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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>06 May, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique</strong> -
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A novel coronavirus (2019-nCoV) or Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that affects humans has been discovered in Wuhan, China, in 2019. Its genome has been sequenced, and the genetic data was quickly made public. We discovered a novel proprotein convertase subtilisin kexin-9 ( PCSK9) cleavage site in the Spike protein of the 2019-nCoV. The recent research also demonstrates that the previously found proprotein convertase 3 (PC3) or furin cleavage site, which was assumed to be unique, is already present in animal corona viruses. In this article, we suggest that the combination of the both proprotein convertase PC3 cleavage site and the PCSK9 site renders SARS-CoV-2 unique in terms of the pathogenicity, potential functional effects, and implications for the development of antiviral drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.04.539453v1" target="_blank">An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique</a>
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<li><strong>Paired associated SARS-CoV-2 spike variable positions: a network analysis approach to emerging variants</strong> -
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Amino acids in variable positions of proteins may be correlated, with potential structural and functional implications. Here, we apply exact tests of independence in R x C contingency tables to examine noise-free associations between variable positions of the SARS-CoV-2 spike protein, using as a paradigm sequences from Greece deposited in GISAID (N=6,683/1,078 full-length) for the period February 29, 2020 to April 26, 2021 that essentially covers the first three pandemic waves. We examine the fate and complexity of these associations by network analysis, using associated positions (exact p[≤]0.001 and Average Product Correction [≥]2) as links and the corresponding positions as nodes . We found a temporal linear increase of positional differences and a gradual expansion of the number of position associations over time, represented by a temporally evolving intricate web, resulting in a non-random complex network of 69 nodes and 252 links. Overconnected nodes corresponded to the most adapted variant positions in the population, suggesting a direct relation between network degree and position functional importance. Modular analysis revealed 25 k-cliques comprising three to 11 nodes. At different k-clique resolutions, one to four communities were formed, capturing epistatic associations of circulating variants (Alpha, Beta, B.1.1.318), but also Delta, which dominated the evolutionary landscape later in the pandemic. Cliques of aminoacidic positional associations tended to occur in single sequences, enabling the recognition of epistatic positions in real-world virus populations. Our findings provide a novel way of understanding epistatic relationships in viral proteins with potential applications in the design of virus control procedures.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.04.539462v1" target="_blank">Paired associated SARS-CoV-2 spike variable positions: a network analysis approach to emerging variants</a>
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<li><strong>The plasma metabolome of long COVID-19 patients two years after infection</strong> -
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Background: One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as long COVID) which has emerged as a consequence of the SARS-CoV-2 epidemic. The World Health Organization (WHO) recognized long COVID as a distinct clinical entity in 2021. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. This has put a tremendous strain on still-overstretched healthcare systems around the world. Methods: In this study, our goal was to assess the plasma metabolome in a total of 108 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin concentrations were measured in long COVID patients by immunoenzymatic assay. Results: The comparison of paired COVID-19/post-COVID-19 samples revealed 53 metabolites that were statistically different (FDR < 0.05). Compared to controls, 29 metabolites remained dysregulated even after two years. Notably, glucose, kynurenine, and certain acylcarnitines continued to exhibit altered concentrations similar to the COVID-19 phase, while sphingomyelins and long saturated and monounsaturated LysoPCs, phenylalanine, butyric acid, and propionic acid levels normalized. Post-COVID-19 patients displayed a heterogeneous metabolic profile, with some showing no symptoms while others exhibiting a variable number of symptoms. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, sarcosine, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Conclusions: Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289456v1" target="_blank">The plasma metabolome of long COVID-19 patients two years after infection</a>
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<li><strong>COVID-19 vaccination at a hospital in Paris: spatial analyses and inverse equity hypothesis</strong> -
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Background: Vaccination against SARS-CoV-2 has been deployed in France since January 2021. Evidence was beginning to show that the most vulnerable populations were the most affected by COVID-19. Without specific action for different population subgroups, the inverse equity hypothesis postulates that people in the least deprived neighbourhoods will be the first to benefit. Methods: We performed a spatial analysis using primary data from the vaccination centre of the Avicenne Hospital in Bobigny (Seine-Saint-Denis, France) from January 8th to September 30th, 2021. We used secondary data to calculate the social deprivation index. We performed flow analysis, k-means aggregation, and mapping. Results: During the period, 32,712 people were vaccinated at the study centre. Vaccination flow to the hospital shows that people living in the least disadvantaged areas were the first to be vaccinated. The number of people immunized according to the level of social deprivation then scales out with slightly more access to the vaccination centre for the most advantaged. The furthest have travelled more than 100 kilometres, and more than 1h45 of transport time to get to this vaccination centre. Access times are, on average, 50 minutes in February to 30 minutes in May 2021. Conclusion: The study confirms the inverse equity hypothesis and shows that vaccination preparedness strategies must take equity issues into account. Public health interventions should be implemented according to proportionate universalism and use community health, health mediation, and outreach activities for more equity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289561v1" target="_blank">COVID-19 vaccination at a hospital in Paris: spatial analyses and inverse equity hypothesis</a>
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<li><strong>COVID-19 risk variant associations with chromatin remodelling, DNA maintenance and surfactant genes are infection dependent in the lung</strong> -
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During viral infection the structure of host chromatin is modified. It is generally assumed that these chromatin modifications will affect variant-gene mapping, and therefore gene expression. What is not clear is how limitations imposed by host germline risk affect the expression changes that occur with infection induced chromatin remodelling. Critically, this lack of information extends to how germline variants associated with severe SARS-CoV-2 impact on tissue-specific gene expression changes in response to infection-induced chromatin conformation changes. Here we combined temporal chromatin conformation data from SARS-CoV-2 stimulated cells with a lung spatial-eQTL gene expression analysis to contextualise the functional effects and contributions of germline risk on the severe phenotypes observed in SARS-CoV-2. We identify changes in lung-specific SARS-CoV-2 risk variant-gene mapping across the infection time course. Our results provide evidence for infection-induced chromatin remodelling that impacts the regulation of genes associated with the severity of SARS-CoV-2 infection. The gene targets we identified are functionally involved in host chromatin modifications and maintenance and the expression of these genes is amplified by SARS-CoV-2-induced epigenetic remodelling. The effect of this remodelling includes transcriptional changes to gene targets such as SMARCA4, NCOR1, DNMT1, DNMT3a, DAXX, and PIAS4, all critical components of epigenetic control mechanisms and SARS-CoV-2 antiviral activity, along with several genes involved in surfactant metabolism. We show how severe-phenotype-associated eQTLs form and break in an infection time-course-dependent manner that mimics positive feedback loops connecting germline variation with the process of viral infection and replication. Our results provide a novel bridge between existing COVID-19 epigenetic research and demonstrate the critical role of epigenomics in understanding SARS-CoV-2-risk-associated gene regulation in the lung.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289478v1" target="_blank">COVID-19 risk variant associations with chromatin remodelling, DNA maintenance and surfactant genes are infection dependent in the lung</a>
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<li><strong>Receipt of anti-SARS-CoV-2 pharmacotherapies among non-hospitalized U.S. Veterans with COVID-19, January 2022 to January 2023</strong> -
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IMPORTANCE Several pharmacotherapies have been authorized to treat non-hospitalized persons with symptomatic COVID-19. Longitudinal information on their use is needed. OBJECTIVE To analyze trends and factors related to prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA). DESIGN, SETTINGS, AND PARTICIPANTS This cohort study evaluated non-hospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023, using VHA and linked Community Care and Medicare databases. EXPOSURES Demographic characteristics, regional and local systems of care including Veterans Integrated Services Networks (VISNs), underlying medical conditions, COVID-19 vaccination. MAIN OUTCOMES AND MEASURES Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any versus no COVID-19 pharmacotherapy. RESULTS Among 285,710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247,358 (86.6%) male; 28,444 (10%) Hispanic; 198,863 (72.7%) White; 61,269 (22.4%) Black) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3.2% (3,285/102,343) in January 2022 to 23.9% (5,180/21,688) in August 2022, and declined slightly to 20.8% (2,194/10,551) by January 2023. Across VISNs, the range in proportion of test-positive patients who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 5.9 to 21.4% and 2.1 to 11.1%, respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR], 1.18, 95% CI 1.14-1.22 for 65 to 74 versus 50 to 64 years; aOR 1.19, 95% CI 1.15-1.23 for 75 versus 50 to 64 years), have a higher Charlson Comorbidity Index (CCI) (aOR 1.52, 95% CI 1.44-1.59 for CCI ≥6 versus 0), and be vaccinated against COVID-19 (aOR 1.25, 95% CI 1.19-1.30 for primary versus no vaccination; aOR 1.47, 95% CI 1.42-1.53 for booster versus no vaccination). Compared with White veterans, Black veterans (aOR 1.06, 95% CI 1.02 to 1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06, 95% CI 1.01-1.11) were more likely to receive treatment. CONCLUSIONS AND RELEVANCE Among veterans who tested positive for SARS-CoV-2 between January 2022 and January 2023, prescription of outpatient COVID-19 pharmacotherapies peaked in August 2022 and declined thereafter. There remain large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289479v1" target="_blank">Receipt of anti-SARS-CoV-2 pharmacotherapies among non-hospitalized U.S. Veterans with COVID-19, January 2022 to January 2023</a>
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<li><strong>Comprehensive Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome.</strong> -
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Wastewater is a discarded human by-product but analyzing it may help us understand the health of communities. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. We conducted a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Over 450 distinct pathogenic viruses were detected. Sequencing reads of established pathogens and emerging viruses correlated to clinical data sets. Viral communities were tightly organized by space and time. Finally, the most abundant human viruses yielded sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289441v1" target="_blank">Comprehensive Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome.</a>
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<li><strong>Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography</strong> -
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Since emergence of the initial SARS-CoV-2 omicron BA.1, BA.2 and BA.5 variants, omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5 omicron. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.02.23289412v1" target="_blank">Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography</a>
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<li><strong>Excess Mortality Resulting from COVID-19 in Turkey during 2020-2021: Regional and Time-Based Analysis</strong> -
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Turkey experienced substantial excess mortality in 2020 and 2021 related to the COVID-19 pandemic. Methods used to estimate excess mortality vary, making comparisons difficult. This study assessed the impact of the COVID-19 pandemic in Turkey, using the TURKSTAT data which became available on February 23, 2023. We applied a quasi-Poisson model to estimate excess mortality during 2020-2021, comparing excess mortality by time periods and socioeconomic factors (SEGE grades). During 2020-2021, Turkey experienced 72,886 excess deaths in 2020 (P-score 16.8%) and 125,540 in 2021 (P-score 28.5%). Excess all-cause mortality varied across SEGE levels, with notable social disparities in pandemic deaths as the highest rates were observed in SEGE 6, the lowest socioeconomic group. An additional 80 excess deaths per 100,000 people were recorded in 2020 and 143 in 2021. This study highlights the importance of a comprehensive approach to address the diverse impacts of the pandemic on health and well-being while considering socioeconomic disparities, and potential areas for improvement in data collection and reporting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.04.23289498v1" target="_blank">Excess Mortality Resulting from COVID-19 in Turkey during 2020-2021: Regional and Time-Based Analysis</a>
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<li><strong>Improved access to diabetic retinopathy screening through primary care-based teleophthalmology during the COVID-19 pandemic</strong> -
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BACKGROUND Eye diseases worldwide, including within the United States, are underdiagnosed and undertreated1. A multitude of factors contribute to this deficiency in eye care including, but not limited to, availability of specialists, transportation and mobility barriers, financial burden, lack of education, and poor patient-physician communication and understanding2,3,4. Teleophthalmology, a paradigm of care delivery in which ocular images are interpreted remotely by an eye specialist, has increased in interest since the COVID-19 pandemic, may offer improved access to necessary eye care5. The need for improved access through teleophthalmology is particularly critical for diabetic retinopathy (DR), the leading cause of new cases of blindness among adults aged 20 to 60 affecting more than 100 million patients worldwide6,7. DR arises when elevated levels of blood sugar resulting from either type 1 or 2 diabetes mellitus damage the blood vessels that supply oxygen and nutrients to the retina, the light-sensing part of the eye. The risk of developing DR is directly related to the length of time that a patient has diabetes and usually does not appear for approximately five years after a type 1 diabetes diagnosis, although it may already be present when type 2 diabetes is diagnosed8. In the absence of glycemic control and/or ophthalmic treatment, the disease may progress through three stages of non-proliferative retinopathy (mild, moderate, severe) before proliferative retinopathy develops. Diabetic macular edema can occur with any stage of retinopathy. If DR is diagnosed early, vision loss may be mitigated or prevented9. An annual fundus examination to screen for DR is critical, however, only about half of all patients with diabetes receive proper screening and less than 40% of patients with a high risk of vision loss ever undergo treatment10,11. In 2010, primary care providers (PCPs) delivered clinical care to approximately 90% of individuals with type 2 diabetes, and the proportion has increased over time12. The importance of primary care practitioners ensuring that their diabetic patients receive recommended eye care is reflected in the Healthcare Effectiveness Data and Information Set (HEDIS). This comprehensive set of quality performance measures across six domains of care guide the primary care of chronic medical conditions like diabetes mellitus and includes assessment of whether a diabetic patient receives diabetic eye screening at least every two years13. Attainment of these quality measures is increasingly important for health-system quality ratings and value-based reimbursement models. Practices are increasingly turning to teleophthalmology programs to aid in this goal of care5,14. Traditionally, DR is diagnosed by an eye specialist via an annual in-person fundoscopic examination. However, with appropriate training, non-ophthalmic clinicians and clinical personnel are able to use a fundus camera to take retinal photos that can then be evaluated by an ophthalmologist typically via a store-and-forward model. DR can be determined with high sensitivity and specificity from fundus photography, and a referral for further ophthalmic evaluation or treatment is made for those patients with retinopathy15. Primary care-based teleophthalmology programs have improved the accessibility and cost-effectiveness of DR screening in both rural and urban settings worldwide and are currently being applied to DR screening more commonly than any other ocular pathology16, 17,18. The ongoing COVID-19 pandemic has exacerbated existing barriers and increased the likelihood of ophthalmic appointment postponement or cancellation rendering teleophthalmology services even more critical to DR screening programs19, 20. The prevalence of diabetes in California is more than 40% above the United States national average21. As a means to improve the ophthalmic health of our patients, the Stanford Teleophthalmology Automated Testing and Universal Screening (STATUS) program was developed as a multi-site teleophthalmology DR screening collaboration between
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289435v1" target="_blank">Improved access to diabetic retinopathy screening through primary care-based teleophthalmology during the COVID-19 pandemic</a>
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<li><strong>Mode Connections For Clinical Incremental Learning: Lessons From The COVID-19 Pandemic</strong> -
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Dynamic distribution shifts caused by evolving diseases and demographic changes require domain-incremental adaptation of clinical deep learning models. However, this process of adaptation is often accompanied by catastrophic forgetting, and even the most sophisticated methods are not good enough for clinical applications. This paper studies incremental learning from the perspective of mode connections, that is, the low-loss paths connecting the minimisers of neural architectures (modes or trained weights) in the parameter space. The paper argues for learning the low-loss paths originating from an existing mode and exploring the learned paths to find an acceptable mode for the new domain. The learned paths, and hence the new domain mode, are a function of the existing mode. As a result, unlike traditional incremental learning, the proposed approach is able to exploit information from a deployed model without changing its weights. Pre-COVID and COVID-19 data collected in Oxford University hospitals are used as a case study to demonstrate the need for domain-incremental learning and the advantages of the proposed approach.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289583v1" target="_blank">Mode Connections For Clinical Incremental Learning: Lessons From The COVID-19 Pandemic</a>
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<li><strong>Primary series and booster COVID-19 vaccine effectiveness in a cohort of healthcare workers in Albania during a BA.1 and BA.2 variant period, January - May 2022</strong> -
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Background Healthcare workers (HCWs) have experienced high rates of COVID-19 morbidity and mortality. We estimated COVID-19 two-dose primary series and monovalent booster vaccine effectiveness (VE) against symptomatic SARS-CoV-2 Omicron (BA.1 and BA.2) infection among HCWs in three Albanian hospitals during January-May 2022. Methods Study participants completed weekly symptom questionnaires, underwent PCR testing when symptomatic, and provided quarterly blood samples for serology. We estimated VE using Cox regression models (1-hazard ratio), with vaccination status as the time-varying exposure and unvaccinated HCWs as the reference group, adjusting for potential confounders: age, sex, prior SARS-CoV-2 infection (detected by PCR, rapid-antigen test or serology), and household size. Results At the start of the analysis period, 76% of 1,462 HCWs had received a primary series, 10% had received a booster dose, and 9% were unvaccinated; 1,307 (89%) HCWs had evidence of prior infection. Overall, 86% of primary series and 98% of booster doses received were BNT162b2. The median time interval from the second dose and the booster dose to the start of the analysis period was 289 days (IQR:210-292) and 30 days (IQR:22-46), respectively. VE against symptomatic PCR-confirmed infection was 34% (95%CI: -36;68) for the primary series and 88% (95%CI: 38;98) for the booster. Conclusions Among Albanian HCWs, most of whom had been previously infected, COVID-19 booster dose offered improved VE during a period of Omicron BA.1 and BA.2 circulation. Our findings support promoting booster dose uptake among Albanian HCWs, which, as of January 2023, was only 20%.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.05.23289503v1" target="_blank">Primary series and booster COVID-19 vaccine effectiveness in a cohort of healthcare workers in Albania during a BA.1 and BA.2 variant period, January - May 2022</a>
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<li><strong>COVID-19 Infection Is Associated with Poor Outcomes in Patients with Intracerebral Hemorrhage</strong> -
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Background: Patients with ischemic stroke and concomitant coronavirus 2019 (COVID-19) infection have worse outcomes than those without this infection. However, research on the impact of COVID-19 infection on outcomes following hemorrhagic stroke remains limited. We aim to study whether concomitant COVID-19 infection leads to worse outcomes in spontaneous intracerebral hemorrhage (ICH).<break><break>Design: We conducted an observational study using data from Get With The Guidelines Stroke, an ongoing, multi-center, nationwide quality assurance registry. <break><break>Methods: We implemented a two-stage design: first, we compared outcomes of ICH patients with and without COVID-19 infection admitted during the pandemic (from March 2020 to February 2021). Second, we compared the same outcomes between ICH patients admitted before (March 2019 to February 2020) and during (March 2020 and February 2021) the pandemic. Main outcomes were poor functional outcome (defined as a modified Rankin Scale of 4 to 6 [mRS] at discharge), mortality and discharge to skilled nursing facility (SNF) or hospice. <break><break>Results: The first stage included 60,091 COVID-19-negative and 1,326 COVID-19-positive ICH patients. In multivariable analyses, ICH patients with versus without COVID-19 infection had 68% higher odds of poor outcome (OR 1.68, 95%CI 1.41-2.01), 51% higher odds of mortality (OR 1.51, CI 1.33-1.71) and 66% higher odds of being discharged to a SNF/hospice (OR 1.66, 95%CI 1.43-1.93). The second stage included 62,743 pre-pandemic and 64,681 intra-pandemic ICH cases. In multivariable analyses, ICH patients admitted during versus before the COVID-19 pandemic had a 10% higher odds of poor outcome (OR 1.10, 95%CI 1.07-1.14), 5% higher mortality (OR 1.05, 95%CI 1.02-1.08) and no significant difference in the risk of being discharged to SNF/hospice (OR 0.93, 95%CI 0.90-0.95). <break><break>Conclusions: The pathophysiology of the COVID-19 infection and changes in healthcare delivery during the pandemic played a role in worsening outcomes in this patient population. Further research is needed to identify these factors and understand their effect on the long-term outcome.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289488v1" target="_blank">COVID-19 Infection Is Associated with Poor Outcomes in Patients with Intracerebral Hemorrhage</a>
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<li><strong>SARS-CoV-2 specific cellular and humoral immunity after bivalent BA.4/5 COVID-19 vaccination in previously infected and non-infected individuals</strong> -
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Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity correlates with subsequent infection. In this observational study, individuals with prior infection (n=64) showed higher vaccine-induced anti-spike IgG antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n=63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T-cell levels towards spike from the parental strain and the Omicron subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T-cell levels. Thus, the magnitude of vaccine-induced neutralizing activity and specific CD4 T-cells after bivalent vaccination may serve as a correlate for protection in previously non-infected individuals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289472v1" target="_blank">SARS-CoV-2 specific cellular and humoral immunity after bivalent BA.4/5 COVID-19 vaccination in previously infected and non-infected individuals</a>
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<li><strong>Descriptive Analysis of SARS-CoV-2 Genomics Data from Ambulatory Patients</strong> -
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Background: The COVID-19 pandemic has been characterized by ongoing evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with concomitant variation in viral transmissibility and morbidity. Within specific timeframes and geographic areas, multiple SARS-CoV-2 variants have coexisted in the human population, each characterized by distinct biologic and clinical features, such as varying susceptibility to neutralizing monoclonal antibodies (nMAbs), a major frontline treatment. As part of an observational real-world data study of the effectiveness of nMAbs for treatment of COVID-19, SARS-CoV-2 viral samples were obtained from patients under treatment, generating paired clinical and genomics data. This paper describes the processing pipeline and findings from the genomics portion of this combined data set. Methods: SARS-CoV-2 sequences were generated from 14,796 diagnostic samples from four large U.S. health systems between July 2020 and March 2022. Among nMAbs-treated patients, samples were collected on the same day as, or prior to, treatment with nMAbs. Thus, these samples represent a snapshot of SARS-CoV-2 variants circulating in the respective patient groups, as opposed to variants that arose in response to specific treatments. Health systems collected viral samples and performed library creation and sequencing according to local protocols, using tiled ARTIC amplicon primers. FASTQ files were submitted to a study data platform and processed through a common pipeline. This pipeline enabled a unified approach to quality control, assembly, and production of genomics features for downstream analysis. Results: Alpha and pre-Alpha SARS-CoV-2 lineages were predominant in the data set prior to June 2021. From June 2021 through November 2021, Delta was the dominant variant. Beginning in December 2021, Omicron was dominant. A variety of mutations associated with decreased nMAbs binding to the spike protein in vitro were detected, including lineage-defining mutations and non-lineage-defining mutations such as E340A, G446V, and S494P. Distinct patterns of sequence gaps and ambiguous base calls were associated with distinct variants. Conclusions: The distribution of SARS-CoV-2 variants, per WHO nomenclature, across epochs in this data set matched concurrent CDC genomic surveillance results across the U.S. Detection of putative nMAbs escape mutations within clinical samples was consistent with FDA decisions to amend EUAs as variants emerged. This genomics data set provides an opportunity to examine associations between SARS-CoV-2 genomic variation and clinical outcomes in the associated EHR data set. The expansion of real-world data sets such as this to study the relationship between viral sequence and treatment outcomes could provide the foundation for future efforts to achieve near-real-time understanding of clinical outcomes related to genomic variation over time, and evidence to update treatment decisions more rapidly and to greater effect during ongoing and future pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.03.23289106v1" target="_blank">Descriptive Analysis of SARS-CoV-2 Genomics Data from Ambulatory Patients</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID-19 Syndrome Lifestyle Intervention Study</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Dietary Supplement: Low carbohydrate diet intervention<br/><b>Sponsor</b>: University of Southern California<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>Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: mHealth Outreach; Other: Care Coordination<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Coping and Resilience Intervention for Adolescents</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents<br/><b>Sponsor</b>: Taipei Medical University<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>Effectiveness of Modified Diaphragmatic Training for Gastroesophageal Reflux Disease Post Covid-19</strong> - <b>Conditions</b>: GERD; Post COVID-19 Condition; Diaphragm Issues<br/><b>Interventions</b>: Other: modified diaphragmatic training; Other: standard diaphragmatic training<br/><b>Sponsor</b>: Indonesia 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>The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants</strong> - <b>Condition</b>: COVID-19 (Coronavirus Disease 2019)<br/><b>Interventions</b>: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10<br/><b>Sponsor</b>: Guangdong Raynovent Biotech Co., Ltd<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>COVID-19 Vaccination Detoxification</strong> - <b>Conditions</b>: COVID-19 Stress Syndrome; COVID-19 Vaccine Adverse Reaction; COVID-19-Associated Thromboembolism; COVID-19 Post-Intensive Care Syndrome; COVID-19-Associated Stroke; COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Atorvastatin Calcium Tablets<br/><b>Sponsor</b>: Yang I. Pachankis<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>A Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ALG-097558; Drug: Placebo; Drug: Midazolam; Drug: Itraconazole; Drug: Carbamazepine; Drug: ALG-097558 in solution formulation; Drug: ALG-097558 in tablet formulation<br/><b>Sponsor</b>: Aligos Therapeutics<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>Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints</strong> - <b>Conditions</b>: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired<br/><b>Intervention</b>: Device: RehaCom<br/><b>Sponsor</b>: Erasmus Medical Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunoadsorption Study Mainz in Adults With Post-COVID Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Post-COVID Syndrome; Post COVID-19 Condition<br/><b>Interventions</b>: Device: Immunoadsorption; Device: Sham-apheresis<br/><b>Sponsor</b>: University Medical Center Mainz<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>Digital Mental Health Care for COVID-19 High-Risk Populations - Phase 2</strong> - <b>Conditions</b>: Stigma, Social; Help-Seeking Behavior<br/><b>Interventions</b>: Other: Adjusted Content Intervention; Other: Non-Adjusted Intervention Video<br/><b>Sponsors</b>: Research Foundation for Mental Hygiene, Inc.; Columbia University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults</strong> - <b>Conditions</b>: SARS-CoV-2; Influenza<br/><b>Interventions</b>: Biological: Fluarix; Biological: mRNA-1083.1; Biological: mRNA-1083.2; Biological: mRNA-1083.3; Biological: mRNA-1010.4; Biological: mRNA-1283.222; Biological: mRNA-1273.222; Biological: mRNA-1010; Biological: Fluzone HD<br/><b>Sponsor</b>: ModernaTX, Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of an Smartphone App Intervention Based on Self-compassion for Mental Health Among University Students</strong> - <b>Condition</b>: Mental Health Issue<br/><b>Interventions</b>: Behavioral: mHealth Intervention Based on Self-Compassion; Behavioral: Psychoeducation Intervention<br/><b>Sponsors</b>: Federal University of Health Science of Porto Alegre; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.<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>Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2</strong> - <b>Conditions</b>: Long COVID; Insulin Resistance; Insulin Sensitivity<br/><b>Interventions</b>: Procedure: Adipose Tissue Biopsy; Diagnostic Test: Steady State Plasma Glucose (SSPG) Test<br/><b>Sponsor</b>: Stanford University<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>Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients</strong> - Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying…</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 anti-inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids</strong> - The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar…</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>Prenol, but Not Vitamin C, of Fruit Binds to SARS-CoV-2 Spike S1 to Inhibit Viral Entry: Implications for COVID-19</strong> - Fruit consumption may be beneficial for fighting infection. Although vitamin C is the celebrity component of fruit, its role in COVID-19 is unclear. Because spike S1 of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and initiate COVID-19, using an α-screen-based assay, we screened vitamin C and other components of fruit for inhibiting the interaction between spike S1 and ACE2. We found that prenol, but neither vitamin C nor other major components of…</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>Orthogonal dual reporter-based gain-of-signal assay for probing SARS-CoV-2 3CL protease activity in living cells: inhibitor identification and mutation investigation</strong> - The main protease (3-chymotrypsin-like protease, 3CLpro) of SARS-CoV-2 has become a focus of anti-coronavirus research. Despite efforts, drug development targeting 3CLpro has been hampered by limitations in the currently available activity assays. Additionally, the emergence of 3CLpro mutations in circulating SARS-CoV-2 variants has raised concerns about potential resistance. Both emphasize the need for a more reliable, sensitive, and facile 3CLpro assay. Here, we report an orthogonal dual…</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 N Protein Triggers Acute Lung Injury via Modulating Macrophage Activation and Infiltration in in vitro and in vivo</strong> - CONCLUSION: SARS-CoV-2 and its N protein but not S protein induced acute lung injury and systemic inflammation, which was closely related to macrophage activation, infiltration and release cytokines.</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>Biogenic silver nanoparticles eradicate of <em>Pseudomonas aeruginosa</em> and Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) isolated from the sputum of COVID-19 patients</strong> - In recent investigations, secondary bacterial infections were found to be strongly related to mortality in COVID-19 patients. In addition, Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA) bacteria played an important role in the series of bacterial infections that accompany infection in COVID-19. The objective of the present study was to investigate the ability of biosynthesized silver nanoparticles from strawberries (Fragaria ananassa L.) leaf extract without a…</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 reactogenicity of heterologous prime-boost vaccination with inactivated COVID-19 and ChAdOx1 nCoV-19 (AZD1222) vaccines, a quasi-experimental study</strong> - The global supply of COVID-19 vaccines has been limited, and concerns have arisen about vaccine supply chain disruptions in developing countries. Heterologous prime-boost vaccination, which involves using different vaccines for the first and second doses, has been proposed to enhance the immune response. We aimed to compare the immunogenicity and safety of a heterologous prime-boost vaccination using an inactivated COVID-19 vaccine and AZD1222 vaccine with that of a homologous vaccination using…</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>Proton Pump Inhibitors, Kidney Damage, and Mortality: An Updated Narrative Review</strong> - Since their approval by the Food and Drug Administration (FDA) in 1989, proton pump inhibitors (PPIs) have become one of the most highly utilized drugs in the United States, assuming a position as one of the top 10 most prescribed medications in the country. The purpose of PPIs is to limit the amount of gastric acid secreted by the parietal cells via irreversible inhibition of the H+/K+-ATPase pump, therefore maintaining an elevated gastric acid pH of greater than 4 for 15-21 h. Even though PPIs…</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>New Ways to Protect the Host from SARS-CoV-2? Lung Microbiome Metabolites Inhibit STAT3 and Modulate the Immunological Network</strong> - COVID-19 caused by the SARS-CoV-2 infection is a systemic disease that affects multiple organs, biological pathways, and cell types. A systems biology approach would benefit the study of COVID-19 in the pandemic as well as the endemic state. Notably, patients with COVID-19 have dysbiosis of lung microbiota whose functional relevance to the host is largely unknown. We carried out a systems biology investigation of the impact of lung microbiome-derived metabolites on host immune system during…</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 Multicenter Randomized Controlled Trial To Evaluate the Efficacy and Safety of Nelfinavir in Patients with Mild COVID-19</strong> - Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> evaluation of some commercially available terpenoids as spike glycoprotein of SARS-CoV-2 - inhibitors using molecular dynamic approach</strong> - Coronavirus, an extremely contagious infections disease had a harmful effect on the world’s population. It is a family of enveloped, single-stranded, positive-strand RNA viruses of Nidovirales order belongs to coroviridae family. At present, worldwide several lakhs of deaths and several billions of infections have been reported. Hence, the focus of the present study was to assess the SARS-CoV-2 enzyme inhibitory potential of certain commercially available terpenoids using Lamarckian genetic…</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>Infection routes, invasion mechanisms, and drug inhibition pathways of human coronaviruses on the nervous system</strong> - So far, numerous studies have reported on how coronaviruses affect the human nervous system. However, these studies mainly focused on the impact of a single coronavirus on the nervous system, and failed to fully report the invasion mechanisms and the rules of symptoms of the seven human coronaviruses. This research can assist medical professionals in identifying the regularity of coronavirus invasion into the nervous system by examining the impacts of human coronaviruses on the nervous system….</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>High-breathable, antimicrobial and water-repellent face mask for breath monitoring</strong> - Face masks with multiple functionalities and exceptional durability have attracted increasing interests during the COVID-19 pandemic. How to integrate the antibacterial property, comfortability during long-time wearing, and breath monitoring capability together on a face mask is still challenging. Here we developed a kind of face mask that assembles the particles-free water-repellent fabric, antibacterial fabric, and hidden breath monitoring device together, resulting in the highly breathable,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice</strong> - OBJECTIVE: An increasing number of studies have reported that numerous patients with coronavirus disease 2019 (COVID-19) and vaccinated individuals have developed central nervous system (CNS) symptoms, and that most of the antibodies in their sera have no virus-neutralizing ability. We tested the hypothesis that non-neutralizing anti-S1-111 IgG induced by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could negatively affect the CNS.</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>Furin as a therapeutic target in cystic fibrosis airways disease</strong> - Clinical management of cystic fibrosis (CF) has been greatly improved by the development of small molecule modulators of the CF transmembrane conductance regulator (CFTR). These drugs help to address some of the basic genetic defects of CFTR; however, no suitable CFTR modulators exist for 10% of people with CF (PWCF). An alternative, mutation-agnostic therapeutic approach is therefore still required. In CF airways, elevated levels of the proprotein convertase furin contribute to the…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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