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188 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>19 November, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Long-term temporal trends in incidence rate and case fatality of sepsis and COVID-19-related sepsis: nationwide registry study</strong> -
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Importance: Sepsis is one of the leading causes of morbidity and mortality. The majority of sepsis cases is attributed to bacterial infections, but virus infections can also induce sepsis. Conflicting results in incidence rates and case fatality trends of sepsis is reported, and how the COVID-19 pandemic influenced these trends are unknown. Objective: To estimate temporal trends in incidence rate and case fatality during a 14-year period from 2008 through 2021, and to assess possible shifts in these trends during the COVID-19 pandemic. Design: A nationwide longitudinal registry study using ICD-10 discharge codes to identify sepsis. Setting: All Norwegian hospitals from 2008 through 2021. Participants: All sepsis cases included 317.705 patients and of these, 222.832 had a first sepsis episode. Main outcomes and measures: Annual age-standardized incidence rates with 95% confidence intervals (CI). Poisson regression was used to estimate changes in incidence rates across time, and logistic regression was used to estimate odds ratios for in-hospital death. Results: Among 12.619.803 adult hospitalizations, 317.705 (2.5%) patients met the sepsis criteria and 222.832 (70.0%) had a first sepsis episode. In the period 2009-2019, the annual incidence rate for a first sepsis episode was stable (incidence rate ratio per year, 0.999; 95% CI, 0.994-1.004), whereas for all sepsis the incidence rate increased by 15.5% during the period (annual incidence rate ratio, 1.013; 95% CI 1.007-1.019). During the COVID-19 pandemic, the incidence rate ratio for a first sepsis was 0.877 (95% CI, 0.829-0.927) in 2020 and 0.929 (95% CI, 0.870-0.992) in 2021, and for all sepsis it was 0.870 (95% CI, 0.810-0.935) in 2020 and 0.908 (95% CI, 0.840-0.980) in 2021, compared to the previous 11-year period. In-hospital deaths declined in the period 2009-2019 (odds ratio per year, 0.954 [95% CI,0.950-0.958]), whereas deaths increased during the COVID-19 pandemic in 2020 (odds ratios, 1.061 [95% CI 1.001-1.124] and in 2021 odds ratio (1.164 [95% CI, 1.098-1.233]). Conclusion and relevance: We found a stable incidence rate of a first sepsis episode during the years 2009-2019. However, the increasing burden of all sepsis admissions indicates that sepsis awareness with updated guidelines and education must continue.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.18.22282501v1" target="_blank">Long-term temporal trends in incidence rate and case fatality of sepsis and COVID-19-related sepsis: nationwide registry study</a>
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<li><strong>Factors associated with release relief of Long COVID symptoms at 12-Months and their impact on daily life</strong> -
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Introduction: Our purpose was to describe the course of Long COVID symptoms after 12-month follow-up, their impact on daily life and the factors associated with the relief of symptoms. Methods: A cross-sectional survey was conducted within an out-patient clinic for Long COVID patients. Participants, who had experienced their initial COVID-19 episode between January, 15 2020 and May 21, 2021, were contacted 12-months post onset. Their characteristics, symptom course at initial COVID-19 episode, Long COVID phase and one year follow-up along with remission status were collected through a questionnaire and a specific post COVID remission scale from complete remission to persistence of symptoms and dependence in daily life activities. Results: Among the 231 long COVID participants who answered the 12-month follow-up questionnaire, 63.2% had developed SARS-CoV-2 antibodies before COVID-19 vaccination. At 12-month follow-up, only 8.7% of the participants felt in complete remission while 28.6% noted a significant improvement of their symptoms. The prevalence rate of most symptoms remained high at 12 months: asthenia 83.1%, neurocognitive and neurological symptoms 91.8%, cardiothoracic symptoms 77.9%, musculoskeletal 78.8%. During Long COVID phase, 62.2% had to stop working at least once and only 32.5% resumed professional activities full time at one year follow-up. The presence of SARS-CoV-2 antibodies before COVID-19 vaccination was associated with an increased probability of significant improvement at one year (aPRR: 1.60, p=0.028) while ageusia at initial Long COVID phase was associated with a lower probability of improvement (aPRR: 0.38, p=0.007). Conclusion: While observing a trend towards some improvement in a majority of long COVID patients at a 12-month follow-up, fatigue, musculoskeletal pain, cardiothoracic symptoms and neurocognitive impairment persisted in most of them. Having developed SARS-CoV-2 antibodies was associated with a better prognosis while persistent ageusia at long COVID phase seems to be associated with the persistence of symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.18.22282459v1" target="_blank">Factors associated with release relief of Long COVID symptoms at 12-Months and their impact on daily life</a>
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<li><strong>In silico docking screen identifies airway host protease targets for human SERPINs</strong> -
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Proteases play key roles in viral replication cycles. They can provide cleavage maturation of viral glycoproteins, processing of viral polyproteins, or disassembly of viral capsids. Thus, proteases constitute ideal targets for antiviral intervention: pharmaceutically, by small molecule inhibitors, or naturally, by host immune responses. Indeed, we and others have shown that individual members of the Serine protease inhibitor (SERPIN) family have specific antiviral function by blocking proteolytic steps inherent to viral replication cycles. Whether additional members of the large SERPIN family possess antiviral activity and whether SERPINs function as part of the antiviral cell-intrinsic immune response, is currently unknown. Here, we found that specific SERPINs are produced upon infection with clinically relevant respiratory viruses in vitro and in vivo, and in concert with classical interferon-stimulated genes. We next developed a structure-based in silico screen to uncover non-canonical SERPIN-protease pairs. We identified several SERPINs with potential antiviral function, including: SERPINE1 targeting cathepsin L, required for SARS-CoV-2 entry; SERPINB8 targeting furin, required for glycoprotein maturation cleavage of numerous viruses; and SERPINB2 targeting adenovirus protease, which suggests the first direct-acting antiviral SERPIN. Our study demonstrates how proteolysis is modulated for antiviral defense and how this process could inform antiviral targets against clinically relevant respiratory pathogens.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.18.517133v1" target="_blank">In silico docking screen identifies airway host protease targets for human SERPINs</a>
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<li><strong>The contribution of population age-sex structure to the excess mortality estimates of 2020-2021 in Denmark, Finland, Iceland, Norway, and Sweden</strong> -
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Background: The Nordic countries are an ideal case study of the COVID-19 pandemic due to their comparability, high data quality, and variable responses. Excess mortality is a key metric but it is sensitive to data quality, model assumptions, and population structure, with diverse estimates published so far. Methods: We investigated the age- and sex-specific mortality patterns during 2020-2021 for the five Nordic countries using annualized age- and sex specific death rates and populations. We compared the total age- and sex-adjusted excess deaths, ratios of actual vs. expected death rates, and age-standardized excess death estimates. We estimated excess deaths with several time periods and sensitivity tests, using 42 sex and age groups. Our models are less sensitive to outlier years than models based on 5 years of data. Results: Age-specific death rates have declining trends that reflect real improving health demographics. Our total excess mortality is close to WHO9s estimates, except higher for Norway and lower for Sweden, partly due to data used. Total excess deaths were dominated by the age group 70-89 years, was not identified in children, and more pronounced in men than women. Sweden had more excess deaths in 2020 than 2021 whereas Finland, Norway, and Denmark had the opposite. Denmark has the highest death rates before and during the pandemic, whereas Sweden in 2020 had the largest mortality increase. The age-standardized mortality of Denmark, Iceland and Norway was lowest in 2020, and 2021 was one of the lowest mortality years for all Nordic countries. We show that neutral baseline methods underestimate excess deaths and we document the importance of outlier mortality years. Conclusions: We provide excess mortality estimates mortality of the Nordic countries in relation to sex and age, with several metrics important in combination for a full understanding and comparison of the countries. We additionally identify important effects such as mortality displacement and sensitivities that affect our estimates and those of other excess mortality models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.18.22282495v1" target="_blank">The contribution of population age-sex structure to the excess mortality estimates of 2020-2021 in Denmark, Finland, Iceland, Norway, and Sweden</a>
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<li><strong>Special Olympics global report on COVID-19 vaccination and reasons not to vaccinate among adults with intellectual disabilities</strong> -
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Introduction The COVID-19 pandemic has disproportionately affected people with intellectual disabilities worldwide. The objective of this study was to identify global rates of COVID-19 vaccination and reasons not to vaccinate among adults with intellectual disabilities (ID) associated with country economic income levels. Methods The Special Olympics COVID-19 online survey was administered in January-February 2022 to adults with ID from 138 countries. Descriptive analyses of survey responses include 95% margins of error. Logistic regression and Pearson Chi-squared tests were calculated to assess associations with predictive variables for vaccination using R 4.1.2 software. Results Participants (n=3560) represented 18 low (n=410), 35 lower-middle (n=1182), 41 upper-middle (n=837), and 44 high (n=1131) income countries. Globally, 76% (74.8-77.6%) received a COVID-19 vaccination while 49.5% (47.9-51.2%) received a COVID-19 booster. Upper-middle (93% (91.2-94.7%)) and high-income country (94% (92.1-95.0%)) participants had the highest rates of vaccination while low-income countries had the lowest rates (38% (33.3-42.7%)). In multivariate regression models, country economic income level (OR = 3.12, 95% CI [2.81, 3.48]), age (OR = 1.04, 95% CI [1.03, 1.05]), and living with family (OR = 0.70, 95% CI [0.53, 0.92]) were associated with vaccination. Among LLMICs, the major reason for not vaccinating was lack of access (41.2% (29.5-52.9%)). Globally, concerns about side effects (42%, (36.5-48.1%)) and parent/guardian not wanting the adult with ID to vaccinate (32% (26.1-37.0%)) were the most common reasons for not vaccinating. Conclusion Adults with ID from low and low-middle income countries reported fewer COVID-19 vaccinations, suggesting reduced access and availability of resources in these countries. Globally, COVID-19 vaccination levels among adults with ID were higher than the general population. Interventions should address the increased risk of infection for those in congregate living situations and family caregiver apprehension to vaccinate this high-risk population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.16.22282406v1" target="_blank">Special Olympics global report on COVID-19 vaccination and reasons not to vaccinate among adults with intellectual disabilities</a>
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<li><strong>Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection</strong> -
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The ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, direct in vivo investigation of trophoblast susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derived bona fide trophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs were highly susceptible to SARS-CoV-2. They expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antiviral drug tests and safety evaluation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.17.516978v1" target="_blank">Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection</a>
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<li><strong>Mindfulness supports emotional resilience in children during the COVID-19 Pandemic</strong> -
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An important aspect of mental health in children is emotional resilience, the capacity to adapt to, and recover from, stressors and emotional challenges. Variation in trait mindfulness, one’s disposition to attend to experiences with an open and nonjudgmental attitude, may be an important individual difference in children that supports emotional resilience. In this study, we investigated whether trait mindfulness was related to emotional resilience in response to stressful changes in education and home-life during the COVID-19 pandemic in the United States. We conducted a correlational study examining self-report data from July 2020 to February 2021, from 163 eight-to-ten-year-old children living in the US. Higher trait mindfulness scores correlated with less stress, anxiety, depression, and negative affect in children, and lower ratings of COVID-19 impact on their lives. Mindfulness moderated the relationship between COVID-19 child impact and negative affect. Children scoring high on mindfulness showed no correlation between rated COVID-19 impact and negative affect, whereas those who scored low on mindfulness showed a positive correlation between child COVID-19 impact and negative affect. Higher levels of trait mindfulness may have helped children to better cope with a wide range of COVID-19 stressors. Future studies should investigate the mechanisms by which trait mindfulness supports emotional resilience in children.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.18.22282510v1" target="_blank">Mindfulness supports emotional resilience in children during the COVID-19 Pandemic</a>
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<li><strong>Comprative evaluation of Advanced Oxidation Processes (AOPs) for reducing SARS-CoV-2 viral load from campus sewage water</strong> -
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Although the presence of SARS-CoV-2 fragments in raw sewage water are not much concerning, since it is a new pathogen and its fate in the environment is poorly understood; therefore efforts are needed for their effective removal. In under-developed countries with poor sewersheds and sanitation practices, the raw sewage water might come in contact with rivers and other water bodies and is generally used by the population for various purposes including drinking water. Hence it is important to properly treat sewage water to reduce public health risks, if any. Our study evaluated various advanced oxidation processes (AOPs) for disinfection of SARS-CoV-2 from sewage water collected from the academic institutional residential campus. The present study is the first report showing hydrodynamic cavitation (HC) used to reduce the SARS-CoV-2 viral load from sewage water. Additionally, we have also evaluated hybrid techniques like HC/O3, HC/O3/H2O2, HC/H2O2, O3/UV, UV/H2O2, UV/H2O2/O3, and O3/H2O2 for the minimization of the SARS-CoV-2 viral load from sewage water. The sewage water treatment techniques were evaluated based on its viral concentration-reducing efficiency by comparing it with the same raw sewage water sample. However, ozone alone and its combination with other disinfecting techniques (like HC, UV, and H2O2) showed >95% SARS-CoV-2 specific RNA-reducing efficiency (also known as viral load). The AOPs treated sewage water was subjected to total nucleic acid isolation followed by RT-qPCR for viral load estimation. Interestingly, all sewage water treatment techniques used in this study significantly reduces both the SARS-CoV-2 viral load as well as PMMoV (faecal indicator) load.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.16.22282387v1" target="_blank">Comprative evaluation of Advanced Oxidation Processes (AOPs) for reducing SARS-CoV-2 viral load from campus sewage water</a>
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<li><strong>Impact of the COVID-19 pandemic on children and adolescents: determinants and association with quality of life and mental health - A cross-sectional study</strong> -
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Background The medium-term impact of the COVID-19 pandemic on the wellbeing of children and adolescents remains unclear. More than two years into the pandemic, we aimed to quantify the frequency and determinants of having been severely impacted by the COVID-19 pandemic and estimate its impact on health-related quality of life (HRQoL) and mental health. Methods Data was drawn from a population-based cohort of children and adolescents, recruited between December 2021 and June 2022, in Geneva, Switzerland. We measured the impact of the pandemic via the Coronavirus impact scale, which assesses the multidimensional impact of the pandemic at the child and family level through parent9s report. A score higher than one standard deviation above the mean was deemed a severe impact. Parents additionally reported about their offspring HRQoL and mental health with validated scales. Determinants of having been severely impacted were assessed with logistic models, as were the associations between having experienced a severe impact and poor HRQoL or mental health. Results Out of 2101 participants aged 2-17, 12.7% had experienced a severe pandemic impact. Having a lasting health condition, a pandemic-related worsening of lifestyle habits or an unfavorable family environment were associated with having been severely impacted by the pandemic. Participants who had experienced a severe pandemic impact were more likely to present poor HRQoL (aOR=3.1; 95%CI: 2.3-4.4) and poor mental health (aOR=3.9; 95%CI: 2.5-6.2). Conclusions The COVID-19 pandemic may have persistent consequences on the wellbeing of children and adolescents, especially among those with health and family vulnerabilities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.18.22282491v1" target="_blank">Impact of the COVID-19 pandemic on children and adolescents: determinants and association with quality of life and mental health - A cross-sectional study</a>
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<li><strong>Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity</strong> -
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Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CD177+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.16.22282338v1" target="_blank">Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity</a>
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<li><strong>Hospital length of stay throughout bed pathways and factors affecting this time: a non-concurrent cohort study of Colombia COVID-19 patients and an unCoVer network project</strong> -
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Predictions of hospital beds occupancy depends on hospital admission rates and the length of stay (LoS) according to bed type (hospital and intensive care unit beds). The objective of this study was to describe the LoS of COVID-19 hospital patients in Colombia during 2020-2021. Accelerated failure time models were used to estimate the LoS distribution according to each bed type and throughout each bed pathway. Acceleration factors and 95% confidence intervals were calculated to measure the effect on LoS of the outcome, sex, age, admission period during the epidemic (i.e., epidemic waves, peaks or valleys, and before/after vaccination period), and patients’ geographic origin. Most of the admitted COVID-19 patients occupied just hospital bed. Recovered patients spent more time in the hospital and intensive care unit than deceased patients. Men had longer LoS than women. In general, the LoS increased with age. Finally, the LoS varied along epidemic waves. It was lower in epidemic valleys than peaks, and became shorter after vaccinations began in Colombia than before. Our study highlights the necessity of analyzing local data on hospital admission rates and LoS to design strategies to prioritize hospital beds resources during the current and future pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.17.22282466v1" target="_blank">Hospital length of stay throughout bed pathways and factors affecting this time: a non-concurrent cohort study of Colombia COVID-19 patients and an unCoVer network project</a>
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<li><strong>Hamsters are a model for COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2</strong> -
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A relevant number of coronavirus disease 2019 (COVID-19) survivors suffers from post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC). Current evidence suggests a dysregulated alveolar regeneration in COVID-19 as a possible explanation for respiratory PASC symptoms, a phenomenon which deserves further investigation in a suitable animal model. This study investigates morphologic and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells accumulate following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of p53 at 6- and 14-days post infection (dpi), indicating a prolonged block in the ADI state. Transcriptome data shows the expression of gene signatures driving ADI cell senescence, epithelial-mesenchymal transition, and angiogenesis. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, persistence of ADI cells, peribronchiolar proliferates, M2-type macrophages, and sub-pleural fibrosis is observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The study provides a suitable translational model for future research on the pathomechanims of PASC and testing of prophylactic and therapeutical approaches.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.17.515635v1" target="_blank">Hamsters are a model for COVID-19 alveolar regeneration mechanisms: an opportunity to understand post-acute sequelae of SARS-CoV-2</a>
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<li><strong>Design and validation of an exposure system for efficient inter-animal SARS-CoV-2 airborne transmission in Syrian hamsters</strong> -
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SARS-CoV-2 is a highly transmissible respiratory pathogen whose main transmission route is airborne. Development of an animal model and exposure system that recapitulates airborne transmission of SARS-CoV-2 is integral for understanding the dynamics of SARS-CoV-2 spread in individuals and populations. Here we designed, built, and characterized a hamster transmission caging and exposure system that allows for efficient SARS-CoV-2 airborne transmission from an infected index animal to naive recipients under unidirectional airflow, without contribution from fomite or direct contact transmission. To validate our system, we assessed a 1:1 or 1:4 ratio of infected index to naive recipient hamsters and compared their virological and clinical measurements after eight hours of airborne exposure. Airborne exposure concentrations and pulmonary deposited dose of SARS-CoV-2 in index and naive hamsters, respectively, were similar in both groups. Daily nasal viral RNA levels, and terminal (day 5) lung viral RNA and infectious virus, and fecal viral RNA levels were statistically similar among 1:1 and 1:4 naive animals. However, virological measurements in the 1:4 naive animals were more variable than the 1:1 naive animals, likely due to hamster piling behavior creating uneven SARS-CoV-2 exposure during the grouped 1:4 airborne exposure. This resulted in slight, but not statistically significant, changes in daily body weights between the 1:1 and 1:4 naive groups. Our report describes a multi-chamber caging and exposure system that allowed for efficient SARS-CoV-2 airborne transmission in single and grouped hamsters. This system can be used to better define airborne transmission dynamics and test transmission-blocking therapeutic strategies against SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.18.517035v1" target="_blank">Design and validation of an exposure system for efficient inter-animal SARS-CoV-2 airborne transmission in Syrian hamsters</a>
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<li><strong>Innate immune response to SARS-1 CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons</strong> -
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Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection causes neurological disease in some patients suggesting that infection can affect both the peripheral and central nervous system (PNS and CNS, respectively). It is not clear whether the outcome of SARS-CoV-2 infection of PNS and CNS neurons is similar, and which are the key factors that cause neurological disease: SARS-CoV-2 infection or the subsequent immune response. Here, we addressed these questions by infecting human induced-pluripotent stem cell-derived CNS and PNS neurons with the beta strain of SARS-CoV-2. Our results show that SARS-CoV-2 infects PNS neurons more efficiently than CNS neurons, despite lower expression levels of angiotensin converting enzyme 2. Infected PNS neurons produced interferon lambda 1, several interferon stimulated genes and proinflammatory cytokines. They also displayed neurodegenerative-like alterations, as indicated by increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and alpha-synuclein and lower levels of nicotinamide mononucleotide adenylyltransferase 2 and beta-III-tubulin. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neurodegeneration, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.18.517047v1" target="_blank">Innate immune response to SARS-1 CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons</a>
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<li><strong>Rising SARS-CoV-2 Seroprevalence and Patterns of Cross-Variant Antibody Neutralization in UK Domestic Cats</strong> -
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Recent evidence confirming cat-to-human SARS-CoV-2 transmission has highlighted the importance of monitoring infection in domestic cats. Although the effects of SARS-CoV-2 infection on feline health are poorly characterized, cats have close contact with humans, and with both domesticated and wild animals. Accordingly, they could act as a reservoir of infection, an intermediate host and a source of novel variants. To investigate the spread of the virus in the cat population, serum samples were tested for SARS-CoV-2 antibodies by ELISA and a pseudotype-based virus neutralization assay, designed to detect exposure to variants known to be circulating in the human population. Overall seroprevalence was 3.2%, peaking at 5.3% in autumn 2021. Variant-specific neutralizing antibody responses were detected with titers waning over time. The variant-specific response in the feline population correlated with and trailed the variants circulating in the human population, indicating multiple ongoing human-to-cat spill-over events.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.18.517046v1" target="_blank">Rising SARS-CoV-2 Seroprevalence and Patterns of Cross-Variant Antibody Neutralization in UK Domestic Cats</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>COVID-19 Bivalent Booster Megastudy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study on Utilization, Adherence, and Acceptability of Voluntary Routine COVID-19 Self-testing Among Students, Staff and Health Workers at Two Institutions in Mizoram, India.</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Diagnostic Test: COVID-19 Self testing and related messaging<br/><b>Sponsors</b>: PATH; UNITAID; Zoram Medical College; Pacchunga University College; ALERT India; Government of Mizoram<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>Assessing Performance of the Testing Done Simple Covid 19 Antigen Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test<br/><b>Sponsors</b>: Testing Done Simple; Nao Medical Urgent Care<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 Evaluate EDP-235 in Non-hospitalized Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: EDP-235; Drug: Placebo<br/><b>Sponsor</b>: Enanta Pharmaceuticals, 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>The LAVA (Lateral Flow Antigen Validation and Applicability) 2 Study for COVID-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Diagnostic Test: Innova Lateral Flow Test<br/><b>Sponsor</b>: Alder Hey Children’s NHS Foundation Trust<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>Q-POC COVID-19 Clinical Evaluation</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Diagnostic Test: RT-PCR Test; Diagnostic Test: Real-time PCR Test<br/><b>Sponsors</b>: QuantuMDx Group Ltd; EDP Biotech; Paragon Rx Clinical; PathAI; PRX Research and Development<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>Acute Rehabilitation in Patients With COVID-19 Pneumonia</strong> - <b>Conditions</b>: COVID-19; Rehabilitation; Physical Medicine<br/><b>Intervention</b>: Procedure: Acute rehabilitation program<br/><b>Sponsor</b>: Institut za Rehabilitaciju Sokobanjska Beograd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of RAY1216 Tablets Compared With Placebo in Patients With Mild to Moderate SARS-CoV-2 Infection</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: RAY1216; Drug: Placebo<br/><b>Sponsor</b>: Guangdong Raynovent 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>Enhancing Protection Against Influenza and COVID-19 for Pregnant Women and Medically at Risk Children</strong> - <b>Conditions</b>: Influenza; COVID-19<br/><b>Intervention</b>: Behavioral: Nudge<br/><b>Sponsor</b>: University of Adelaide<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 Trial Evaluate the Immunogenicity and Safety of Recombinant COVID-19 Omicron-Delta Variant Vaccine (CHO Cell)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron-Delta Recombinant Novel Coronavirus Protein Vaccine (CHO cells); Biological: Recombinant Novel Coronavirus Protein Vaccine (CHO cells)<br/><b>Sponsor</b>: Anhui Zhifei Longcom Biologic Pharmacy 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>COVID-19 Antibody Responses in Cystic Fibrosis</strong> - <b>Conditions</b>: COVID-19; Cystic Fibrosis<br/><b>Intervention</b>: Biological: Blood sample<br/><b>Sponsors</b>: Hospices Civils de Lyon; Queen’s University, Belfast<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1, Randomised, Double-blinded, Placebo-controlled, Dose-escalation Study to Evaluate the Safety and Immunogenicity of RH109 as Booster</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: Lyophilized COVID-19 mRNA Vaccine; Drug: Sodium chloride<br/><b>Sponsors</b>: Wuhan Recogen Biotechnology Co., Ltd.; Shenzhen Rhegen Biotechnology Co., Ltd.; Wuhan Rhegen 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>Message Communicating Latest Data on COVID Transmission in Patient’s Area</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Message From Local Pharmacy Team</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Planning Message Recommending Same Time/Location as Last Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Gastrointestinal, liver, pancreas, oral and psychological long-term symptoms of COVID-19 after recovery; A review</strong> - Due to the importance of control and prevention of COVID-19-correlated long-term symptoms, the present review article has summarized what has been currently known regarding the molecular and cellular mechanisms linking COVID-19 to important long-term complications including psychological complications, liver and gastrointestinal manifestations, oral signs as well as even diabetes. COVID-19 can directly affect the body cells through their Angiotensin-converting enzyme 2 [ACE-2] to induce…</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>Pexidartinib (PLX3397) through restoring hippocampal synaptic plasticity ameliorates social isolation-induced mood disorders</strong> - Social behavior is essential for the well-being and survival of individuals. However, social isolation is a serious public health issue, especially during the COVID-19 pandemic, affecting a significant number of people worldwide, and can lead to serious psychological crises. Microglia, innate immune cells in the brain, are strongly implicated in the development of psychiatry. Although many microglial inhibitors have been used to treat depression, there is no literature report on pexidartinib…</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>Discovery and mechanism of action of Thonzonium bromide from an FDA-approved drug library with potent and broad-spectrum inhibitory activity against main proteases of human coronaviruses</strong> - Although the effective drugs or vaccines have been developed to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their efficacy may be limited for the viral evolution and immune escape. Thus, it is urgently needed to develop the novel broad-spectrum antiviral agents to control the coronavirus disease 2019 (COVID-19) global pandemic. The 3C-like protease (3CL^(pro)) is a highly conserved cysteine proteinase that plays a pivotal role in processing the viral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study</strong> - CONCLUSIONS: There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.</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 GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice</strong> - Gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain. GABA-Rs are also expressed by 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and 2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries. These biological properties suggest that GABA-R agonists may have potential for treating COVID-19. We previously reported that GABA-R agonist…</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>Translation suppression underlies the restrained COVID-19 mRNA vaccine response in the high-risk immunocompromised group</strong> - CONCLUSIONS: This is the first study to demonstrate that ISs, sirolimus and mycophenolate inhibited Co-mV-induced Sp protein synthesis via translation repression. Selective use of tacrolimus or drug holiday of sirolimus can be a potential means to rescue translation-dependent Sp protein production. These findings lay a strong foundation for guiding future studies aimed at improving Co-mV responses in high-risk IC patients.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 modulates inflammatory responses of alveolar epithelial type II cells <em>via</em> PI3K/AKT pathway</strong> - CONCLUSION: The findings of our study, showed that SARS-CoV-2 S protein suppressed inflammatory responses in alveolar epithelial type II cells at early stages of infection through activation of the PI3K/AKT pathway. Thus, our results suggest that at early stages SARS-CoV-2 S protein signals inhibit immune responses to the virus allowing it to propagate the infection while in combination with TLR2 signals enhances PAI-1 expression, potentially affecting the local coagulation cascade.</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>Nucleotide and nucleoside-based drugs: past, present, and future</strong> - Nucleotide and nucleoside-based analogue drugs are widely used for the treatment of both acute and chronic viral infections. These drugs inhibit viral replication due to one or more distinct mechanisms. It modifies the virus’s genetic structure by reducing viral capacity in every replication cycle. Their clinical success has shown strong effectiveness against several viruses, including ebolavirus, hepatitis C virus, HIV, MERS, SARS-Cov, and the most recent emergent SARS-Cov2. In this review,…</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>User experience reevaluation and diffusion of technology in the context of compulsory usage illustrated by the example of telepsychotherapy-a literature review</strong> - CONCLUSIONS: Telepsychohtherapy has become an integral part of psychotherapeutic care. A hybrid system in close coordination between provider and patient may prevail, addressing individual needs of both parties to achieve optimal care and provider well-being. This requires transparent regulations, guidelines, and standards.</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 a potent dual-function inhibitor for hIMPDH isoforms by computer-aided drug discovery approaches</strong> - Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme in de novo biosynthesis of purine nucleotides. Due to this important role, it is a great target to drug discovery for a wide range of activities, especially immunosuppressant in heart and kidney transplantation. Both human IMPDH isoforms are expressed in stimulated lymphocytes. In addition to the side effects of existing drugs, previous studies have mainly focused on the type II isoform. In this study, virtual screening 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>Herbo-mineral formulation, Divya-Swasari-Vati averts SARS-CoV-2 pseudovirus entry into human alveolar epithelial cells by interfering with spike protein-ACE 2 interaction and IL-6/TNF-α /NF-κB signaling</strong> - The herbo-mineral formulation, Divya-Swasari-Vati (DSV), is a well-known Ayurvedic medication for respiratory ailments. In a recent pre-clinical study, DSV rescued humanized zebrafish from SARS-CoV-2 S-protein-induced pathologies. This merited for an independent evaluation of DSV as a SARS-CoV-2 entry inhibitor in the human host cell and its effectiveness in ameliorating associated cytokine production. The ELISA-based protein-protein interaction study showed that DSV inhibited the interactions…</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>Local Anesthetic Like Inhibition of the Cardiac Na<sup>+</sup> Channel Nav1.5 by Chloroquine and Hydroxychloroquine</strong> - CONCLUSION: This study demonstrated that CQ and HCQ exert LA-typical effects on Nav1.5 involving the proposed LA binding site, thus contributing to their arrhythmogenic properties.</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>XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection</strong> - The unprecedented emergence and spread of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, underscores the need for diagnostic and therapeutic technologies that can be rapidly tailored to novel threats. Here, we show that site-specific RNA endonuclease XNAzymes - artificial catalysts composed of single-stranded synthetic xeno-nucleic acid oligonucleotides (in this case 2’-deoxy-2’-fluoro-β-D-arabino nucleic acid) - may be designed, synthesised and screened within days, enabling…</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>AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity</strong> - Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at…</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>Repositioning of anti-dengue compounds against SARS-CoV-2 as viral polyprotein processing inhibitor</strong> - A therapy for COVID-19 (Coronavirus Disease 19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains elusive due to the lack of an effective antiviral therapeutic molecule. The SARS-CoV-2 main protease (Mpro), which plays a vital role in the viral life cycle, is one of the most studied and validated drug targets. In Several prior studies, numerous possible chemical entities were proposed as potential Mpro inhibitors; however, most failed at various stages of drug…</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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