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<title>26 September, 2023</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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Assessing the Impact of Language Barriers on Telehealth Utilization And Subsequent Clinical Outcomes in Patients with Cancer During the COVID-19 Pandemic and Beyond</strong> -
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Importance: The COVID-19 pandemic prompted a surge in telehealth utilization. However, language barriers have emerged as a potential obstacle to effective telemedicine engagement, impacting millions of limited English proficient (LEP) individuals. Understanding the role of English proficiency in telehealth outcomes is critical, particularly in cancer care, where consistent follow-up and communication are vital. Objective: The primary objective of this study is to assess the relationship between telehealth use and clinical outcomes in cancer patients while concurrently exploring the effects of English language proficiency on telehealth utilization. Design: This study utilizes a retrospective cohort design, encompassing cancer patients seen at the Chao Comprehensive Cancer Center between March 1, 2020, and December 31, 2022. The study incorporates both in-person and telehealth visits, examining the association between encounter type and clinical outcomes. Setting: The study took place at an NCI-designated cancer center, offering a controlled setting for assessing telehealth utilization and its consequences in cancer care. Participants: The study includes 7,890 patients with more than one outpatient visit during the study period. The majority of our cohort consists of English, Spanish and Vietnamese-speaking patients. Main Outcome(s) and Measure(s): Primary outcomes include the association between telehealth utilization and clinical outcomes, such as hospitalization rates, duration of hospital admissions, rates of readmission, and patient mortality. Results: There was decreased telehealth utilization in non-English speaking cancer patients throughout the pandemic. Increased telehealth utilization was associated with higher rates of admission, irrespective of cancer type. Additionally, telehealth visits were associated with higher rates of subsequent readmissions and longer duration of subsequent admissions compared to in-person visits. Spanish-speaking patients utilizing telehealth had higher rates of re-admission compared to English speakers utilizing telehealth. Patients who died had higher rates of telehealth utilization compared to patients who survived. Conclusions and Relevance: This study highlights the implications of telehealth usage in healthcare outcomes and the role of language barriers in telehealth engagement among cancer patients. The study underscores the need to optimize telehealth usage and minimize its limitations to enhance the quality of cancer care in a telehealth-driven era.
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🖺 Full Text HTML: <a href="https://osf.io/5g2st/" target="_blank">Assessing the Impact of Language Barriers on Telehealth Utilization And Subsequent Clinical Outcomes in Patients with Cancer During the COVID-19 Pandemic and Beyond</a>
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<li><strong>Lack of detection of SARS-CoV-2 in British wildlife 2020-21 and first description of a stoat (Mustela erminea) Minacovirus</strong> -
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Repeat spill over of SARS-CoV-2 into new hosts has highlighted the critical role of cross species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spill-over include Mustelidae (mink, ferrets and related animals) and cricetid rodents (hamsters and related animals). These predispositions led us to screen British wildlife with sarbecovirus specific qPCR and pan coronavirus PCR assays for SARS-CoV-2 using samples collected during the human pandemic to establish if widespread spill-over was occurring. Fourteen wildlife species (n=402) were tested, including : 2 Red Foxes (Vulpes vulpes), 101 Badgers (Meles meles), 2 wild American Mink (Neovison vison), 41 Pine Marten (Martes martes), 2 Weasels (Mustela nivalis), 7 Stoats (Mustela erminea), 108 Water Voles (Arvicola amphibius), 39 Bank voles (Myodes glareolous), 10 Field Voles ( Microtus agrestis), 15 Wood Mice (Apodemus sylvaticus), 1 Common Shrew (Sorex aranaeus), 2 Pygmy Shrews (Sorex minutus), 2 Hedgehogs (Erinaceus europaeus) and 75 Eurasian Otters (Lutra lutra). No cases of SARS-CoV-2 were detected in any animals, however a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.28.538769v3" target="_blank">Lack of detection of SARS-CoV-2 in British wildlife 2020-21 and first description of a stoat (Mustela erminea) Minacovirus</a>
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</div></li>
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<li><strong>Sleep quality worsened in an evening chronotype compared to others: a year-long longitudinal cohort study with prolonged lockdowns and restriction relaxations in RECETOX MU university employees</strong> -
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Background. In 2020, people around the world were challenged by the outbreak of the COVID-19 pandemic. Countries responded with various restrictions, including lockdowns and stay-at-home orders, in an attempt to prevent the spread of the disease. Citizens were thus subjected to unprecedented uncertainty and stress. Prolonged exposure to such conditions may impact human health and well-being. One of the core aspects of proper physiological functioning is sleep. This prospective longitudinal study aims to investigate sleep quality and its relationship to chronotype over a year-long period from September 2020. Methods and findings. Our year-long longitudinal prospective study focused on an employee cohort (N=54) at the Research Centre for Toxic Compounds in the Environment (RECETOX) of Masaryk University in the Czech Republic. During the first half of this period, three lockdowns with a cumulative duration of 100 days were imposed. During the second half of this period, the imposed restrictions were relaxed. Individuals were measured quarterly, i.e. at five time points. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) while chronotype was established using the Reduced Morningness-Eveningness Questionnaire (rMEQ). We also used Perceived Stress Scale (PSS-14), Beck Depression Inventory (BDI-II), and General Anxiety Disorder-7 (GAD-7) to address potential confounders. The response rates of valid measurements across time points ranged from 87.04 % to 61.11 %. Our results show that sleep quality significantly worsened across the year for the evening chronotype but improved for the neutral and early chronotypes. Overall, over the year the incidence of poor sleep decreased by 16.13 % with 95% CI [-6.10%; 37.16%]. We did not find any significant sex differences in sleep quality. Perceived stress, symptoms of anxiety and depression were positively significantly associated with sleep problems in all measurements except in June. This study is limited by the small sample, decreasing number of individuals in chronotype categories and the lack of information on napping behavior. Conclusion. These findings shed new light on the long-term influence of pandemic-related restrictions on individuals and particularly on the potentially more vulnerable evening chronotypes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.22.23295980v1" target="_blank">Sleep quality worsened in an evening chronotype compared to others: a year-long longitudinal cohort study with prolonged lockdowns and restriction relaxations in RECETOX MU university employees</a>
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<li><strong>Association of Cognitive Deficits with Sociodemographic Characteristics among Adults with Post-COVID Conditions: Findings from the United States Household Pulse Survey</strong> -
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Background People infected with COVID-19 may continue to experience symptoms for several weeks or even months after acute infection, a condition known as long COVID. Cognitive problems such as memory loss are among the most commonly reported symptoms of long COVID. However, a comprehensive evaluation on the risks of cognitive decline following COVID infection among different sociodemographic groups has not been undertaken at the national level in the United States. Methods We conducted a secondary analysis on the datasets from U.S. Census Bureau Household Pulse Survey, encompassing the data collected from June 1, 2022 to December 19, 2022. Based on a cohort of 385,370 individuals aged 18 or older, we employed logistic regression analyses to examine the association between self-reported cognitive deficits and different sociodemographic factors among individuals with long COVID conditions. Results Among individuals aged 18 or older, 44.7% percent of survey respondents report having been diagnosed with COVID in the past, and 29.0% of those with previous COVID infection experienced long COVID symptoms lasting for more than 3 months. We have demonstrated that individuals with long COVID had significantly higher risk of experiencing cognitive deficits compared to those with no history of COVID infection. Furthermore, females, young adults, people with multiple races, or low levels of education attainment are at high risk of cognitive deficits if they experience long COVID. At the state level, the prevalence of cognitive deficits among long COVID patients varied across different US states, with the highest prevalence in West Virginia and Kentucky, and the lowest prevalence in Connecticut and Maryland. The variation could be due to differences in racial composition and education level among long COVID patients in the four states. Conclusions The risks of cognitive deficits among adults with post-COVID conditions are substantial. Various sociodemographic groups can have different risks of developing cognitive deficits after experiencing long COVID. Findings of this large-scale study can help identify sociodemographic groups at higher risk of cognitive deficits, and facilitate medical interventions and guide resource allocation to target populations at risk and to prioritize areas with a high rate of cognitive decline.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.22.23295981v1" target="_blank">Association of Cognitive Deficits with Sociodemographic Characteristics among Adults with Post-COVID Conditions: Findings from the United States Household Pulse Survey</a>
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<li><strong>Moving Biosurveillance Beyond Coded Data: AI for Symptom Detection from Physician Notes</strong> -
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Background Real-time surveillance of emerging infectious diseases necessitates a dynamically evolving, computable case definition, which frequently incorporates symptom-related criteria. For symptom detection, both population health monitoring platforms and research initiatives primarily depend on structured data extracted from electronic health records. Objective To validate and test an artificial intelligence (AI) based Natural Language Processing (NLP) pipeline for detecting COVID-19 symptoms from physician notes. Methods Subjects in this retrospective cohort study are patients 21 years old and younger, who presented to a pediatric emergency department (ED) at a large academic children9s hospital between March 1, 2020 and May 31, 2022. ED notes for all patients were processed with an NLP pipeline tuned to detect the mention of 11 COVID-19 symptoms based on CDC criteria. For a gold standard, 3 subject matter experts labeled 226 ED notes and had strong agreement (F1=98.6; PPV=97.2; Recall=100.0). F1, PPV, and recall were used to compare the performance of both NLP and ICD-10 to the gold standard chart review. As a formative use case, variations in symptom patterns were measured across SARS-Cov2 variant eras. Results There were 85,678 ED encounters during the study period, 4.0% with patients with COVID-19. NLP was more accurate at identifying encounters with patients that had any of the COVID-19 symptoms (F1=79.6) than ICD-10 codes (F1=45.1%). NLP accuracy was higher for positive symptoms (recall=93%) than ICD-10 (recall=30%). However, ICD-10 accuracy was higher for negative symptoms (specificity=99.4%) than NLP (specificity=91.7%). Congestion or runny nose showed the highest accuracy difference: NLP F1=82.8%, ICD-10 F1=4.2%. Prevalence of NLP symptoms among patients with COVID-19 differed across variant eras. And patients with COVID-19 were more likely to have each symptom than patients without this disease. Effect sizes (odds ratios) varied across pandemic eras. Conclusions This study establishes the value of AI based NLP as a highly effective tool for real-time COVID-19 symptom detection in pediatric patients, outperforming traditional ICD-10 methods. It also reveals the evolving nature of symptom prevalence across different virus variants, underscoring the need for dynamic, technology-driven approaches in infectious disease surveillance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.24.23295960v1" target="_blank">Moving Biosurveillance Beyond Coded Data: AI for Symptom Detection from Physician Notes</a>
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<li><strong>Coronavirus and Post-COVID-19 Syndrome: A Systematic Review</strong> -
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Coronavirus infectious Disease 2019 (COVID-19) was first reported in Wuhan, China, and with its rapidly mutating variants, it soon became a global concern. In response to the pandemic, intensive research and development efforts led to the development of six vaccines approved by the World Health Organization (WHO). Coronavirus is divided into four genera: alpha, beta, gamma and delta. Its unstable ssRNA resulted in multiple strains in a short period, which acted as a selection pressure for transmissibility. Sequelae of COVID-19 infection include multiple syndromes which have been reported at high incidence globally. Using the Cochrane guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we present a systematic review of the most common syndromes reported. A total of 12 eligible studies were included in this review. Syndromes reported in the literature include immune thrombocytopenic purpura (ITP), viral encephalomyelitis, hemophagocytic lymphohistiocytosis, thrombotic thrombocytopenic purpura (TTP), Guillain-Barre syndrome (GBS) and postural orthostatic tachycardia syndrome (POTS). We cover the hypothesized pathophysiology, presenting symptoms and treatment for each respective syndrome. We aim to discuss coronavirus and its variants to provide a foundation on which to examine the syndromes manifested after COVID-19 infection (post-COVID-19 syndrome).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.24.23296022v1" target="_blank">Coronavirus and Post-COVID-19 Syndrome: A Systematic Review</a>
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<li><strong>Analyzing Pain Patterns in the Emergency Department: Leveraging Clinical Text Deep Learning Models for Real-World Insights</strong> -
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Objective: To estimate the prevalence of patients presenting in pain to an inner-city emergency department (ED), describing this population, their treatment, and the effect of the COVID-19 pandemic. Materials and Methods: We applied a clinical text deep learning model to the free text nursing assessments to identify the prevalence of pain on arrival to the ED. Using interrupted time series analysis, we examined the prevalence over three years. We describe this population pre- and post-pandemic in terms of their demographics, arrival patterns and treatment. Results: 55.16% (95%CI 54.95% - 55.36%) of all patients presenting to this ED had pain on arrival. There were significant differences in demographics, arrival and departure patterns between those patients with and without pain. The COVID-19 pandemic initially precipitated a decrease followed by a sharp, sustained rise in the prevalence of pain on arrival, altering the population arriving in pain and their treatment. Discussion The application of a clinical text deep learning model has successfully identified the prevalence of pain on arrival. The description of this population and their treatment forms the basis of intervention to improve care for patients presenting with pain. The combination of the clinical text deep learning model and interrupted time series analysis has identified the effects of the COVID-19 pandemic on pain care in the ED. Conclusion A clinical text deep learning model has led to identifying the prevalence of pain on arrival and was able to identify the effect a major pandemic had on pain care in this ED.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.24.23296019v1" target="_blank">Analyzing Pain Patterns in the Emergency Department: Leveraging Clinical Text Deep Learning Models for Real-World Insights</a>
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<li><strong>Modeling the Transmission Mitigation Impact of Testing for Infectious Diseases</strong> -
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A fundamental question of any program focused on the testing and timely diagnosis of a communicable disease is its effectiveness in reducing community transmission. Unfortunately, direct estimation of this effectiveness is difficult in practice, elevating the value of mathematical modeling that can predict it from first principles. Here, we introduce testing effectiveness (TE), defined as the fraction by which transmission is reduced via testing and post-diagnosis isolation at the population scale, and develop a mathematical model that estimates it from the interactions of tests, within-host pathogen dynamics, and arbitrarily complex testing behaviors. While our model generalizes across pathogens, we demonstrate its flexibility through an analysis of three respiratory pathogens, influenza A, respiratory syncytial virus (RSV), and both pre-vaccine and post-vaccine era SARS-CoV-2, quantifying TE across post-exposure, post-symptom, and routine testing scenarios. We show that TE varies considerably by strategy and pathogen, with optimal testing depending on the number of tests available and when they are used. This work quantifies tradeoffs about when and how to test, providing a flexible framework to guide the use and development of current and future diagnostic tests to control transmission of infectious diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.22.23295983v1" target="_blank">Modeling the Transmission Mitigation Impact of Testing for Infectious Diseases</a>
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<li><strong>Omicron Breakthrough Infection Elicits Superior Humoral and Mucosal Immune Responses to SARS-CoV-2 Variants than an Intramuscular Booster Dose</strong> -
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Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show that mild BT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary IgG and IgA levels against the Omicron Spike and enhanced reactivity to the ancestral Spike for the IgA isotype, which also reacted with SARS-CoV-1. Serum neutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for mucosal vaccines to emulate the enhanced mucosal and humoral immunity induced by Omicron without exposing individuals to the risks associated with SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.22.23295541v1" target="_blank">Omicron Breakthrough Infection Elicits Superior Humoral and Mucosal Immune Responses to SARS-CoV-2 Variants than an Intramuscular Booster Dose</a>
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<li><strong>Is influenza B/Yamagata extinct and what public health implications could this have? An updated literature review and comprehensive assessment of global surveillance databases.</strong> -
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Introduction: Early after the start of the COVID-19 pandemic, a major drop in the number of influenza B/Yamagata detections was observed globally. Given the potential public health implications, particularly with regards to influenza vaccination, we conducted a systematic review of influenza B/Yamagata virus circulation data from multiple complementary sources of information. Methods: We searched articles published until 20th March 2023 in PubMed and EMBASE; examined epidemiological and virological influenza data for 2020-2023 contained in the publicly available WHO-FluNet and GISAID (Global Initiative on Sharing All Influenza Data) global databases, or collected by the multi-national Global Influenza Hospital Surveillance Network (GIHSN) study; and looked for influenza data in the webpages of respiratory viruses surveillance systems from countries worldwide. Results: Highly consistent findings were found across all sources of information, with a progressive decline of influenza B/Yamagata detections from 2020 onwards across all world regions, both in absolute terms (total number of cases), the positivity rate, and as a fraction of influenza B detections. Isolated influenza B/Yamagata cases continue to be sporadically reported, and these are typically vaccine-derived, mistaken data entries or under investigation. Discussion: While it is still too early to conclude that B/Yamagata is (or will soon become) extinct, the current epidemiological and virological data call for a rapid response in terms of influenza prevention practices, particularly regarding the formulation of influenza vaccines. The current epidemiological situation is unprecedented in recent decades, underlying the importance of continuously and carefully monitoring the circulation of influenza viruses (as well as SARS-CoV-2 and the other respiratory viruses) in the coming years.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.25.23296068v1" target="_blank">Is influenza B/Yamagata extinct and what public health implications could this have? An updated literature review and comprehensive assessment of global surveillance databases.</a>
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<li><strong>Micrometer-thick, porous, nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties</strong> -
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Development of coating technologies for electrochemical sensors that consistently exhibit antifouling activities when exposed to diverse and complex biological environments over extended time is vital for development more effective medical devices and diagnostics. Here, we describe a micrometer-thick, porous nanocomposite coating with both exceptional antifouling and electroconducting properties that greatly enhance the sensitivity of electrochemical sensors. Nozzle-assisted printing of oil-in-water emulsion is used to create a 1 micrometer thick coating composed of cross-linked albumin with interconnected pores, which also contains electroconducting gold nanowires. Using this approach, the antifouling conductive coating can be deposited only on the surface of the working electrode, and not on the reference and counter electrodes, which greatly facilitates the fabrication and functionality of multiplexed electrochemical sensors. The layer effectively resists biofouling and maintains rapid electron transfer kinetics for over one month when exposed directly to complex biological fluids, including serum and nasopharyngeal secretions. Compared to previously described thinner (nanometer thick) antifouling electroconductive coating made with drop casting or a spin coating of the same thickness, the nozzle-printed sensors coated with this thick porous nanocomposite exhibited sensitivities that were enhanced by 3.75- to 17-fold when three different target biomolecules were tested. As a result, emulsion-coated, multiplexed electrochemical sensors coated were able to carry out simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid, antigen, and host antibody in clinical specimens with high sensitivity and specificity. This thick porous emulsion coating technology may provide a way to address hurdles currently restricting the application of electrochemical sensors for point-of-care (POC) diagnostic applications, as well as their use in implantable devices and other healthcare monitoring systems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.23.23296012v1" target="_blank">Micrometer-thick, porous, nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties</a>
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<li><strong>Conducting developmental research online vs. in-person: A meta-analysis</strong> -
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An increasing number of psychological experiments with children are being conducted using online platforms, in part due to the COVID-19 pandemic. Individual replications have compared the findings of particular experiments online and in-person, but the general effect of online data collection on data collected from children is still unknown. Therefore, the current meta-analysis examines how the effect sizes of developmental studies conducted online compare to the same studies conducted in-person. Our pre-registered analysis includes 145 effect sizes calculated from 24 papers with 2440 children, ranging in age from four months to six years. We examined several moderators of the effect of online testing, including the role of dependent measure (looking vs verbal), online study method (moderated vs unmoderated), and age. The mean effect size of studies conducted in-person (d = .68) was slightly larger than the mean effect size of their counterparts conducted online (d = .54), but this difference was not significant. Additionally, we found no significant moderating effect of dependent measure, online study method, or age. Overall, the results of the current meta-analysis suggest developmental data collected online are generally comparable to data collected in-person.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/qc6fw/" target="_blank">Conducting developmental research online vs. in-person: A meta-analysis</a>
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<li><strong>On some general characteristics of the spread of the COVID epidemic</strong> -
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An analytical model for calculating the spread of the COVID-19 epidemic is described, and it is shown that the main patterns of epidemic development are determined by three dimensionless complexes representing the ratios of transmission rates, contact limitation due to lockdown, and population vaccination. A comparison of statistical data on the growth of the epidemic in Germany, Berlin and its various neighbourhoods shows that the development of the epidemic depends to a large extent on the ethnic composition of the population. In the same way as it is accepted in some sections of physics, it is proposed to use the methods of similarity theory to investigate the regularities of the emergence and development of the epidemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.22.23295959v1" target="_blank">On some general characteristics of the spread of the COVID epidemic</a>
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<li><strong>Causal Inference for Estimation of Vaccine Effects from Time-to-Event Data</strong> -
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Vaccine is the most efficient method for controlling of infectious disease. Vaccine effectiveness estimation is extremely important in monitoring vaccine efficacy and controlling disease spreading. To study about the COVID-19 vaccine effectiveness from EHR data, we apply the counterfactual reasoning method with deep neural network for vaccine effectiveness estimation from the time-to-event data which are extracted from Optum EHR dataset. The estimated vaccine effectiveness by the counterfactual reasoning is compared with the Cox regression model and Random survival forest model. The preliminary results show that the proposed model is more unbiased than the Cox regression and Random survival forest models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.24.23296040v1" target="_blank">Causal Inference for Estimation of Vaccine Effects from Time-to-Event Data</a>
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<li><strong>A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system</strong> -
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Nirmatrelvir was the first protease inhibitor (PI) specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate Mpro resistance mutations, we passaged a previously developed chimeric vesicular stomatitis virus (VSV-Mpro) with increasing, yet suboptimal concentrations of nirmatrelvir, using Wuhan-1 and Omicron Mpro variants, and selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2. The resistance phenotype of a subset of mutations was characterized against clinically available PIs (nirmatrelvir and ensitrelvir) with cell-based and biochemical assays. Moreover, we showed the putative molecular mechanism of resistance based on in silico molecular modelling. These findings will help to understand SARS-CoV-2 protease-inhibitor-resistance mechanisms, the relevance of specific in the clinic and thereby inform treatment decisions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.22.558628v1" target="_blank">A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system</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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: Placebo; Drug: Metformin<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Psychosomatic, Physical Activity or Both for Post-covid19 Syndrom</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Exercise Therapy; Behavioral: Psychotherapy<br/><b>Sponsors</b>: Hannover Medical School; Health Insurance Audi BKK; occupational health service Volkswagen AG; Helmholtz Centre for Infection Research<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>SA55 Injection: a Potential Therapy for the Prevention and Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SA55 Injection; Other: Placebo for SA55 injection<br/><b>Sponsor</b>: Sinovac Life Sciences Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Assess the Safety, Tolerability and Preliminary Efficacy of HH-120 for the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120; Drug: placebo<br/><b>Sponsor</b>: Huahui Health<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>A Study to Investigate the Prevention of COVID-19 withVYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Drug: VYD222; Drug: Normal saline<br/><b>Sponsor</b>: Invivyd, Inc.<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>Omicron BA.4/5-Delta COVID-19 Vaccine Phase I Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron BA.4/5-Delta strain recombinant novel coronavirus protein vaccine (CHO cells); Biological: Placebo<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention<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>Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents</strong> - <b>Conditions</b>: Vaccine-Preventable Diseases; COVID-19 Pandemic; Health-Related Behavior; Health Knowledge, Attitudes, Practice; Narration<br/><b>Interventions</b>: Behavioral: Baseline surveys; Behavioral: Digital Storytelling Intervention; Behavioral: Information Control Intervention<br/><b>Sponsors</b>: Arizona State University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<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>Non-pharmacological and TCM-based Treatment for Long COVID Symptoms</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Behavioral: Acupuncture and TCM-based lifestyle management<br/><b>Sponsor</b>: The Hong Kong Polytechnic 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>Cell Therapy With Treg Cells Obtained From Thymic Tissue (thyTreg) to Control the Immune Hyperactivation Associated With COVID-19 (THYTECH2)</strong> - <b>Condition</b>: Systemic Inflammatory Response Syndrome<br/><b>Interventions</b>: Biological: Allogeneic thyTreg 5.000.000; Biological: Allogeneic thyTreg 10.000.000<br/><b>Sponsors</b>: Hospital General Universitario Gregorio Marañon; Instituto de Salud Carlos III<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>SA55 Novel Coronavirus Broad-spectrum Neutralizing Antibody Nasal Spray in Health People</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: SA55 nasal spray<br/><b>Sponsor</b>: Sinovac Life Sciences Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Bioequivalence Trial of Fasting Single Oral STI-1558 Capsule in Healthy Chinese Subjects</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: STI-1558<br/><b>Sponsor</b>: Zhejiang ACEA Pharmaceutical Co. Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mind Body Intervention for Long COVID</strong> - <b>Conditions</b>: Long COVID; Post-Acute Sequelae of COVID-19; COVID Long-Haul<br/><b>Intervention</b>: Behavioral: Mind Body Intervention #1<br/><b>Sponsor</b>: Beth Israel Deaconess Medical Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of Covid-19 Aerosol Box On Intubation Success Rate</strong> - <b>Condition</b>: Intubation; Difficult or Failed<br/><b>Interventions</b>: Device: Intubation using aerosol box; Device: Intubation without aerosol box<br/><b>Sponsor</b>: Universiti Kebangsaan Malaysia Medical Centre<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>Safety of Simultaneous mRNA COVID-19 Vaccine With Other Childhood Vaccines in Young Children</strong> - <b>Conditions</b>: Fever After Vaccination; Fever; Seizures Fever<br/><b>Interventions</b>: Biological: Pfizer-BioNTech COVID-19 Vaccine; Biological: Routine Childhood Vaccinations<br/><b>Sponsors</b>: Duke University; Kaiser Permanente; Columbia University; Children’s Hospital Medical Center, Cincinnati; Centers for Disease Control and Prevention<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>SA55 Injection Phase II Study in the Treatment of Mild/Moderate COVID-19 Patients</strong> - <b>Condition</b>: Infection of Upper Respiratory Tract Caused by 2019-nCoV<br/><b>Intervention</b>: Drug: SA55 Injection<br/><b>Sponsor</b>: Sinovac Life Sciences Co., Ltd.<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>Host range, transmissibility and antigenicity of a pangolin coronavirus</strong> - The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration…</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>NETs induce persistent lung tissue damage via thromboinflammation without altering virus resolution in a mouse coronavirus model</strong> - BACKGROUND: During infection, neutrophil extracellular traps (NETs) are associated with severity of pulmonary diseases such as acute respiratory disease syndrome. NETs induce subsequent immune responses, are directly cytotoxic to pulmonary cells and highly procoagulant. Anticoagulation treatment was shown to reduce in-hospital mortality, indicating thromboinflammatory complications. However, little data is available on the involvement of NETs in secondary events after virus clearance, which can…</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>Computational analysis of the interactions between Ebselen and derivatives with the active site of the main protease from SARS-CoV-2</strong> - The main protease (M^(pro)) of the novel coronavirus SARS-CoV-2 is a key target for developing antiviral drugs. Ebselen (EbSe) is a selenium-containing compound that has been shown to inhibit Mpro in vitro by forming a covalent bond with the cysteine (Cys) residue in the active site of the enzyme. However, EbSe can also bind to other proteins, like albumin, and low molecular weight compounds that have free thiol groups, such as Cys and glutathione (GSH), which may affect its availability and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection</strong> - Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential prophylactics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-mediated antiviral activity and its susceptibility to viral subversion remain incompletely understood. Pretreatment of cells with iBETs inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. The antiviral activity manifested itself by reduced reporter expression of recombinant…</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>Computational study on the mechanisms of inhibition of SARS-CoV-2 M<sup>pro</sup> by aldehyde warheads based on DFT</strong> - SARS-CoV-2 main protease, M^(pro), plays a crucial role in the virus replication cycle, making it an important target for antiviral research. In this study, a simplified model obtained through truncation is used to explore the reaction mechanism of aldehyde warhead compounds inhibiting M^(pro) at the level of density functional theory. According to the calculation results, proton transfer (P_T)-nucleophilic attack (N_A) is the rate-determining step in the entire reaction pathway. The water…</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>Heat shock protein 90 inhibition in the endothelium</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>Determinants of <em>de novo</em> B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections</strong> - Vaccine-induced immunity may impact subsequent de novo responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1…</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>Recurrent Viral Capture of Cellular Phosphodiesterases that Antagonize OAS-RNase L</strong> - Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions is less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were…</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>Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA</strong> - Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1mΨ), reduce the interferon response and enhance expression levels. Multiple attempts…</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>Regulation of human interferon signaling by transposon exonization</strong> - Innate immune signaling is essential for clearing pathogens and damaged cells, and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I…</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>Modelling and analysis of the complement system signalling pathways: roles of C3, C5a and pro-inflammatory cytokines in SARS-CoV-2 infection</strong> - The complement system is an essential part of innate immunity. It is activated by invading pathogens causing inflammation, opsonization, and lysis via complement anaphylatoxins, complement opsonin’s and membrane attack complex (MAC), respectively. However, in SARS-CoV-2 infection overactivation of complement system is causing cytokine storm leading to multiple organs damage. In this study, the René Thomas kinetic logic approach was used for the development of biological regulatory network (BRN)…</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>Utility of coproporphyrin-I determination in first-in-human study for early evaluation of OATP1B inhibitory potential based on investigation of ensitrelvir, an oral SARS-CoV-2 3C-like protease inhibitor</strong> - Coproporphyrin-I (CP-I) has been investigated as an endogenous biomarker of organic anion transporting polypeptide (OATP) 1B. Here, we determined the CP-I concentrations in a cocktail drug-drug interaction (DDI) study of ensitrelvir to evaluate the OATP1B inhibitory potential because ensitrelvir had increased plasma concentrations of rosuvastatin in this study, raising concerns about breast cancer resistance protein and OATP1B inhibition. Furthermore, CP-I concentrations were compared between…</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>Protection of eIF2B from inhibitory phosphorylated eIF2: a viral strategy to maintain mRNA translation during the PKR-triggered integrated stress response</strong> - The integrated stress response (ISR) protects cells from a variety of insults. Once elicited (e.g. by virus infections), it eventually leads to the block of mRNA translation. Central to the ISR are the interactions between translation initiation factors eIF2 and eIF2B. Under normal conditions, eIF2 drives the initiation of protein synthesis through hydrolysis of GTP, which becomes replenished when binding to the guanine nucleotide exchange factor (GEF) eIF2B. The antiviral branch of the ISR 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>Computational analysis of substrate recognition of Sars-Cov-2 Mpro main protease</strong> - M^(pro) main protease takes an essential role in the Sars-Cov-2 viral life cycle by releasing the individual protein from the single poly-peptide chain via proteolytic cleavage in the beginning of the viral infection. Interfering with this step by inhibiting the protease with small compound-based inhibitors has been proven to be an effective strategy to treat the infection. Thus, understanding the substrate recognition mechanism of the M^(pro) main protease has gained great interest from 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>Green synthesis, characterization, anti-SARS-CoV-2 entry, and replication of lactoferrin-coated zinc nanoparticles with halting lung fibrosis induced in adult male albino rats</strong> - The ethanolic extract of Coleus forskohlii Briq leaves was employed in the green synthesis of zinc nanoparticles (Zn-NPs) by an immediate, one-step, and cost-effective method in the present study. Zn-NPs were coated with purified bovine lactoferrin (LF) and characterized through different instrumental analysis. The biosynthesized Zn-NPs were white in color revealing oval to spherical-shaped particles with an average size of 77 ± 5.50 nm, whereas LF-coated Zn-NPs (LF-Zn-NPs) revealed a larger…</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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