Covid-19 Sentry

Contents

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

From Preprints

• The role of SARS-CoV-2 genomic surveillance and innovative analytical platforms for informing public health preparedness in Bengaluru, India. -

  A comprehensive SARS-CoV-2 genomic surveillance programme that integrates logistics, laboratory work, bioinformatics, analytics, and timely reporting was deployed through a public-private partnership in the city of Bengaluru, Karnataka in India. As a result, 12461 samples have been sequenced and reported to the Karnataka State public health officials as time-sensitive, decision support during the last one year and uploaded in global public databases in a timely manner. This programme has developed an analytics platform for studying SARS-CoV-2 sequences and their epidemiological context. Continuous sequencing effort enabled timely detection of emergence of Omicron variant in India and the subsequent spread of the same and its sub-lineages with more logistic growth (BA.10, BA.12 and BA.5) in Bengaluru. Our data also helped to provide timely information on variants to determine which of the Variants of Concern tracked globally, were observed in Bengaluru, ensuring targeted efforts and reducing unwarranted fear. This effort highlights the importance of, and the urgent need to, increase genomic surveillance to support the states with limited sequencing and bioinformatics capacity. We describe the development and deployment of this end-to-end solution for genomic surveillance of SARS-CoV-2 in the city of Bengaluru.

  🖺 Full Text HTML: The role of SARS-CoV-2 genomic surveillance and innovative analytical platforms for informing public health preparedness in Bengaluru, India.
• Healthcare utilization following SARS-CoV-2 infection in children and adolescents with chronic conditions: An EHR-based Cohort Study from the RECOVER Program -

  Background Chronic medical conditions are a risk factor for moderate or severe COVID-19 in children, but little is known about post-acute sequelae of SARS-CoV-2 infection (PASC) in children with chronic medical conditions (CMCs). To understand whether SARS-CoV-2 infection led to potential exacerbation of underlying chronic disease in children, we explored whether children with CMCs had increased healthcare utilization in the post-acute (28 days after infection) period compared to children with CMCs without SARS-CoV-2 infection. Methods We conducted a retrospective, matched-cohort study using electronic health record data collected from 8 pediatric health care systems participating in the PEDSnet network. We included children <21 years of age with a wide array of chronic conditions, defined by the presence of diagnostic codes, who were diagnosed with COVID-19 between March 1, 2020 and February 28, 2022. Cohort entry was defined by presence of a positive SARS-CoV-2 PCR test (polymerase chain reaction or antigen) or diagnostic codes for COVID-19, PASC or MIS-C. A comparison cohort of patients testing negative or without these conditions was matched using a stratified propensity score model and exact matching on age group, race/ethnicity, institution, test location, and month of cohort entry. A negative binomial model was used to examine our primary outcome: composite and setting-specific (inpatient, outpatient, ED) utilization rate ratios between the positive and comparison cohorts. Secondary outcomes included time to first utilization in the post-acute period, and utilization stratified by severity at cohort entry. Results We identified 748,692 patients with at least one chronic condition, 78,744 of whom met inclusion criteria for the COVID-19 cohort. 96% of patients from the positive cohort were matched. Cohorts were well-balanced for chronic condition clusters, total number of conditions, time since first diagnosis, baseline utilization, cohort entry period, age, sex, race/ethnicity and test location. We found that among children with chronic medical conditions, those with COVID-19 had higher healthcare utilization than those with no recorded COVID-19 diagnosis or positive test, with utilization rate ratio of 1.21 (95% CI: 1.18-1.24). The utilization was highest for inpatient care with utilization rate ratio of 2.03 (95% CI: 1.85-2.23) but the utilization was increased across all settings. Hazard ratios estimated in time-to-first-utilization analysis mirrored these results. Patients with severe or moderate acute COVID-19 illness had greater increases in utilization in all settings than those with mild or asymptomatic disease. Conclusions We found that care utilization in all settings was increased following COVID-19 in children with chronic medical conditions in the post-acute period, particularly in the inpatient setting. Increased utilization was correlated with more severe COVID-19. Additional research is needed to better understand the reasons for higher care utilization by studying condition-specific outcomes in children with chronic disease.

  🖺 Full Text HTML: Healthcare utilization following SARS-CoV-2 infection in children and adolescents with chronic conditions: An EHR-based Cohort Study from the RECOVER Program
• Brain imaging and neuropsychological assessment of individuals recovered from mild to moderate SARS-CoV-2 infection -

  Importance: As SARS-CoV-2 infections have been shown to affect the central nervous system, it is crucial to investigate associated alterations of brain structure and neuropsychological sequelae to help address future health care needs. Objective: To determine whether a mild to moderate SARS-CoV-2 infection is associated with alteration of brain structure detected by magnetic resonance imaging (MRI) and neuropsychological deficits. Design, Setting and Participants: Following a case-control design, 223 non-vaccinated individuals with a positive polymerase chain reaction test (PCR) for SARS-CoV-2 obtained between 1 March and 31 December 2020 received MRI and neuropsychological assessments within the framework of the Hamburg City Health Study (median 9.7 months after testing). Two hundred twenty-three healthy controls, examined prior to the SARS-CoV-2 pandemic, were drawn from the main study and matched for age, sex, education and cardiovascular risk factors. Exposure: Infection with SARS-CoV-2 confirmed by a positive PCR. Main Outcomes and Measures: Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load and neuropsychological test scores. Results: The present analysis included 223 individuals recovered from mainly mild to moderate SARS-CoV-2 infections (100 female/123 male, age [years], mean +- SD, 55.54 +- 7.07) and 223 matched healthy controls (93 female/130 male, 55.74 +- 6.60). Among all 11 MR imaging markers tested, significant differences between groups were found in global measures of mean diffusivity and extracellular free-water which were both elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 +- 0.018 vs. 0.142 +- 0.017, P<.001; mean diffusivity [10-3 mm2/s]: 0.747 +- 0.021 vs. 0.740 +- 0.020, P<.001). Classification accuracy for detecting post-SARS-CoV-2 individuals based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Conclusions and Relevance: Our findings suggest that subtle changes in white matter extracellular water content may last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

  🖺 Full Text HTML: Brain imaging and neuropsychological assessment of individuals recovered from mild to moderate SARS-CoV-2 infection
• Diagnostic accuracy of SARS-CoV-2 rapid antigen self-tests in asymptomatic individuals in the Omicron period: cross sectional study -

  Objectives To assess the performances of three commonly used rapid antigen diagnostic tests (Ag-RDTs) used as self-tests in asymptomatic individuals in the Omicron period. Design Cross-sectional diagnostic test accuracy study. Setting Three public health service COVID-19 test sites in the Netherlands. Participants 3,600 asymptomatic individuals aged ≥16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Interventions Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex (Flowflex), MP Biomedicals (MPBio), or Siemens-Healthineers Clinitest (Clinitest)) to perform unsupervised at home within three hours and blinded to the RT-PCR result. Main Outcome(s) and Measures(s) Diagnostic accuracies (sensitivity, specificity, positive and negative predictive values) of each self-test compared to RT-PCR. Results Overall sensitivities of the three self-tests were 27.5% (95% CI: 21.3-34.3%) for Flowflex, 20.9% (13.9-29.4%) for MPBio, and 25.6% (19.1-33.1%) for Clinitest. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (95% CI: 37.6-59.2%), 37.8% (22.5-55.2%), and 40.0% (29.5-51.2%), respectively. No consistent differences were found in sensitivities by COVID-19 vaccination status, having had a prior SARS-CoV-2 infection, gender or age across the three self-tests. Specificities were >99% for all tests in most analyses. Conclusions The sensitivities of three commonly used SARS-CoV-2 Ag-RDTs when used as self-tests in asymptomatic individuals in the Omicron period, were very low. Our findings indicate that Ag-RDT self-testing in asymptomatic individuals may only detect the minority of infections at that point in time and may not be sufficient to prevent the spreading of the virus to other (vulnerable) persons. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield of the self-tests, and individuals should certainly be advised to re-test when symptoms develop.

  🖺 Full Text HTML: Diagnostic accuracy of SARS-CoV-2 rapid antigen self-tests in asymptomatic individuals in the Omicron period: cross sectional study
• Manifestations Associated with Post Acute Sequelae of SARS-CoV2 Infection (PASC) Predict Diagnosis of New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies -

  Acute COVID-19 infection can be followed by persistent or newly diagnosed manifestations in many different organ systems, referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Numerous studies have shown an increased risk of being diagnosed with new-onset psychiatric disease in the first 21-120 days following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of receiving a diagnosis of new-onset psychiatric disease following COVID-19. Here, we perform a retrospective electronic health record (EHR) cohort study to evaluate whether non-psychiatric PASC-AMs can predict whether patients will receive a diagnosis of new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 65 clinical organizations which are harmonized using the Observational Medical Outcomes Partnership (OMOP) data model. Non-psychiatric PASC-AMs were recorded 21-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. OMOP codes were mapped to 178 Human Phenotype Ontology (HPO) terms that represent PASC-AMs. Logistic regression was applied to predict newly diagnosed psychiatric disease occurrence based on age, sex, race, pre-existing comorbidities, and PASC-AMs in eleven categories. The cohort of 1,135,973 individuals with acute COVID-19 had a mean age of 40.5 years and included 56.0% females. We found a significant association for seven of the HPO categories with newly diagnosed psychiatric disease, with odds ratios highest for neurological (2.30, 2.24-2.36) and cardiovascular (1.77, 1.69-1.85) PASC-AMs. Secondary analysis revealed that the proportions of 95 of 154 individual phenotypic features differed significantly among patients diagnosed with different psychiatric diseases (anxiety, mood disorders, dementia, and psychosis). Neurological, pulmonary, gastrointestinal, endocrine, cardiovascular, constitutional, and ENT PASC-AMs are each associated with an increased risk of newly diagnosed psychiatric disease. This suggests that the total burden of PASC-AMs influences the risk of receiving a diagnosis of a new-onset psychiatric disease. This finding may be used to inform psychiatric screening following acute COVID-19 by identifying high-risk patients.

  🖺 Full Text HTML: Manifestations Associated with Post Acute Sequelae of SARS-CoV2 Infection (PASC) Predict Diagnosis of New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies
• Analysing COVID treatment outcomes in dedicated wards at a large university hospital in northern Poland. A result-based observational study. -

  Introduction Presenting outcomes of patients hospitalised for coronavirus disease (COVID-19) should be put in context and comparison with other facilities. Number of statistical parameters can be used to compare effectiveness of treatment, however varied methodology applied in studies can impede or hinder a reliable comparison. The aim of this study is to present outcomes of COVID-19 treatment in our facility using simplest parameters allowing for intercenter comparison – case fatality ratio (CFR), length of stay (LOS) and transparent patients characteristics, and to discuss factors affecting mortality in COVID-19. Methods The data were collected from patients hospitalized in COVID-19 general and ICU isolation wards in the University Clinical Centre (UCC) in Gdansk, Poland, from November 2020 to June 2021, using a computer-based patient record system. The group consisted of 642 patients – 144 (39,1 %) were women and 391 (60,9 %) were men, with a median age of 69 (IQR 59-78) years. Values of LOS and CFR were calculated and analysed. Results Overall CFR for the analysed period was 24,8 %, varying from 19,9 % in January to May 2021 to 33,8 % in November to December 2020. CFR was 18,9 % in general ward and 70,7 % in ICU. All ICU patients required intubation and mechanical ventilation, and forty-four (75,9 %) of them developed acute respiratory distress syndrome (ARDS). Average length of stay was 13,1 (± 7,1) days. Conclusion CFR in the general ward in UCC was analogous to published outcomes, but higher in our ICU ward. It resulted from more rigorous ICU admittance criteria in UCC compared to other facilities, which corresponds with patients severe clinical condition and unfavourable prognosis. Heterogeneity of methods assessing initial clinical condition in different facilities makes a meaningful intercenter comparison challenging. In this study, we propose simple and transparent statistical and clinical parameters applicable in an intercenter analysis.

  🖺 Full Text HTML: Analysing COVID treatment outcomes in dedicated wards at a large university hospital in northern Poland. A result-based observational study.
• A Case-Crossover Phenome-wide Association Study (PheWAS) for Understanding Post-COVID-19 Diagnosis Patterns -

  Importance: Post COVID-19 condition (PCC) is known to affect a large proportion of COVID-19 survivors. Robust study design and methods are needed to understand post-COVID-19 diagnosis patterns in all COVID-19 survivors, not just the ones clinically diagnosed with PCC. Objective: To assess which diagnoses appear more frequently after a COVID-19 infection and how they differ by COVID-19 severity and vaccination status. Design: We applied a case-crossover phenome-wide association study (PheWAS) in a retrospective cohort of COVID-19 survivors, comparing the occurrences of 1,649 diagnosis-based phenotype codes (PheCodes) pre- and post-COVID-19 infection periods in the same individual using a conditional logistic regression. Setting: Patients tested for or diagnosed with COVID-19 at Michigan Medicine from March 10, 2020 through May 1, 2022. Participants: 36,856 SARS-CoV-2-positive patients and 141,615 age- and sex-matched SARS-CoV-2-negative patients as a comparison group for sensitivity analysis. Exposure: SARS-CoV-2 virus infection as determined by RT-PCR testing and/or clinical evaluation. Main Outcomes and Measures: We compared the rate of occurrence of 1,649 disease classification codes in “pre-” and “post-COVID-19 periods”. We studied how this pattern varied by COVID-19 severity and vaccination status at the time of infection. Results: Using a case-crossover PheWAS framework, we found mental, circulatory, and respiratory disorders to be strongly associated with the “post-COVID-19 period” for the overall COVID-19-positive cohort. A total of 325 PheCodes reached phenome-wide significance (p<3e-05), and top hits included cardiac dysrhythmias (OR=1.7 [95%CI: 1.6-1.9]), respiratory failure, insufficiency, arrest (OR=3.1 [95%CI: 2.7-3.5]) and anxiety disorder (OR=1.7 [95%CI: 1.6-1.8]). In the patients with severe disease, we found stronger associations with many respiratory and circulatory disorders, such as pneumonia (p=2.1e-18) and acute pulmonary heart disease (p=2.4e-8), and the “post-COVID-19 period,” compared to those with mild/moderate disease. Test negative patients exhibited a somewhat similar association pattern to those fully vaccinated, with mental health and chronic circulatory diseases rising to the top of the association list in these groups. Conclusions and Relevance: Our results confirm that patients experience myriad symptoms more than 28 days after SARS-CoV-2 infection, but especially mental, circulatory, and respiratory disorders. Our case-crossover PheWAS approach controls for within-person confounders that are time-invariant. Comparison to test negatives with a similar design helped identify enrichment specific to COVID-19. As we look into the future, we must be aware of COVID-19 survivors9 healthcare needs in the period after infection.

  🖺 Full Text HTML: A Case-Crossover Phenome-wide Association Study (PheWAS) for Understanding Post-COVID-19 Diagnosis Patterns
• Medical complaints after 3 vs 2 doses SARS-CoV-2 mRNA vaccination -

  Aims: To examine whether individuals vaccinated with three doses of mRNA SARS-CoV-2 vaccines have an altered incidence of medical complaints compared to individuals not vaccinated with three doses. Methods: Using longitudinal exact 1:1 matching on days since 2nd dose, calendar month and a set of covariates, we obtained a matched sample with 138 581 individuals aged 18-70 years that had the 3rd dose at 20-30 weeks after the 2nd dose and an equally large control group that did not. Main outcomes were medical records of common complaints seen in primary care for up to 90 days after the treatment. Results: Depending on type of complaint, the estimated 90-day cumulative incidence varied between 70 and 5000 per 100 000 individuals. Among individuals aged 18-44 years, the number of medical complaints was lower for individuals with three doses: Fatigue: 662, 95% confidence interval=473-850, shortness of breath: 160 (90-230) and brain fog: 65 (22-108) fewer per 100 000 vaccinated. No decrease in incidence was observed for musculoskeletal pain, cough or heart palpitations. When individuals where censored from the analysis from the date of positive SARS-CoV-2 test, these absolute differences were smaller. Similar analyses gave higher estimates among individuals aged 45-70 years, yet more ambiguous results when censored at positive test. Conclusion: Individuals vaccinated with dose 3 had reduced incidence of complaints compared to matched controls with only 2 doses. Analyses with vs without censoring at positive test implied that this reduction might be explained by a reduced COVID-19 incidence among the 3-dose-vaccinated.

  🖺 Full Text HTML: Medical complaints after 3 vs 2 doses SARS-CoV-2 mRNA vaccination
• Carbohydrate-Binding Protein from Stinging Nettle as Fusion Inhibitor for SARS-CoV-2 Variants of Concern -
  Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks entry of pseudotyped SARS-CoV-2 in A549.ACE2+-TMPRSS2 cells, with IC50 values ranging from 0.32 to 1.22 microM. Furthermore, UDA prevents viral replication of the early Wuhan-Hu-1 strain in Vero E6 cells (IC50 = 225 nM), but also the replication of SARS-CoV-2 variants of concern, including Alpha, Beta and Gamma (IC50 ranging from 115 to 171 nM). In addition, UDA exerts antiviral activity against the latest circulating Delta and Omicron variant in U87.ACE2+ cells (IC50 values are 1.6 and 0.9 microM, respectively). Importantly, when tested in Air-Liquid Interface (ALI) primary lung epithelial cell cultures, UDA preserves antiviral activity against SARS-CoV-2 (20A.EU2 variant) in the nanomolar range. Surface plasmon resonance (SPR) studies demonstrated a concentration-dependent binding of UDA to the viral spike protein of SARS-CoV-2, suggesting interference of UDA with cell attachment or subsequent virus entry. Moreover, in additional mechanistic studies with cell-cell fusion assays, UDA inhibited SARS-CoV-2 spike protein-mediated membrane fusion. Finally, pseudotyped SARS-CoV-2 mutants with N-glycosylation deletions in the S2 subunit of the spike protein remained sensitive to the antiviral activity of UDA. In conclusion, our data establish UDA as a potent and broad-spectrum fusion inhibitor for SARS-CoV-2.
  🖺 Full Text HTML: Carbohydrate-Binding Protein from Stinging Nettle as Fusion Inhibitor for SARS-CoV-2 Variants of Concern
• Impact and mitigation of sampling bias to determine viral spread: evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations -
  Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies that enables reconstructing the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (BASTA and MASCOT). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for CTMC. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for CTMC, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.
  🖺 Full Text HTML: Impact and mitigation of sampling bias to determine viral spread: evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations
• Correlation of Alpha-1 Antitrypsin Levels and Exosome Associated Neutrophil Elastase Endothelial Injury in Subjects with SARS-CoV2 Infection -
  Background: Severe acute respiratory syndrome caused by a novel coronavirus 2 (SARS-CoV-2) has infected more than 18 million people worldwide. The activation of endothelial cells is a hallmark of signs of SARS-CoV-2 infection that includes altered integrity of vessel barrier and endothelial inflammation. Objectives: Pulmonary endothelial activation is suggested to be related to the profound neutrophil elastase (NE) activity, which is necessary for sterilization of phagocytosed bacterial pathogens. However, unopposed activity of NE increases alveolocapillary permeability and extracellular matrix degradation. The uncontrolled protease activity of NE during the inflammatory phase of lung diseases might be due to the resistance of exosome associated NE to inhibition by alpha-1 antitrypsin. Method: 31 subjects with a diagnosis of SARS-CoV2 infection were recruited in the disease group and samples from 30 voluntaries matched for age and sex were also collected for control. Results: We measured the plasma levels of exosome-associated NE in SARS-CoV-2 patients which, was positively correlated with the endothelial damage in those patients. Notably, we also found strong correlation with plasma levels of alpha-1 antitrypsin and exosome-associated NE in SARS-CoV-2 patients. Using macrovascular endothelial cells, we also observed that purified NE activity is inhibited by purified alpha-1 antitrypsin while, NE associated with exosomes are resistant to inhibition and show less sensitivity to alpha-1 antitrypsin inhibitory activity, in vitro. Conclusions: Our results point out the role of exosome-associated NE in exacerbation of endothelial injury in SARS-CoV-2 infection. We have demonstrated that exosome-associated NE could be served as a new potential therapeutic target of severe systemic manifestations of SARS-CoV-2 infection.
  🖺 Full Text HTML: Correlation of Alpha-1 Antitrypsin Levels and Exosome Associated Neutrophil Elastase Endothelial Injury in Subjects with SARS-CoV2 Infection
• Chronumental: time tree estimation from very large phylogenies -
  Phylogenetic trees are an important tool for interpreting sequenced genomes, and their interrelationships. Estimating the date associated with each node of such a phylogeny creates a “time tree”, which can be especially useful for visualising and analysing evolution of organisms such as viruses. Several tools have been developed for time-tree estimation, but the sequencing explosion in response to the SARS-CoV-2 pandemic has created phylogenies so large as to prevent the application of these previous approaches to full datasets. Here we introduce Chronumental, a tool that can rapidly infer time trees from phylogenies featuring large numbers of nodes. Chronumental uses stochastic gradient descent to identify lengths of time for tree branches which maximise the evidence lower bound under a probabilistic model, implemented in a framework which can be compiled into XLA for rapid computation. We show that Chronumental scales to phylogenies featuring millions of nodes, with chronological predictions made in minutes, and is able to accurately predict the dates of nodes for which it is not provided with metadata.
  🖺 Full Text HTML: Chronumental: time tree estimation from very large phylogenies
• Building Emotion Awareness and Mental Health (BEAM): Study protocol for a randomized controlled trial of the BEAM App-based program for mothers of children 18-36 months. -
  Background: The prevalence of maternal depression and anxiety has increased during the COVID-19 pandemic and pregnant individuals are experiencing concerningly elevated levels of mental health symptoms worldwide. Many individuals may now be at heightened risk of postpartum mental health disorders. Recent evidence suggests that the cognitive development of children born during the pandemic has been impacted. There are significant concerns that a cohort of children may be at-risk for impaired self-regulation and mental illness due to elevated exposure to perinatal maternal mental illness. The intergenerational effects of maternal mental illness are most pronounced when depression persists. With both an increased prevalence of depression and limited availability of services due to the pandemic, there is an urgent need for accessible eHealth interventions for mothers of young children. The aims of this trial are to evaluate the efficacy of the Building Emotion Awareness and Mental Health (BEAM) app-based program for reducing maternal depression symptoms (primary outcome) as well as for improving anxiety symptoms, family relationships, parenting, mother and child functioning (secondary outcomes) compared to treatment as usual (TAU). Methods: A two-arm randomized controlled trial (RCT) with repeated measures will be used to evalute the efficacy of the BEAM intervention compared to TAU among a sample of 140 mothers with children aged 18 to 36 months, who self-report moderate-to-severe symptoms of depression and/or anxiety. Individuals will be recruited online and those randomized to the treatment group will participate in 10 weeks of modules on mental health and parenting, an online social support forum, and weekly group teletherapy sessions. Assessment of depression (primary outcome), family relationship quality, anxiety, parenting, and mother and child functioning will occur at 18-36 months postpartum (pre-test, T1), immediately after the last week of the BEAM intervention (post-test, T2), and at 3 months after the intervention (follow-up, T3). Primary outcomes will also be assessed weekly throughout the 10 week intervention. Discussion: eHealth interventions have the potential to address elevated maternal mental health symptoms, parenting stress, and child funtioning concerns during and after the COVID-19 pandemic and provide accessible programming to mothers who are in need of support. This RCT will build on an open pilot trial of the BEAM program and provide further evaluation of this evidence-based intervention for mothers experiencing depression. Findings will increase understanding of depression and parenting stress in mothers with young children and reveal the potential for long-term improvements in maternal and child health and family well-being.
  🖺 Full Text HTML: Building Emotion Awareness and Mental Health (BEAM): Study protocol for a randomized controlled trial of the BEAM App-based program for mothers of children 18-36 months.
• Short-Term Effects of Short-Term Work: Dynamics in Fatigue across Two National Lockdowns -
  Objective: Anecdotal evidence suggests work fatigue has increased during the COVID-19 pandemic, and work interventions to offset stresses have been effective. Our study sought to test these propositions, documenting and describing the complexity of worker well-being around two lockdown periods. Methods: Using 17 waves of data from a longitudinal study in Germany (December 2019 to June 2021, n = 1,053 employees), we model discontinuous changes in work fatigue and how participation in a government-sponsored short-term work program (Kurzarbeit) affected change trajectories. Results: The COVID-19 pandemic has not invariably resulted in work fatigue, and individuals with Kurzarbeit at the first lockdown (but not the second) showed significantly larger decreases in each form of fatigue at this transition. Conclusions: Future policy interventions will require more contextual nuance to effectively support worker well-being during public health crises.
  🖺 Full Text HTML: Short-Term Effects of Short-Term Work: Dynamics in Fatigue across Two National Lockdowns
• Coping During Covid 19 Facilitator Manual -
  This manual has been created to assist mental health professionals in delivering and facilitating the two hour evidence-based online CBT program “Coping during COVID-19”. It overviews the eight module course, designed to support those who are struggling with symptoms of anxiety and depression due theCOVID-19 crisis.
  🖺 Full Text HTML: Coping During Covid 19 Facilitator Manual

From Clinical Trials

• Immuno-bridging Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Interventions:   Biological: COVID-19 Protein Subunit Recombinant Vaccine;   Biological: Active Comparator
  Sponsors:   PT Bio Farma;   Fakultas Kedokteran Universitas Indonesia;   Faculty of Medicine Universitas Diponegoro;   Faculty of Medicine Universitas Andalas;   Faculty of Medicine Universitas Hassanudin
  Recruiting

• A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised - Condition:   COVID-19
  Interventions:   Drug: Nirmatrelvir;   Drug: Ritonavir;   Drug: Placebo for nirmatrelvir;   Drug: Placebo for ritonavir
  Sponsor:   Pfizer
  Not yet recruiting

• A Randomized Controlled Trial of a Digital, Self-testing Strategy for COVID-19 Infection in South Africa. - Condition:   COVID-19
  Interventions:   Device: Abbott Panbio rapid antigen self-tests;   Other: COVIDSmart CARE! app
  Sponsors:   McGill University Health Centre/Research Institute of the McGill University Health Centre;   University of Cape Town Lung Institute
  Not yet recruiting

• Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients - Condition:   Severe COVID-19
  Interventions:   Biological: Coronavirus-2-specific T cells;   Other: standard of care (SOC)
  Sponsors:   George Papanicolaou Hospital;   General Hospital Of Thessaloniki Ippokratio
  Recruiting

• Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) - Condition:   COVID-19
  Interventions:   Drug: FB2001;   Drug: FB2001 placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Not yet recruiting

• Immunogenicity and Safety Study of One Booster Dose of Trivalent COVID-19 Vaccine (Vero Cell), Inactivated - Condition:   COVID-19
  Interventions:   Biological: Trivalent COVID-19 Vaccine (Vero Cell), Inactivated, Prototype Strain, Delta Strain and Omicron Strain;   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:   Sinovac Biotech (Colombia) S.A.S.;   Sinovac Life Sciences Co., Ltd.
  Not yet recruiting

• Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities - Condition:   COVID-19
  Interventions:   Behavioral: Full Intervention;   Other: Enhanced Usual Care
  Sponsors:   Kaiser Permanente;   Patient-Centered Outcomes Research Institute;   Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
  Recruiting

• A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: PanCytoVir™ (probenecid);   Drug: Placebo
  Sponsor:   TrippBio, Inc.
  Not yet recruiting

• Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough - Condition:   Post COVID-19
  Intervention:   Drug: Montelukast Sodium Tablets
  Sponsor:   Assiut University
  Completed

• Topical Antibacterial Agents for Prevention of COVID-19 - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Drug: Neosporin;   Other: Vaseline
  Sponsors:   Yale University;   Bill and Melinda Gates Foundation
  Not yet recruiting

• Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study - Condition:   Post-COVID19 Condition
  Interventions:   Combination Product: Plasma Exchange Procedure;   Other: Sham Plasma Exchange Procedure
  Sponsors:   Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia;   IrsiCaixa;   Banc de Sang i Teixits
  Not yet recruiting

• Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection - Conditions:   COVID-19;   Rehabilitation
  Intervention:   Other: resistance respiratory training with the use of respiratory muscle trainer
  Sponsor:   Medical University of Bialystok
  Recruiting

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19 Omicron) mRNA Vaccine (Phase 1) - Condition:   COVID-19
  Intervention:   Biological: ABO1009-DP
  Sponsor:   Suzhou Abogen Biosciences Co., Ltd.
  Not yet recruiting

• A Study to Evaluate Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19) mRNA Vaccines - Condition:   COVID-19
  Interventions:   Biological: ABO1009-DP;   Biological: ABO-CoV.617.2;   Other: Placebo
  Sponsor:   Suzhou Abogen Biosciences Co., Ltd.
  Not yet recruiting

• Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients - Conditions:   COVID-19;   Dysglycemia
  Interventions:   Drug: Insulin;   Drug: Subcutaneous Insulin
  Sponsor:   Benha University
  Completed

From PubMed

• Immune checkpoint inhibitors in kidney transplant recipients: a multicentre, single-arm, phase 1 study - BACKGROUND: Most kidney transplant recipients with cancer stop or reduce immunosuppressive therapy before starting treatment with an immune checkpoint inhibitor, and approximately 40% of such patients will develop allograft rejection. Isolated immunosuppression reduction might be associated with organ rejection. Whether immunosuppression manipulation, immune checkpoint inhibition, or both, induce organ rejection is difficult to ascertain. The aim of this study was to examine the risk of…

• Synthesis and structure-activity relationship study of saponin-based membrane fusion inhibitors against SARS-CoV-2 - We previously discovered that triterpenoid saponin platycodin D inhibits the SARS-CoV-2 entry to the host cell. Herein, we synthesized various saponin derivatives and established a structure-activity relationship of saponin-based antiviral agents against SARS-CoV-2. We discovered that the C3-glucose, the C28-oligosaccharide moiety that consist of (→3)-β-d-Xyl-(1 → 4)-α-l-Rham-(1 → 2)-β-d-Ara-(1 → ) as the last three sugar units, and the C16-hydroxyl group were critical components of…

• Structural Basis of Main Proteases of Coronavirus Bound to Drug Candidate PF-07304814 - New variants of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) emerged and spread rapidly all over the world, which strongly supports the need for pharmacological options to complement vaccine strategies. Main protease (M^(pro) or 3CL^(pro)) is a critical enzyme in the life cycle of SARS-CoV-2 and appears to be highly conserved among different genera of coronaviruses, making it an ideal target for the development of drugs with broad-spectrum property. PF-07304814 developed by…

• Size and Zeta Potential Clicked Germination Attenuation and Anti-Sporangiospores Activity of PEI-Functionalized Silver Nanoparticles against COVID-19 Associated Mucorales (Rhizopus arrhizus) - The SARS-CoV-2 infections in Indian people have been associated with a mucormycotic fungal infection caused by the filamentous fungi Rhizopus arrhizus. The sporangiospores of R. arrhizus are omnipresent in the environment and cause infection through inhalation or ingestion of contaminated air and foods. Therefore, the anti-sporangiospore activity of polyethyleneimine functionalized silver nanoparticles (PEI-f-Ag-NPs) with variable size and surface charge as a function of the molecular weight of…

• Cyanidin-3-O-glucoside and Peonidin-3-O-glucoside-Rich Fraction of Black Rice Germ and Bran Suppresses Inflammatory Responses from SARS-CoV-2 Spike Glycoprotein S1-Induction In Vitro in A549 Lung Cells and THP-1 Macrophages via Inhibition of the NLRP3 Inflammasome Pathway - Black rice is a functional food that is high in anthocyanin content, primarily C3G and P3G. It possesses nutraceutical properties that exhibit a range of beneficial effects on human health. Currently, the spike glycoprotein S1 subunit of SARS-CoV-2 (SP) has been reported for its contribution to pathological inflammatory responses in targeting lung tissue and innate immune cells during COVID-19 infection and in the long-COVID phenomenon. Our objectives focused on the health benefits of the C3G…

• Bulgarian Medicinal Extracts as Natural Inhibitors with Antiviral and Antibacterial Activity - CONCLUSION: The antipathogenic potential of extracts of H. perforatum and G. glabra suggests their effectiveness as antimicrobial agents. All 13 extracts of the Bulgarian medicinal plants studied can be used to reduce viral yield in a wide range of viral infections.

• From Repurposing to Redesign: Optimization of Boceprevir to Highly Potent Inhibitors of the SARS-CoV-2 Main Protease - The main protease (M^(pro)) of the betacoronavirus SARS-CoV-2 is an attractive target for the development of treatments for COVID-19. Structure-based design is a successful approach to discovering new inhibitors of the M^(pro). Starting from crystal structures of the M^(pro) in complexes with the Hepatitis C virus NS3/4A protease inhibitors boceprevir and telaprevir, we optimized the potency of the alpha-ketoamide boceprevir against the M^(pro) by replacing its P1 cyclobutyl moiety by a γ-lactam…

• The Nucleoside/Nucleotide Analogs Tenofovir and Emtricitabine Are Inactive against SARS-CoV-2 - The urgent response to the COVID-19 pandemic required accelerated evaluation of many approved drugs as potential antiviral agents against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using cell-based, biochemical, and modeling approaches, we studied the approved HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTIs) tenofovir (TFV) and emtricitabine (FTC), as well as prodrugs tenofovir alafenamide (TAF) and tenofovir disoproxilfumarate (TDF) for…

• In Silico Screening of Novel TMPRSS2 Inhibitors for Treatment of COVID-19 - COVID-19, a pandemic caused by the virus SARS-CoV-2, has spread globally, necessitating the search for antiviral compounds. Transmembrane protease serine 2 (TMPRSS2) is a cell surface protease that plays an essential role in SARS-CoV-2 infection. Therefore, researchers are searching for TMPRSS2 inhibitors that can be used for the treatment of COVID-19. As such, in this study, based on the crystal structure, we targeted the active site of TMPRSS2 for virtual screening of compounds in the FDA…

• Phytochemical Analysis, Antimutagenic and Antiviral Activity of Moringa oleifera L. Leaf Infusion: In Vitro and In Silico Studies - Moringa oleifera (M. oleifera) leaves are rich in nutrients and antioxidant compounds that can be consumed to prevent and overcome malnutrition. The water infusion of its leaf is the easiest way to prepare the herbal drink. So far, no information is available on the antioxidant, antimutagenic, and antivirus capacities of this infusion. This study aimed to determine the composition of the bioactive compounds in M. oleifera leaf infusion, measuring for antioxidant and antimutagenic activity, and…

• Potent Activity of a High Concentration of Chemical Ozone against Antibiotic-Resistant Bacteria - BACKGROUND: Health care-associated infections (HAIs) are a significant public health problem worldwide, favoring multidrug-resistant (MDR) microorganisms. The SARS-CoV-2 infection was negatively associated with the increase in antimicrobial resistance, and the ESKAPE group had the most significant impact on HAIs. The study evaluated the bactericidal effect of a high concentration of O(3) gas on some reference and ESKAPE bacteria.

• Multi-Step In Silico Discovery of Natural Drugs against COVID-19 Targeting Main Protease - In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (M^(pro)) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with PRD_002214, the co-crystallized ligand of M^(pro) (PDB ID: 6LU7), and favored thirty…

• Peptidomimetic inhibitors of TMPRSS2 block SARS-CoV-2 infection in cell culture - The transmembrane serine protease 2 (TMPRSS2) primes the SARS-CoV-2 Spike (S) protein for host cell entry and represents a promising target for COVID-19 therapy. Here we describe the in silico development and in vitro characterization of peptidomimetic TMPRSS2 inhibitors. Molecular docking studies identified peptidomimetic binders of the TMPRSS2 catalytic site, which were synthesized and coupled to an electrophilic serine trap. The compounds inhibit TMPRSS2 while demonstrating good off-target…

• Inhibitor induced conformational changes in SARS-COV-2 papain-like protease - SARS-CoV-2’s papain-like protease (PL^(pro)) interaction with ligands has recently been explored with a myriad of crystal structures. We used molecular dynamics (MD) simulations to study different PL^(pro)-ligand complexes, their ligand-induced conformational changes, and interactions. We focused on inhibitors reported with known IC(50) against PL^(pro), namely GRL-0617, XR8-89, PLP_Snyder530, and Sander’s recently published compound 7 (CPD7), and compared these trajectories against the…

• Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later - CONCLUSIONS: High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.

From Patent Search