Covid-19 Sentry

Contents

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

From Preprints

• The use and acceptability of preprints in health and social care settings: a scoping review -
  Background: Preprints are open and accessible scientific manuscript or report that is shared publicly, through a preprint server, before being submitted to a journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The scoping review explored the current evidence on the use and acceptability of preprints in health and social care settings by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
  🖺 Full Text HTML: The use and acceptability of preprints in health and social care settings: a scoping review
• 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
• XBB.1.5 Spike Protein COVID-19 Vaccine Induces Broadly Neutralizing and Cellular Immune Responses Against EG.5.1 and Emerging XBB Variants -
  Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces cross-neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4+ T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023-2024 COVID-19 vaccination campaign.
  🖺 Full Text HTML: XBB.1.5 Spike Protein COVID-19 Vaccine Induces Broadly Neutralizing and Cellular Immune Responses Against EG.5.1 and Emerging XBB Variants
• Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 enhances antibody evasion and ACE2 binding -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants like EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. Specifically, L455F and F456L evades Class 1 NAbs, which could reduce the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.
  🖺 Full Text HTML: Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 enhances antibody evasion and ACE2 binding
• How much should we sequence? An analysis of the Swiss SARS- CoV-2 surveillance effort -

  Background During the SARS-CoV-2 pandemic, many countries directed substantial resources towards genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. Aim We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic dataset from Switzerland, comprising more than 143k sequences. Methods We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. Results The impact of downsampling on VOC detection is disparate for the three VOC lineages , but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. Conclusion A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage dependent - something that is unknown at the time of sequencing - and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.

  🖺 Full Text HTML: How much should we sequence? An analysis of the Swiss SARS- CoV-2 surveillance effort
• Association between pre-existing conditions and hospitalization, intensive care services and mortality from COVID-19, a cross sectional analysis of an international global health data repository -

  Objective To investigate the association between pre-existing conditions and hospitalization, need for intensive care services (ICU) and mortality due to COVID-19. Methods We used data on all cases recorded in the Global Health Data repository up to the 10th of March 2021 to carry out a cross-sectional analysis of associations between cardiovascular diseases (CVD), hypertension, diabetes, obesity, lung diseases and kidney disease and hospitalization, ICU admission and mortality due to COVID-19. The Global Health repository reported data from 137 countries, but only Brazil, Mexico and Cuba reported more than 10 COVID-19 cases in participants with preexisting conditions. We used multivariable logistic regression to compute adjusted odds ratios (aOR) of the three outcomes for each pre-existing condition in ten-year age groups from 0-9 years and up to 110-120 years. Results The Global Health repository held 25 900 000 records of confirmed cases of COVID-19, of which 2 900 000 cases were from Brazil, Mexico and Cuba. The overall adjusted odds of hospitalization for the selected pre-existing condition were; CVD (OR 1.7, 95%CI 1.7-1.7), hypertension (OR 1.5, 95%CI 1.4-1.5), diabetes (OR 2.2, 95%CI 2.1-2.2), obesity (OR 1.7, 95%CI 1.6-1.7), kidney disease (OR 5.5, 95%CI 5.2-5.7) and lung disease (OR 1.9, 95%CI 1.8-1.9). The overall adjusted odds of ICU admission for each pre-existing condition were; CVD (OR 2.1, 95%CI 1.8-2.4), hypertension (OR 1.3, 95%CI 1.2-1.4), diabetes (OR 1.7, 95%CI 1.5-1.8), obesity (OR 2.2, 95%%CI 2.1-2.4), kidney disease (OR 1.4, 95%CI 1.2-1.7) and lung disease (OR 1.1, 95%CI 0.9-1.3). The overall adjusted odds of mortality for each pre-existing condition were; CVD (OR 1.7, 95%CI 1.6-1.7), hypertension (OR 1.3, 95%CI 1.3-1.4), diabetes (OR 2.0, 95%CI 1.9-2.0), obesity (OR 1.9, 95%CI 1.8-2.0), kidney disease (OR 2.7, 95%CI 2.6-2.9) and lung disease (OR 1.6, 95%CI 1.5-1.7). The odds of each outcome were considerably larger in children and young adults with these preexisting conditions than for adults, especially for kidney disease, CVD, and diabetes. Conclusion This analysis of a global health repository confirms associations between pre-existing diseases and clinical outcomes of COVID-19. The odds of these outcomes are especially elevated in children and young adults with these preexisting conditions.

  🖺 Full Text HTML: Association between pre-existing conditions and hospitalization, intensive care services and mortality from COVID-19, a cross sectional analysis of an international global health data repository
• Vaccination status and re-infection among COVID patients admitted in COVID High Dependency Unit (HDU) of a tertiary hospital in Eastern Nepal: A cross-sectional study -

  Introduction The relationship between COVID-19 vaccination and Coronavirus disease severity and outcomes remain topics of significant interest. This cross-sectional study done among COVID-19 patients admitted to the High-dependency unit of a tertiary hospital in Eastern Nepal aimed to assess the association between vaccination status, prior infection, and disease outcomes, and the modification of these associations by the presence or absence of comorbidities. Methodology Demographic and clinical data were collected from 102 COVID-19 patients admitted to the High-Dependency Unit of Mechi Zonal Hospital, including information on vaccination status, comorbidities, disease severity, and outcomes. Statistical analysis, including chi-square tests and Fisher9s exact tests, was performed to examine the associations. Results Among the study participants, 49% had received at least one dose of COVID-19 vaccine. Vaccinated individuals had a significantly lower rate of severe disease compared to non-vaccinated individuals (χ2=10.05, p=0.002). Recovery and mortality rates did not differ significantly between the two groups (χ2=1.008, p=0.315). However, when stratified by comorbidities, vaccinated individuals with comorbidities had higher recovery rates compared to non-vaccinated individuals (85.29% vaccinated vs. 25.00% non-vaccinated, Fisher9s exact test p=0.024). Vaccinated individuals, both with and without comorbidities, had lower rates of severe disease compared to non-vaccinated individuals. However, the association was found to be significant only in individuals with comorbidities (12.50% vaccinated without comorbidities vs. 47.92% non-vaccinated, p=0.017; 23.53% vaccinated with comorbidities vs. 75.00% non-vaccinated, p=0.065). Conclusion Our findings suggest that COVID-19 vaccination is associated with a reduced risk of severe disease among individuals with or without comorbidities and decreased risk of mortality among those with comorbidities. However, larger studies are needed to validate these findings and further explore the impact of vaccination on disease outcomes. These findings support the ongoing efforts to promote COVID-19 vaccination as a crucial public health intervention.

  🖺 Full Text HTML: Vaccination status and re-infection among COVID patients admitted in COVID High Dependency Unit (HDU) of a tertiary hospital in Eastern Nepal: A cross-sectional study
• A retrospective longitudinal study of adenovirus group F, norovirus GI and GII, rotavirus, and enterovirus nucleic-acids in wastewater solids at two wastewater treatment plants: Solid-liquid partitioning and relation to clinical testing data -

  Background: Enteric infections are important causes of morbidity and mortality, yet clinical surveillance is limited. Wastewater-based epidemiology (WBE) has been used to study community circulation of individual enteric viruses and panels of respiratory diseases, but there is limited work studying concurrent circulation of a suite of important enteric viruses. Methods: A retrospective WBE study was carried out at two wastewater treatment plants located in California, United States. Using droplet digital polymerase chain reaction (PCR), we measured concentrations of human adenovirus group F, enteroviruses, norovirus genogroups I and II, and rotavirus nucleic-acids in wastewater solids two times per week for 26 months (n=459 samples) between 2/1/21 and 4/14/23. A novel probe-based PCR assay was developed and validated for adenovirus. We compared viral nucleic-acid concentrations to positivity rates for viral infections from clinical specimens submitted to a local clinical laboratory to assess concordance between the data sets. Findings: We detected all viral targets in wastewater solids. At both wastewater treatment plants, human adenovirus group F and norovirus GII nucleic-acids were detected at the highest concentrations (median concentrations greater than 105 cp/g), while rotavirus RNA was detected at the lowest concentrations (median on the order of 103 cp/g). Rotavirus, adenovirus group F, and norovirus nucleic-acid concentrations were positivity associated with clinical specimen positivity rates. Concentrations of tested viral nucleic-acids exhibited complex associations with SARS-CoV-2 and other respiratory viral nucleic-acids in wastewater, suggesting divergent transmission patterns. Interpretation: This study provides evidence for the use of wastewater solids for the sensitive detection of enteric virus targets in WBE programs aimed to better understand the spread of enteric disease at a localized, community level without limitations associated with testing many individuals. Wastewater data can inform clinical, public health, and individual decision making aimed to reduce transmission of enteric disease.

  🖺 Full Text HTML: A retrospective longitudinal study of adenovirus group F, norovirus GI and GII, rotavirus, and enterovirus nucleic-acids in wastewater solids at two wastewater treatment plants: Solid-liquid partitioning and relation to clinical testing data
• Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19 -

  Although severe coronavirus disease 19 (COVID-19) and hospitalization associated with COVID-19 are generally preventable among healthy vaccine recipients, patients with immunosuppression have poor immunogenic responses to COVID-19 vaccines and remain at high risk of infection with SARS-CoV-2 and hospitalization. Additionally, monoclonal antibody therapy is limited by the emergence of novel SARS-CoV-2 variants that have serially escaped neutralization. In this context, there is interest in understanding the clinical benefit associated with COVID-19 convalescent plasma collected from persons who have been both naturally infected with SARS-CoV-2 and vaccinated against SARS-CoV-2 (vax-plasma). Thus, we report the clinical outcome of 208 immunocompromised outpatients who were diagnosed with COVID-19 and who received contemporary COVID-19 specific therapeutics (standard of care group) and a subgroup who also received concomitant treatment with very high titer COVID-19 convalescent plasma (vax-plasma group) with a specific focus on hospitalization rates. The overall hospitalization rate was 1% (1 of 123 patients) in the vax-plasma group and 6% (5 of 85 patients) in the standard of care group, which corresponded to a relative risk reduction of 83%. Evidence of efficacy in nonvaccinated patients cannot be inferred from these data because 94% (196 of 208 patients) of patients were vaccinated. In vaccinated patients with immunosuppression and COVID-19, the addition of vax-plasma or very high titer COVID-19 convalescent plasma to COVID-19 specific therapies reduced the risk of disease progression leading to hospitalization.

  🖺 Full Text HTML: Outpatient treatment with concomitant vaccine-boosted convalescent plasma for patients with immunosuppression and COVID-19
• Clinical pattern and diagnostic of comorbidity of respiratory tuberculosis and viral pneumonia caused by Herpesvirus Simplex, Human Cytomegalovirus and SARS-CoV-2 in patients with late-stage HIV infection with immunodeficiency -

  Aim. To study features of social status, clinical pattern and diagnosis in cases of comorbidity of respiratory tuberculosis and viral pneumonia caused by Herpesvirus Simplex of type 1, Human Cytomegalovirus and SARS-CoV-2 in patients with late-stage HIV infection with immunodeficiency. Materials and methods. The prospective study included 25 patients with comorbid condition of respiratory tuberculosis with Mycobacterium tuberculosis in excreta, herpesvirus and coronavirus pneumonia, and 21 patients with respiratory tuberculosis as well as cytomegalovirus and coronavirus pneumonia (1a and 2a main groups) and, respectively, 25 and 21 similar patients, but without coronavirus pneumonia (1b and 2b comparison group) in the late stages of HIV infection with immunodeficiency. For the etiological diagnosis of herpesvirus and cytomegalovirus pneumonia, the PCR test was used for recognition of DNA of Herpesvirus Simplex of type 1 and Human Cytomegalovirus in the diagnostic material of respiratory tract and for the etiological diagnosis of coronavirus pneumonia, the PCR for recognition of RNA was used to reveal SARS-CoV-2. Statistical analysis of the data was performed by the use of the Microsoft Office Excel 2019 software for calculation of group mean, standard error of mean and confidence interval. Results. The comorbidity of respiratory tuberculosis, herpes-, cytomegalo- and coronavirus pneumonia in patients with late-stage HIV infection in the phase of progression and in the absence of ART was characterized by severe immunodeficiency and generalization of tuberculosis with multiple extrapulmonary lesions. The results displayed similarity of clinical manifestations and visualization of changes in CT-picture in cases of comorbidity the diseases which hampers their recognition due to simultaneous combination of several pathologies with similar clinical manifestations that requires a complex etiological diagnosis of the specific diseases to prescribe a timely comprehensive treatment and reduce lethality in this severe contingent of patients. Conclusion. Patients with respiratory tuberculosis and HIV infection registered in the office of tuberculosis care for HIV-infected individuals in the antituberculosis dispensary represent a group of high risk from COVID-19 infection and CVP disease, and, in cases of combination with severe immunodeficiency, HVP and CMVP, the patients should be regularly subjected to preventive studies for timely detection of COVID-19 for the purpose of their emergency isolation and treatment.

  🖺 Full Text HTML: Clinical pattern and diagnostic of comorbidity of respiratory tuberculosis and viral pneumonia caused by Herpesvirus Simplex, Human Cytomegalovirus and SARS-CoV-2 in patients with late-stage HIV infection with immunodeficiency
• Validation of neutralizing antibody titers for estimating vaccine effectiveness for the Omicron SARS-CoV-2 variant, BA.1 -

  Background: The emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to immune escape and reduced vaccine effectiveness. Neutralizing antibody titers could be used to quickly estimate vaccine effectiveness (VE), because they can be easily measured following the emergence of a new virus variant and have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens. However, few studies have examined VE-neutralizing antibody titer relationships with multiple virus variants, and none have validated relationships for immune evasive variants. Methods: We leveraged variation among vaccines and virus variants to estimate VE-neutralizing antibody titer relationships across a 54-fold range of neutralizing antibody titers for two endpoints for COVID-19: symptomatic disease, and hospitalization. We predicted VEs for Omicron three days after the first neutralizing antibody titer became available. We tested these predictions using subsequently collected observational VE data. Findings: For two mRNA vaccines (mRNA-1273, BNT162b2), fitted models predicted that infection with the BA.1 Omicron variant would increase the risk of hospitalization 2.8-4.4-fold and increase the risk of symptomatic disease 1.7-4.2-fold compared to the Delta variant. However, a third vaccine dose was predicted to restore protection. Out-of-sample validation data indicated that model predictions were quite accurate, with all predictions being within 10% of observed VE estimates, and all empirical estimates fell within the model prediction intervals. Interpretation: These analyses demonstrate that models using neutralizing antibody titers can provide rapid VE estimates which can inform vaccine design and selection.

  🖺 Full Text HTML: Validation of neutralizing antibody titers for estimating vaccine effectiveness for the Omicron SARS-CoV-2 variant, BA.1
• Nebulised dornase alfa reduces inflammation and improves clinical outcomes in severe COVID-19: a randomised clinical trial -

  Background: Cell-free (cf)-DNA, from cellular sources, including Neutrophil Extracellular Traps (NETs), is found in the circulation of COVID-19 patients and may contribute to immune dysregulation. This study determined whether pulmonary administration of the endonuclease, dornase alfa, reduced systemic inflammation by degrading local and systemic cf-DNA. Methods: Eligible patients were randomized (3:1) to receive twice-daily nebulised dornase alfa in addition to best available care (BAC) or BAC alone for seven days or until discharge. A 2:1 ratio of matched contemporary controls (CC) provided additional comparators. The primary endpoint was improvement in C-reactive protein (CRP) over time, analysed using a repeated-measures mixed model, adjusted for baseline factors. Results: Between June 2020-October 2021 we recruited 39 evaluable patients: 30 randomised to dornase alfa; 9 randomised to BAC; with 60 CC. Dornase alfa reduced CRP by 33% compared to BAC. Least squares (LS) mean post-dexamethasone CRP fell from 101.9mg/L to 23.23 mg/L in the BAC+ dornase alfa group versus a fall from 99.5mg/L to 34.82 mg/L in the BAC group at 7 days; P=0.01. This effect of dornase alfa on CRP was confirmed with subgroup and sensitivity analyses. Dornase alfa increased the chance of live discharge by 63% (HR 1.63, 95% CI 1.01 to 2.61, P=0.03), increased lymphocyte counts (LSmean 1.08 vs 0.87, P=0.02) and reduced circulating cf-DNA and the coagulopathy marker D-dimer (LS mean: 570.78 vs 1656.96 μg/mL, P=0.004). Dornase alfa was well-tolerated. Conclusions: We provide proof-of-concept evidence that dornase alfa can reduce pathogenic inflammation in hospitalised patients with COVID-19 pneumonia.

  🖺 Full Text HTML: Nebulised dornase alfa reduces inflammation and improves clinical outcomes in severe COVID-19: a randomised clinical trial
• Epidemiological modeling of SARS-CoV-2 in white-tailed deer (Odocoileus virginianus) reveals conditions for introduction and widespread transmission -
  Emerging infectious diseases with zoonotic potential often have complex socioecological dynamics and limited ecological data, requiring integration of epidemiological modeling with surveillance. Although our understanding of SARS-CoV-2 has advanced considerably since its detection in late 2019, the factors influencing its introduction and transmission in wildlife hosts, particularly white-tailed deer (Odocoileus virginianus), remain poorly understood. We use a Susceptible-Infected-Recovered-Susceptible epidemiological model to investigate the spillover risk and transmission dynamics of SARS-CoV-2 in wild and captive white-tailed deer populations across various simulated scenarios. We found that captive scenarios pose a higher risk of SARS-CoV-2 introduction from humans into deer herds and subsequent transmission among deer, compared to wild herds. However, even in wild herds, the transmission risk is often substantial enough to sustain infections. Furthermore, we demonstrate that the strength of introduction from humans influences outbreak characteristics only to a certain extent. Transmission among deer was frequently sufficient for widespread outbreaks in deer populations, regardless of the initial level of introduction. We also explore the potential for fence line interactions between captive and wild deer to elevate outbreak metrics in wild herds that have the lowest risk of introduction and sustained transmission. Our results indicate that SARS-CoV-2 could be introduced and maintained in deer herds across a range of circumstances based on testing a range of introduction and transmission risks in various captive and wild scenarios. Our approach and findings will aid One Health strategies that mitigate persistent SARS-CoV-2 outbreaks in white-tailed deer populations and potential spillback to humans.
  🖺 Full Text HTML: Epidemiological modeling of SARS-CoV-2 in white-tailed deer (Odocoileus virginianus) reveals conditions for introduction and widespread transmission
• Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis -
  Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression in concert with emergency hematopoiesis. Epigenetic changes, notably in the form of histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA methylation to this process remains poorly understood. Using an ex vivo sepsis model, we discovered broad changes in DNA methylation throughout the genome of exhausted monocytes, including at several genes previously implicated as major drivers of immune dysregulation during sepsis and Covid-19 infection (e.g. Plac8). Methylome alterations are driven in part by Wnt signaling inhibition in exhausted monocytes, and can be reversed through treatment with DNA methyltransferase inhibitors, Wnt agonists, or immune training molecules. Importantly, these changes are recapitulated in septic mice following cecal slurry injection, resulting in stable changes at critical immune genes that support the involvement of DNA methylation in acute and long-term monocyte dysregulation during sepsis.
  🖺 Full Text HTML: Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis
• SenePy: Unveiling the Cell-Type Specific Landscape of Cellular Senescence through Single-Cell Analysis in Living Organisms -
  Senescent cells accumulate in tissues with organismal age and contribute causally to multiple chronic diseases. In vivo senescent cell phenotypes are heterogeneous because cellular context and stressors vary by cell type and tissue. Due to the variability of senescence programs, there is no universal method to identify senescent cells and even widely used markers, such as CDKN2A, are not ubiquitous. Therefore, we interrogated the Tabula Muris Senis mouse single-cell aging atlas and an array of single-cell datasets from human donors that spanned many ages to find cell-specific signatures of cellular senescence. We derived 75 mouse and 65 human senescence signatures from individual cell populations. CDKN2A and other markers of senescence were overrepresented in these signatures but there were many novel senescence genes present at higher rates. Within individual cell populations, we observed multiple programs of senescence with distinct temporal and transcriptional characteristics. We packaged the signatures along with a single-cell scoring method into an open-source package: SenePy. SenePy signatures better recapitulate cellular senescence than available methods when tested on multiple in vivo RNA-seq datasets and a p16ink4a reporter single-cell dataset. We used SenePy to map the kinetics of senescent cell accumulation across 97 cell types from humans and mice. SenePy also generalizes to disease-associate senescence and we used it to identify an increased burden of senescent cells in COVID-19 and myocardial infarction. This work provides a significant advancement towards our ability to identify and characterize in vivo cellular senescence.
  🖺 Full Text HTML: SenePy: Unveiling the Cell-Type Specific Landscape of Cellular Senescence through Single-Cell Analysis in Living Organisms

From Clinical Trials

• THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL - Condition:   COVID-19
  Intervention:   Dietary Supplement: Neomune
  Sponsors:   Universitas Sriwijaya;   M. Djamil General Hospital
  Completed

• Study of Obeldesivir in Children and Adolescents With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Obeldesivir
  Sponsor:   Gilead Sciences
  Not yet recruiting

• KAND567 Versus Placebo in Subjects Hospitalized With COVID-19 - Condition:   Covid19
  Interventions:   Drug: KAND567;   Drug: Microcrystalline cellulose
  Sponsor:   Kancera AB
  Terminated

• Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome - Conditions:   Post-COVID-19 Syndrome;   Long-COVID-19 Syndrome
  Intervention:   Behavioral: Aerobic Exercise Training
  Sponsors:   University of Witten/Herdecke;   Verein und Institut für Rehabilitationsforschung Norderney
  Completed

• Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong - Conditions:   Digital Health Literacy;   COVID-19
  Intervention:   Behavioral: Digital health literacy intervention
  Sponsor:   The Hong Kong Polytechnic University
  Not yet recruiting

• A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection - Condition:   COVID-19
  Interventions:   Drug: Experimental: Primary Cohort;   Other: Placebo Comparator: Primary Cohort - Placebo
  Sponsor:   University of Chicago
  Active, not recruiting

• COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease - Conditions:   Sickle Cell Disease;   COVID-19 Vaccine;   Vaccine Hesitancy
  Intervention:   Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video
  Sponsors:   Duke University;   American Society of Hematology
  Not yet recruiting

• Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations - Conditions:   Influenza;   COVID-19;   Influenza Immunogencity;   COVID-19 Immunogenicity
  Interventions:   Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster);   Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster);   Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)
  Sponsors:   Duke University;   Centers for Disease Control and Prevention;   Arizona State University;   University Hospitals Cleveland Medical Center;   University of Pittsburgh;   Washington University School of Medicine;   Valleywise Health;   VA Northeast Ohio Health Care;   Senders Pediatrics
  Not yet recruiting

• Leveraging Community Health Workers to Combat COVID-19 and Mental Health Misinformation in Haiti, Malawi, and Rwanda - Conditions:   Mental Health;   COVID-19;   Misinformation
  Interventions:   Behavioral: Card-Sorting Activity (Pre-intervention design);   Behavioral: SMS Crafting (Pre-intervention design);   Behavioral: SMS Messaging
  Sponsors:   Harvard Medical School (HMS and HSDM);   Partners in Health
  Active, not recruiting

• Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh - Condition:   Pulmonary Pathology
  Intervention:   Behavioral: Pulmonary Rehabilitation
  Sponsor:   Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  Active, not recruiting

• A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Varients in Healthy Individuals - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Intervention:   Biological: BNT162b2 (Omi XBB.1.5)
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19. - Condition:   Nervous System Diseases
  Interventions:   Drug: Tianeptine;   Drug: Placebo
  Sponsors:   Military Institute od Medicine National Research Institute;   ABM Industries
  Recruiting

• Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition - Condition:   Cognitive Behavioral Therapy
  Intervention:   Behavioral: cognitive behavioral therapy
  Sponsor:   Tri-Service General Hospital
  Not yet recruiting

• The Effectiveness of Natural Resources for Reducing Stress - Conditions:   Distress, Emotional;   COVID-19
  Interventions:   Combination Product: Balneotherapy plus complex;   Combination Product: Combined nature resources treatment;   Other: Nature therapy procedure
  Sponsors:   Klaipėda University;   Research Council of Lithuania
  Active, not recruiting

• Study of LAU-7b for the Treatment of Long COVID in Adults - Condition:   Long COVID
  Interventions:   Drug: LAU-7b for 3 cycles;   Drug: LAU-7b for 1 cycle, then placebo;   Other: Placebo for 3 cycles
  Sponsor:   Laurent Pharmaceuticals Inc.
  Not yet recruiting

From PubMed

• The use of Ephedra herbs in the treatment of COVID-19 - CONCLUSION: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.

• Integrated network pharmacology analysis and in vitro validation revealed the underlying mechanism of Xiyanping injection in treating coronavirus disease 2019 - CONCLUSION: Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.

• Engineered clinical-grade mesenchymal stromal cells combating SARS-CoV-2 omicron variants by secreting effective neutralizing antibodies - CONCLUSIONS: Our data suggested that engineered clinical-grade MSCs secreting effective neutralizing antibodies as cellular production machines had the potential to combat SARS-CoV-2 infection, which provided a new avenue for effectively treating the older and immunocompromised COVID-19 patients.

• CircMIB2 therapy can effectively treat pathogenic infection by encoding a novel protein - The mRNA therapy is widely used in the treatment of diseases due to its efficient characteristics, and the COVID-19 vaccine is the application of mRNA therapy. However, due to the instability of mRNA, mRNA vaccines often need lots of modifications to ensure its stability. Recent research shows that circRNA with stable RNA structure can encode protein, which provides a new direction for mRNA therapy. Here, we discovered a novel circRNA (circMIB2) derived from E3 ubiquitin-protein ligase MIB2…

• Social network, political climate, income inequality, and Americans uptake of monovalent COVID-19 booster - The COVID-19 pandemic has posed an unprecedented impact on Americans for over three years. To control the damage, a booster shot becomes increasingly necessary because the efficacy of the initial vaccine is waning and new variants of the virus are emerging. This study aims to understand factors at both individual and state levels that influence one’s decision to take the monovalent booster. We merged data from a national survey administered in the Spring of 2022 with state-level indicators of…

• Reduced concentration performance and heartbeat-evoked potential in individuals with a history of a SARS-CoV-2 infection - The goal of characterizing long-term psychological and neural consequences of a SARS-CoV-2 infection has recently gained importance. Here, we examined the effect of a prior SARS-CoV-2 infection on neural markers of exteroceptive (P300) and interoceptive (heartbeat-evoked potential; HEP) signal processing, as well as on neuropsychological tests of attention, inhibition and episodic memory, in 23 adults with a self-reported history of SARS-CoV-2 infection versus 23 healthy controls. We found that…

• Posttranslational ISGylation of NLRP3 by HERCs enzymes facilitates inflammasome activation in models of inflammation - The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a crucial component of the innate immune system that initiates inflammatory responses. Post-translational modifications (PTMs) of NLRP3, including ubiquitination and phosphorylation, control inflammasome activation and determine the intensity of inflammation. However, the role of other PTMs in controlling NLRP3 inflammasome activation remains unclear. This study founded that toll-like receptor (TLR) priming induced…

• We Cannot Put This Genie Back in the Bottle: Qualitative Interview Study Among Family Medicine Providers About Their Experiences With Virtual Visits During the COVID-19 Pandemic - CONCLUSIONS: This study highlights the transition from in-person to virtual visits during the pandemic from the perspective of family medicine providers. Generally, family medicine providers’ perceptions of the shift to virtual visits were positive, especially regarding team-based care. Challenges involved virtual inhibition, particularly for providers. Providers described ways they integrated virtual care with aspects of in-person care, creating a hybrid environment. The genie is out of the…

• The Behavioral Inhibition System and Engagement With, and Influence By, COVID-19 and Election-Based Misinformation - The negative impact of misinformation on public discourse and public safety is increasingly a focus of attention. From the COVID-19 pandemic to national elections, exposure to misinformation has been linked to conflicting perceptions of social, economic, and political issues, which has been found to lead to polarization, radicalization, and acts of violence at the individual and group level. While a large body of research has emerged examining the development and spread of misinformation, little…

• Arbidol increases the survival rate by mitigating inflammation in suckling mice infected with human coronavirus OC43 virus - Human coronavirus OC43 (HCoV-OC43) often causes common cold and is able to neuroinvasive, but it can also induce lower respiratory tract infections (LRTI) especially in children and the elderly adults with underlying diseases. HCoV-OC43 infections currently have no approved antiviral treatment. Arbidol (ARB) is a broad-spectrum antiviral and is an antiviral medication for the treatment of influenza used in Russia and China. Due to its multiple mechanisms of action, such as inhibition of viral…

• Immunogenicity and safety assessment of a SARS-CoV-2 recombinant spike RBD protein vaccine (Abdala) in paediatric ages 3-18 years old: a double-blinded, multicentre, randomised, phase 1/2 clinical trial (ISMAELILLO study) - BACKGROUND: COVID-19 in paediatric ages could result in hospitalizations and death. In addition, excluding children from vaccination could turn them into reservoirs of the SARS-COV-2. Safe and effective COVID-19 vaccines are urgently needed for large-scale paediatric vaccination. ISMAELILLO study aimed to evaluate safety and immunogenicity of two strengths of a new recombinant receptor-binding domain (RBD) protein vaccine (Abdala) in paediatric population.

• Growth hormone-releasing hormone antagonist MIA-602 inhibits inflammation induced by SARS-CoV-2 spike protein and bacterial lipopolysaccharide synergism in macrophages and human peripheral blood mononuclear cells - COVID-19 is characterized by an excessive inflammatory response and macrophage hyperactivation, leading, in severe cases, to alveolar epithelial injury and acute respiratory distress syndrome. Recent studies have reported that SARS-CoV-2 spike (S) protein interacts with bacterial lipopolysaccharide (LPS) to boost inflammatory responses in vitro, in macrophages and peripheral blood mononuclear cells (PBMCs), and in vivo. The hypothalamic hormone growth hormone-releasing hormone (GHRH), in…

• Retrospective observational study of changes in serum cytokines and adiponectin with continuous plasma exchange with dialysis therapy for severe COVID-19 - CONCLUSION: Our results suggest that cPED therapy is an effective treatment for COVID-19.

• The nucleotide-sensing Toll-Like Receptor 9/Toll-Like Receptor 7 system is a potential therapeutic target for IgA nephropathy - The progression determinants of IgA nephropathy (IgAN) are still not fully elucidated. We have previously demonstrated that the mucosal activation of toll-like receptor (TLR) 9, which senses microbial unmethylated CpG DNA, influences progression by producing aberrantly-glycosylated IgA. However, numerous recent reports of patients with IgAN presenting with gross hematuria after the mRNA vaccination for coronavirus disease 2019 suggest that the RNA-sensing system also exacerbates IgAN. Here, we…

• Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine - Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection…

From Patent Search