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188 lines
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<title>27 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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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Do text messages increase voter registration? Evidence from RCTs with a local authority and an advocacy organisation in the UK</strong> -
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<div>
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In the wake of the Covid-19 pandemic, text messages have become an increasingly attractive tool of voter registration. At the same time, in countries without automated registration, advocacy organisations play a more prominent role in supplementing the efforts of official bodies in registering voters. However, most available, robust evidence on whether voter registration campaigns work is based on campaigns conducted by official bodies charged with electoral registration. We present the results of two RCTs that aimed to increase voter registration in the UK using SMS-text messages, relying mainly on behavioural messaging. One was conducted by a local authority, while the other was implemented by an issue advocacy organisation that had no prior involvement in voter registration. In line with previous findings, the local authority’s text messages resulted in an increased registration rate of eight percentage-points, which translates into a three percentage-point increase in voter turnout. However, the advocacy organisation’s text messages neither increased voter registration, nor turnout, no matter whether the text message offered a personal follow-up conversation, or not. Given that many voter registration campaigns are run by advocacy organisations and text messages are an increasingly important mobilisation tool, this raises questions about the scope conditions of existing findings.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/adr9g/" target="_blank">Do text messages increase voter registration? Evidence from RCTs with a local authority and an advocacy organisation in the UK</a>
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</div></li>
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<li><strong>Impact of BA.1, BA.2, and BA.4/BA.5 Omicron Mutations on Therapeutic Monoclonal Antibodies</strong> -
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<div>
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The emergence of Omicron SARS-CoV-2 subvariants (BA.1, BA.2, BA.4, and BA.5) with an unprecedented number of mutations in their receptor-binding domain (RBD) of the spike-protein has fueled a new surge of COVID-19 infections, posing a major challenge to the efficacy of existing vaccines and monoclonal antibody (mAb) therapeutics. Here, a thorough and systematic molecular dynamics (MD) simulation study is conducted to investigate how the RBD mutations on these subvariants affect the interactions with broad mAbs including AstraZeneca (COV2-2196 and COV2-2130), Brii Biosciences (BRII-196), Celltrion (CT-P59), Eli Lilly (LY-CoV555 and LY-CoV016), Regeneron (REGN10933 and REGN10987), Vir Biotechnology (S309), and S2X259. Our results show a complete loss of binding for COV2-2196, BRII-196, CT-P59, and LY-CoV555 with all Omicron RBDs. REGN10987 also loses its binding against BA.1 but partially retains against BA.2 and BA.4/5. The reduction in binding is either significant for LY-CoV016 and REGN10933 or moderate for COV2-2130. S309 and S2X259 retain their binding strength against BA.1 but decrease against others. We introduce a mutational escape map for each mAb to identify the key RBD sites and critical mutation. Overall, our findings suggest that majority of therapeutic mAbs have diminished or lost their activity against Omicron subvariants, indicating the urgent need for a new therapeutic mAb, modifying current ones with a better mAb design, or seeking an alternative approach.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.25.521903v1" target="_blank">Impact of BA.1, BA.2, and BA.4/BA.5 Omicron Mutations on Therapeutic Monoclonal Antibodies</a>
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</div></li>
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<li><strong>Amplification and extraction free quantitative detection of viral nucleic acids and single-base mismatches using magnetic signal amplification circuit</strong> -
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<div>
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Established nucleic acid detection assays require extraction and purification before sequence amplification and/or enzymatic reactions, hampering their widespread applications in point-of-care (POC) formats. Magnetic immunoassays based on magnetic particle spectroscopy and magnetic nanoparticles (MNPs) are isothermal, extraction- and purification-free, and can be quantitative and benchtop, making them suitable for POC settings. Here, we demonstrate a Magnetic signal Amplification Circuit (MAC) that combines specificity of toehold-mediated DNA strand displacement with magnetic response of MNPs to a clustering/declustering process. Our MAC assays require neither amplification nor extraction of target nucleic acids, and reveal four times better sensitivity than that of a magnetic circuit without signal amplification. Using MAC, we detect a highly specific 43 nucleotides sequence of SARS-CoV-2 virus. The MAC enables sensing both DNA and RNA targets with varying lengths and resolving single-base mismatches. Our MAC can be a powerful tool for translating research of nucleic acids detection to the clinic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.24.521858v1" target="_blank">Amplification and extraction free quantitative detection of viral nucleic acids and single-base mismatches using magnetic signal amplification circuit</a>
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</div></li>
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<li><strong>A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates</strong> -
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<div>
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While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly booster vaccine, and as a primary vaccine for pediatric use including in infants.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.25.521784v1" target="_blank">A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates</a>
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</div></li>
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<li><strong>In Vitro Inhibition of SARS-CoV-2 Infection by Bromhexine hydrochloride</strong> -
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<div>
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The world enduring the SARS CoV-2 pandemic, and although extensive research has been conducted on the issue, only a few antivirals have been approved up to date to treat patients with COVID-19. Bromhexine hydrochloride was previously identified as a potent inhibitor of TMPRSS2, an essential protease for ACE-2 virus receptor interactions. In the present study, we investigated whether bromhexine treatment could reduce SARS CoV-2 replication in vitro. To evaluates the effectiveness of bromhexine against SARS COV-2 infection, viral load was measured using Caco-2 cell lines that express TMPRSS2. Our molecular docking results indicate that bromhexine displays an affinity with the active site of TMPRSS2. The drug was able to significantly inhibit SARS CoV-2, both parental and P1 variant strains, infection in the Caco-2 cell line, reducing about 40% of SARS-CoV-2 entrance, and about 90% of viral progeny in the supernatant 48h post-infection. Furthermore, bromhexine did not exhibit any direct virucidal activity on SARS CoV-2. In conclusion, bromhexine hydrochloride efficiently disrupts SARS CoV-2 infection in vitro and has the potential to become an effective antiviral agent in COVID-19 treatment.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.23.521817v1" target="_blank">In Vitro Inhibition of SARS-CoV-2 Infection by Bromhexine hydrochloride</a>
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</div></li>
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<li><strong>Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16</strong> -
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<div>
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The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-methyltransferase and NSP14 through its N7 methyltransferase activity, which are essential for the replication of the viral genome as well as evading the host’s innate immunity. NSP10 acts as a crucial cofactor and stimulator of NSP14 and NSP16. To further understand the role of NSP10, we carried out a comprehensive analysis of >13 million globally collected whole-genome sequences (WGS) of SARS-CoV-2 obtained from the Global Initiative Sharing All Influenza Data (GISAID) and compared it with the reference genome Wuhan/WIV04/2019 to identify all currently known variants in NSP10. T12I, T102I, and A104V in NSP10 have been identified as the three most frequent variants and characterized using X-ray crystallography, biophysical assays, and enhanced sampling simulations. In contrast to other proteins such as spike and NSP6, NSP10 is significantly less prone to mutation due to its crucial role in replication. The functional effects of the variants were examined for their impact on the binding affinity and stability of both NSP14-NSP10 and NSP16-NSP10 complexes. These results highlight the limited changes induced by variant evolution in NSP10 and reflect on the critical roles NSP10 plays during the SARS-CoV-2 life cycle. These results also indicate that there is limited capacity for the virus to overcome inhibitors targeting NSP10 via the generation of variants in inhibitor binding pockets.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.23.521761v1" target="_blank">Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16</a>
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<li><strong>A large-scale serological survey in pets from October 2020 through June 2021 in France shows significantly higher exposure to SARS-CoV-2 in cats</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect many animals, including pets such as dogs and cats. Many studies have documented infection in companion animals by bio-molecular and serological methods. However, only a few have compared seroprevalence in cats and dogs from the general population, and these studies were limited by small sample sizes and collections over short periods. Our goal was to obtain a more accurate evaluation of seroprevalence in companion animals in France and to determine whether cats and dogs differ in their exposure to SARS-CoV-2. For this purpose, we conducted an extensive SARS-CoV-2 serological survey of 2036 cats and 3577 dogs sampled by veterinarians during medical examinations in clinics throughout France. Sampling was carried out from October 2020 through June 2021, a period encompassing the second and third waves of SARS-CoV-2 infections in humans in the country. Using a microsphere immunoassay targeting receptor binding domain and trimeric spike protein, we found 7.1% seroprevalence in pets, in a subset of 308 seropositive samples, 26.3% had neutralizing antibodies. We found that cats were significantly more likely to test positive than dogs, with seropositivity rates of 9.3% and 5.9% in cats and dogs, respectively. Finally, data for both species showed that seroprevalence was lower in older animals and was not associated with the date of sampling or the sex of the animal. Our results show that cats are significantly more sensitive to SARS-CoV-2 than dogs, in line with experimental studies showing that cats are more susceptible than dogs. This study reinforces that pets are commonly infected or exposed to SARS-CoV-2, emphasizing the importance of a One-Health approach to the SARS-CoV-2 pandemic and raising the question of vaccination of companion animals in close contact with humans.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.23.521567v1" target="_blank">A large-scale serological survey in pets from October 2020 through June 2021 in France shows significantly higher exposure to SARS-CoV-2 in cats</a>
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<li><strong>Comparison of multiple whole-genome and Spike-only sequencing protocols for estimating variant frequencies via wastewater-based epidemiology</strong> -
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Sequencing of SARS-CoV-2 in wastewater provides a key opportunity to monitor the prevalence of variants spatiotemporally, potentially facilitating their detection simultaneously with, or even prior to, observation through clinical testing. However, there are multiple sequencing methodologies available. This study aimed to evaluate the performance of alternative protocols for detecting SARS-CoV-2 variants. We tested the detection of two synthetic RNA SARS-CoV-2 genomes in a wide range of ratios and at two concentrations representative of those found in wastewater using whole-genome and Spike-gene-only protocols utilising Illumina and Oxford Nanopore platforms. We developed a Bayesian hierarchical model to determine the predicted frequencies of variants and the error surrounding our predictions. We found that most of the sequencing protocols detected polymorphic nucleotide frequencies at a level that would allow accurate determination of the variants present at higher concentrations. Most methodologies, including the Spike-only approach, could also predict variant frequencies with a degree of accuracy in low-concentration samples but, as expected, with higher error around the estimates. All methods were additionally confirmed to detect the same prevalent variants in a set of wastewater samples. Our results provide the first quantitative statistical comparison of a range of alternative methods that can be used successfully in the surveillance of SARS-CoV-2 variant frequencies from wastewater.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.22.22283855v1" target="_blank">Comparison of multiple whole-genome and Spike-only sequencing protocols for estimating variant frequencies via wastewater-based epidemiology</a>
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</div></li>
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<li><strong>EFFECTIVENESS OF CASIRIVIMAB-IMDEVIMAB AND SOTROVIMAB MONOCLONAL ANTIBODY TREATMENT AMONG HIGH-RISK PATIENTS WITH SARS-CoV-2 INFECTION: A REAL-WORLD EXPERIENCE</strong> -
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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can evade neutralizing antibodies, raising concerns about the effectiveness of anti-spike monoclonal antibodies (mAb). METHODS: This study reports a retrospective data analysis in Banner Health Care System. Out of 109,788 adult patients who tested positive for COVID-19, the study cohort was split into patients who received Casirivimab-Imdevimab (Cas-Imd) (N=10,836; Delta-predominant period 6/2021-11/2021) and Sotrovimab (N=998; Omicron-predominant period 12/2021-1/2022) mAb compared to propensity-matched control groups (N=10,836 and N=998), respectively. Index date was the date of mAb administration or the date of positive COVID-19 testing. The primary and secondary outcomes were the incidence of composite outcome (all-cause hospitalization and/or mortality) and ICU admission at 30-days following index date, respectively. RESULTS: Compared to the propensity-matched untreated control cohort, the Cas-Imd mAb reduced the composite outcome (from 7.5% to 3.7%; difference: -3.8% [95% CI: (-4.4%, -3.2%)], p <0.01) regardless of their vaccination status, while Sotrovimab mAb did not (5.0% vs. 3.8%; difference: -1.2% [95% CI: (-3.1%, 0.7%)], p =0.22). In terms of the secondary outcome, similarly Cas-Imd mAb decreased ICU admission during the first hospitalization (from 1.5% to 0.5%; difference: -1.0% [95% CI: (-1.3%, -0.7%)], p <0.01) compared to the control group, whereas Sotrovimab mAb did not (0.9% vs. 0.6%; difference: -0.3% [95% CI: (-1.2%, 0.6%)], p =0.61). Comparing the periods, the Omicron-predominant period was associated with lower composite outcome than that during the Delta-predominant period. CONCLUSIONS: Cas-Imd mAb was effective against the SARS-CoV-2 Delta variant, however sotrovimab lacked efficacy in patients with SARS-CoV-2 Omicron-predominant period.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.23.22283921v1" target="_blank">EFFECTIVENESS OF CASIRIVIMAB-IMDEVIMAB AND SOTROVIMAB MONOCLONAL ANTIBODY TREATMENT AMONG HIGH-RISK PATIENTS WITH SARS-CoV-2 INFECTION: A REAL-WORLD EXPERIENCE</a>
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<li><strong>Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During the COVID-19 Pandemic</strong> -
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Objective. This study was conducted to identify rates of pediatric nirmatrelvir/ritonavir (Paxlovid) prescriptions overall and by patient characteristics. Methods. Patients up to 23 years old with a clinical encounter and a nirmatrelvir/ritonavir (Paxlovid, n/r) prescription in a PEDSnet-affiliated institution between December 1, 2021 and September 14, 2022 were identified using electronic health record (EHR) data. Results. Of the 1,496,621 patients with clinical encounters during the study period, 920 received a nirmatrelvir/ritonavir prescription (mean age 17.2 years; SD 2.76 years). 40% (367/920) of prescriptions were provided to individuals aged 18-23, and 91% (838/920) of prescriptions occurred after April 1, 2022. The majority of patients (70%; 648/920) had received at least one COVID-19 vaccine dose at least 28 days before nirmatrelvir/ritonavir prescription. Only 40% (371/920) of individuals had documented COVID-19 within the 0 to 6 days prior to receiving a nirmatrelvir/ritonavir prescription. 53% (485/920) had no documented COVID-19 infection in the EHR. Among nirmatrelvir/ritonavir prescription recipients, 64% (586/920) had chronic or complex chronic disease and 9% (80/920) had malignant disease. 38/920 (4.5%) were hospitalized within 30 days of receiving nirmatrelvir/ritonavir. Conclusion. Clinicians prescribe nirmatrelvir/ritonavir infrequently to children. While individuals receiving nirmatrelvir/ritonavir generally have significant chronic disease burden, a majority are receiving nirmatrelvir/ritonavir prescriptions without an EHR-recorded COVID-19 positive test or diagnosis. Development and implementation of concerted pediatric nirmatrelvir/ritonavir prescribing workflows can help better capture COVID-19 presentation, response, and adverse events at the population level.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.23.22283868v1" target="_blank">Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During the COVID-19 Pandemic</a>
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<li><strong>Methodological approaches to optimize multiplex oral fluid SARS-CoV-2 IgG assay performance and correlation with serologic and neutralizing antibody responses</strong> -
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Background. Oral fluid (hereafter, saliva) is a non-invasive and attractive alternative to blood for SARS-CoV-2 IgG testing; however, the heterogeneity of saliva as a matrix poses challenges for immunoassay performance. Objectives. To optimize performance of a magnetic microparticle-based multiplex immunoassay (MIA) for SARS-CoV-2 IgG measurement in saliva, with consideration of: i) threshold setting and validation across different MIA bead batches; ii) sample qualification based on salivary total IgG concentration; iii) calibration to U.S. SARS-CoV-2 serological standard binding antibody units (BAU); and iv) correlations with blood-based SARS-CoV-2 serological and neutralizing antibody (nAb) assays. Methods. The salivary SARS-CoV-2 IgG MIA included 2 nucleocapsid (N), 3 receptor-binding domain (RBD), and 2 spike protein (S) antigens. Gingival crevicular fluid (GCF) swab saliva samples were collected before December, 2019 (n=555) and after molecular test-confirmed SARS-CoV-2 infection from 113 individuals (providing up to 5 repeated-measures; n=398) and used to optimize and validate MIA performance (total n=953). Combinations of IgG responses to N, RBD and S and total salivary IgG concentration (μg/mL) as a qualifier of nonreactive samples were optimized and validated, calibrated to the U.S. SARS-CoV-2 serological standard, and correlated with blood-based SARS-CoV-2 IgG ELISA and nAb assays. Results. The sum of signal to cutoff (S/Co) to all seven MIA SARS-CoV-2 antigens and disqualification of nonreactive saliva samples with >15 μg/mL total IgG led to correct classification of 62/62 positives (sensitivity [Se]=100.0%; 95% confidence interval [CI]=94.8%, 100.0%) and 108/109 negatives (specificity [Sp]=99.1%; 95% CI=97.3%, 100.0%) at 8-million beads coupling scale and 80/81 positives (Se=98.8%; 95% CI=93.3%, 100.0%] and 127/127 negatives (Sp=100%; 95% CI=97.1%, 100.0%) at 20-million beads coupling scale. Salivary SARS-CoV-2 IgG crossed the MIA cutoff of 0.1 BAU/mL on average 9 days post-COVID-19 symptom onset and peaked around day 30. Among n=30 matched saliva and plasma samples, salivary SARS-CoV-2 MIA IgG levels correlated with corresponding-antigen plasma ELISA IgG (N: ρ=0.67, RBD: ρ=0.76, S: ρ =0.82; all p<0.0001). Correlations of plasma SARS-CoV-2 nAb assay area under the curve (AUC) with salivary MIA IgG (N: ρ=0.68, RBD: ρ=0.78, S: ρ =0.79; all p<0.0001) and with plasma ELISA IgG (N: ρ=0.76, RBD: ρ=0.79, S: ρ =0.76; p<0.0001) were similar. Conclusions. A salivary SARS-CoV-2 IgG MIA produced consistently high Se (>98.8%) and Sp (>99.1%) across two bead coupling scales and correlations with nAb responses that were similar to blood-based SARS-CoV-2 IgG ELISA data. This non-invasive salivary SARS-CoV-2 IgG MIA could increase engagement of vulnerable populations and improve broad understanding of humoral immunity (kinetics and gaps) within the evolving context of booster vaccination, viral variants and waning immunity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.22.22283858v1" target="_blank">Methodological approaches to optimize multiplex oral fluid SARS-CoV-2 IgG assay performance and correlation with serologic and neutralizing antibody responses</a>
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<li><strong>Risk of Suicide Attempts and Self-Directed Violence after SARS-CoV-2 Infection: Outcomes from an Emulated Trial of a Nationwide Observational Matched Cohort of US Veterans</strong> -
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Importance: The negative health-related effects of SARS-CoV-2 infection may include increased risk for self-directed violence. Objective: To assess suicide attempts and other self-directed violence risk among US Veterans with a positive polymerase chain reaction (PCR) test for SARS-CoV-2 infection compared to matched uninfected Veterans. Design, Setting, and Participants: Using a target trial emulation design supported by comprehensive electronic health records from the US Veterans Health Administration, Veterans who had a positive PCR test between March 1, 2020 and March 31, 2021 were matched with non-infected comparators. Monthly matching was anchored to first positive PCR test for each patient. Groups were followed for one-year thereafter. Exposure: Positive SARS-CoV-2 PCR. Main Outcomes and Measures: Suicide attempts and self-directed violence documented in electronic health records by a VHA provider. Hazard ratios (HR) for time to first suicide attempt and self-directed violence (separate models) for the infected versus comparator group were measured using Cox regression models. Analyses were performed for short-term (days 1-30), long-term (days 31-365) and one-year (days 1-365) and further stratified by age and prior self-directed-violence history. Sensitivity analyses included censoring to address comparators crossing over by later testing positive for SARS-CoV-2. Results: Among the 1,190,974 Veterans included, during the one-year period after the index date; 3,078 (0.258%) had a suicide attempt and 2,887 (0.242%) had self-directed violence. Regardless of follow-up duration, the HRs for suicide attempts and self-directed violence were higher for the infected group. For suicide attempts, short-term HR=2.54 (95% Confidence Interval [CI]: 2.05 to 3.15), long-term HR=1.30 (CI: 1.19 to 1.43) and one-year HR= 1.41 (CI: 1.30, 1.54). For self-directed violence, short-term HR=1.94 (CI: 1.51 to 2.49), long-term HR=1.32 (CI: 1.20 to 1.45), and one-year HR=1.38 (CI:1.26, 1.51). Conclusions and Relevance: In matched cohorts, Veterans who had a positive SARS-CoV-2 PCR test had a higher risk of suicide attempt and self-directed violence that were greatest within the first 30 days and present for at least one year following. These findings highlight the importance of assessing patient experiences of suicide attempt and other forms of self-directed violence during different time periods post-infection to identify opportunities to augment prevention efforts and support those affected.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.23.22283902v1" target="_blank">Risk of Suicide Attempts and Self-Directed Violence after SARS-CoV-2 Infection: Outcomes from an Emulated Trial of a Nationwide Observational Matched Cohort of US Veterans</a>
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<li><strong>Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection</strong> -
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There is limited data directly comparing the effectiveness of COVID-19 vaccines. We compared rates of SARS-CoV-2 Omicron BA.1/2 infection in Australian adults during March to May 2022 who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose. As a primary course, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For booster dose, respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60). Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines, but further studies are required due to small numbers of recipients of ChAdOx-1 nCov-19 and NVX-CoV2373.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.22.22283869v1" target="_blank">Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection</a>
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<li><strong>Unequal Recovery in Colorectal Cancer Screening Following the COVID-19 Pandemic: A Comparative Microsimulation Analysis</strong> -
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The aftermath of the initial phase of the COVID-19 pandemic may contribute to the widening of disparities in access to colorectal cancer (CRC) screening due to differential disruptions to CRC screening. This comparative microsimulation analysis uses two CISNET CRC models to simulate the impact of ongoing screening disruptions induced by the COVID-19 pandemic on long-term CRC outcomes. We evaluate three channels through which screening was disrupted: delays in screening, regimen switching, and screening discontinuation. The impact of these disruptions on long-term colorectal cancer (CRC) outcomes was measured by the number of Life-years lost due to CRC screening disruptions compared to a scenario without any disruptions. While short-term delays in screening of 3-18 months are predicted to result in minor life-years loss, discontinuing screening could result in much more significant reductions in the expected benefits of screening. These results demonstrate that unequal recovery of screening following the pandemic can widen disparities in colorectal cancer outcomes and emphasize the importance of ensuring equitable recovery to screening following the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.23.22283887v1" target="_blank">Unequal Recovery in Colorectal Cancer Screening Following the COVID-19 Pandemic: A Comparative Microsimulation Analysis</a>
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<li><strong>No patient is the same; lessons learned from antibody repertoire profiling in hospitalized severe COVID-19 patients</strong> -
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Here, by using mass spectrometry-based methods IgG1 and IgA1 clonal repertoires were monitored quantitatively and longitudinally in more than 50 individual serum samples obtained from 17 COVID-19 patients admitted to intensive care units because of acute respiratory distress syndrome. These serological clonal profiles were used to examine how each patient reacted to a severe SARS-CoV-2 infection. All 17 donors revealed unique polyclonal repertoires and changes after infection. Substantial changes over time in the IgG1 and/or IgA1 clonal repertoires were observed in individual patients, with several new clones appearing following the infection, in a few cases leading to a few very high abundant IgG1 and/or IgA1 clones dominating the repertoire. Several of these clones were de novo sequenced through combinations of top-down, middle-down and bottom-up proteomics approaches. This revealed several sequence features in line with sequences deposited in the SARS-CoV-specific database of antibodies. In other patients, the serological Ig profiles revealed the treatment with tocilizumab, as after treatment, this IgG1-mAb dominated the serological IgG1 repertoire. Tocilizumab clearance could be monitored and a half-life of approximately 6 days was established in these patients. Overall, our longitudinal monitoring of IgG1 and IgA1 repertoires of individual donors reveals that antibody responses are highly personalized traits of each patient, affected by the disease and the chosen clinical treatment. The impact of these observations argues for a more personalized and longitudinal approach in patients diagnostics, both in serum proteomics as well as in monitoring immune responses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.23.22283896v1" target="_blank">No patient is the same; lessons learned from antibody repertoire profiling in hospitalized severe COVID-19 patients</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study 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>Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above（Negative Antibody Against COVID-19）</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: One dose group; Biological: Two doses group; Biological: Aged 18-59 years; Biological: Aged 60 years old and above<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech 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>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 COPE Study: Pilot Intervention to Improve Symptom Self-management and Coping in Adults With Post COVID-19</strong> - <b>Conditions</b>: Post COVID-19 Condition; Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: 6-Week Self-Management Group<br/><b>Sponsor</b>: University of Washington<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>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>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>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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</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>Infectivity of pseudotyped SARS-CoV-2 variants of concern in different human cell types and inhibitory effects of recombinant spike protein and entry-related cellular factors</strong> - Since the report of the first COVID-19 case in 2019, SARS-CoV-2 variants of concern (VOCs) have continued to emerge, manifesting diverse infectivity, evasion of host immunity and pathology. While ACE2 is the predominant receptor of SARS-CoV-2, TMPRSS2, Kim-1, NRP-1, CD147, furin, CD209L and CD26 have also been implicated as viral entry-related cofactors. To understand the variations in infectivity and pathogenesis of VOCs, we conducted infection analysis in human cells from different organ…</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 prediction of SARS-CoV-2 main protease inhibition with filtering by position of ligand</strong> - The paper analyzes a set of equations that adequately predict the IC50 value for SARS-CoV-2 main protease inhibitors. The training set was obtained using filtering by criteria independent of prediction of target value. It included 76 compounds, and the test set included nine compounds. We used the values of energy contributions obtained in the calculation of the change of the free energy of complex by MMGBSA method and a number of characteristics of the physical and chemical properties of 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>Impacts of video communication on psychological well-being and cosmetic surgery acceptance</strong> - Video communication via platforms such as Zoom has been routinely used as a communication tool during the COVID-19 pandemic. Scientific evidence has suggested that constant video communication can have detrimental consequences such as “Zoom fatigue”, inhibiting collaboration, and new information exchange. The current study focuses on the effects of using video communication technology on self-esteem, affect, and image perception under the framework of objective self-awareness (OSA). We…</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 new intracellular targeting motif in the cytoplasmic tail of the spike protein may act as a target to inhibit SARS-CoV-2 assembly</strong> - Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a threat to global public health, underscoring the urgent need for the development of preventive and therapeutic measures. The spike (S) protein of SARS-CoV-2, which mediates receptor binding and subsequent membrane fusion to promote viral entry, is a major target for current drug development and vaccine design. The S protein comprises a large N-terminal extracellular domain, a transmembrane domain, and a short…</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>Regulatory role of endoplasmic reticulum resident chaperone protein ERp29 in anti-murine β-coronavirus host cell response</strong> - Gap junctional intercellular communication (GJIC) involving astrocytes is important for proper CNS homeostasis. As determined in our previous studies, trafficking of the predominant astrocyte GJ protein, Connexin43 (Cx43), is disrupted in response to infection with a neurotropic murine β-coronavirus (MHV-A59). However, how host factors are involved in Cx43 trafficking and the infection response is not clear. Here, we show that Cx43 retention due to MHV-A59 infection was associated with increased…</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>Cenicriviroc for the treatment of COVID-19: first interim results of a randomised, placebo-controlled, investigator-initiated, double-blind phase II trial</strong> - CONCLUSION: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical 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>Mammalian hybrid prophagophore is a precursor to autophagosomes</strong> - SUMMARYThe precursors to mammalian autophagosomes originate from pre-existing membranes contributed by a number of sources, and subsequently enlarge through intermembrane lipid transfer, then close to sequester the cargo, and merge with lysosomes to degrade the cargo. Using cellular and in vitro membrane fusion analyses coupled with proteomic and biochemical studies we show that autophagosomes are formed from a hybrid membrane compartment referred to as a prophagophore or HyPAS (hybrid…</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>Booster shot of inactivated SARS-CoV-2 vaccine induces potent immune responses in people living with HIV</strong> - CONCLUSIONS: PLWH receiving booster shot of inactivated vaccines generate higher antibody responses than the second dose, but lower than that in HCs. Decreased anti-BA.4/5 responses than that of WT impede the protective effect of the third dose on Omicron prevalence. This article is protected by copyright. All rights reserved.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A novel poly (4-methyl-1-pentene)/polypropylene (PMP/PP) thin film composite (TFC) artificial lung membrane for enhanced gas transport and excellent hemo-compatibility</strong> - Extracorporeal membrane oxygenation is a technique that provides short-term supports to the heart and lungs. It removes CO(2) from the blood and provides enough oxygen, which is a huge help in the fight against COVID-19. As the key component, the artificial lung membranes have evolved in three generations including silicon, polypropylene and poly (4-methyl-1-pentene). Herein, we for the first time design and fabricate a novel poly (4-methyl-1-pentene)/polypropylene (PMP/PP) thin film composite…</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>Identification of Human miRNA Biomarkers Targeting the SARS-CoV-2 Genome</strong> - SARS-CoV-2 poses a great challenge toward mankind, majorly due to its evolution and frequently occurring variants. On the other hand, in human hosts, microRNA (miRNA) plays a vital role in replication and propagation during a viral infection and can control the biological processes. This may be essential for the progression of viral infection. Moreover, human miRNAs can play a therapeutic role in treatment of different viral diseases by binding to the target sites of the virus genome, thereby…</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>Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path</strong> - The SARS-CoV-2 pandemic is an ongoing threat to global health, and the continuing emergence of contagious variants highlights the urgent need for additional antiviral therapy to attenuate COVID-19 disease. The SARS-CoV-2 main protease (3CL^(pro)) presents an attractive target for such therapy due to its high sequence conservation and key role in the viral life cycle. In this study, we designed a fluorescent-luminescent cell-based reporter for the detection and quantification of 3CL^(pro)…</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>Desire to stay shorter time at the shopping mall: insight from protection motivation (PMT), behavioral inhibition system (BIS), reactance, and expectancy theories</strong> - After withdrawing the movement control order (MCO), new variant (Omicron) of COVID-19 returns as an outbreak again. Therefore, consumers are very much informed by various media to be more cautious in visiting shopping malls and spend less time in there. The purpose of this study was to identify the predictors influencing the desire to stay shorter at the shopping mall. This study was conducted in Malaysia, with the application of three psychological theories and one behavioural theory. This is…</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 BCL-2 and Jak 1/2 inhibitors: Cure and treatment of HIV-1 and other viral infections</strong> - B cell lymphoma 2 (BCL-2) family proteins are involved in the mitochondrial apoptotic pathway and are key modulators of cellular lifespan, which is dysregulated during human immunodeficiency virus type 1 (HIV-1) and other viral infections, thereby increasing the lifespan of cells harboring virus, including the latent HIV-1 reservoir. Long-lived cells harboring integrated HIV-1 DNA is a major barrier to eradication. Strategies reducing the lifespan of reservoir cells could significantly impact…</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>Protective role of engineered extracellular vesicles loaded quercetin nanoparticles as anti-viral therapy against SARS-CoV-2 infection: A prospective review</strong> - Quercetin (QCT) is a naturally occurring phenolic flavonoid compound with inbuilt characteristics of antioxidant, anti-inflammatory, and immune protection. Several recent studies have shown that QCT and QCTits nanoparticles have therapeutic potential against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Novel therapeutics also include the implication of extracellular vesicles (EVs) to protect from SARS-CoV-2 viral infection. This article highlighted 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>Comparison of ribavirin degradation in the UV/H<sub>2</sub>O<sub>2</sub> and UV/PDS systems: Reaction mechanism, operational parameter and toxicity evaluation</strong> - Residues in surface water of ribavirin, which used extensively during the COVID-19 pandemic, have become an emerging issue due to its adverse impact on the environment and human health. UV/H(2)O(2) and UV/peroxydisulfate (PDS) have different degradation effects on ribavirin, and the same operational parameter have different effects on the two processes. In this study, the reaction mechanism and degradation efficiency for ribavirin were studied to compare the differences under UV/H(2)O(2) and…</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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