Covid-19 Sentry

Contents

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

From Preprints

• Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer -
  Observational studies are being used more and more in psychology and medicine since they provide a wealth of data for real-world issues. Their biggest drawback is the lack of falsification due to the control mechanisms of control conditions being unavailable. However, the Covid-19 pandemic and the isolation policies related to it have provided an environment in which researchers can use natural experimental design to establish causal pathways in phenomena. Here we demonstrate how Covid-19-related changes can be used to investigate causal effects behind Home Advantage (HA), a robust phenomenon in which sport teams are more successful when they play in front of their fans. HA theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. Covid-19 has provided the perfect control condition for disentangling the causal links of the HA as sport teams have played at home but without the presence of fans. Using our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously instead of in isolation as was previously the case, we demonstrate how Covid-19 enables us to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, our paper also provides information about the practical implementation of mediation and moderated mediation mixed-effects models in the Bayesian framework. Similar implementations can be adapted in other medical and social science fields.
  🖺 Full Text HTML: Bayesian Framework for Moderated Mediation Using Covid-19-caused Natural Experiment: Modeling Home Advantage in Soccer
• Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model -
  Home Advantage (HA) is a robust phenomenon in which sport teams or individuals are more successful when they play in front of their fans. There are a number of causes of HA, but most theories assume that the crowd support spurs home players to better performance and biases referees, and that these two factors in turn influence the result. The interest in HA has grown during the Covid-19 pandemic as most competitions were taking place behind closed doors, a perfect control condition for disentangling the causal effects behind HA. Despite the presence of useful conceptual frameworks, most previous research has focused on investigating isolated individual factors. Here we review our newly developed Home Advantage Mediated (HAM) model, which considers all individual factors and their interrelations simultaneously. HAM assumes that the crowd effects are mediated through other relevant factors, such as referee bias and team performance. Most importantly, HAM can be formally expressed as a mediation model, a technique widely employed in social sciences for investigating causal pathways. We demonstrate how researchers can use HAM to model the HA in European football and how moderating variables, such as Covid-19 and absence of fans, can be incorporated in the model to disentangle the processes behind the HA phenomenon. Besides throwing new (modeling) light on one of the most robust phenomena in sport, we also provide information about practical implementation of mediation and moderated mediation models in the Bayesian framework. Similar implementations can be adapted for use in other sport science domains.
  🖺 Full Text HTML: Revising Home Advantage in Sport – Home Advantage Mediation (HAM) Model
• The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions -
  The Covid-19 pandemic has significantly altered the way sporting events are observed. With the absence or limited presence of spectators in stadiums, the traditional advantage enjoyed by home teams has diminished considerably. This underscores the notion that the support of home fans can often be considered a key factor of the home advantage (HA) phenomenon, wherein teams perform better in front of their own supporters. However, the impact of reduced attendance on games with higher stakes, as opposed to low-stakes friendly matches, remains uncertain. In this study, we investigate the recently concluded European football championship (EURO 20), wherein several teams had the advantage of playing at home in high-stakes games with only one-third of the stadium capacity filled. Firstly, we demonstrate that the Covid-19 restrictions, leading to reduced fan attendance, resulted in a nearly 50% decrease in HA compared to the HA exhibited by the same teams during the qualification stage preceding EURO 20, even after accounting for team strength. Secondly, we show that while low-stakes friendly matches generally exhibit a smaller overall HA compared to high-stakes games, the absence of fans led to a similar reduction in HA during the low-stakes matches. Utilizing the recently developed Home Advantage Mediated (HAM) model (Bilalić et al., 2021, Scientific Reports, 21558), we were able to attribute the reduction in both high- and low-stakes games to poorer team performance, with no significant contribution from referee bias.
  🖺 Full Text HTML: The Effect of COVID-19 on Home Advantage in High- and Low-Stake Situations: Evidence from the European National Football Competitions
• Home Advantage during the COVID-19 Pandemic in European football -
  The home advantage (HA) is a robust phenomenon in soccer whereby the home team wins more games and scores more goals than the away team. One explanation is that the home crowd spurs on home team performance and causes the referee to unconsciously favour the home team. The Covid-19 pandemic provided a unique opportunity to assess this explanation for HA, as European soccer leagues played part of the 2019/2020 season with crowds present and concluded with crowds absent. Using multi-level modelling we compared team performance and referee decisions pre-Covid (crowd present) and post-Covid (crowd absent) across 9,528 games from 15 leagues in 11 countries. HA (goals scored and points gained) was significantly reduced post pandemic, which reflected the inferior performance of the home team. In addition, referees awarded significantly fewer sanctions against the away teams, and home teams created significantly fewer attacking opportunities when they played without fans.
  🖺 Full Text HTML: Home Advantage during the COVID-19 Pandemic in European football
• Towards mitigating health inequity via machine learning: a nationwide cohort study to develop and validate ethnicity-specific models for prediction of cardiovascular disease risk in COVID-19 patients -

  Background Emerging data-driven technologies in healthcare, such as risk prediction models, hold great promise but also pose challenges regarding potential bias and exacerbation of existing health inequalities, which have been observed across diseases such as cardiovascular disease (CVD) and COVID-19. This study addresses the impact of ethnicity in risk prediction modelling for cardiovascular events following SARS-CoV-2 infection and explores the potential of ethnicity-specific models to mitigate disparities. Methods This retrospective cohort study utilises six linked datasets accessed through National Health Service (NHS) England9s Secure Data Environment (SDE) service for England, via the BHF Data Science Centre9s CVD-COVID-UK/COVID-IMPACT Consortium. Inclusion criteria were established, and demographic information, risk factors, and ethnicity categories were defined. Four feature selection methods (LASSO, Random Forest, XGBoost, QRISK) were employed and ethnicity-specific prediction models were trained and tested using logistic regression. Discrimination (AUROC) and calibration performance were assessed for different populations and ethnicity groups. Findings Several differences were observed in the models trained on the whole study cohort vs ethnicity-specific groups. At the feature selection stage, ethnicity-specific models yielded different selected features. AUROC discrimination measures showed consistent performance across most ethnicity groups, with QRISK-based models performing relatively poorly. Calibration performance exhibited variation across ethnicity groups and age categories. Ethnicity-specific models demonstrated the potential to enhance calibration performance for certain ethnic groups. Interpretation This research highlights the importance of considering ethnicity in risk prediction modelling to ensure equitable healthcare outcomes. Differences in selected features and asymmetric calibration across ethnicities underscore the necessity of tailored approaches. Ethnicity-specific models offer a pathway to addressing disparities and improving model performance. The study emphasises the role of data-driven technologies in either alleviating or exacerbating existing health inequalities. Keywords Prediction, machine learning, electronic health records, bias, ethnicity.

  🖺 Full Text HTML: Towards mitigating health inequity via machine learning: a nationwide cohort study to develop and validate ethnicity-specific models for prediction of cardiovascular disease risk in COVID-19 patients
• Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: a prospective cohort study. -

  Introduction Healthcare workers (HCWs) from an interprovincial Canadian cohort were asked to give serial blood samples to identify factors associated with anti-receptor binding domain (anti-RBD) IgG response to the SARS-CoV-2 virus. Methods Members of the HCW cohort donated blood samples four months after their first SARS-CoV-2 immunization and again at 7, 10 and 13 months. Date and type of immunizations and dates of SARS-CoV-2 infection were collected at each of four contacts, together with information on immunologically-compromising conditions and current therapies. Blood samples were analyzed centrally for anti-RBD IgG and anti-nucleocapsid IgG (Abbott Architect, Abbott Diagnostics). Records of immunization and SARS-CoV-2 testing from public health agencies were used to assess the impact of reporting errors on estimates from the random-effects multivariable model fitted to the data. Results 2752 of 4567 vaccinated cohort participants agreed to donate at least one blood sample. Modelling of anti-RBD IgG titer from 8903 samples showed an increase in IgG with each vaccine dose and with first infection. A decrease in IgG titer was found with the number of months since vaccination or infection, with the sharpest decline after the third dose. An immunization regime that included mRNA1273 (Moderna) resulted in higher anti-RBD IgG. Participants reporting multiple sclerosis, rheumatoid arthritis or taking selective immunosuppressants, tumor necrosis factor inhibitors, calcineurin inhibitors and antineoplastic agents had lower anti-RBD IgG. Supplementary analyses showed higher anti-RBD IgG in those reporting side-effects of vaccination, no relation of anti-RBD IgG to obesity and lower titers in women immunized early in pregnancy. Sensitivity analysis results suggested no important bias in the self-report data. Conclusion Creation of a prospective cohort was central to the credibility of results presented here. Serial serology assessments, with longitudinal analysis, provided effect estimates with enhanced accuracy and a clearer understanding of medical and other factors affecting response to vaccination.

  🖺 Full Text HTML: Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: a prospective cohort study.
• Changes in stillbirths and child and youth mortality in 2020 and 2021 during the Covid-19 pandemic -

  Background: The COVID-19 pandemic9s impact on mortality, especially among the elderly, has been extensively studied. While COVID-19 rarely causes direct mortality in children and youth, the pandemic9s indirect effects might harm these age groups. Yet, its influence on stillbirths and mortality rates in neonates, infants, children, and youth remains poorly understood. This study examines disruptions in such trends across 95 countries in 2020 and 72 in 2021, providing the inaugural comprehensive analysis of COVID-199s effect on young mortality and stillbirths. Methods: We estimate expected mortality levels in a non-pandemic setting and calculate relative mortality changes (p-scores) by applying generalized linear models to data from civil registers and vital statistics systems (CRSV) and from the Health Management Information System (HMIS). We then use these estimates to analyze, for each age group, the distribution of country-specific mortality changes and the proportion of countries experiencing mortality deficits, no changes, and excess. Results: For most countries and territories, stillbirths and mortality at ages under 25 did not differ from expected levels in 2020 and 2021. However, when focusing on the countries that did show changes, more countries experienced mortality deficits than excess. The exception was stillbirths in both years and mortality among neonates and those aged 10-24 in 2021, where more countries had an excess rather than a deficit. Overall, a quarter of the countries examined experienced increases in stillbirths and young adult mortality (20-24). Conclusion: Despite global disruptions to essential services, stillbirths and youth mortality were as expected in most countries, defying expectations. However, this doesn9t dismiss hypotheses suggesting delayed adverse effects on the youngest that may require more time to be noticeable at the population level. Close and long-term monitoring of health and deaths among children and youth, particularly in low-income and lower-middle-income countries, is required to fully understand the lasting impacts of the COVID-19 pandemic.

  🖺 Full Text HTML: Changes in stillbirths and child and youth mortality in 2020 and 2021 during the Covid-19 pandemic
• Infectious touching: Has COVID-19 changed our perceptions of social touch? A neural and behavioral study -
  Social touch is essential for reducing stress, improving mood and fostering a sense of social connectedness. Stimuli related to social touch are generally perceived as positive. Nevertheless, the social restrictions imposed by the COVID-19 pandemic may have changed the way human beings perceive and react to social touch. Indeed, the social distancing imposed by the pandemic may have had long term effects on human perceptions of social touch. In the current study, we examined how perceptions of interpersonal touch in social interactions were affected by the COVID-19 pandemic. Specifically, we compared behavioral and neural responses to observed social touch between two groups: pre- and post-COVID-19. Participants in both groups rated the pleasantness of photos of social touch between humans, nonsocial touch between inanimate objects or non-touch photos of either two humans or inanimate objects. We hypothesized that social touch in the post-COVID-19 group would induce hypervigilance due to the risk of infection. In line with our predictions, we found behavioral changes in perceptions of social touch among participants in this group, who rated photos with touch as less pleasant than did participants in the pre-COVID-19 group. Participants in the post-COVID-19 group also rated photos with humans as less pleasant than did participants in the pre-COVID-19 group. Additionally, EEG analysis revealed neural changes in the ERP components associated with hypervigilance: P1 and LPP. Contrary to pre-COVID-19 measures showing more positive P1 amplitudes for touch than for non-touch photos, after COVID-19 no differences in P1 amplitudes were found between touch and non-touch photos. Furthermore, after COVID-19 the P1 amplitudes for human and inanimate photos in the touch condition were similar, a pattern that did not emerge prior to COVID-19. These findings suggest that COVID-19 had a surprising impact on human perceptions of social touch, such that observing nonsocial touch evoked more positive emotions than observing human touch. Further, these findings may reflect shifts in attention or changes in the salience of touch-related information due to the altered circumstances brought about by the pandemic. Overall, our results indicate that COVID-19 has modified human perceptions of social touch, providing evidence that the pandemic has affected individuals' perceptual and evaluative processes and highlighting the importance of considering social and environmental factors in understanding subjective experiences.
  🖺 Full Text HTML: Infectious touching: Has COVID-19 changed our perceptions of social touch? A neural and behavioral study
• Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus -
  Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad ACE2 usage and that RBD mutations further expand receptor promiscuity and enable human ACE2 utilization. We determined a cryoEM structure of the PRD-0038 RBD bound to R. alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryoEM and monoclonal antibody reactivity revealed its distinct antigenicity relative to SARS-CoV-2 and identified PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicited greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared to SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.
  🖺 Full Text HTML: Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus
• Circulation of SARS-CoV-2 and co-infection with Plasmodium falciparum in Equatorial Guinea -

  The impact of COVID-19 in Africa has been a big concern since the beginning of the pandemic. However, low incidence of COVID-19 case severity and mortality has been reported in many African countries, although data are highly heterogeneous and, in some regions, like Sub-Saharan Africa, very scarce. Many of these regions are also the cradle of endemic infectious diseases like malaria. The aim of this study was to determine the prevalence of SARS-CoV-2, the diversity and origin of circulating variants as well as the frequency of co-infections with malaria in Equatorial Guinea. For this purpose, we conducted antigen diagnostic tests for SARS-CoV-2, and microscopy examinations for malaria of 1,556 volunteers at six health centres in Bioko and Bata from June to October 2021. Nasopharyngeal swab samples were also taken for molecular detection of SARS-CoV-2 by RT-qPCR and whole genome viral sequencing. We report 3.0% of SARS-CoV-2 and 24.4% of malaria prevalence over the sampling in Equatorial Guinea. SARS-CoV-2 cases were found at a similar frequency in all age groups, whereas the age groups most frequently affected by malaria were children (36.8% [95% CI 30.9-42.7]) and teenagers (34.7% [95% CI 29.5-39.9]). We found six cases of confirmed co-infection of malaria and SARS-CoV-2 distributed among all age groups, representing a 0.4% frequency of co-infection in the whole sampled population. Interestingly, the majority of malaria and SARS-CoV-2 co-infections were mild. We obtained the genome sequences of 43 SARS-CoV-2 isolates, most of which belong to the lineage Delta (AY.43) and that according to our pandemic-scale phylogenies were introduced from Europe in multiple occasions (7 transmission groups and 17 unique introductions). This study is relevant in providing first-time estimates of the actual prevalence of SARS-CoV-2 in this malaria-endemic country, with the identification of circulating variants, their origin, and the occurrence of SARS-CoV-2 and malaria co-infection.

  🖺 Full Text HTML: Circulation of SARS-CoV-2 and co-infection with Plasmodium falciparum in Equatorial Guinea
• The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study -

  Objectives: This study aimed to assess the impact of the COVID-19 lockdown on the screening and diagnosis of breast, colorectal, lung, and prostate cancer. The study also investigated whether the rates returned to pre-pandemic levels by December 2021. Design: Cohort study. Setting: Electronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. Participants: The study included individuals registered with CPRD GOLD between January 2017 and December 2021, with at least 365 days of prior observation. Main outcome measures: The study focused on screening, diagnostic tests, referrals and diagnoses of first-ever breast, colorectal, lung, and prostate cancer. Incidence rates (IR) were stratified by age, sex and region, and incidence rate ratios (IRR) were calculated to compare rates during and after lockdown with the reference period before lockdown. Forecasted rates were estimated using negative binomial regression models. Results: Among 5,191,650 eligible participants, the initial lockdown resulted in reduced screening and diagnostic tests for all cancers, which remained dramatically reduced across the whole observation period for almost all tests investigated. For cancer incidence rates, there were significant IRR reductions in breast (0.69), colorectal (0.74), and prostate (0.71) cancers. However, the reduction in lung cancer incidence (0.92) was non-significant. Extrapolating to the entire UK population, an estimated 18,000 breast, 13,000 colorectal, 10,000 lung, and 21,000 prostate cancer diagnoses were missed from March 2020 to December 2021. Conclusion: The national COVID-19 lockdown in the UK had a substantial impact on cancer screening, diagnostic tests, referrals and diagnoses. Although incidence rates started to recover after the lockdown, they remained significantly lower than pre-pandemic levels for breast and prostate cancers and associated tests. Delays in diagnosis are likely to have adverse consequences on cancer stage, treatment initiation, mortality rates, and years of life lost. Urgent strategies are needed to identify undiagnosed cases and address the long-term implications of delayed diagnoses.

  🖺 Full Text HTML: The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study
• MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management -

  The COVID-19 pandemic brought not only global devastation but also an unprecedented infodemic of false or misleading information that spread rapidly through online social networks. Network analysis plays a crucial role in the science of fact-checking by modeling and learning the risk of infodemics through statistical processes and computation on mega-sized graphs. This paper proposes MEGA, Machine Learning-Enhanced Graph Analytics, a framework that combines feature engineering and graph neural networks to enhance the efficiency of learning performance involving massive graphs. Infodemic risk analysis is a unique application of the MEGA framework, which involves detecting spambots by counting triangle motifs and identifying influential spreaders by computing the distance centrality. The MEGA framework is evaluated using the COVID-19 pandemic Twitter dataset, demonstrating superior computational efficiency and classification accuracy.

  🖺 Full Text HTML: MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management
• A hematopoietic stem cell subset that retains memory of prior inflammatory stress accumulates in aging and clonal hematopoiesis -
  Hematopoietic stem cells (HSC) must persist through a lifetime of infections to ensure life-long blood production, but whether molecular adaptations following inflammatory stress recovery in HSC are linked to aging and clonal hematopoiesis (CH) are unclear. Here, we performed single cell (sc) Multiomics on human HSC isolated from a xenograft inflammation-recovery model. Two transcriptionally and epigenetically distinct HSC subsets expressing canonical HSC programs were identified. Only one showed scATACseq and scRNAseq changes after recovery from TNF or lipopolysaccharide treatment. This inflammatory memory HSC (HSC-iM) program is enriched in memory T cells and HSC from recovered COVID-19 patients. Importantly, HSC-iM accumulates with age and with CH. Overall, a human HSC subset that retains memory of prior inflammatory stress has implications towards HSC fitness and leukemia transformation.
  🖺 Full Text HTML: A hematopoietic stem cell subset that retains memory of prior inflammatory stress accumulates in aging and clonal hematopoiesis
• Effect of Higher-Dose Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial -

  Background: The impact of fluvoxamine in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) remains uncertain. Our objective was to assess the effectiveness of fluvoxamine 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Methods: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were age >=30 years with confirmed SARS-CoV-2 infection and >=2 acute COVID-19 symptoms for <=7 days. Participants were randomized to receive fluvoxamine 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days or to placebo. The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 50 years (IQR 40-60), 66% were female, 45% identified as Hispanic/Latino, and 77% reported >=2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09; P(efficacy) = 0.4]). Additionally, unadjusted, median time to sustained recovery was 10 days (95% CI 10-11) in both the intervention and placebo group. No deaths were reported. Thirty-five participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 14 in the fluvoxamine group compared with 21 in the placebo group (HR 0.69; 95% CrI 0.27-1.21; P(efficacy)=0.86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo). Conclusions: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov (NCT04885530).

  🖺 Full Text HTML: Effect of Higher-Dose Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial
• Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction in COVID-19 -
  Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is an emerging global public health crisis. Angiotensin converting enzyme 2 (ACE2) and trans-membrane protease serine 2 (TMPRSS2) are the two major host factors that contribute to the virulence of SARS-CoV-2 and pathogenesis of coronavirus disease-19 (COVID-19). Animal to human transmission of SARS-CoV-2 is considered as a rare event that necessarily required strong evolutionary adaptations. Till date no other human cellular receptors were identified beside ACE2 for SARS-CoV-2 entry inside the human cell. Proteolytic cleavage of viral spike (S)-protein and ACE2 by TMPRSS2 began the entire host-pathogen interaction initiated with the physical binding of ACE2 to S-protein. SARS-CoV-2 S-protein binds to ACE2 with much higher affinity and stability than that of SARS-CoV’s. Molecular interactions between ACE2-S and TMMPRSS2-S are crucial and preciously mediated by specific residues. Structural stability, binding affinity and level of expression of these three interacting proteins are key susceptibility factors for COVID-19. Specific protein-protein interactions (PPI) are being identified that explains uniqueness of SARS-CoV-2 infection. Amino acid substitutions due to naturally occurring genetic polymorphisms potentially alter these PPIs and poses further clinical heterogeneity of COVID-19. Repurposing of several phytochemicals and approved drugs against ACE2, TMPRSS2 and S-protein have been proposed that could inhibit PPI between them. We have also identified some novel lead phytochemicals present in Azadirachta indica and Aloe barbadensis which could be utilized for further in vitro and in vivo anti-COVID-19 drug discovery. Uncovering details of ACE2-S and TMPRSS2-S interactions would further contribute in the future research on COVID-19.
  🖺 Full Text HTML: Contributions of human ACE2 and TMPRSS2 in determining host-pathogen interaction in COVID-19

From Clinical Trials

• A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL - Condition:   COVID-19
  Interventions:   Biological: hAd5-S-Fusion+N-ETSD;   Biological: Placebo (0.9% (w/v) saline)
  Sponsor:   ImmunityBio, Inc.
  Completed

• Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations - Conditions:   Immunosuppression;   COVID-19
  Intervention:   Biological: NVX-CoV2372
  Sponsors:   University of Wisconsin, Madison;   Novavax
  Not yet recruiting

• Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations - Conditions:   Influenza;   COVID-19
  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

• Reducing COVID-19 Vaccine Hesitancy Among Hispanic Parents - Conditions:   Vaccine-Preventable Diseases;   COVID-19 Pandemic;   Health-Related Behavior;   Health Knowledge, Attitudes, Practice;   Narration
  Interventions:   Behavioral: Baseline surveys;   Behavioral: Digital Storytelling Intervention;   Behavioral: Information Control Intervention
  Sponsors:   Arizona State University;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  Not yet recruiting

• Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia - Condition:   Bronchoalveolar Lavage
  Intervention:   Procedure: Bronchoalveolar Lavage
  Sponsors:   Mohamed Abd Elmoniem Mohamed;   Marwa Salah Abdelrazek Ghanem;   Mohammad Khairy El-Badrawy;   Tamer Ali Elhadidy;   Dalia Abdellateif Abdelghany
  Completed

• Evaluation of Safety and Immunogenicity of a SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2) Booster Vaccine (LEM-mR203) - Conditions:   COVID-19 Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: LEM-mR203;   Biological: Placebo
  Sponsor:   Lemonex
  Not yet recruiting

• Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults - Condition:   SARS-CoV-2 Infection
  Intervention:   Biological: B/HPIV3/S-6P
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   Johns Hopkins Bloomberg School of Public Health;   National Institutes of Health (NIH)
  Recruiting

• A Study to Determine the Tolerability of Intranasal LMN-301 - Condition:   COVID-19
  Intervention:   Biological: LMN-301
  Sponsor:   Lumen Bioscience, Inc.
  Not yet recruiting

• The Effect of Cognitive Behavioral Therapy on Post-Traumatic Stress Symptoms in Nursing Students - Condition:   Trauma and Stressor Related Disorders
  Intervention:   Other: Cognitive Behavioral Therapy Group
  Sponsor:   Necmettin Erbakan University
  Active, not recruiting

• Long COVID Immune Profiling - Conditions:   Long COVID;   POTS - Postural Orthostatic Tachycardia Syndrome;   Autonomic Dysfunction
  Interventions:   Diagnostic Test: IL-6;   Diagnostic Test: cytokines (IL-17, and IFN-ɣ);   Behavioral: Compass 31
  Sponsors:   Vanderbilt University Medical Center;   American Heart Association
  Not yet recruiting

• A Study of Healthy Microbiome, Healthy Mind - Conditions:   Critical Illness;   COVID-19;   PICS;   Cognitive Impairment;   Mental Health Impairment;   Weakness, Muscle;   Dysbiosis
  Intervention:   Behavioral: Fermented Food Diet
  Sponsor:   Mayo Clinic
  Not yet recruiting

From PubMed

• Association between levels of IgG antibodies from vaccines and Omicron symptomatic infection among children and adolescents in China - CONCLUSION: The risk of developing a symptomatic infection can be predicted independently by tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens. High IgG levels can inhibit viral replication, vastly reduce the risk of symptomatic infections and promote a virus-negative conversion, especially when IgG quantitative detection was ≥3.44 S/CO, a potential threshold for protection and booster strategy in the future. More data and research are needed in the future to validate the predictive…

• Identification of essential genes associated with SARS-CoV-2 infection as potential drug target candidates with machine learning algorithms - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the fast discovery of effective treatments to fight this worldwide concern. Several genes associated with the SARS-CoV-2, which are essential for its functionality, pathogenesis, and survival, have been identified. These genes, which play crucial roles in SARS-CoV-2 infection, are considered potential therapeutic targets. Developing drugs against these essential genes to inhibit their regular functions could be a good approach…

• Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets - The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions…

• Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge - Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including…

• Suramin inhibits SARS-CoV-2 nucleocapsid phosphoprotein genome packaging function - The coronavirus disease 2019 (COVID-19) pandemic is fading, however its etiologic agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues posing - despite the availability of licensed vaccines - a global health threat, due to the potential emergence of vaccine-resistant SARS-CoV-2 variants. This makes the development of new drugs against COVID-19 a persistent urgency and sets as research priority the validation of novel therapeutic targets within the SARS-CoV-2 proteome….

• Inhalable dry powder containing remdesivir and disulfiram: Preparation and in vitro characterization - The respiratory tract, as the first and most afflicted target of many viruses such as SARS-CoV-2, seems to be the logical choice for delivering antiviral agents against this and other respiratory viruses. A combination of remdesivir and disulfiram, targeting two different steps in the viral replication cycle, has showed synergistic activity against SARS-CoV-2 in-vitro. In this study, we have developed an inhalable dry powder containing a combination of remdesivir and disulfiram utilizing the…

• MICROVASCULAR ENDOTHELIAL ACTIVATION/DYSFUNCTION AND DYSREGULATION OF THE ANGIOPOIETIN-TIE2 SYSTEM IN THE PATHOGENESIS OF LIFE-THREATENING INFECTIONS - Microvascular endothelial activation/dysfunction has emerged as an important mechanistic pathophysiological process in the development of morbidity and mortality in life-threatening infections. The angiopoietin-Tie2 system plays an integral role in the regulation of microvascular endothelial integrity. Angiopoietin-1 (Ang-1), produced by platelets and pericytes, is the cognate agonistic ligand for Tie2, promoting endothelial quiescence and inhibiting microvascular leak. Angiopoietin-2 (Ang-2),…

• Prime editor-mediated functional reshaping of ACE2 prevents the entry of multiple human coronaviruses, including SARS-CoV-2 variants - The spike protein of SARS-CoV-2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS-CoV-2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike-focused vaccines and therapeutics. Compared with the fast-evolving spike protein, targeting host ACE2…

• Targeting host calcium channels and viroporins: a promising strategy for SARS-CoV-2 therapy - Despite passing the pandemic phase of the COVID-19, researchers are still investigating various drugs. Previous evidence suggests that blocking the calcium channels may be a suitable treatment option. Ca^(2+) is required to enhance the fusion process of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also, some important inflammatory factors during SARS-CoV-2 infection are dependent on Ca^(2+) level. On the other hand, viroporins have emerged as attractive targets for antiviral…

• Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 - Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus formation. This hyperinflammation is dependent on high levels of anti-spike IgG with aberrant Fc tail glycosylation, leading to Fcγ receptor hyperactivation. For development of immune-regulatory therapeutics, drug specificity is crucial to counteract excessive…

• Safety and Immunogenicity of the BNT162b2 Vaccine Coadministered with Seasonal Inactivated Influenza Vaccine in Adults - CONCLUSIONS: BNT162b2 coadministered with SIIV elicited immune responses that were noninferior to those elicited by BNT162b2 alone and SIIV alone, and BNT162b2 had an acceptable safety profile when coadministered with SIIV. The results of this study support the coadministration of BNT162b2 and SIIV in adults.

• Farnesoid X receptor enhances epithelial ACE2 expression and inhibits viral-induced IL-6 secretion: implications for intestinal symptoms of SARS-CoV-2 - CONCLUSION: By virtue of its ability to modulate epithelial ACE2 expression and inhibit virus-mediated pro-inflammatory cytokine release, FXR represents a promising target for development of new approaches to prevent intestinal manifestations of SARS-CoV-2.

• Targeting spike glycans to inhibit SARS-CoV2 viral entry - SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…

• PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner - ADP-ribosyltransferases (ARTs) mediate the transfer of ADP-ribose from NAD^(+) to protein or nucleic acid substrates. This modification can be removed by several different types of proteins, including macrodomains. Several ARTs, also known as PARPs, are stimulated by interferon indicating ADP-ribosylation is an important aspect of the innate immune response. All coronaviruses (CoVs) encode for a highly conserved macrodomain (Mac1) that is critical for CoVs to replicate and cause disease,…

• Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials - Azvudine (FNC) is a synthetic nucleoside analog used to treat adult patients living with human immunodeficiency virus-1 (HIV-1) infection with high viral load. After phosphorylation, Azvudine inhibits RNA-dependent RNA polymerase, leading to the discontinuation of RNA chain synthesis in viruses. In addition, Azvudine is the first dual-target nucleoside oral drug worldwide to simultaneously target reverse transcriptase and viral infectivity factors in the treatment of HIV infection. On 9 August…

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