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190 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>07 July, 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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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Intracardiac Thrombus in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes</strong> -
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Background: COronaVIrus Disease 2019 (COVID-19) has been observed to be associated with a hypercoagulable state. Intracardiac thrombosis is a serious complication but has seldom been evaluated in COVID-19 patients. We assessed the incidence, associated factors, and outcomes of COVID-19 patients with intracardiac thrombosis. Methods: COVID-19 inpatients during 2020 were retrospectively identified from the national inpatient sample (NIS) database, and data retrieved regarding clinical characteristics, intracardiac thrombosis, and adverse outcomes. Multivariable logistic regression was performed to identify the clinical factors associated with intracardiac thrombosis and in-hospital mortality and morbidities. Results: A total of 1,683,785 COVID-19 inpatients were identified in 2020 from NIS, with a mean age of 63.8 ± 1.6 years, and 32.2% females. Intracardiac thrombosis was present in 0.001% (1,830) patients. Overall, in-hospital outcomes include all-cause mortality 13.2% (222,695/1,683,785), cardiovascular mortality 3.5%, cardiac arrest 2.6%, acute coronary syndrome (ACS) 4.4%, heart failure 16.1%, stroke 1.3% and acute kidney injury (AKI) 28.3%. The main factors associated with intracardiac thrombosis were a history of congestive heart failure and coagulopathy. Intracardiac thrombosis was independently associated with a higher risk of in-hospital all-cause mortality (OR: 3.32, 95% CI: 2.42-4.54, p<0.001), cardiovascular mortality (OR: 2.95, 95% CI: 1.96-4.44, p<0.001), cardiac arrest (OR: 2.04, 95% CI: 1.22-3.43, p=0.006), ACS (OR: 1.62, 95% CI: 1.17-2.22, p=0.003), stroke (OR: 3.10, 95% CI: 2.11-4.56, p<0.001), and AKI (OR: 2.13 95% CI: 1.68-2.69, p<0.001), but not incident heart failure (p=0.27). Conclusion: Although intracardiac thrombosis is rare in COVID-19 inpatients, its presence was independently associated with higher risks of in-hospital mortality and most morbidities. Prompt investigations and treatments for intracardiac thrombosis are warranted when there is a high index of suspicion and a confirmed diagnosis respectively.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.05.23292278v1" target="_blank">Intracardiac Thrombus in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes</a>
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</div></li>
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<li><strong>Immunogenicity and safety of heterologous Omicron BA.1 and bivalent SARS-CoV-2 recombinant spike protein booster vaccines: a phase 3, randomized, clinical trial</strong> -
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Background. Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone, or as a bivalent preparation in combination with the prototype vaccine (NVX CoV2373), to assess antibody responses to SARS-CoV-2. Methods. Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed. Results. Of participants who received trial vaccine (N=829), those administered NVX-CoV2515 (n=286) demonstrated superior neutralizing antibody response to BA.1 versus NVX-CoV2373 (n=274) at Day 14 (geometric mean titer ratio [95% CI]: 1.6 [1.33, 2.03]). Seroresponse rates [n/N; 95% CI] were 73.4% [91/124; 64.7, 80.9] for NVX-CoV2515 versus 50.9% [59/116; 41.4, 60.3] for NVX-CoV2373. All formulations were similarly well-tolerated. Conclusions. NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.05.23291954v1" target="_blank">Immunogenicity and safety of heterologous Omicron BA.1 and bivalent SARS-CoV-2 recombinant spike protein booster vaccines: a phase 3, randomized, clinical trial</a>
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<li><strong>Compartmental mixing models for vaccination-status-based societal separation regarding viral respiratory diseases</strong> -
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Background: Societal separation of unvaccinated people from public spaces has been a novel and controversial COVID-era public health practice in many countries. Models exploring potential consequences of vaccination-status-based separation have not considered how separation influences the contact frequencies in the separated groups; we systematically investigate implementing effects of separation on person-to-person contact frequencies and show this critically determines the predicted epidemiological outcomes, focusing on the attack rates in the vaccinated and unvaccinated populations and the share of infections among vaccinated people that were due to contacts with infectious unvaccinated people. Methods: We describe a susceptible-infectious-recovered (SIR) two-population model for vaccinated and unvaccinated groups of individuals that transmit an infectious disease by person-to-person contact. The degree of separation between the two groups, ranging from zero to complete separation, is implemented using the like-to-like mixing approach developed for sexually-transmitted diseases [1-3], adapted for presumed SARS-CoV-2 transmission. We allow the contact frequencies for individuals in the two groups to be different and depend, with variable strength, on the degree of separation. Results: Separation can either increase or decrease the attack rate among the vaccinated, depending on the type of separation (isolating or compounding), and the contagiousness of the disease. For diseases with low contagiousness, separation can cause an attack rate in the vaccinated, which does not occur without separation. Interpretation: There is no blanket epidemiological advantage to separation, either for the vaccinated or the unvaccinated. Negative epidemiological consequences can occur for both groups.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.21.22279035v3" target="_blank">Compartmental mixing models for vaccination-status-based societal separation regarding viral respiratory diseases</a>
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<li><strong>The K+/Na+ innate immune system is involved in the susceptibility to and severity of COVID-19: a systematic review and retrospective cohort study</strong> -
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Abstract Background: From single-cellular to multicellular organisms, a natural nonspecific immune system, called the K+/Na+ innate immune system, has recently been proposed to play an important role in the process of fighting against viral infection, however, there is little direct research evidence. This study aimed to evaluate whether the changes in serum K+/Na+ concentrations are associated with susceptibility and severity of SARS-CoV-2 infection. Methods: We systematically searched PubMed, the Web of Science Core Collection, MedRxiv and BioRxiv databases for articles published between Jan 1, 2020 and Dec 14, 2022. We extracted the serum K+/Na+ concentration data of patients with COVID-19 from 112 published studies after removing inappropriate articles according to the defined criteria and analyzed the relationship between the serum k+/Na+ concentrations and the illness severity of patients. Then we used a cohort of 244 patients with COVID-19 for a retrospective analysis. Results: The mean serum k+/Na+ concentrations in patients with COVID-19 were 3.99 and 138.0 mmol/L, respectively, which were much lower than the mean levels in the population (4.40 and 142.0, respectively). The mean serum Na+ concentration in severe/critical patients (136.8) was significantly lower than those in mild and moderate patients (139.4 and 138.0, respectively). Such findings were confirmed in a retrospective cohort study, of which the mean serum k+/Na+ concentrations in all patients were 4.0 and 137.5 mmol/L, respectively. The significant differences in serum Na+ concentrations were found between the mild (139.2) and moderate (137.2) patients, and the mild and severe/critical (136.6) patients, which were correlated to the illness severity of patients. Conclusions: These findings may indicate the importance of a natural immune system constructed by intracellular potassium and extracellular sodium ions in the fight against viral infection and provide new ideas for the prevention and treatment of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.03.23292126v1" target="_blank">The K+/Na+ innate immune system is involved in the susceptibility to and severity of COVID-19: a systematic review and retrospective cohort study</a>
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<li><strong>DECLINE OF HANDWASHING AND MASKING AMONG THE GENERAL POPULATION IN POST COVID-19 PANDEMIC: INSIGHTS FROM A MIXED METHODS STUDY IN GHANA</strong> -
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COVID-19 has now entered the endemic stage where the virus is widespread with less fatality than it was in 2020. Restrictions and mandates such as handwashing and masking are eased although the pandemic is not yet over. Many have concluded that we have reached a point that marks the end of the pandemic spurring changes in public behavior. However, SARS-CoV-2 is still causing deaths every day and cases have not plateaued at low level. Better knowledge on why people have relented in handwashing and masking is needed to guide the development of effective interventions against future waves of the infection. In this study, we explored factors contributing to this pattern of behavior in Ghana. Questionnaires were administered to 350 respondents, via social media (WhatsApp, LinkedIn, Twitter, Facebook, reedit,) and these were used to determine the level of handwashing and masking at the first stage of study. Screening and scoring of the questionnaires were used to estimate the level of these activities at the second stage. Among all respondents, we identified and selected 279 participants at the second stage: 95 as decliners, 120 non-regulars, and 64 maintainers according to their level of these activities and adapted scoring criteria. For each category, a group of 5 participants were randomly selected to take part in an in-depth interview. The theory of planned behavior guided our analysis. Six themes emerged from the analysis with the acronym, IMPASE; inconvenience and contamination, Mass population, pandemic patterns and regulations, Availability, Safety and infection prevention, environment and activity. These themes appeared to have elements relating to another component of the theory of planned behavior. Collectively, the environment (Subjective norms) and pattern of pandemic and regulation (Perceived behavioral control) interact with each other to ultimately influence handwashing and masking. Declining and non-regularity were associated with inconvenience and contamination. Maintenance is associated with the environment and activity. Thus, public educational campaigns must be intensified to highlight and address these themes. The public health authorities, employers and, essential services could play an important role in enforcing and disseminating such information.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.03.23292119v1" target="_blank">DECLINE OF HANDWASHING AND MASKING AMONG THE GENERAL POPULATION IN POST COVID-19 PANDEMIC: INSIGHTS FROM A MIXED METHODS STUDY IN GHANA</a>
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<li><strong>Characterization of a fieldable process for airborne virus detection</strong> -
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Rapid, on-site, airborne virus detection is a requirement for timely action against the spread of air-transmissible infectious diseases. This applies both to future threats and to common viral diseases, such as influenza and COVID-19, which hit vulnerable populations yearly with severe consequences. The ultra-low concentrations of virus in the air make airborne virus detection difficult, yet readily infect individuals when breathed. Here, we propose a fieldable process that includes an enrichment step to concentrate collected genetic material in a small volume. The enrichment approach uses capillary electrophoresis and an RT-qPCR-compatible buffer, which allow enrichment of the RNA by about 5-fold within only 10 minutes of operation. Our detection process consists of air sampling through electrostatic precipitation, RNA extraction via heating, RNA enrichment, and RT-qPCR for detection. We optimized each step of the process and estimated a detection sensitivity of 3106±2457 genome copies (gc) per m<sup>3</sup> of air. We then performed an integration experiment and confirmed a sensitivity of 5654 gc/m<sup>3</sup> with a detection rate of 100% and a sensitivity of 4221 gc/m<sup>3</sup> with a detection rate of 78.6%. When using fast RT-qPCR, the latency of the whole process is down to 61 minutes. Given that our sensitivity falls in the low range of influenza and SARS-CoV-2 concentrations reported in indoor spaces, our study shows that, with enrichment, airborne pathogen detection can be made sufficiently sensitive for practical use.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.03.23292170v1" target="_blank">Characterization of a fieldable process for airborne virus detection</a>
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<li><strong>When are predictions useful? A new method for evaluating epidemic forecasts</strong> -
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We introduce the Weighted Contextual Interval Score (WCIS), a new method for evaluating the performance of short-term interval-form forecasts. The WCIS provides a pragmatic utility-based characterization of probabilistic predictions, developed in response to the challenge of evaluating forecast performances in the turbulent context of the COVID-19 pandemic. Current widely-used scoring techniques generally fall into two groups: those that generate an individually interpretable metric, and those that generate a comparable and aggregable metric. The WCIS harmonizes these attributes, resulting in a normalized score that is nevertheless intuitively representative of the in-situ quality of individual forecasts. This method is expressly intended to enable practitioners and policy-makers who may not have expertise in forecasting but are nevertheless essential partners in epidemic response to use and provide insightful analysis of predictions. In this paper, we detail the methodology of the WCIS and demonstrate its utility in the context of US state-level COVID-19 predictions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.29.23292042v1" target="_blank">When are predictions useful? A new method for evaluating epidemic forecasts</a>
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<li><strong>Symptoms of Depression among Outpatients with Acute Respiratory Infection in Metropolitan Local Government Areas of Kaduna State, Nigeria</strong> -
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Background The novel SARS-CoV-2 virus that causes Coronavirus disease (COVID-19) has redefined global health and response to Acute Respiratory Infection (ARI). The outbreak of a cluster of influenza-like illnesses in Wuhan, China, has morphed into a pandemic in the last quarter of 2019, stretching from South East Asia to Europe, The Americas, Africa, and the Australian subcontinent. Materials and Methods We shall utilize a cross-sectional, observational design to investigate the prevalence of symptoms of depression among outpatients with ARI and describe the characteristics of outpatients with ARI in Kaduna State. Results The prevalence of symptoms of depression was 19.6% for respondents with symptoms of ARI, and 14.4%, for those without symptoms of ARI. On no risk of depression, we had a higher proportion of the respondents without symptoms of ARI (86%) than those with symptoms of depression (80%) (M=318.4, SD=29.62 case, and M=344.0, SD=14.2 control, r=0.88, CI=13.5 to 6.5, P=0.000952). Likewise, in the category with mild risk of depression, respondents without symptoms of ARI were fewer (10%) than those with symptoms of depression (15%) (M=58.4, SD=26.0 case, and M=42.1, SD=12.7 control, r=0.86, CI=11.8 to 5.8, P=0.0136. There was no significant difference between respondents with symptoms of ARI and without symptoms of ARI in the categories of moderate (M=13.6, SD=5.1 case, and M=11.6, SD=4.6 control, r=0.87, CI=2.3 to 2.1, P=0.178) and high (M=5.6, SD=2.5 case, and M=4.4, SD=3.2 control, r=0.61, CI=1.2 to 1.5, P=0.174) risk of depression. Conclusion Symptoms of depression were commoner among respondents who presented with symptoms of Acute Respiratory Infection (ARI) at the Outpatient Department (OPD). However, further explanatory research is needed to establish causality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.02.23292139v1" target="_blank">Symptoms of Depression among Outpatients with Acute Respiratory Infection in Metropolitan Local Government Areas of Kaduna State, Nigeria</a>
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<li>**Spike-Induced Disturbances (SPAS*): An Analysis of Common Suspected Adverse Experiences Associated With Covid-19 Vaccines** -
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This review/analysis gives a first impression of numerous adverse events related to Covid-19 vaccination, which have received little attention to date, are often unexplained, but are nevertheless very distressing. Frequently observed organ-related ADRs after Covid-19 vaccination were such of the nervous system, musculoskeletal system, gastrointestinal tract, and skin. The involvement of almost all organs in the side effect spectrum of Covid-19 vaccines demonstrates their systemic efficacy. As shown by the ADRs occurrence even after numerous days to weeks, the duration of spike production obviously lasts longer than claimed. The key role is played by the interaction between the spike subunit S1 and the membrane-bound enzyme ACE2, the receptor for SARS-CoV. Downregulation of ACE2 by spikes and following activation of RAAS can lead to numerous clinically relevant disorders, such as vasoconstriction, tissue ischemia, induction of proliferative processes, increased oxidative stress, inflammation, or coagulation disorders, as previously shown for cardiovascular reactions. It is proposed to use the collective term “SPAS” (in German: Spike ausgelöste Störungen) - spike induced disturbances for side effects based on this mode of action. The common mode of action and only slightly different frequencies of adverse events and fatal outcomes do not indicate any principal differences in adverse event profiles of the individual spike-based Covid-19 vaccines. A class-specific side effect profile can be assumed. Knowledge and awareness of the comprehensive adverse event profile of the novel Covid-19 vaccines and their potential dangerousness may improve vaccine safety.
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🖺 Full Text HTML: <a href="https://osf.io/q94bn/" target="_blank">Spike-Induced Disturbances (SPAS*): An Analysis of Common Suspected Adverse Experiences Associated With Covid-19 Vaccines</a>
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<li><strong>Suspected Cardiovascular Side Effects of two Covid-19 Vaccines</strong> -
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Fatalities or cardiovascular side effects of vaccines were rather uncommon in the past. So far, numerous reports of side effects and deaths associated with Covid-19 vaccination have been accepted behind the background of the pandemic situation and the priority vaccinated elderly population at the beginning of the vaqccination campaign. Cardiac and heart circulatory disturbances resp. cardiovascular side effects associated with the application of Covid-19 vaccines have not been recognized up to now with the exception of thrombotic/embolic side effects and cases of myo-/pericarditis. But the mechanism of action suggests that downregulation of ACE2 by non-neutralised spike proteins may have cardiovascular effects. The objective of this analysis was to determine the total number of reported adverse events and fatalities and to record suspected important cardiovascular adverse events up to the cut-off date in European countries. Therefore, a current review/analysis of spontaneously reported fatalities as well as of adverse events after application of Covid-19 vaccines has been performed. Data were retrieved from the EudraVigilance web reports of the European Medicines Agency (EMA), partly also from the safety reports of the German PEI. Covid-19 vaccine-associated suspected side effects and related deaths are alarming. Surprisingly, numerous cardiovascular reactions were reported, many of which were life-threatening. Cardiac and heart circulatory caused fatalities alone accounted for about 33% of all ComirnatyR vaccine-related deaths. The second most important side effects were vascular thrombotic/embolic side effects, often also associated with serious consequences. Based on their quality and quantity, these side effects seem to be characteristic for spike-producing vaccines and do not appear to be substance-specific. Further investigations are needed to clarify the approximately 3.5 times more frequent cases of sinus vein thrombosis and the some different frequent cases of thrombotic/embolic events after VaxzevriaR. The hypothesis could be confirmed. Because of their importance and their sometimes life-threatening consequences, cardiovascular side effects need to be better communicated. Limitations of the investigation result from the individual reporting and recording procedure, the lack of detailed individual information and the lack of an appropriate comparison population.
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🖺 Full Text HTML: <a href="https://osf.io/gh9u2/" target="_blank">Suspected Cardiovascular Side Effects of two Covid-19 Vaccines</a>
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<li><strong>Empty streets, busy Internet. A time series analysis of cybercrime and fraud trends during COVID-19</strong> -
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There have been many warnings about the rising threat of cybercrime and fraud resulting from the COVID-19 lockdown measures and the associated increase in Internet use. However, there is still relatively little data with which to support the alerts and any changes may be nuanced. The present paper applies time series analysis methods to historical data on cybercrime and fraud reported to Action Fraud in the UK to examine whether any potential increases are beyond normal crime variability. Furthermore, the discrepancies between fraud types and individual and organisation victims are also analysed. The results show that while both total cybercrime and total fraud did increase beyond predicted levels, the changes in victimisation were not homogenous across fraud types and victims. The implications of these findings on how changes in routine activities in the UK have influenced cybercrime and fraud opportunities are discussed in relation to policy, practice and academic debate.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/38wfy/" target="_blank">Empty streets, busy Internet. A time series analysis of cybercrime and fraud trends during COVID-19</a>
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<li><strong>An appraisal of the scope of domestic tourism in Dooars foothills tourist circuit in the post-pandemic scenario</strong> -
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COVID-19 has wreaked havoc on world economy including tourism and hospitality industry. While international tourism has been on a slump for most of the last three years, people and organisations involved in the sector need to focus on domestic tourism for a slow but steady turn around. India with a huge share of annual domestic tourists is better positioned to cope up with this scenario. Tourism Department, Govt. of West Bengal has been promoting and developing different tourist circuits in the state for the last two decades. Dooars circuit, located in a comparatively backward region in the northern foothills of the state deserves more attention. With various kinds of tourist spots and events, it attracts visitors throughout the year. Impact of the pandemic and subsequent lockdown has been felt here too. The tourism sector has suffered a setback and most of the people associated with it, have lost their earning and livelihood. Thus promoting domestic tourism in Dooars is the only feasible way to protect the industry and its workers. The present paper attempts to make an appraisal of the tourism infrastructure and services available at different tourist attractions spread over the region. It aims to suggest some policies for improvement of the tourism scenario in general and domestic tourism in particular.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/r7vgk/" target="_blank">An appraisal of the scope of domestic tourism in Dooars foothills tourist circuit in the post-pandemic scenario</a>
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<li><strong>A cost-effectiveness analysis of Molnupiravir and Paxlovid in three African countries</strong> -
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Objective: To assess the cost-effectiveness of two COVID-19 oral antivirals (COAVs) Paxlovid and Molnupiravir compared to the standard of care, in Ghana, Rwanda and Zambia. Methods: We modelled costs (2022 US$) and health outcomes in the acute phase of the COVID-19 disease from a public payer9s perspective in three unvaccinated target populations (1) patients aged 65 years and above (elderly); (2) adult patients with at least one other underlying risk factors for disease severity; and (3) all adult patients. In addition, we conducted a series of sensitivity and scenario analyses. Results: In elderly patients, Paxlovid was less costly and more effective (i.e., dominated) than standard of care in all three study countries. Molnupiravir dominated standard of care in Rwanda and Zambia and an incremental cost-effectiveness ratio (ICER) was estimated at US$1023.58 per disability-adjusted life year (DALY) averted in Ghana. In adults with other underlying risk factors, Paxlovid dominated in Rwanda and Zambia while Molnupiravir dominated in Rwanda. Neither Paxlovid nor Molnupiravir were cost-effective in the all-adult group in any country context. Incremental net monetary benefit for Paxlovid was consistently higher than for Molnupiravir. In COVID-19 vaccinated patients, Paxlovid was cost-effective for elderly patients in Zambia and Rwanda but not in Ghana. Key determinants of cost-effectiveness were COAV price, likelihood of early treatment initiation, and hospitalization rates. Conclusion: In African settings similar to Zambia, Ghana or Rwanda, COAVs could be cost-effective in populations who are unvaccinated, and at high risk of progression to severe COVID-19. More evidence is needed to determine cost-effectiveness for patients that are unvaccinated but have previously been infected with COVID-19 and may have developed some immune protection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.05.23292205v1" target="_blank">A cost-effectiveness analysis of Molnupiravir and Paxlovid in three African countries</a>
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<li><strong>The receptor binding domain of SARS-CoV-2 spike protein fused with the type IIb E. coli heat-labile enterotoxin A subunit as an intranasal booster after mRNA vaccination</strong> -
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The outbreak of SARS-CoV-2 infections had led to the COVID-19 pandemic which has a significant impact on global public health and the economy. The spike (S) protein of SARS-CoV-2 contains the receptor binding domain (RBD) which binds to human angiotensin-converting enzyme 2 receptor. Numerous RBD-based vaccines have been developed and recently focused on the induction of neutralizing antibodies against the immune evasive Omicron BQ.1.1 and XBB.1.5 subvariants. In this preclinical study, we reported the use of a direct fusion of the type IIb Escherichia coli heat-labile enterotoxin A subunit with SARS CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate. The results showed that intranasal immunization with the RBD-LTA fusion protein in BALB/c mice elicited potent neutralizing antibodies against the Wuhan-Hu-1 and several SARS-CoV-2 variants as well as the production of IgA antibodies in bronchoalveolar lavage fluids (BALFs). Furthermore, the RBD-LTA fusion protein was used as a second-dose booster after bivalent mRNA vaccination. The results showed that the neutralizing antibody titers elicited by the intranasal RBD-LTA booster were similar to the bivalent mRNA booster, but the RBD-specific IgA titers in sera and BALFs significantly increased. Overall, this preclinical study suggests that the RBD-LTA fusion protein could be a promising candidate as a mucosal booster COVID-19 vaccine.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.05.547781v1" target="_blank">The receptor binding domain of SARS-CoV-2 spike protein fused with the type IIb E. coli heat-labile enterotoxin A subunit as an intranasal booster after mRNA vaccination</a>
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<li><strong>Discovering host protein interactions specific for SARS-CoV-2 RNA genome</strong> -
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SARS-CoV-2, a positive single-stranded RNA virus, interacts with host cell proteins throughout its life cycle. These interactions are necessary for the host to recognize and hinder the replication of SARS-CoV-2. For the virus, to translate, transcribe and replicate its genetic material. However, many details of these interactions are still missing. We focused on the proteins binding to the highly structured 5’ and 3’ end regions of SARS-CoV-2 RNA that were predicted by the catRAPID algorithm to attract numerous proteins, exploiting RNA-Protein Interaction Detection coupled with Mass Spectrometry (RaPID-MS) technology. The validated interactors, which agreed with our predictions, include pseudouridine synthase PUS7 that binds to both ends of the viral RNA. Nanopore direct-RNA sequencing confirmed that the RNA virus is heavily modified, and PUS7 consensus regions were found in both SARS-CoV-2 RNA end regions. Notably, a modified site was detected in the viral Transcription Regulatory Sequence - Leader (TRS-L) and can influence the viral RNA structure and interaction propensity. Overall, our data map host protein interactions within SARS-CoV-2 UTR regions, pinpointing to a potential role of pseudouridine synthases and post-transcriptional modifications in the viral life cycle. These findings contribute to understanding virus-host dynamics and may guide the development of targeted therapies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.18.499583v2" target="_blank">Discovering host protein interactions specific for SARS-CoV-2 RNA genome</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>Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine<br/><b>Sponsor</b>: PT Bio Farma<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>Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Ivermectin Tablets; Drug: Colchicine 0.5 MG; Drug: Standared managment<br/><b>Sponsor</b>: Ain Shams University<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 Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-2; Biological: SCTV01E<br/><b>Sponsor</b>: Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Standard implementation webinar and online training; Behavioral: Virtual facilitation<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Arkansas; University of South Carolina; National Institute on Minority Health and Health Disparities (NIMHD)<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>LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Hospitalized COVID-19 Patients<br/><b>Interventions</b>: Drug: Lopinavir / Ritonavir; Drug: Remdesivir (RDV); Drug: Tocilizumab; Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)<br/><b>Sponsors</b>: Lebanese University; Hospital Saydet Zgharta 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>Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Resistance Training<br/><b>Sponsor</b>: Józef Piłsudski University of Physical Education<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>Comprehensive Imaging Exam of Convalesced COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; COVID Long-Haul<br/><b>Interventions</b>: Other: Magnetic Resonance Imaging; Other: Ultra-High Resolution Computed Tomography (CT) Scan<br/><b>Sponsors</b>: Johns Hopkins University; Canon Medical Systems, USA<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>Multimodal Long Covid19</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Other: Multimodal intervention in Long Covid19<br/><b>Sponsors</b>: Universidad de Magallanes; Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG; Clinical Hospital Dr. Lautaro Navarro Avaria<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines<br/><b>Interventions</b>: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg<br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia<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>Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection; Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection<br/><b>Sponsor</b>: Clover Biopharmaceuticals AUS Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB002V14; Biological: LYB002V14A; Biological: LYB002CA<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2/3 Heterologous Boosting Study With Different Dose Levels of Monovalent SARS-CoV-2 rS Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2373 (5μg); Biological: NVX-CoV2601 (5μg); Biological: NVX-CoV2601(5μg); Biological: NVX-CoV2601 (35μg); Biological: NVX-CoV2601(35μg); Biological: NVX-CoV2601(50μg); Biological: Bivalent BA.4/5<br/><b>Sponsor</b>: Novavax<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001</strong> - <b>Conditions</b>: COVID-19; Vaccine Reaction<br/><b>Interventions</b>: Biological: LYB001; Biological: CoronaVac<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Placebo; Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]<br/><b>Sponsor</b>: Hellenic Institute for the Study of Sepsis<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19</strong> - <b>Conditions</b>: Coronavirus Disease; COVID-19; Long Covid-19; Telerehabilitation<br/><b>Interventions</b>: Device: KNEESUP smart knee assistive device + KNEESUP care APP; Device: KNEESUP care APP; Behavioral: Healthy consulation<br/><b>Sponsor</b>: Shang-Lin Chiang<br/><b>Recruiting</b></p></li>
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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>Individuals at risk for severe COVID-19 in whom ritonavir-containing therapies are contraindicated or may lead to interactions with concomitant medications: a retrospective analysis of German health insurance claims data</strong> - CONCLUSION: Administering ritonavir-containing COVID-19 therapy can be challenging as thorough medical record review and close monitoring are required. In some cases, ritonavir-containing treatment may not be appropriate due to contraindications, risk of pDDIs, or both. For those individuals, an alternative ritonavir-free treatment should be considered.</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>e-Pharmacophore modeling and in silico study of CD147 receptor against SARS-CoV-2 drugs</strong> - Coronavirus has left severe health impacts on the human population, globally. Still a significant number of cases are reported daily as no specific medications are available for its effective treatment. The presence of the CD147 receptor (human basigin) on the host cell facilitates the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Therefore, the drugs that efficiently alter the formation of CD147 and spike protein complex could be the right drug candidate to inhibit 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>Investigating theobromine as a potential anti-human coronaviral agent</strong> - Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan-coronaviral agents by targeting…</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 Nsp1 mediated mRNA degradation requires mRNA interaction with the ribosome</strong> - Nsp1 is a SARS-CoV-2 host shutoff factor that both represses cellular translation and promotes host RNA decay. However, it is unclear how these two activities are connected and interact with normal translation processes. Here, we performed mutational analyses of Nsp1, and these revealed that both the N and C terminal domains of Nsp1 are important for translational repression. Furthermore, we demonstrate that specific residues in the N terminal domain are required for cellular RNA degradation but…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing Polyether Ionophores as a New-Class of Anti-SARS-Cov-2 Agents as Adjunct Therapy</strong> - The emergence of SARS-CoV-2 and its variants have posed a significant threat to humankind in tackling the viral spread. Furthermore, currently repurposed drugs and frontline antiviral agents have failed to cure severe ongoing infections effectively. This insufficiency has fuelled research for potent and safe therapeutic agents to treat COVID-19. Nonetheless, various vaccine candidates have displayed a differential efficacy and need for repetitive dosing. The FDA-approved polyether ionophore…</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>Prolonged Exposure to Remdesivir Inhibits the Human Ether-A-Go-Go-Related Gene Potassium Current</strong> - Remdesivir, approved for the treatment of coronavirus disease (COVID-19), has been associated with QTc interval prolongation and torsade de pointes (TdP) in case reports. However, data are conflicting regarding the ability of remdesivir to inhibit the human ether-a-go-go-related (hERG)-related current. The objective of this study was to investigate the effects remdesivir and its primary metabolite, GS-441524, on hERG-related currents. Human embryonic kidney (HEK 293) cells stably expressing hERG…</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 KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression</strong> - Identification of host determinants of coronavirus infection informs mechanisms of pathogenesis and may provide novel therapeutic targets. Here, we demonstrate that the histone demethylase KDM6A promotes infection of diverse coronaviruses, including SARS-CoV, SARS-CoV-2, MERS-CoV and mouse hepatitis virus (MHV) in a demethylase activity-independent manner. Mechanistic studies reveal that KDM6A promotes viral entry by regulating expression of multiple coronavirus receptors, including ACE2, DPP4…</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>Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals</strong> - The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid protein….</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>Conformational response to ligand binding of TMPRSS2, a protease involved in SARS-CoV-2 infection: Insights through computational modeling</strong> - Thanks to the considerable research which has been undertaken in the last few years to improve our understanding of the biology and mechanism of action of SARS-CoV-2, we know how the virus uses its surface spike protein to infect host cells. The transmembrane prosthesis, serine 2 (TMPRSS2) protein, located on the surface of human cells, recognizes the cleavage site in the spike protein, leading to the release of the fusion peptide and entry of the virus into the host cells. Because of its role,…</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>Respiratory infections in children and adolescents in Germany during the COVID-19 pandemic</strong> - CONCLUSIONS: While the measures taken were effective in inhibiting the number of respiratory infections for almost 1.5 years, moderately frequent but rather mild COVID-19 cases occurred when measures were lifted. When Omicron emerged in 2022 COVID-19 became moderately frequent but led predominantly to mild illnesses. For RSV and influenza, the measures resulted in changes in their annual timing and intensity.</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>Maternal prenatal attachment during the COVID-19 pandemic: exploring the roles of pregnancy-related anxiety, risk perception, and well-being</strong> - Pregnant women have faced novel physical and mental health risks during the pandemic. This situation is remarkable because a parent’s emotional bond with their unborn baby (also known as prenatal attachment) is related to the parent’s mental state. Prenatal attachment helps parents psychologically prepare for the transition into parenthood. Moreover, it plays a pivotal role in the future parentchild relationship and psychosocial development of the baby. Based on the available literature, 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>Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants</strong> - SARS-CoV-2 poses an unprecedented threat to the world as the causative agent of the COVID-19 pandemic. Among a handful of therapeutics developed for the prevention and treatment of SARS-CoV-2 infection, ensitrelvir is the first noncovalent and nonpeptide oral inhibitor targeting the main protease (M^(pro)) of SARS-CoV-2, which recently received emergency regulatory approval in Japan. Here we determined a 1.8-Å structure of M^(pro) in complex with ensitrelvir, which revealed that ensitrelvir…</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>Intranasal VLP-RBD vaccine adjuvanted with BECC470 confers immunity against Delta SARS-CoV-2 challenge in K18-hACE2-mice</strong> - As the COVID-19 pandemic transitions into endemicity, seasonal boosters are a plausible reality across the globe. We hypothesize that intranasal vaccines can provide better protection against asymptomatic infections and more transmissible variants of SARS-CoV-2. To formulate a protective intranasal vaccine, we utilized a VLP-based platform. Hepatitis B surface antigen-based virus like particles (VLP) linked with receptor binding domain (RBD) antigen were paired with the TLR4-based 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>Synthesis and characterization of n-phosphonium chitosan and its virucidal activity evaluation against coronavirus</strong> - Despite the worldwide vaccination effort against COVID-19, the demand for biocidal materials has increased. One promising solution is the chemical modification of polysaccharides, such as chitosan, which can provide antiviral activity through the insertion of cationic terminals. In this study, chitosan was modified with (4-carboxybutyl) triphenylphosphonium bromide to create N-phosphonium chitosan (NPCS), a quaternized derivative. The resulting NPCS samples with three degrees of substitution…</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 receptor tyrosine kinase inhibitor CP-724714 inhibits SADS-CoV related swine diarrhea coronaviruses infection in vitro</strong> - The outbreak of the COVID-19 epidemic in 2020 has caused unprecedented panic among all mankind, pointing the major importance of effective treatment. Since the emergence of the swine acute diarrhea syndrome coronavirus (SADS-CoV) at the end of 2017, multiple reports have indicated that the bat-related SADS-CoV possesses a potential threat for cross-species transmission. Vaccines and antiviral drugs development deserve more attention. In this study, we found that the HER2 phosphorylation…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<script>AOS.init();</script></body></html>
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