissions were averted in the Delta period (72.3%) than in the Omicron period (63.4%). Conclusion COVID-19 vaccination prevented a large number of hospitalisations. Although the estimated number of hospitalisations during the study period could not have occurred realistically due to limits on health care, these findings underline the public health importance of the vaccination campaign to policy makers and the public.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.20.22283713v2" target="_blank">Number of COVID-19 hospitalisations averted by vaccination: Estimates for the Netherlands, January 6, 2021 through August 30, 2022</a>
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<li><strong>Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</strong> -
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Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine -either heterologous (PHH-1V group) or homologous (BNT162b2 group)- in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001), 1.31 (p=0.0007) and 0.86 (p=0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p<0.0001), 0.65 (p<0.0001) and 0.56 (p=0.003) for the Beta variant; 1.01 (p=0.92), 0.88 (p=0.11) and 0.52 (p=0.0003) for the Delta variant; and 0.59 (p=<0.0001), 0.66 (p<0.0001) and 0.57 (p=0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and Delta SARS-CoV-2 variants, as well as the currently circulating Omicron BA.1. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277210v3" target="_blank">Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</a>
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<li><strong>Emergence and antibody evasion of BQ and BA.2.75 SARS-CoV-2 sublineages in the face of maturing antibody breadth at the population level</strong> -
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The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and related sub-lineages. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants at two levels: (i) we tracked over 400,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using antibody pools. (ii) we mapped the antibody response at the individual level using blood from strigently curated vaccine and convalescent cohorts. In pooled antibody samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases we observed increased antibody breadth to variants that were yet to be in circulation. Resolution of viral neutralisation at the cohort level supported equivalent coverage across prior and emerging variants with emerging isolates BQ.1.1, XBB.1 and BR.2.1 the most evasive. Further, these emerging variants were resistant to Evusheld, whilst neutralization resistance to Sotrovimab was restricted to BQ.1.1 and further supported by lack of Spike glycoprotein binding to this variant. An outgrowth advantage through better utilization of TMPRSS2 was observed across BQ lineages and not those derived from BA.2.75. We conclude at this current point in time that variants derived from BQ lineages can evade antibodies at levels equivalent to their most evasive BA.2.75 counterparts but sustain an entry phenotype that would promote an additional outgrowth advantage.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.06.22283000v2" target="_blank">Emergence and antibody evasion of BQ and BA.2.75 SARS-CoV-2 sublineages in the face of maturing antibody breadth at the population level</a>
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</div></li>
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<li><strong>Omicron-associated mortality for principal causes other than COVID-19, including mortality with a confirmed SARS-CoV-2 infection, and ICU admissions with an Omicron infection in adults aged over 60 years in France</strong> -
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Background: With the emergence of the Omicron variant, an increasing proportion of SARS-CoV-2 associated deaths have a principal cause of death other than COVID-19. In France, between Nov. 1, 2021 – July 31, 2022, in addition to 33,353 deaths with the principal cause of COVID-19, there were 9,638 deaths with a confirmed SARS-CoV-2 infection with a principal cause of death other than COVID-19 (as well as SARS-CoV-2-associated deaths with an undetected SARS-CoV-2 infection). Methods: We examined the relation between mortality for COVID-19, mortality for other causes, and ICU admissions with a SARS-CoV-2-infection in adults aged over 60y in France. Results: The number of deaths with principal causes other than COVID-19 in France between July 2021-June 2022 was greater than the corresponding number between July 2020-June 2021 by 20,860 (95% CI (11241,30421)) after adjusting for pre-pandemic trends in mortality (compared to the increase of 3,078 in the number of deaths with a SARS-CoV-2 infection with principal causes other than COVID-19 between the two time periods). During the period of Omicron circulation (Nov. 1, 2021 - Nov. 13, 2022), there was a strong association between the rates of ICU admission with a SARS-CoV-2 infection in adults aged over 60y and (a) rates of COVID-19 deaths (correlation=0.96 (0.92,0.97)); (b) rates of mortality with principal causes other than COVID-19 (correlation=0.89 (0.82,0.94)). Proportions of ICU admissions for causes other than COVID-19 among all ICU admissions with a SARS-CoV-2 infection in older adults were lower during the periods when rates of COVID-19 disease in the community were higher. Conclusions: The significant increase in mortality with principal causes other than COVID-19, as well as the decreases in the proportions of ICU admissions for causes other than COVID-19 among all ICU admissions with a SARS-CoV-2 infection in older adults during the periods when rates of COVID-19 disease in the community were higher suggest under-detection of Omicron infections in associated complications that did not manifest themselves as COVID-19, which is related to the treatment of SARS-CoV-2 infection in those complications.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22283529v3" target="_blank">Omicron-associated mortality for principal causes other than COVID-19, including mortality with a confirmed SARS-CoV-2 infection, and ICU admissions with an Omicron infection in adults aged over 60 years in France</a>
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</div></li>
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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>A Study for Immunocompromised Patients for Pre Exposure Prophylaxis of COVID-19 With AZD5156.</strong> - <b>Condition</b>: COVID 19<br/><b>Interventions</b>: Biological: Placebo; Biological: AZD5156; Biological: AZD7442 (EVUSHELD™)<br/><b>Sponsor</b>: AstraZeneca<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>101-PGC-005 for the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: 101-PGC-005; Drug: Dexamethasone<br/><b>Sponsor</b>: 101 Therapeutics<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 Clinical Study to Assess Preliminary Efficacy, Safety and Tolerability of HH-120 Nasal Spray in COVID-19 Patients</strong> - <b>Condition</b>: Coronavirus Disease 2019(COVID-19)<br/><b>Intervention</b>: Biological: HH-120 Nasal Spray<br/><b>Sponsor</b>: Beijing Ditan 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>COVID-19 Booster Study in Healthy Adults in Australia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent Moderna; Biological: Novavax<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; 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>Effect of N-Acetylcysteine on Neutrophil Lymphocyte Ratio And Length of Stay In COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: N-acetyl cysteine<br/><b>Sponsor</b>: Universitas Sebelas Maret<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>Baldachin: Ceiling HEPA-filtration to Prevent Nosocomial Transmission of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Baldachin<br/><b>Sponsor</b>: University Hospital Inselspital, Berne<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>Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly; Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled; Drug: Standard of care<br/><b>Sponsor</b>: Promomed, LLC<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>Study of GST-HG171/Ritonavir Compared With Placebo in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: GST-HG171/Ritonavir; Drug: Placebo<br/><b>Sponsor</b>: Fujian Akeylink Biotechnology 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 PhaseⅡ Study to Evaluate the Safety & Immunogenicity of SARS-CoV-2 Alpha/Beta/Delta/Omicron Variants COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: SCTV01E; Biological: Placebo (normal saline)<br/><b>Sponsor</b>: Sinocelltech 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>The Efficacy of Azvudine and Paxlovid in High-risk Patients With COVID-19: A Prospective Randomized Controlled Trial</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Paxlovid group<br/><b>Sponsors</b>: Southeast University, China; Hohhot First Hospital, Hohhot, Inner Mongolia, China<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>ICBT for Psychological Symptoms Related to the COVID-19 Pandemic Remaining After Societal Opening</strong> - <b>Condition</b>: Depression and Anxiety Symptoms Related to the COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Internet-based Cognitive Behavioral Therapy<br/><b>Sponsor</b>: Linkoeping University<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>Effectiveness of Supportive Psychotherapy Through Internet-Based Teleconsultation on Psychological and Somatic Symptoms, Neutrophil-Lymphocyte Ratio, and Heart Rate Variability in Post Covid-19 Syndrome Patients</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Supportive Psychotherapy<br/><b>Sponsor</b>: Indonesia University<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>Graphene Photothermal Adjuvant Therapy for Mild Corona Virus Disease 2019: A Prospective Randomized Controlled Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Graphene spectrum light wave therapy room<br/><b>Sponsors</b>: Southeast University, China; Hohhot First 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>ARVAC - A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Intervention</b>: Biological: ARVAC-CG vaccine (recombinant protein vaccine against SARS-CoV-2)<br/><b>Sponsors</b>: Laboratorio Pablo Cassara S.R.L.; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina<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>The KIN-FAST Trial (KIN001 For Accelerated Symptoms Termination) in Non Hospitalized Patients Infected With SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: KIN001; Drug: KIN001-Placebo<br/><b>Sponsor</b>: Kinarus AG<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<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 advanced technologies against COVID-19: Prevention, Detection, and Treatments</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>Antiviral activity of pyrimidine containing compounds: Patent review</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>IFITM3 is a host restriction factor that inhibits porcine transmissible gastroenteritis virus infection</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>Programmable DNA biocomputing circuits for rapid and intelligent screening of SARS-CoV-2 variants</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>Severe COVID-19 patients show a dysregulation of the NLRP3 inflammasome in circulating neutrophils</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>Antigenic Characterization of Human Monoclonal Antibodies for Therapeutic Use against H7N9 Avian Influenza Virus</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>Porcine Hemagglutinating Encephalomyelitis Virus Co-Opts Multivesicular-Derived Exosomes for Transmission</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>Testosterone suppression combined with high dose estrogen as potential treatment of SARS-CoV-2. A mini review</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>The Biological Causes and Consequences of COVID-19: ACE I/D Polymorphism and In-Silico Screening of Potential Bioactive Phytochemicals Against COVID-19</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Insulin may promote SARS-CoV-2 cell entry and replication in diabetes patients</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>The Oral Cavity Potentially Serving as a Reservoir for SARS-CoV-2 but Not Necessarily Facilitating the Spread of COVID-19 in Dental Practice</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>The effectiveness of the intermediate and therapeutic doses of enoxaparin in COVID-19 patients: A comparative study of factor Xa inhibition</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>Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003</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>Therapeutic role of mTOR inhibitors in control of SARS-CoV-2 viral replication</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>A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies</strong> - No abstract</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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