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192 lines
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<title>10 September, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Recognition and Cleavage of Human tRNA Methyltransferase TRMT1 by the SARS-CoV-2 Main Protease</strong> -
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The SARS-CoV-2 main protease (Mpro) plays a crucial role in the production of functional viral proteins during infection and, like many viral proteases, can also target and cleave host proteins to subvert their cellular functions. Here, we show that the human tRNA methyltransferase TRMT1 can be recognized and cleaved by SARS-CoV-2 Mpro. TRMT1 installs the N2,N2-dimethylguanosine (m2,2G) modification at the G26 position of mammalian tRNA, which promotes global protein synthesis, cellular redox homeostasis, and has links to neurological disability. We find that Mpro can cleave endogenous TRMT1 in human cell lysate, resulting in removal of the TRMT1 zinc finger domain that is required for tRNA modification activity in cells. Evolutionary analysis shows that the TRMT1 cleavage site is highly conserved in mammals, except in Muroidea, where TRMT1 may be resistant to cleavage. In primates, regions outside of the cleavage site with rapid evolution could indicate possible adaptation to ancient viral pathogens. To visualize how Mpro recognizes the TRMT1 cleavage sequence, we determined the structure of a TRMT1 peptide in complex with Mpro, which reveals a substrate binding conformation distinct from the majority of available SARS-CoV-2 Mpro-peptide complexes. Kinetic parameters for peptide cleavage showed that while TRMT1(526-536) is cleaved much slower than the Mpro nsp4/5 autoprocessing sequence, it is proteolyzed with comparable efficiency to the Mpro-targeted nsp8/9 viral cleavage site. Mutagenesis studies and molecular dynamics simulations together indicate that kinetic discrimination occurs during a later step of Mpro-mediated proteolysis that follows substrate binding. Our results provide new information about the structural basis for Mpro substrate recognition and cleavage that could help inform future therapeutic design and raise the possibility that proteolysis of human TRMT1 during SARS-CoV-2 infection may impact protein translation or oxidative stress response and contribute to viral pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.20.529306v3" target="_blank">Recognition and Cleavage of Human tRNA Methyltransferase TRMT1 by the SARS-CoV-2 Main Protease</a>
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</div></li>
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<li><strong>Partial Face Visibility and Facial Cognition: An Electroencephalography and Eye-Tracking Investigation</strong> -
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<div>
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Face masks became a part of everyday life in the SARS-CoV-2 pandemic. Previous studies showed that the face cognition mechanism involves holistic face processing, and the absence of face features could lower cognition ability. This is opposed to the experience during the pandemic, when people were able to correctly recognize faces, although the mask covered a part of the face. This paper shows a strong correlation in face cognition based on the EEG and eye-tracking data between the full and partial faces. We observed two event-related potentials, P3a in the frontal lobe and P3b in the parietal lobe, as subcomponents of P300. Both P3a and P3b were lowered when the eyes were invisible, and P3a evoked by the nose covered was larger than the full face. The eye-tracking data showed that 16 out of 18 participants focused on the eyes associated with the EEG results. Our results demonstrate that the eyes are the most crucial feature of facial cognition. Moreover, the face with the nose covered might enhance cognition ability due to the visual working memory capacity. Our experiment shows the possibility of people recognizing faces using both holistic face processing and structural face processing. Furthermore, people can recognize the masked face as well as the full face in similar cognition patterns due to the high correlation in the cognition mechanism.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.07.556282v1" target="_blank">Partial Face Visibility and Facial Cognition: An Electroencephalography and Eye-Tracking Investigation</a>
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</div></li>
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<li><strong>Prevalence and predictors of self-medication for COVID-19 among slum dwellers in Jinja City, Uganda</strong> -
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Introduction: Self-medication is a serious public health concern globally and is more prevalent in underserved populations, especially in resource limited settings. The lack of effective treatment for COVID-19 and poor access to healthcare were drivers of self-medication. We investigated the prevalence and associated factors with self-medication for COVID-19 among slum dwellers in a Ugandan slum. Methods and materials: We conducted a cross-sectional study using randomly selected respondents from slums in Jinja city, Uganda. Households were proportionately selected from the slums and one participant with confirmed or self-reported COVID-19 during 2021 was recruited. Poisson regression with robust standard errors was used to determine the crude (CPR) and adjusted prevalence ratios (APR) (95% CI) of factors associated with self-medication. Variables were selected apriori and backward elimination approach used to fit the final multivariate model in which variables with a P≤ 0.05 were included. Results: Overall, 517 respondents were recruited, median age (years) was 31 (26-40), and 59% were male. The prevalence of self-medication for COVID-19 was 87.23% (451/517), 95% CI: [84.00%-90.00%] and 56% knew that self-medication was dangerous. Age≥50 years, compared to 20-29 years [APR: 1.12, 95% CI:1.05, 1.20], being female [APR: 1.07, 95% CI: 1.02, 1.13], minor [APR: 1.62, 95% CI: 1.25, 2.11], and severe symptoms [APR: 1.51, 95% CI: 1.16, 1.96], access to internet [APR: 1.13, 95% CI: 1.07, 1.20]. Having medical insurance [APR: 0.63, 95% CI: 0.46, 0.87] and awareness about laws against self-medication [APR: 0.89, 95% CI: 0.81, 0.97] were associated with a lower risk of self-medication. Conclusion: The prevalence of self-medication in slum dwellers in Uganda was high despite high awareness about its dangers. Self-medication was common in those with severe symptoms and those access to internet. There is need to control infodemia and improve health insurance cover in informal settlements within Uganda.
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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/10.1101/2023.09.08.23295267v1" target="_blank">Prevalence and predictors of self-medication for COVID-19 among slum dwellers in Jinja City, Uganda</a>
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<li><strong>Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant</strong> -
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Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the first isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. BA.2.86 did not have significantly more escape than Omicron XBB.1.5 from neutralizing immunity elicited by infection of Omicron subvariants ranging from BA.1 to XBB, either by infection alone or as breakthrough infection in vaccinated individuals. Neutralization escape was present relative to earlier strains: BA.2.86 showed extensive escape both relative to ancestral virus in sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 in sera from Omicron BA.1 infected individuals. We did not observe substantial differences in viral properties in cell culture relative to XBB.1.5. Both BA.2.86 and XBB.1.5 produced infection foci of similar size, had similar cytopathic effect (both lower than ancestral SARS-CoV-2), and had similar replication dynamics. We also investigated the relationship of BA.2.86 to BA.2 sequences and found that the closest were BA.2 samples from Southern Africa circulating in early 2022. These observations suggest that BA.2.86 is more closely related to sequences from Southern Africa than other regions and so may have evolved there, and that evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295250v1" target="_blank">Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant</a>
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<li><strong>How immunity shapes the long-term dynamics of seasonal influenza</strong> -
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Since its emergence in 1968, influenza A H3N2 has caused yearly epidemics in temperate regions. While infection confers immunity against antigenically similar strains, new antigenically distinct strains that evade existing immunity regularly emerge (9antigenic drift9). Immunity at the individual level is complex, depending on an individual9s lifetime infection history. An individual9s first infection with influenza typically elicits the greatest response with subsequent infections eliciting progressively reduced responses (9antigenic seniority9). The combined effect of individual-level immune responses and antigenic drift on the epidemiological dynamics of influenza are not well understood. Here we develop an integrated modelling framework of influenza transmission, immunity, and antigenic drift to show how individual-level exposure, and the build-up of population level immunity, shape the long-term epidemiological dynamics of H3N2. Including antigenic seniority in the model, we observe that following an initial decline after the pandemic year, the average annual attack rate increases over the next 80 years, before reaching an equilibrium, with greater increases in older age-groups. Our analyses suggest that the average attack rate of H3N2 is still in a growth phase. Further increases, particularly in the elderly, may be expected in coming decades, driving an increase in healthcare demand due to H3N2 infections. We anticipate our findings and methodological developments will be applicable to other antigenically variable pathogens. This includes the recent pandemic pathogens influenza A H1N1pdm09, circulating since 2009, and SARS-CoV-2, circulating since 2019. Our findings highlight that following the short-term reduction in attack rates after a pandemic, if there is any degree of antigenic seniority then a resurgence in attack rates should be expected over the longer-term. Designing and implementing studies to assess the dynamics of immunity for H1N1pdm09, SARS-CoV-2, and other antigenically variable pathogens may help anticipate any long-term rises in infection and health burden.
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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/10.1101/2023.09.08.23295244v1" target="_blank">How immunity shapes the long-term dynamics of seasonal influenza</a>
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<li><strong>Disease trajectories in hospitalized COVID-19 patients are predicted by clinical and peripheral blood signatures representing distinct lung pathologies.</strong> -
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Linking clinical biomarkers and lung pathology still is necessary to understand COVID-19 pathogenesis and the basis of progression to lethal outcomes. Resolving these knowledge gaps enables optimal treatment approaches of severe COVID-19. We present an integrated analysis of longitudinal clinical parameters, blood biomarkers and lung pathology in COVID-19 patients from the Brazilian Amazon. We identified core signatures differentiating severe recovered patients and fatal cases with distinct disease trajectories. Progression to early death was characterized by rapid and intense endothelial and myeloid activation, presence of thrombi, mostly driven by SARS-CoV-2 + macrophages. Progression to late death was associated with systemic cytotoxicity, interferon and Th17 signatures and fibrosis, apoptosis, and abundant SARS-CoV-2 + epithelial cells in the lung. Progression to recovery was associated with pro-lymphogenic and Th2-mediated responses. Integration of antemortem clinical and blood biomarkers with post-mortem lung-specific signatures defined predictors of disease progression, identifying potential targets for more precise and effective treatments.
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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/10.1101/2023.09.08.23295024v1" target="_blank">Disease trajectories in hospitalized COVID-19 patients are predicted by clinical and peripheral blood signatures representing distinct lung pathologies.</a>
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</div></li>
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<li><strong>SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression</strong> -
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<div>
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The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556788v1" target="_blank">SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression</a>
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<li><strong>Early combination with remdesivir, nirmatrelvir/ritonavir and sotrovimab for the treatment of COVID-19 in immunocompromised hosts</strong> -
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Background: Immunocompromised patients with COVID-19 have higher morbidity and mortality than general population. Some authors have successfully used antiviral combination, but never in the early phase of the infection. Methods: Retrospective cohort study to describe efficacy and safety of the combination of 2 antivirals, with or without a mAb, both in early (within 10 days from symptoms) and in later phase (after 10 days) of SARS-CoV-2 infection in immunocompromised patients admitted to our facility. Results: We treated 11 patients (7 in early phase and 4 in later phase of COVID-19) with 10 days of intravenous remdesivir plus 5 days of oral nirmatelvir/ritonavir, also combined with sotrovimab in 10/11 cases. Notably, 100% of the <early> patients reached virological clearance at day 30 from the end of the therapy and were alive and well at follow-up, whereas corresponding figures in the <late> patients were 50% and 75%. Patients in late group more frequently needed oxygen supplementation (p=0.015) and steroid therapy (p=0.045) during admission and reached higher a COVID-19 severity (p=0.017). Discussion: The combination of antiviral and sotrovimab in early phase of COVID-19 in immunocompromised patients is well tolerated and associated with 100% of virological clearance. Patients treated later have lower response rate and higher disease severity, but a causative role of the therapy in such finding is yet to be demonstrated.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295202v1" target="_blank">Early combination with remdesivir, nirmatrelvir/ritonavir and sotrovimab for the treatment of COVID-19 in immunocompromised hosts</a>
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<li><strong>Uncovering the implications of IFN-I in severe COVID-19 neutrophil inflammasome</strong> -
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Excessive inflammation defines COVID-19 pathophysiology. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation. We conducted transcriptomic profiling of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, which revealed a pronounced type I interferon (IFN-I) gene signature in severe COVID-19, compared to mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 did not exhibit this signature and displayed a distinct immature neutrophil phenotype. PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation but reduced responsiveness to exogenous inflammasome priming. Interestingly, while mature neutrophils efficiently released IL-1? upon inflammasome activation, they were poor producers of IL-18. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes, which was confirmed in a COVID-19 mouse model. Overall, these findings underscore the crucial role of neutrophil inflammasomes in driving inflammation during severe COVID-19 and opens promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295190v1" target="_blank">Uncovering the implications of IFN-I in severe COVID-19 neutrophil inflammasome</a>
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<li><strong>Comparison of Different PCR Methods for the Detection of SARS-CoV-2 RNA in Wastewater Based on the Reported Incidence of COVID-19 in Finland</strong> -
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The spatial and temporal changes of the COVID–19 pandemic have been monitored with wastewater–based surveillance, which many countries have applied to their national public health monitoring measures. The most commonly used methods for the detection of SARS–CoV–2 in wastewater are RT–qPCR and RT–ddPCR. Previous comparisons of the two methods have produced conflicting results; some found RT–ddPCR to be more sensitive, one found RT–qPCR to be more sensitive, and others found them to be equal in sensitivity. This research was conducted to further study these two methods as well as two different RNA extraction methodologies and gene assays for the detection of SARS–CoV–2 in wastewater. We compared two RT–qPCR kits and RT–ddPCR based on sensitivity, variability, and the correlation of SARS–CoV–2 gene copy numbers in wastewater with the incidence of COVID–19. Our results indicate that the most sensitive and low–variance method to detect SARS–CoV–2 in wastewater was RT–ddPCR. However, we obtained the best correlation between COVID-19 incidence and SARS–CoV–2 gene copy number in wastewater using RT–qPCR (CC = 0.697, p < 0.001). We found a significant difference in sensitivity between the two RT–qPCR kits, one having a significantly lower limit of detection and a higher percentage of positive samples than the other. Furthermore, the CDC N1 primers and probe were the most sensitive for both RT–qPCR kits, while there was no significant difference between the tested gene targets using RT–ddPCR. For the most sensitive RT–qPCR, the use of different RNA extraction kits affected the result. All methods showed a trend between COVID–19 incidence and SARS–CoV–2 gene copy numbers in wastewater. In addition, we tested an isothermal amplification method for the detection of SARS–CoV–2 RNA in wastewater. It proved to be a viable option if results are expected quickly, resources are limited, and presence–absence information is sufficient.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295183v1" target="_blank">Comparison of Different PCR Methods for the Detection of SARS-CoV-2 RNA in Wastewater Based on the Reported Incidence of COVID-19 in Finland</a>
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<li><strong>Effectiveness of BNT162b2 COVID-19 Vaccination in Children Aged 5–17 Years in the United States</strong> -
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Importance: COVID–19 vaccines are authorized for use in children in the United States; real–world assessment of vaccine effectiveness in children is needed. Objective: To estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer–BioNTech) COVID-19 vaccine in US children. Design: A cohort study of children aged 5—17 years vaccinated with BNT162b2 matched with unvaccinated children. Setting: Participants identified in Optum and CVS Health insurance administrative claims databases were linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Participants: Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Exposure: BNT162b2 vaccinations were identified using IIS vaccination records and insurance claims. Main Outcomes and Measures: Two COVID–19 outcome definitions were evaluated: COVID–19 diagnosis in any medical setting and COVID–19 diagnosis in hospitals/emergency departments (EDs). Propensity score–weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant–specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results: There were 453,655 eligible vaccinated children one–to–one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person– years; CVS Health, 44.1 per 10,000 person– years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID–19 (meta–analyzed VE = 38% [95% CI, 36%–40%]) and hospital/ED–diagnosed COVID-19 (meta–analyzed VE = 61% [95% CI, 56%–65%]). VE estimates were lowest among children 5—11 years and during the omicron variant era. Conclusions and Relevance: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID–19 and hospital/ED–diagnosed COVID–19 in children; observed VE estimates differed by age group and variant era.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.06.23294426v1" target="_blank">Effectiveness of BNT162b2 COVID-19 Vaccination in Children Aged 5–17 Years in the United States</a>
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<li><strong>Effect of the 2022 COVID-19 booster vaccination campaign in 50 year olds in England: regression discontinuity analysis in OpenSAFELY</strong> -
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Background: SARS-CoV-2 vaccines are highly effective in preventing severe COVID-19 but require boosting to maintain protection. Changes to circulating variants and prevalent natural immunity may impact on real-world effectiveness of boosters in different time periods and in different populations. Methods: With NHS England approval, we used linked routine clinical data from >24 million patients to evaluate the effectiveness of the 2022 combined COVID-19 autumn booster and influenza vaccine campaign in non-clinically vulnerable 50-year-olds in England using a regression discontinuity design. Our primary outcome was a composite of 6-week COVID-19 emergency attendance, COVID-19 unplanned hospitalisation, or death. The secondary outcomes were: respiratory hospitalisations or death; any unplanned hospitalisation; and any death. Results: Our study included 1,917,375 people aged 45-54 years with no evidence of being in a high-risk group prioritised for vaccination. By 26 November 2022, booster vaccine coverage was 11.1% at age 49.75 years increasing to 39.7% at age 50.25 years. The estimated effect of the campaign on the risk of the primary outcome in 50-year-olds during weeks 7-12 after the campaign start was -0.4 per 100,000 (95% CI -7.8, 7.1). For the secondary outcomes the estimated effects were: -0.6 per 100,000 (95%CI -13.5, 12.3) for respiratory outcomes; 5.0 per 100,000 (95%CI -40.7, 50.8) for unplanned hospitalisations; and 3.0 per 100,000 (95%CI -2.7, 8.6) for any death. The results were similar when using different follow-up start dates, different bandwidths, or when estimating the effect of vaccination (rather than the campaign). Conclusion: This study found little evidence that the autumn 2022 vaccination campaign in England was associated with a reduction in severe COVID-19-related outcomes among non-clinically vulnerable 50-year-olds. Possible explanations include the low risk of severe outcomes due to substantial pre-existing vaccine- and infection-induced immunity. Modest booster coverage reduced the precision with which we could estimate effectiveness. The booster campaign may have had effects beyond those estimated, including reducing virus transmission and incidence of mild or moderate COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295194v1" target="_blank">Effect of the 2022 COVID-19 booster vaccination campaign in 50 year olds in England: regression discontinuity analysis in OpenSAFELY</a>
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<li><strong>Epidemiological insight into the possible drivers of Lassa fever in an endemic area of Southwestern Nigeria from 2017 and 2021</strong> -
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Background Lassa fever (LF) is a viral disease transmitted between animals and humans, commonly found in West Africa, including Nigeria. The region experiences an estimated annual total of about 2 million LF cases in humans, leading to 5,000 to 10,000 deaths. Strikingly, up to 80% of LF-infected individuals show no symptoms, making its true incidence hard to determine in endemic populations. We investigated LF distribution, mortality, survival patterns, and contributing factors during a local outbreak in Nigeria, from 2017 to 2021. Method Data from the Integrated Disease Surveillance and Response weekly line list for 2017 to 2021 were extracted. The survival pattern of LF patients was visualized with the Kaplan-Meier curve, binary logistic regression model was employed to explore LF-associated factors and level of statistical significance (α) was set at 5%. Result Overall, 4,554 participants were recruited between 2017 and 2021. Their average age varied from 31.82 ± 20.0 to 37.85 ± 17.89. LF-positive patients decreased from 26.9% in 2017 to 17.7% in 2021, paralleling the mortality trend. In 2021, patient survival ranged from 5 to 30 days. Male patients had lower survival odds in the initial 10 days of hospitalization, improved chances from days 10 to 20, and reduced probabilities beyond day 20. Residence location and age were significant factors (p<0.05) associated with LF in Ondo State. Conclusion The decline in LF cases in 2021 could be attributed to the ongoing intervention by Nigerian Centre for Disease Control or the disruption caused by the COVID-19 pandemic in 2020. To address LF challenges in hotspot areas, we propose Community Action Networks that would operate using the One Health approach involving local stakeholders sustainably to promote Early Warning/Early Response system in high-risk settings and mitigate LF-related issues.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.06.23295111v1" target="_blank">Epidemiological insight into the possible drivers of Lassa fever in an endemic area of Southwestern Nigeria from 2017 and 2021</a>
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<li><strong>Predictors of SARS-CoV-2 anti-Spike IgG antibody levels following two COVID-19 vaccine doses among children and adults in the Canadian CHILD Cohort</strong> -
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Background: Vaccination helps prevent SARS-CoV-2 infection and severe COVID-19. However, vaccine-induced humoral immune responses vary among individuals and wane over time. We aimed to describe the SARS-CoV-2 anti-spike IgG antibody response to vaccination and identify health and demographic factors associated with this response among children and adults. Methods: We studied a subset of double-vaccinated children (n= 151; mean age: 12 ±1.5 years, 46% female) and adults (n= 995; 44 ±6.0 years, 60% female) from the Canadian CHILD Cohort. Dried blood spots were collected over two time periods (March 2021 to September 2021; October 2021 to January 2022). Antibody levels were quantified using automated chemiluminescent ELISAs. Demographic, vaccination, and health data were collected via online questionnaires. Associations were determined using multivariable regression. Results: Our cohort had SARS-CoV-2 anti-spike seropositivity rate of 97% following two COVID-19 vaccine doses. In both children and adults, the highest antibody levels were observed around three months post-vaccination and did not differ by biological sex. Higher antibody levels were associated with: prior SARS-CoV-2 infection (β=0.15 scaled luminescence units, 95%CI, 0.06-0.24), age <18 years (β=0.15, 95%CI 0.05-0.26) and receiving the Moderna mRNA (β=0.23, 95%CI 0.11-0.34) or Pfizer-BioNTech mRNA vaccines (β= 0.10, 95%CI, 0.02-0.18) vs. a combination of mRNA and Oxford-AstraZeneca viral vector vaccines. There were no differences in antibody levels when comparing a 3-8 vs. 9-16-week interval between vaccine doses. Interpretation: We identified key factors associated with post-vaccination antibody responses in children and adults, which could help improve future vaccine development and deployment among different population subgroups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.06.23294696v1" target="_blank">Predictors of SARS-CoV-2 anti-Spike IgG antibody levels following two COVID-19 vaccine doses among children and adults in the Canadian CHILD Cohort</a>
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<li><strong>Computational Methods for Characterizing Research Outputs, Collaborative Networks and Thematic Concentration: a Case Study in Primary Care Research Evaluation</strong> -
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Objective: Research impact is difficult to measure, evaluate and report. This study aims to demonstrate how computational scientometric methods, including bibliometric, network analytic, and thematic summary measures can efficiently characterize complex scientific disciplines, such as primary care research. Methods: We used a retrospective cohort design. The study included N=17 international academic primary care research departments. A scientometric database was curated using a bottom-up methodology, which included peer-reviewed research articles/reviews, and associated meta-data, published between 01/01/2017 and 31/12/2022. Publication-level bibliometric information was queried from the Scopus application programming interface (API). The Altmetrics API was used to extract publication-level indicators of social engagement. Network analytic visualizations and statistics characterized research collaboration. Topic models and keyword mining characterized the main thematic areas of primary care research. At an author-level, we investigated correlations between bibliometric, altmetric, network analytic and topical summary measures. Results: Our analysis included N=591 primary care researchers (from 17 institutions) who produced 13,047 unique peer-reviewed articles over the study timeframe. These 13,047 research articles were published in 2,237 unique journal titles; cited 231,121 times; and received broad social uptake (605,349 Twitter tweets, 36,982 mainstream media mentions, 884 Wikipedia references, and 1,127 policy document citations). The 591 researchers collaborated with 35,585 unique co-authors resulting in 20,808,886 pair-wise collaborations. The median number of authors per publication was 7 (IQR: 4-10; min=1; max=3,391). Frequently occurring keywords/n-grams and latent topical vectors, highlighted the diversity of primary care research. Clinical research themes included: physical/mental health conditions, disease prevention and screening, issues in primary/obstetric/emergency/palliative-care, and public health. Methodological research themes included: research synthesis/appraisal, statistical/epidemiological inference, study design, qualitative research, mixed methods, health economics, medical education, and quality improvement. Many themes were stable over the study timeframe. COVID-19 emerged as an important research theme from 2020 through 2022. Topic vectors encoding clinical medicine were positively correlated with bibliometric, altmetric and network centrality measures, whereas, vectors encoding qualitative methods, medical education, and public health were negatively correlated with these same metrics. Conclusions: Multi-metric, computational scientometric methods offer an efficient, transparent, and reproducible means for characterizing the research output of complex scientific disciplines, such as primary care research.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295220v1" target="_blank">Computational Methods for Characterizing Research Outputs, Collaborative Networks and Thematic Concentration: a Case Study in Primary Care Research Evaluation</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<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>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>: University of Witten/Herdecke; Institut für Rehabilitationsforschung Norderney<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>: Immunosuppression; COVID-19<br/><b>Intervention</b>: Biological: NVX-CoV2372<br/><b>Sponsors</b>: University of Wisconsin, Madison; 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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<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>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH)<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>Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition</strong> - <b>Condition</b>: Cognitive Behavioral Therapy<br/><b>Intervention</b>: Behavioral: cognitive behavioral therapy<br/><b>Sponsor</b>: Tri-Service General Hospital<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 Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<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>Pre-probiotic Supplementation for Post-covid Fatigue Syndrome</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Dietary Supplement: Dietary Supplement: Experimental; Dietary Supplement: Dietary Supplement: Placebo<br/><b>Sponsor</b>: University of Novi Sad, Faculty of Sport and Physical Education<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>Long COVID Immune Profiling</strong> - <b>Conditions</b>: Long COVID; POTS - Postural Orthostatic Tachycardia Syndrome; Autonomic Dysfunction<br/><b>Interventions</b>: Diagnostic Test: IL-6; Diagnostic Test: cytokines (IL-17, and IFN-ɣ); Behavioral: Compass 31<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis<br/><b>Intervention</b>: Behavioral: Fermented Food Diet<br/><b>Sponsor</b>: Mayo Clinic<br/><b>Not yet 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>Nirmatrelvir/ritonavir-induced elevation of blood tacrolimus levels in a patient in the maintenance phase post liver transplantation</strong> - Nirmatrelvir is an orally administered anti-SARS-CoV-2 drug used in combination with ritonavir, the drug-metabolizing cytochrome P450 (CYP) 3A inhibitor, to evade metabolism and extend bioavailability. Meanwhile, the immunosuppressant tacrolimus is a CYP3A4/5 substrate, and CYP3A inhibition results in drug-drug interactions. Herein, we report the case of a coronavirus disease 19 (COVID-19) patient in the maintenance phase post liver transplantation, receiving tacrolimus treatment, with a marked…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparison of Zinc Oxide Nanoparticle Integration into Non-Woven Fabrics Using Different Functionalisation Methods for Prospective Application as Active Facemasks</strong> - The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP…</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>Membrane-Targeting Perylenylethynylphenols Inactivate Medically Important Coronaviruses via the Singlet Oxygen Photogeneration Mechanism</strong> - Perylenylethynyl derivatives have been recognized as broad-spectrum antivirals that target the lipid envelope of enveloped viruses. In this study, we present novel perylenylethynylphenols that exhibit nanomolar or submicromolar antiviral activity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and feline infectious peritonitis virus (FIPV) in vitro. Perylenylethynylphenols incorporate into viral and cellular membranes and block the entry of the virus into the host cell….</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>Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?</strong> - Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with 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>Small Molecules Targeting Viral RNA</strong> - The majority of antivirals available target viral proteins; however, RNA is emerging as a new and promising antiviral target due to the presence of highly structured RNA in viral genomes fundamental for their replication cycle. Here, we discuss methods for the identification of RNA-targeting compounds, starting from the determination of RNA structures either from purified RNA or in living cells, followed by in silico screening on RNA and phenotypic assays to evaluate viral inhibition. Moreover,…</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>Screening, Synthesis and Biochemical Characterization of SARS-CoV-2 Protease Inhibitors</strong> - The severe acute respiratory syndrome-causing coronavirus 2 (SARS-CoV-2) papain-like protease (PL^(pro)) and main protease (M^(pro)) play an important role in viral replication events and are important targets for anti-coronavirus drug discovery. In search of these protease inhibitors, we screened a library of 1300 compounds using a fluorescence thermal shift assay (FTSA) and identified 53 hits that thermally stabilized or destabilized PL^(pro). The hit compounds structurally belonged to two…</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 Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19</strong> - Thymalin is an immunomodulatory drug containing a polypeptide extract of thymus that has demonstrated efficacy in the therapy of acute respiratory distress syndrome and chronic obstructive pulmonary disease, as well as in complex therapy related to severe COVID-19 in middle-aged and elderly patients.. KE and EW dipeptides are active substances of Thymalin. There is evidence that KE stimulates cellular immunity and nonspecific resistance in organisms, exerting an activating effect on macrophages,…</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>Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants</strong> - The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown…</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>Nano-Enabled Antivirals for Overcoming Antibody Escaped Mutations Based SARS-CoV-2 Waves</strong> - This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology 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>Macrophage-Derived Chemokine MDC/CCL22: An Ambiguous Finding in COVID-19</strong> - Macrophage-derived chemokine (MDC/CCL22) is a chemokine of the C-C subfamily. It is involved in T-cellular maturation and migration. Our previous research shows that plasma CCL22/MDC tends to show a statistically significant depletion of concentrations in acute patients and convalescents when compared to healthy donors. In the current work, we investigate existing views on MDC/CCL22 dynamics in association with various pathologies, including respiratory diseases and, specifically, COVID-19….</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>USE OF RECOMBINANT S1 PROTEIN WITH hFc FOR ANALYSIS OF SARS-COV-2 ADSORPTION AND EVALUATION OF DRUGS THAT INHIBIT ENTRY INTO VERO E6 CELLS</strong> - The significant number of deaths and cases of infection by the new coronavirus SARS-CoV-2 requires an urgent demand for effective and available drugs for the treatment of COVID-19.However, the need for biosafety level 3 (NB-3) laboratories for experiments with the virus has made it very difficult for such research to meet this demand. It is known that angiotensin-converting enzyme 2 (ACE2), located on the surface of host cells, is the viral receptor for the spike (S) protein of SARS-CoV-2. This…</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 of new non-covalent and covalent inhibitors targeting SARS-CoV-2 papain-like protease and main protease</strong> - Global coronavirus disease 2019 (COVID-19) pandemic still threatens human health and public safety, and the development of effective antiviral agent is urgently needed. The SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) are vital proteins in viral replication and promising therapeutic targets. Additionally, PLpro also modulates host immune response by cleaving ubiquitin and interferon-stimulated gene product 15 (ISG15) from ISGylated host proteins. In this report, we identified…</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>Broad-Spectrum Antiviral Effect of Cannabidiol Against Enveloped and Nonenveloped Viruses</strong> - Introduction: Cannabidiol (CBD), the main non-psychoactive cannabinoid of the Cannabis sativa plant, is a powerful antioxidant compound that in recent years has increased interest due to causes effects in a wide range of biological functions. Zika virus (ZIKV) is a virus transmitted mainly by the Aedes aegypti mosquitoes, which causes neurological diseases, such as microcephaly and Guillain-Barre syndrome. Although the frequency of viral outbreaks has increased recently, no vaccinations or…</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 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-β and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by…</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>Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19</strong> - CONCLUSION: High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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