Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Impact of the COVID-19 Pandemic on Undergraduate Research in the Department of Biology at Western University: Effect on project types, learning outcomes, and student perceptions. -
  Undergraduate research is a high impact practice that offers numerous benefits to students, academic institutions, and the wider scientific community. Unfortunately, undergraduate research has faced restrictions due to the COVID-19 pandemic. This study aimed to assess how the COVID-19 pandemic has impacted: (1) the number and types of undergraduate research projects performed in the Department of Biology at the University of Western Ontario, and (2) the satisfaction-levels and perceived learning outcomes of students performing these projects. This study also aimed to incorporate a One Health framework through an emphasis on stakeholder involvement and the need for future action. A survey of 33 students who completed an undergraduate research project in the Department of Biology in the 2020/2021 academic year, and 68 students who completed an undergraduate research project in the 5 years prior was conducted. In keeping with the One Health approach, key stakeholders were identified, and a stakeholder map was constructed. The number of projects performed did not change dramatically despite COVID-19 restrictions. However, a shift towards dry research was observed with 87.9% of students in the 2020/2021 academic year conducting dry research, compared to 16.4% of students in the 5 years prior. Students who conducted research in the 2020/2021 academic year indicated lower overall levels of satisfaction and enjoyment, though their perceived learning outcomes were consistent with students who completed their projects in the 5 years prior. 53 key stakeholders from academia, government, industry, media, and the public were identified. Students provided invaluable feedback on their undergraduate research experiences that can be used to improve the quality of undergraduate research courses in the Department of Biology in the future. Findings may be of use to other departments and educational institutions that are seeking to improve their own undergraduate research courses amidst the COVID-19 pandemic or looking to incorporate experiential-based learning techniques into existing online courses.
  🖺 Full Text HTML: Impact of the COVID-19 Pandemic on Undergraduate Research in the Department of Biology at Western University: Effect on project types, learning outcomes, and student perceptions.
• Case of Myocarditis, Pericarditis, and Fatal Aortic Dissection following Covid-19 mRNA Vaccination -
  We present a case study of a 34-year-old male who was in apparent good health prior to his COVID-19 mRNA vaccination. Sixteen days after his first dose, he experienced acute inflammation, sudden thoracic aortic dissection, and pericardial tamponade, rapidly leading to his death. Studies suggest that young males, in particular, appear to be at increased risk of adverse cardiac events following COVID-19 mRNA vaccination. However, we propose that certain information gaps exist in the criteria that inform both public health agencies and the public on incidence rates in certain presentations of even severe myocarditis and cardiac adverse events following COVID-19 vaccination, as is often mentioned within COVID-19 vaccine myocarditis studies and is evident within the findings of this young man’s important case presentation.
  🖺 Full Text HTML: Case of Myocarditis, Pericarditis, and Fatal Aortic Dissection following Covid-19 mRNA Vaccination
• nf-core/airrflow: an adaptive immune receptor repertoire analysis workflow employing the Immcantation framework -
  Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a valuable experimental tool to study the immune state in health and following immune challenges such as infectious diseases, (auto)immune diseases, and cancer. Several tools have been developed to reconstruct B cell and T cell receptor sequences from AIRR-seq data and infer B and T cell clonal relationships. However, currently available tools offer limited parallelization across samples, scalability or portability to high-performance computing infrastructures. To address this need, we developed nf-core/airrflow, an end-to-end bulk and single-cell AIRR-seq processing workflow which integrates the Immcantation Framework following BCR and TCR sequencing data analysis best practices. The Immcantation Framework is a comprehensive toolset, which allows the processing of bulk and single-cell AIRR-seq data from raw read processing to clonal inference. nf-core/airrflow is written in Nextflow and is part of the nf-core project, which collects community contributed and curated Nextflow workflows for a wide variety of analysis tasks. We assessed the performance of nf-core/airrflow on simulated sequencing data with sequencing errors and show example results with real datasets. To demonstrate the applicability of nf-core/airrflow to the high-throughput processing of large AIRR-seq datasets, we validated and extended previously reported findings of convergent antibody responses to SARS-CoV-2 by analyzing 97 COVID-19 infected individuals and 99 healthy controls, including a mixture of bulk and single-cell sequencing datasets. Using this dataset, we extended the convergence findings to 20 additional subjects, highlighting the applicability of nf-core/airrflow to validate findings in small in-house cohorts with reanalysis of large publicly available AIRR datasets. nf-core/airrflow is available free of charge, under the MIT license on GitHub (https://github.com/nf-core/airrflow). Detailed documentation and example results are available on the nf-core website at (https://nf-co.re/airrflow).
  🖺 Full Text HTML: nf-core/airrflow: an adaptive immune receptor repertoire analysis workflow employing the Immcantation framework
• Development and validation of a federated learning framework for detection of subphenotypes of multisystem inflammatory syndrome in children -

  Background Multisystem inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection. The highly diverse clinical features of MIS-C necessities characterizing its features by subphenotypes for improved recognition and treatment. However, jointly identifying subphenotypes in multi-site settings can be challenging. We propose a distributed multi-site latent class analysis (dMLCA) approach to jointly learn MIS-C subphenotypes using data across multiple institutions. Methods We used data from the electronic health records (EHR) systems across nine U.S. childrens hospitals. Among the 3,549,894 patients, we extracted 864 patients < 21 years of age who had received a diagnosis of MIS-C during an inpatient stay or up to one day before admission. Using MIS-C conditions, laboratory results, and procedure information as input features for the patients, we applied our dMLCA algorithm and identified three MIS-C subphenotypes. As validation, we characterized and compared more granular features across subphenotypes. To evaluate the specificity of the identified subphenotypes, we further compared them with the general subphenotypes identified in the COVID-19 infected patients. Findings Subphenotype 1 (46.1%) represents patients with a mild manifestation of MIS-C not requiring intensive care, with minimal cardiac involvement. Subphenotype 2 (25.3%) is associated with a high risk of shock, cardiac and renal involvement, and an intermediate risk of respiratory symptoms. Subphenotype 3 (28.6%) represents patients requiring intensive care, with a high risk of shock and cardiac involvement, accompanied by a high risk of >4 organ system being impacted. Importantly, for hospital-specific clinical decision-making, our algorithm also revealed a substantial heterogeneity in relative proportions of these three subtypes across hospitals. Properly accounting for such heterogeneity can lead to accurate characterization of the subphenotypes at the patient-level. Interpretation Our identified three MIS-C subphenotypes have profound implications for personalized treatment strategies, potentially influencing clinical outcomes. Further, the proposed algorithm facilitates federated subphenotyping while accounting for the heterogeneity across hospitals.

  🖺 Full Text HTML: Development and validation of a federated learning framework for detection of subphenotypes of multisystem inflammatory syndrome in children
• In silico assessment of immune cross protection between BCoV and SARS-CoV-2 -
  Background: Humans have long shared infectious agents with cattle, and the bovine-derived human common cold OC-43 CoV is a not-so-distant example of cross-species viral spill over of coronaviruses. Human exposure to the Bovine Coronavirus (BCoV) is certainly common, as the virus is endemic in most high-density cattle-raising regions. Since BCoVs are phylogenetically close to SARS-CoV-2, it is possible that cross-protection against COVID-19 occurs in people exposed to BCoV. Methods: This article shows an in silico investigation of human cross-protection to SARS-CoV-2 due to BCoV exposure. We determined HLA recognition and human B lymphocyte reactivity to BCoV epitopes using bioinformatics resources. A retrospective geoepidemiological analysis of COVID-19 was then performed to verify if BCoV/SARS-CoV-2 cross-protection could have occurred in the field. Brazil was used as a model for the epidemiological analysis of the impact of livestock density, as a proxy for human exposure to BCoV, on the prevalence of COVID-19 in people. Results: As could be expected from their classification in the same Betacoronavirus genus, we show that several human B and T epitopes are shared between BCoV and SARS-CoV-2. This raised the possibility of cross-protection of people from exposure to the bovine coronavirus. Analysis of field data added partial support to the hypothesis of viral cross-immunity from human exposure to BCoV. There was a negative correlation between livestock geographical density and COVID-19. Whole-Brazil data showed areas in the country in which COVID-19 prevalence was disproportionally low (controlled by normalization by transport infrastructure). Areas with high cattle density had lower COVID-19 prevalence in these low-risk areas. Conclusions: These data are hypothesis-raising indications that cross-protection is possibly being induced by human exposure to the Bovine Coronavirus.
  🖺 Full Text HTML: In silico assessment of immune cross protection between BCoV and SARS-CoV-2
• No Substitute for the Real Thing? Physical and Digital Cultural Participation in Denmark during the COVID-19 Pandemic: A Research Note -
  In this research note, we analyze the impact of the COVID-19 pandemic on cultural participation. We use rich survey data from Denmark to construct pooled time-series cross-sectional data for each month of the years 2019-2021 and report three findings. First, participation in physical cultural activities (e.g., attending a concert or a museum) plummeted during two lockdowns and did not return to its pre-pandemic level by the end of 2021. Second, participation in digital activities (e.g., reading a digital book or following a museum on social media) did not change much during the pandemic. Overall, we find little evidence of substitution from physical to digital cultural participation during the COVID-19 lockdown in Denmark. Third, socioeconomic gradients in cultural participation decreased during the pandemic for physical cultural participation, but did not change for digital cultural participation. We end by discussing what we can learn from our results about how social disruptions affect patterns of cultural participation and inequality.
  🖺 Full Text HTML: No Substitute for the Real Thing? Physical and Digital Cultural Participation in Denmark during the COVID-19 Pandemic: A Research Note
• Stratification in Parents’ Selection of Developmentally Appropriate Books for Children: Register-based Evidence from Danish Public Libraries -
  This paper studies socioeconomic gradients in selecting developmentally appropriate children’s books from public libraries. I draw on research on developmental gradients in parental inputs to hypothesize that families with high socioeconomic status (SES) are more likely to select books that match children’s developmental stage in order to best improve children’s learning environments. In contrast to previous survey-based research, I use behavioral data on the actual books families have selected from libraries. Based on Danish registry data that cover all books borrowed from public libraries in 2020, I find that highly educated families are more likely to use libraries and borrow more books when they use libraries, but they do not select a larger share of developmentally appropriate books; in fact, they select a slightly lower share. In contrast, I find only a weak positive income gradient for the amount of books borrowed and the share of developmentally appropriate books. The supplementary analyses show that results are robust across families with children of different ages and to account for nonrandom selection into the sample of library users, socioeconomic differences in children’s reading skills, and the impact of library lockdowns due to Covid-19. I conclude that stratification in library book selection is more prominent concerning the voraciousness with which highly educated parents provide reading inputs (more books) than how discriminating they are in terms of selecting developmentally appropriate books.
  🖺 Full Text HTML: Stratification in Parents’ Selection of Developmentally Appropriate Books for Children: Register-based Evidence from Danish Public Libraries
• Safety Monitoring of Bivalent COVID-19 mRNA Vaccines Among Recipients 6 months and Older in the United States -

  Importance Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes post-licensure. Objective To evaluate health outcomes following bivalent COVID-19 Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273.222) vaccination among individuals 6 months and older in the United States. Design Monthly monitoring of health outcomes from August 2022 to July 2023 in four administrative claims databases. Descriptive analyses monitored vaccine uptake, outcome counts and coadministration of bivalent COVID-19 and influenza vaccines. Sequential analyses tested for elevated risk of each outcome in a prespecified post-vaccination risk interval, or a period of hypothesized elevation based on clinical guidance, compared to a historical baseline. Participants and Exposures Persons 6 months and older who received a bivalent COVID-19 BNT162b2 or mRNA-1273.222 vaccine during the study period, with continuous enrollment in a medical insurance plan from the start of an outcome-specific clean interval to the COVID-19 vaccination date. Vaccines were identified using product-specific codes from medical coding systems. Health Outcomes Twenty outcomes were monitored in BNT162b2 vaccine recipients 6 months-4 years, and mRNA-1273.222 vaccine recipients 6 months-5 years. Twenty-one outcomes were monitored in BNT162b2 vaccine recipients 5-17 years and mRNA-1273.222 vaccine recipients 6-17 years. Eighteen outcomes were monitored in persons 18 years and older for both mRNA vaccines. Results Overall, 13.9 million individuals 6 months and older received a single bivalent COVID-19 mRNA vaccine. The statistical threshold for a signal was met for two outcomes in one database: anaphylaxis following bivalent BNT162b2 and mRNA-1273.222 vaccines in persons 18-64 years and myocarditis/pericarditis following bivalent BNT162b2 vaccines in individuals 18-35 years. There were no signals identified in young children. Conclusions Results were consistent with prior observations from published studies on COVID-19 vaccine safety. This study supports the safety profile of bivalent COVID-19 mRNA vaccines and the conclusion that the benefits of vaccination outweigh the risks.

  🖺 Full Text HTML: Safety Monitoring of Bivalent COVID-19 mRNA Vaccines Among Recipients 6 months and Older in the United States
• An ecological study of COVID-19 outcomes among Florida counties -

  Background: During the COVID-19 pandemic, Florida reported some of the highest number of cases and deaths in the US; however, county-level variation in COVID-19 outcomes has not been comprehensively investigated. The present ecological study aimed to assess corelates of COVID-19 outcomes among Florida counties that explain variation in case rates, mortality rates, and case fatality rates (CFR) across pandemic waves. Method: We obtained county-level administrative data and COVID-19 case reports from public repositories. We tested spatial autocorrelation to assess geographic clustering in COVID-19 outcomes: case rate, mortality rate, and CFR. Stepwise linear regression was employed to test the association between case, death, and CFR and 18 demographic, socioeconomic, and health-related county-level predictors. Results: We found mortality rate and CFR were significantly higher in rural counties compared to urban counties, among which significant differences in vaccination coverage was also observed. Multivariate analysis found that the percentage of the population aged over 65 years, the percentage of the obese people, and the percentage of rural population were significant predictors of COVID-19 case rate. Median age, vaccination coverage, percentage of people who smoke, and percentage of the population with diabetes were significant influencing factors for CFR. Importantly, vaccination coverage was significantly associated with a reduction in case rate (R = -0.26, p = 0.03) and mortality (R = -0.51, p < 0.001). Last, we found that spatial dependencies play a role in explaining variations in COVID-19 CFR among Florida counties. Conclusion: Our findings emphasize the need for targeted, equitable public health strategies to reduce disparities and enhance population resilience during public health crises. We further inform future spatial-epidemiological analyses and present actionable data for policies related to preparedness and response to current and future epidemics in Florida and elsewhere.

  🖺 Full Text HTML: An ecological study of COVID-19 outcomes among Florida counties
• Superspreading of SARS-CoV-2: a systematic review and meta-analysis of event attack rates and individual transmission patterns -

  SARS-CoV-2 superspreading occurs when transmission is highly efficient and/or an individual infects many others, contributing to rapid spread. To better quantify heterogeneity in SARS-CoV-2 transmission, particularly superspreading, we performed a systematic review of transmission events with data on secondary attack rates or contact tracing of individual index cases published before September 2021, prior to emergence of variants of concern and widespread vaccination. We reviewed 592 distinct events and 9,883 index cases from 491 papers. Meta-analysis of secondary attack rates identified substantial heterogeneity across 12 event types/settings, with the highest transmission (25-35%) in co-living situations including households, nursing homes, and other congregate housing. Among index cases, 67% produced zero secondary cases and only 3% (287) infected >5 secondary cases (“superspreaders”). The highest percentage of superspreaders was among symptomatic individuals, individuals aged 49-64 years, and individuals with over 100 total contacts. However, only 55% of index cases reported age, sex, symptoms, real-time PCR cycle threshold values, or total contacts. Despite the limitations, our review highlighted that SARS-CoV-2 superspreading is more likely in settings with prolonged close contact and among symptomatic adults with many contacts. Enhanced reporting on transmission events and contact tracing could help explain heterogeneity and facilitate control efforts.

  🖺 Full Text HTML: Superspreading of SARS-CoV-2: a systematic review and meta-analysis of event attack rates and individual transmission patterns
• Predicting COVID-19 cases across a large university campus using complementary built environment and wastewater surveillance approaches -

  Background Environmental surveillance of SARS-CoV-2 via wastewater has become an invaluable tool for population-level surveillance. Built environment sampling may provide complementary spatially-refined detection for viral surveillance in congregate settings such as universities. Methods We conducted a prospective environmental surveillance study at the University of Ottawa between September 2021 and April 2022. Floor surface samples were collected twice weekly from six university buildings. Samples were analyzed for the presence of SARS-CoV-2 using RT-qPCR. A Poisson regression was used to model the campus-wide COVID-19 cases predicted from the fraction of floor swabs positive for SARS-CoV-2 RNA, building CO₂ levels, Wi-Fi usage, and SARS-CoV-2 RNA levels in regional wastewater. We used a mixed-effects Poisson regression analysis to model building-level cases using viral copies detected in floor samples as a predictor. A random intercepts logistic regression model tested whether floor samples collected in high-traffic areas were more likely to have SARS-CoV-2 present than low-traffic areas. Results Over the 32-week study period, we collected 554 floor swabs at six university buildings. Overall, 13% of swabs were PCR-positive for SARS-CoV-2, with positivity ranging between 4.8% and 32.7% among university buildings. Both floor swab positivity (Spearman r = 0.74, 95% CI: 0.53-0.87) and regional wastewater signal (Spearman r = 0.50, 95% CI: 0.18-0.73) were positively correlated with on-campus COVID-19 cases. In addition, built environment detection was a predictor of cases linked to individual university buildings (IR _{log10(copies) + 1} = 17, 95% CI: 7-44). There was no significant difference in detection between floors sampled in high-traffic versus low-traffic areas (OR = 1.3, 95% CI: 0.8-2.1). Conclusions Detection of SARS-CoV-2 RNA on floors and viral RNA levels found in wastewater were strongly associated with the incidence of COVID-19 cases on a university campus. These data suggest a potential role for institutional built environment sampling, used together with wastewater surveillance, for predicting COVID-19 cases at both campus-wide and building level scales.

  🖺 Full Text HTML: Predicting COVID-19 cases across a large university campus using complementary built environment and wastewater surveillance approaches
• Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative -

  Background: As SARS-CoV-2 has transitioned from a pandemic to endemic disease, the majority of new infections have been among previously infected individuals. To manage the risks and benefits of ongoing COVID-19 policies, it is important to understand whether prior infection modifies the severity of subsequent infections. Methods: We used data from first and second COVID-19 episodes in the National COVID Cohort Collaborative (N3C), a collection of health systems who provide de-identified electronic health records for research purposes. Our analysis was a sequential series of nested trial emulations. In the first of two analytic stages, we created a month-specific model of the probability of prior infection for each individual. In the second stage, we used an ordinal logistic regression with inverse probability weights calculated in the first stage to simulate a series of monthly trials comparing severity between the cohorts of first and second infections. In addition to cohort-wide effect estimates, we also conducted analyses among race/ethnicity, sex, and age subgroups. Results: From an initial cohort of 7,446,481 combined first and second infections, we identified a cohort of 2,227,484 infections, among which 7.6% were second infections. Ninety-four percent of patients with two recorded infections experienced mild disease for both. The overall odds ratio (OR) for more severe disease with prior infection was 1.06 (95% confidence interval [CI]: 1.03 to 1.10). Monthly point estimates of the OR ranged from 0.56 (95% CI: 0.37 to 0.84) in October 2020 to 1.64 (95% CI: 1.33 to 2.00) in February 2023. In most subgroups, the effect of prior infection was significant. In 8 out of 10 subgroups, the maximum monthly OR occurred after the minimum monthly OR, suggesting that protection has waned throughout the pandemic. Conclusion: Overall, prior infection was associated with a significant slightly elevated risk of severe disease. This effect varied month to month. As the pandemic proceeded, the effect of prior infection tended to evolve from generally protective during the pre-Omicron era to unprotective during the Omicron era. This points to the need for continued strategies to avert and minimize the harms of COVID-19, rather than relying upon immunity acquired through previous infection.

  🖺 Full Text HTML: Influence of Prior SARS-CoV-2 Infection on COVID-19 Severity: Evidence from the National COVID Cohort Collaborative
• Characterising information gains and losses when collecting multiple epidemic model outputs -

  Background. Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results. Methods. We compared July 2022 projections from the European COVID-19 Scenario Modelling Hub. Five modelling teams projected incidence in Belgium, the Netherlands, and Spain. We compared projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model9s quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data. Results. By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models9 quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes. Conclusions. We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort9s aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts.

  🖺 Full Text HTML: Characterising information gains and losses when collecting multiple epidemic model outputs
• No Utilitarians in a Pandemic? Shifts in Moral Reasoning during the COVID-19 Global Health Crisis -
  The COVID-19 pandemic poses many real-world moral dilemmas, which can pit the needs and rights of the many against the needs and rights of the few. We investigated the influence of this contemporary global crisis on moral judgments in older adults, who are at greatest personal risk from the pandemic. We hypothesized that during this pandemic, individuals would give fewer utilitarian responses to hypothetical dilemmas, accompanied by higher levels of confidence and emotion elicitation. Our pre-registered analysis (https://osf.io/g2wtp) involved two waves of data collection, before (2014) and during (2020) the COVID-19 pandemic, regarding three categories of moral dilemmas (personal rights, agent-centered permissions, and special obligations). While utilitarian responses considered across all categories of dilemma did not differ, participants during the 2020 wave gave fewer utilitarian responses to dilemmas involving personal rights; that is, they were less willing to violate the personal rights of others to produce the best overall outcomes.
  🖺 Full Text HTML: No Utilitarians in a Pandemic? Shifts in Moral Reasoning during the COVID-19 Global Health Crisis
• The global and specific cardiovascular burden of spike-based Covid-19 1 Vaccination -
  Aims: The aim of this investigation was to determine whether the global and cardiovascular 10 burden associated with spike-based Covid-19 vaccination has continued to increase. 11 Methods and results: An updated analysis of spontaneously reported individual cases with 12 ADRs and their fatal outcomes associated with Covid-19 vaccines, as well as adverse 13 cardiovascular events caused by the spike-inducing vaccine Tozinameran, was performed. 14 Data were retrieved from the EudraVigilance web reports of the European Medicines Agency 15 (EMA). All evaluated adverse events correspond to the search terms of the EudraVigilance 16 based on clinical characterisation. 17 The total number of individual cases (n=2256506; i.e. 2338/day) with adverse effects that were 18 fatal in 2.3% (n=51740; i.e. 54 deaths/day), as well as the wide range of reports of 19 cardiovascular adverse effects, have revealed the unusual magnitude and specificity of these 20 events. 21 Tachycardia, arrhythmia, atrial fibrillation/flatter, bradyarrhythmia and impaired stimulus 22 formation and conduction (n=57438 combined) dominated the cardiovascular side effect profile 23 of Tozinameran, followed by blood pressure increase (n=25907), myo-/pericarditis (n=23775), 24 heart failure, cardiomyopathy, cardiac flatter/fibrillation, cardiac arrest, circulatory collaps 25 (n=16778 combined) and coronary artery disease/myocardial infarction (n=9912). The 26 importance of acute cardiovascular reactions is underlined by the fact that deaths caused by 27 them accounted for at least one third (35%) of all deaths associated with Tozinameran’s side 28 effects 29 Based on individual assessment, ARBs are currently recommended in the treatment of spike-30 induced symptoms. 31 Conclusions: The spectrum of side effects of spike-based Covid-19 vaccines is more extensive 32 and severe than is generally known, Adverse cardiovascular events convincingly reflect the 33 mode of spike action, namely down-regulating of the cardiovascular protective enzyme ACE2 34 resulting in increasing Ang II concentrations. A fundamental re-evaluation of the benefit-risk 35 assessment of these novel vaccines is mandatory. Health professionals should be educated about 36 the consequences of spike-induced ACE2 downregulation, the resulting symptoms and 37 therapeutic options.
  🖺 Full Text HTML: The global and specific cardiovascular burden of spike-based Covid-19 1 Vaccination

From Clinical Trials

• Long COVID-19 [11C]CPPC Study - Conditions: COVID Long-Haul
  Interventions: Drug: [11C]CPPC Injection; Drug: [11C]CPPC Injection
  Sponsors: Johns Hopkins University; Radiological Society of North America
  Not yet recruiting

• Thrombohemorrhagic Complications of COVID-19 - Conditions: COVID-19 (Coronavirus Disease 2019)
  Interventions: Diagnostic Test: Prevention algorithm
  Sponsors: Volgograd State Medical University
  Active, not recruiting

• Combined Use of Immunoglobulin and Pulse Steroid Therapies in Severe Covid-19 Patients - Conditions: Pulse Steroid and Immunoglobulins Drugs in Covid 19 Patients
  Interventions: Drug: pulse steroid and nanogam
  Sponsors: Konya City Hospital
  Completed

• Beneficial Effects of Natural Products on Management of Xerostomia - Conditions: Xerostomia; Diabetes Mellitus; Hypertension; Post COVID-19 Condition
  Interventions: Other: (Manuka honey-green tea- ginger)
  Sponsors: British University In Egypt
  Completed

• Eficacia Ventilatoria y Remolacha - Conditions: SARS CoV 2 Infection; Muscle Disorder; Fatigue
  Interventions: Dietary Supplement: Remolacha
  Sponsors: Hospital de Mataró
  Recruiting

• Diet and Fasting for Long COVID - Conditions: Long Covid19; Long COVID
  Interventions: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting
  Sponsors: Pacific Northwest University of Health Sciences
  Recruiting

• The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia - Conditions: Post COVID-19 Condition
  Interventions: Other: Protein powder and Resistance exercise
  Sponsors: Mahidol University; National Health Security Office, Thailand
  Not yet recruiting

• Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico - Conditions: Long Covid19
  Interventions: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management)
  Sponsors: University of Puerto Rico; National Institutes of Health (NIH)
  Recruiting

• Treatment of Persistent Post-Covid-19 Smell and Taste Disorders - Conditions: Post-covid-19 Persistent Smell and Taste Disorders
  Interventions: Drug: Cerebrolysin; Other: olfactory and gustatory trainings
  Sponsors: Sherifa Ahmed Hamed
  Completed

• A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults - Conditions: COVID-19; COVID-19 Immunisation
  Interventions: Biological: TI-0010; Biological: Placebo
  Sponsors: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna
  Recruiting

From PubMed

• DON/DRP-104 as potent serine protease inhibitors implicated in SARS-CoV-2 infection: Comparative binding modes with human TMPRSS2 and novel therapeutic approach - Human transmembrane serine protease 2 (TMPRSS2) is an important member of the type 2 transmembrane serine protease (TTSP) family with significant therapeutic markings. The search for potent TMPRSS2 inhibitors against severe acute respiratory syndrome coronavirus 2 infection with favorable tissue specificity and off-site toxicity profiles remains limited. Therefore, probing the anti-TMPRSS2 potential of enhanced drug delivery systems, such as nanotechnology and prodrug systems, has become…

• Fluoxetine exerts anti-inflammatory effects on human epidermal keratinocytes and suppresses their endothelin release - Fluoxetine is a safe antidepressant with remarkable anti-inflammatory actions; therefore, we aimed to investigate its effects on immortalized (HaCaT) as well as primary human epidermal keratinocytes in a polyinosinic-polycytidylic acid (p(I:C))-induced inflammatory model. We found that a non-cytotoxic concentration (MTT-assay, CyQUANT-assay) of fluoxetine significantly suppressed p(I:C)-induced expression and release of several pro-inflammatory cytokines (Q-PCR, cytokine array, ELISA), and it…

• Flavonoids derived from medicinal plants as a COVID-19 treatment - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 disease. Through its viral spike (S) protein, the virus enters and infects epithelial cells by utilizing angiotensin-converting enzyme 2 as a host cell’s receptor protein. The COVID-19 pandemic had a profound impact on global public health and economies. Although various effective vaccinations and medications are now available to prevent and treat COVID-19, natural compounds derived from medicinal plants,…

• Mutational analysis of SARS-CoV-2 ORF6-KPNA2 binding interface and identification of potent small molecule inhibitors to recuse the host immune system - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced on 31 December, 2019, and was identified as the causative agent of the global COVID-19 pandemic, leading to a pneumonia-like disease. One of its accessory proteins, ORF6, has been found to play a critical role in immune evasion by interacting with KPNA2 to antagonize IFN signaling and production pathways, resulting in the inhibition of IRF3 and STAT1 nuclear translocation. Since various mutations have been observed in ORF6,…

• Intraepithelial Inclusions on Urinalysis Screening among COVID-19 Cases: Are they Covicytes?-A Hospital-Based Cohort Study with Narrative Review - CONCLUSIONS: This study reported COVID-19-associated urinary cytomorphological abnormalities and interesting unique inclusions (Covicytes) that may be a result of underlying inflammatory changes, reactive hyperplasia, degenerative changes, or defective endocytosed vacuoles. The possible etiologies for renal inclusions were reviewed. We recommend compulsory baseline and follow-up urinary cytology screening for all COVID-19-suspected patients to detect and predict delayed AKI before clinical and…

• Marine natural products and human immunity: novel biomedical resources for anti-infection of SARS-CoV-2 and related cardiovascular disease - Marine natural products (MNPs) and marine organisms include sea urchin, sea squirts or ascidians, sea cucumbers, sea snake, sponge, soft coral, marine algae, and microalgae. As vital biomedical resources for the discovery of marine drugs, bioactive molecules, and agents, these MNPs have bioactive potentials of antioxidant, anti-infection, anti-inflammatory, anticoagulant, anti-diabetic effects, cancer treatment, and improvement of human immunity. This article reviews the role of MNPs on…

• Antibodies against SARS-CoV-2 non-structural protein 3 cross-react with human muscle cells and neuroglial cells - Coronavirus Disease 2019 (COVID-19) vaccines protect the public and limit viral spread. However, inactivated viral vaccines use the whole virus particle, which contains many non-capsid proteins that may cause adverse immune responses. A report has found that the ADP-ribose-binding domains of SARS-CoV-2 non-structural protein 3 (NSP3) and human poly(ADP-ribose) polymerase family member 14 (PARP14) share a significant degree of homology. Here, we further show that antibodies against 2019 novel…

• Eculizumab led to beneficial clinical course in a patient with generalized myasthenia gravis who developed COVID 19-associated pneumonia - A 74-year-old woman developed myasthenia gravis (MG) at the age of 32. She had a thymoma removed the following year, but her MG symptoms did not stabilize, and she required frequent hospitalization for fast-acting treatment (FT). She started eculizumab in March of two years ago and was followed up on an outpatient basis as her MG symptoms became milder. In February of this year, she was admitted to our hospital due to mild COVID-19-associated pneumonia with general malaise and fever. Her…

• Lower respiratory tract single-cell RNA sequencing and neutrophil extracellular trap profiling of COVID-19-associated pulmonary aspergillosis: a single centre, retrospective, observational study - BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is a severe superinfection with the fungus Aspergillus affecting patients who are critically ill with COVID-19. The pathophysiology and the role of neutrophil extracellular traps (NETs) in this infection are largely unknown. We aimed to characterise the immune profile, with a focus on neutrophils and NET concentrations, of critically ill patients with COVID-19, with or without CAPA.

• An ensemble docking-based virtual screening and molecular dynamics simulation of phytochemical compounds from Malaysian Kelulut Honey (KH) against SARS-CoV-2 target enzyme, human angiotensin-converting enzyme 2 (ACE-2) - The human angiotensin-converting enzyme 2 (ACE-2) receptor is a metalloenzyme that plays an important role in regulating blood pressure by modulating angiotensin II. This receptor facilitates SARS-CoV-2 entry into human cells via receptor-mediated endocytosis, causing the global COVID-19 pandemic and a major health crisis. Kelulut honey (KH), one of Malaysian honey recently gained attention for its distinct flavour and taste while having many nutritional and medicinal properties. Recent study…

• Anti-COVID-19 Potential of Withaferin-A and Caffeic Acid Phenethyl Ester - CONCLUSION: Wi-A and CAPE possess multimodal anti-COVID-19 potential, and their combination (Wi-ACAPE) is expected to provide better activity and hence warrant further attention in the laboratory and clinic.

• Recurrent viral capture of cellular phosphodiesterases that antagonize OAS-RNase L - Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions are less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were…

• Inhibitory Activity of Flavonoid Scaffolds on SARS-CoV-2 3CL^pro: Insights from the Computational and Experimental Investigations - The emergence of the COVID-19 situation has become a global issue due to the lack of effective antiviral drugs for treatment. Flavonoids are a class of plant secondary metabolites that have antiviral activity against SARS-CoV-2 through inhibition of the main protease (3CL^(pro)). In this study, 22 flavonoids obtained from natural sources and semisynthetic approaches were investigated for their inhibitory activity against SARS-CoV-2 3CL^(pro), along with cytotoxicity on Vero cells. The…

• Triterpenoidal Saponins from the Leaves of Aster koraiensis Offer Inhibitory Activities against SARS-CoV-2 - Triterpenoidal saponins have been reported to be able to restrain SARS-CoV-2 infection. To isolate antiviral compounds against SARS-CoV-2 from the leaves of Aster koraiensis, we conducted multiple steps of column chromatography. We isolated six triperpenoidal saponins from A. koraiensis leaves, including three unreported saponins. Their chemical structures were determined using HR-MS and NMR data analyses. Subsequently, we tested the isolates to assess their ability to impede the entry of the…

• Assessing Genomic Mutations in SARS-CoV-2: Potential Resistance to Antiviral Drugs in Viral Populations from Untreated COVID-19 Patients - Naturally occurring SARS-CoV-2 variants mutated in genomic regions targeted by antiviral drugs have not been extensively studied. This study investigated the potential of the RNA-dependent RNA polymerase (RdRp) complex subunits and non-structural protein (Nsp)5 of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to accumulate natural mutations that could affect the efficacy of antiviral drugs. To this aim, SARS-CoV-2 genomic sequences isolated from 4155 drug-naive individuals from…

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