Covid-19 Sentry

Contents

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

From Preprints

• Genome-wide association study reveals different T cell distributions in peripheral blood of healthy individuals at high genetic risk of type 1 diabetes and long COVID -

  The immune system plays a crucial role in many human diseases. In this context, genome-wide association studies (GWAS) offer valuable insights to elucidate the role of immunity in health and disease. The present multi-omics study aimed to identify genetic determinants of immune cell type distributions in the blood of healthy individuals and to assess whether the distributions of these cells may play a role for autoimmune and COVID-19 disease risk. To this end, the frequencies of different immune cells in 483 healthy individuals from the Berlin Aging Study II were quantified using flow cytometry, and GWAS was performed for 92 immune cell phenotypes. Additionally, we performed linear regression analyses of immune cell distributions using polygenic risk scores (PRS) based on prior GWAS for five autoimmune diseases as well as for COVID-19 infection and post-COVID syndrome (“long COVID”). We validated seven previously described immune loci and identified 13 novel loci showing genome-wide significant (α=5.00E-8) association with different immune cell phenotypes. The most significant novel signal was conferred by the SLC52A3 locus, encoding for a riboflavin transporter protein, which was associated with na&iumlve CD57+ CD8+ T cells (p=4.13E-17) and colocalized with SLC52A3 expression. Several novel loci contained immunologically plausible candidate genes, e.g., variants near TBATA and B3GAT1 representing genes associated with T cell phenotypes. The PRS of type 1 diabetes were significantly associated with CD8+ T cells at different differentiation states (p≤7.02E-4), and PRS of long COVID were associated with early-differentiated CD4+ T cells (p≤1.54E-4). In conclusion, our extensive immune cell GWAS analyses highlight several novel genetic loci of likely relevance for immune system function. Furthermore, our PRS analyses point to a shared genetic basis between immune cell distributions in healthy adults and T1D (CD8+ T cells) as well as long COVID (CD4+ T cells).

  🖺 Full Text HTML: Genome-wide association study reveals different T cell distributions in peripheral blood of healthy individuals at high genetic risk of type 1 diabetes and long COVID
• Implementation of Smart Triage combined with a quality improvement program for children presenting to facilities in Kenya and Uganda: An interrupted time series analysis. -

  PLOS DH (298/300 word limit) Sepsis occurs predominantly in low-middle-income countries. Sub-optimal triage contributes to poor early case recognition and outcomes from sepsis. We evaluated the impact of Smart Triage using improved time to intravenous antimicrobial administration in a multisite interventional study. Smart Triage was implemented (with control sites) in Kenya (February 2021-December 2022) and Uganda (April 2020-April 2022). Children presenting to the outpatient departments with an acute illness were enrolled. A controlled interrupted time series was used to assess the effect on time from arrival at the facility to intravenous antimicrobial administration. Secondary analyses included antimicrobial use, admission rates and mortality (NCT04304235). During the baseline period, the time to antimicrobials decreased significantly in Kenya (132 and 58 minutes) at control and intervention sites, but less in Uganda (3 minutes) at the intervention site. Then, during the implementation period in Kenya, the time to IVA at the intervention site decreased by 98 min (57%, 95% CI 81-114) but increased by 49 min (21%, 95% CI: 23-76) at the control site. In Uganda, the time to IVA initially decreased but was not sustained, and there was no significant difference between intervention and control sites. At the intervention sites, there was a significant reduction in IVA utilization of 47% (Kenya) and 33% (Uganda), a reduction in admission rates of 47% (Kenya) and 33% (Uganda) and a 25% (Kenya) and 75% (Uganda) reduction in mortality rates compared to the baseline period. We showed significant improvements in time to intravenous antibiotics in Kenya but not Uganda, likely due to COVID-19, a short study period and resource constraints. The reduced antimicrobial use and admission and mortality rates are remarkable and welcome benefits but should be interpreted cautiously as these were secondary outcomes. This study underlines the difficulty of implementing technologies and sustaining quality improvement in resource-poor health systems.

  🖺 Full Text HTML: Implementation of Smart Triage combined with a quality improvement program for children presenting to facilities in Kenya and Uganda: An interrupted time series analysis.
• Physicians experiences with telemedicine during the COVID-19 pandemic in India -

  Purpose: Digital health is an important factor in Indias healthcare system. Inclusive policy measures, a fertile technological landscape, and relevant infrastructural development with unprecedented levels of telemedicine adoption catalysed by the recent COVID-19 pandemic have thrown open new possibilities and opportunities for clinicians, end-users, and other stakeholders. Nevertheless, there are still several challenges to properly integrating and scaling telemedicine use in India. This studys objective was to understand the views of practising physicians in India on the use of telemedicine and the challenges experienced during the accelerated rollout during the first wave of the COVID-19 pandemic. Methods: We acquired data through an anonymous, cross-sectional, internet-based survey of physicians (n=444) across India on the COVID-19 frontline. These responses were subjected to qualitative data analysis (via inductive coding and thematic analyses) and descriptive statistics, as appropriate. Results: Most responses (n=51) were categorised under a code indicating that telemedicine-led healthcare delivery compromised treatment quality. The second largest proportion of responses (n=22) suggested that Accessibility, quality and maturity of software and hardware infrastructure was a considerable challenge. Conclusions: Despite the considerable uptake, perceived benefits, and the foreseen positive role of telemedicine in India, several challenges of telemedicine use (viz., technical, user experience-based integration, and non-user-based integration challenges) have been identified. These must be addressed through suggested relevant opportunities to realise telemedicines potential and help inform the future design of effective telemedicine policy and practice in India.

  🖺 Full Text HTML: Physicians experiences with telemedicine during the COVID-19 pandemic in India
• Factors associated with knowledge, attitudes, and behaviors regarding antiviral medications for COVID-19 among US adults -

  Background: Little is known about public perceptions of antivirals for the treatment of mild-to-moderate COVID-19 in the United States (US). Our objective was to explore adult perceptions toward COVID-19 antivirals with the goal of improving outreach communications about antivirals for COVID-19. Methods: During July 2022, potential respondents 18 years and older were randomly sampled from a national opt-in, non-representative, cross-sectional internet panel, with oversampling of African Americans, Hispanics, and adults 65 years and older. Respondents were asked about sociodemographic factors, and knowledge, attitudes, and perceptions regarding COVID-19 antivirals. Results were weighted to represent the non-institutionalized US adult population. Results: Among 1,155 respondents, 51% were female, 60% were 18-49 years, 21% were 50-64 years, and 19% were 65 years or older. Compared to those aged 18-49 years and 50-64 years, a greater proportion of adults 65 years and older were knowledgeable about COVID-19 antivirals and would take them if they tested positive or their doctor recommended them. Adults 65 years and over and those reporting immunosuppression or disability had the highest rates of willingness to take antivirals. For all groups, the proportion of people willing to take antivirals increased by >20% if recommended by their doctor. Respondents in the 50-64 and 65+ groups who were sure they would take COVID-19 antivirals were more likely to be fully vaccinated and less likely to be living in isolation. Conclusion: Groups that are less likely to have been vaccinated, those living in isolation, and those not sure about whether they would take an antiviral or not may be at risk for not receiving treatment to prevent severe COVID-19 outcomes. However, trust in doctor recommendations may be enough to overcome individual patient concerns about COVID-19 antivirals. Targeted initiatives to educate those at risk for severe COVID-19 outcomes about the effectiveness of antivirals, including those who are unvaccinated given their increased risk of severe disease, may be needed to further lower this population9s risk of severe COVID-19.

  🖺 Full Text HTML: Factors associated with knowledge, attitudes, and behaviors regarding antiviral medications for COVID-19 among US adults
• SARS-COV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice -
  The coronavirus disease of 2019 (COVID-19) pandemic that has led to more than 700 million confirmed cases and near 7 million deaths. Although Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus mainly infects the respiratory system, neurological complications are widely reported in both acute infection and long-COVID cases. Despite the success of vaccines and antiviral treatments, neuroinvasiveness of SARS-CoV-2 remains as an important question, which is also centered on the mystery whether the virus is capable of breaching the barriers into the central nervous system. By studying the K18-hACE2 infection model, we observed clear evidence of microvascular damage and breakdown of the blood-brain barrier (BBB). Mechanistically, SARS-CoV-2 infection caused pericyte damage, tight junction loss, endothelial activation and vascular inflammation, which together drive microvascular injury and BBB impairment. In addition, the blood-cerebrospinal fluid barrier at the choroid plexus was also impaired after infection. Therefore, cerebrovascular and choroid plexus dysfunctions are important aspects of COVID-19 and may contribute to the neurological complications both acutely and in long COVID.
  🖺 Full Text HTML: SARS-COV-2 induces blood-brain barrier and choroid plexus barrier impairments and vascular inflammation in mice
• Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity -
  Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk.
  🖺 Full Text HTML: Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity
• Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion -
  The unceasing circulation of SARS-CoV-2 leads to the continuous emergence of novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 and JN.1 variants, representing >80% of circulating variants in January 2024. The XBB subvariants carry few but recurrent mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30 additional changes. These variants replicated in IGROV-1 but no longer in Vero E6 and were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting the highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees and BA.1/BA.2-infected individuals were markedly lower compared to BA.1, without major differences between variants. An XBB breakthrough infection enhanced NAb responses against both XBB and BA.2.86 variants. JN.1 displayed lower affinity to ACE2 and higher immune evasion properties compared to BA.2.86.1. Thus, while distinct, the evolutionary trajectory of these variants combines increased fitness and antibody evasion.
  🖺 Full Text HTML: Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion
• Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders -
  The coronavirus disease of 2019 (COVID-19) pandemic is characterized by sequential emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and lineages outcompeting previously circulating ones because of, among other factors, increased transmissibility and immune escape. We devised an unsupervised deep learning AutoEncoder for viral genomes anomaly detection to predict future dominant lineages (FDLs), i.e., lineages or sublineages comprising >= 10% of viral sequences added to the GISAID database on a given week. The algorithm was trained and validated by assembling global and country specific data sets from 16,187,950 Spike protein sequences sampled between December 24th, 2019, and November 8th, 2023. The AutoEncoder flags low frequency FDLs (0.01% - 3%), with median lead times of 4-16 weeks. Over time, positive predictive values oscillate, decreasing linearly with the number of unique sequences per data set, showing average performance up to 30 times better than baseline approaches. The B.1.617.2 vaccine reference strain was flagged as FDL when its frequency was only 0.01%, more than one year earlier of being considered for an updated COVID-19 vaccine. Our AutoEncoder, applicable in principle to any pathogen, also pinpoints specific mutations potentially linked to increased fitness, and may provide significant insights for the optimization of public health pre-emptive intervention strategies.
  🖺 Full Text HTML: Forecasting dominance of SARS-CoV-2 lineages by anomaly detection using deep AutoEncoders
• The Importance of Cause-of-Death Certification for the COVID-19 Burden Assessment: the Case of Central Europe -
  Background: In Central Europe, the increase in mortality during the COVID-19 pandemic exceeded the number of deaths registered due to coronavirus disease. Miscertification of COVID-19 has been suggested as one of the possible explanations. Analysis of all mentions from death certificates allows us to identify cases where COVID-19 was reported as a contributing rather than the underlying cause of death (UCoD). Methods: Analysis of 187,000 death certificates with a COVID-19 mention from Austria, Bavaria, Czechia, Lithuania and Poland, 2020–2021. Cause of Death Association Indicators (CDAIs) and Contributing CDAIs were calculated to identify and measure the strength of associations between COVID-19, reported as UCoD or not, and all other medical mentions. Results: Death certificates reporting COVID-19 included on average more medical information than other death certificates. In 171,600 deaths with COVID-19 as the UCoD, ten groups of comorbidities and ten types of complications revealed significant and strong association with COVID-19. Further 15,700 deaths were certified with COVID-19 only as a contributing condition, of which almost 20% were assigned to typical coronavirus complications, such as cerebral infarction, Acute Myocardial Infarction, renal failure. In Austria, Bavaria, Czechia and Lithuania the reported scale of COVID-19 mortality would have been 18-27% higher had COVID-19 been coded as the UCoD in all the cases. Conclusions: Complete death certificate information allows us to assess the scale of COVID-19 miscertification and the burden of COVID-19. Deaths registered with a coronavirus comorbidity were equivalent to the total estimated excess mortality in Austria and Czech Republic, and a large proportion of in Lithuania and Bavaria.
  🖺 Full Text HTML: The Importance of Cause-of-Death Certification for the COVID-19 Burden Assessment: the Case of Central Europe
• Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals -
  Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on sarbecovirus response breadths elicited by mosaic-8b, admix-8b (8 homotypics), and homotypic SARS-CoV-2, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies derived from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced with mosaic-8b boosting, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.
  🖺 Full Text HTML: Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals
• Use of substances to cope predicts PTSD symptom persistence: Investigating patterns of interactions between PTSD symptoms and its maintaining mechanisms -
  Objective. Post-traumatic stress disorder (PTSD) remains a growing public health challenge across the globe and is associated with negative and persistent long-term consequences. The last decades of research identified different mechanisms associated with the development and persistence of PTSD, including maladaptive coping strategies, cognitive and experiential avoidance, positive, and negative metacognitions. Despite these advances, little is known about how these different processes interact with specific PTSD symptoms, and how they influence each other over time at the within-person level. Method. Leveraging a large (N > 1,800) longitudinal dataset representative of the Norwegian population during the COVID-19 pandemic, this pre-registered study investigated these symptom-process interactions over an eight-month period. Results. Our panel graphical vector autoregressive (GVAR) network model revealed the dominating role of substance use to cope in predicting higher levels of PTSD symptoms over time and increases in PTSD symptomatology within more proximal time-windows (i.e., within six weeks). Threat monitoring was associated with increased suicidal ideation, while threat monitoring itself was increasing upon decreased avoidance behavior, greater presence of negative metacognitions, and higher use of substances to cope. Conclusions. Our findings speak to the importance of attending to different coping strategies, particularly the use of substances as a coping behavior in efforts to prevent PTSD chronicity upon symptom onset. We outline future directions for research efforts to better understand the complex interactions and temporal pathways leading up to the development and maintenance of PTSD symptomatology.
  🖺 Full Text HTML: Use of substances to cope predicts PTSD symptom persistence: Investigating patterns of interactions between PTSD symptoms and its maintaining mechanisms
• Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates -

  The ongoing evolution of the SARS-CoV-2 virus has led to a move to update vaccine antigens in 2022 and 2023. These updated antigens were chosen and approved based on in vitro neutralisation titres against recent SARS-CoV-2 variants. However, unavoidable delays in viral manufacture and distribution meant that the updated booster vaccine was no longer well matched to the circulating SARS-CoV-2 variant by the time of its deployment. Understanding whether the updating of booster vaccine antigens improves immune responses to subsequent SARS-CoV-2 circulating variants is a major priority in justifying future vaccine updates. Here we analyse all available data on the immunogenicity of variant containing SARS-CoV-2 vaccines and their ability to neutralise later circulating SARS-CoV-2 variants. We find that updated booster antigens give a 1.4-fold [95%CI 1.07-1.82] greater increase in neutralising antibody levels when compared with a historical vaccine immunogen. We then use this to predict the relative protection that can be expected from an updated vaccine even when the circulating variant has evolved away from the updated vaccine immunogen. These findings help inform the roll out of future booster vaccination programs.

  🖺 Full Text HTML: Predicting COVID-19 booster immunogenicity against future SARS-CoV-2 variants and the benefits of vaccine updates
• Can longitudinal electronic health record data identify patients at higher risk of developing long COVID? -

  With hundreds of millions of COVID-19 infections to date, a considerable portion of the population has developed or will develop long COVID. Understanding the prevalence, risk factors, and healthcare costs of long COVID can be of significant societal importance. To investigate the utility of large-scale electronic health record (EHR) data in identifying and predicting long COVID, we analyzed data from the National COVID Cohort Collaborative (N3C), a longitudinal EHR data repository from 65 sites in the US with over 8 million COVID-19 patients. We characterized the prevalence of long COVID using a few different types of definition to illustrate their relative strengths and weaknesses. Then we developed a machine learning model to predict the risk of developing long COVID using demographic factors and comorbidity in the EHR. The risk factors for long COVID include patient age; sex; smoking status; and comorbidities characterized by the Charlson Comorbidity Index.

  🖺 Full Text HTML: Can longitudinal electronic health record data identify patients at higher risk of developing long COVID?
• Mechanistic models of humoral kinetics following COVID-19 vaccination -

  Introduction: Future COVID-19 vaccine programmes need to take into account the variable responses elicited by different vaccines and their waning protection over time. Existing descriptions of antibody response to COVID-19 vaccination convey limited information about the mechanisms of antibody production and maintenance. Methods: We describe the antibody dynamics elicited by COVID-19 vaccination with two biologically-motivated mathematical models of antibody production by plasma cells and subsequent decay. We fit the models using Markov Chain Monte Carlo to seroprevalence data from 14,602 uninfected individuals collected via the primary care network in England between May 2020 and September 2022. We ensure our models are structurally and practically identifiable when using anti- body data alone. We analyse the effect of age, vaccine type, number of doses, and the interval between doses on antibody production and longevity of response. Results: We find evidence that individuals over 35 years of age who received a second dose of ChAdOx1-S generate a persistent antibody response suggestive of long-lived plasma cell induction, while individuals that receive two doses of BNT162b2, or one dose of either vaccine do not. We also find that plasamblast productive capacity, the likely driver of short-term antibody responses, is greater in younger people than older people (≤ 4.5 fold change in point estimates), people vaccinated with two doses than people vaccinated with one dose (≤ 12 fold change), and people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S (≤ 440 fold change). The effect of age on antibody dynamics is more pronounced in people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S. We find the half-life of an antibody to be between 23 - 106 days. Conclusion: Routinely-collected seroprevalence data are a valuable source of information for characterising within-host mechanisms of antibody production and persistence. Extended sampling and linking seroprevalence data to outcomes would allow for powerful conclusions about how humoral kinetics protect against disease.

  🖺 Full Text HTML: Mechanistic models of humoral kinetics following COVID-19 vaccination
• Dimensionality reduction distills complex evolutionary relationships in seasonal influenza and SARS-CoV-2 -
  Public health researchers and practitioners commonly infer phylogenies from viral genome sequences to understand transmission dynamics and identify clusters of genetically-related samples. However, viruses that reassort or recombine violate phylogenetic assumptions and require more sophisticated methods. Even when phylogenies are appropriate, they can be unnecessary or difficult to interpret without specialty knowledge. For example, pairwise distances between sequences can be enough to identify clusters of related samples or assign new samples to existing phylogenetic clusters. In this work, we tested whether dimensionality reduction methods could capture known genetic groups within two human pathogenic viruses that cause substantial human morbidity and mortality and frequently reassort or recombine, respectively: seasonal influenza A/H3N2 and SARS-CoV-2. We applied principal component analysis (PCA), multidimensional scaling (MDS), t-distributed stochastic neighbor embedding (t-SNE), and uniform manifold approximation and projection (UMAP) to sequences with well-defined phylogenetic clades and either reassortment (H3N2) or recombination (SARS-CoV-2). For each low-dimensional embedding of sequences, we calculated the correlation between pairwise genetic and Euclidean distances in the embedding and applied a hierarchical clustering method to identify clusters in the embedding. We measured the accuracy of clusters compared to previously defined phylogenetic clades, reassortment clusters, or recombinant lineages. We found that MDS maintained the strongest correlation between pairwise genetic and Euclidean distances between sequences and best captured the intermediate placement of recombinant lineages between parental lineages. Clusters from t-SNE most accurately recapitulated known phylogenetic clades and recombinant lineages. Both MDS and t-SNE accurately identified reassortment groups. We show that simple statistical methods without a biological model can accurately represent known genetic relationships for relevant human pathogenic viruses. Our open source implementation of these methods for analysis of viral genome sequences can be easily applied when phylogenetic methods are either unnecessary or inappropriate.
  🖺 Full Text HTML: Dimensionality reduction distills complex evolutionary relationships in seasonal influenza and SARS-CoV-2

From Clinical Trials

• Investigating the Effectiveness of Vimida - Conditions: Long COVID; Post COVID-19 Condition
  Interventions: Behavioral: vimida
  Sponsors: Gaia AG; Medical School Hamburg; Institut Long-Covid Rostock
  Not yet recruiting

• Effects of Physiotherapy Via Video Calls on Cardiopulmonary Functions, Physical Function, Cognitive Function, Activity Daily Livings, and Quality of Life in Patients With COVID-19 - Conditions: COVID-19; Long COVID-19; Cardiopulmonary Function; Physical Function
  Interventions: Behavioral: Exercise training
  Sponsors: Chulabhorn Hospital
  Enrolling by invitation

• Acute Cardiovascular Responses to a Single Exercise Session in Patients With Post-COVID-19 Syndrome - Conditions: Post-Acute COVID-19 Syndrome
  Interventions: Behavioral: Exercise session; Behavioral: Control session
  Sponsors: University of Nove de Julho
  Not yet recruiting

• Reducing Respiratory Virus Transmission in Bangladeshi Classrooms - Conditions: SARS-CoV2 Infection; Influenza Viral Infections; Respiratory Viral Infection
  Interventions: Device: Box Fan; Device: UV Germicidal Irradiation Lamp Unit; Device: Combined: Box Fan and UV Germicidal Irradiation Lamp Units
  Sponsors: Stanford University; Centers for Disease Control and Prevention; International Centre for Diarrhoeal Disease Research, Bangladesh
  Not yet recruiting

• SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19 - Conditions: Anxiety; COVID-19 Pandemic
  Interventions: Behavioral: Mindfulness
  Sponsors: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International
  Not yet recruiting

• A Study to Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults - Conditions: Influenza, Human; SARS-CoV-2 Infection; COVID-19
  Interventions: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo
  Sponsors: Pfizer
  Recruiting

• The Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus - Conditions: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus
  Interventions: Behavioral: Nutritional Intervention
  Sponsors: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo
  Completed

• The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management - Conditions: Trauma; COVID-19 Pandemic
  Interventions: Other: epidemyolojical
  Sponsors: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
  Completed

• Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age. - Conditions: SARS CoV 2 Infection
  Interventions: Biological: BIMERVAX
  Sponsors: Hipra Scientific, S.L.U; Veristat, Inc.; VHIR; Asphalion
  Recruiting

• A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid - Conditions: Long COVID; Post-Acute COVID-19 Syndrome
  Interventions: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management
  Sponsors: University of Texas Southwestern Medical Center
  Not yet recruiting

• Study on the Effect of Incentive Spirometer-based Respiratory Training on the Long COVID-19 - Conditions: COVID-19 Pandemic; Diabetes; Hypertension; Cardiac Disease; Long COVID
  Interventions: Behavioral: Incentive Spirometer respiratory training
  Sponsors: National Taipei University of Nursing and Health Sciences; Tri-Service General Hospital
  Not yet recruiting

• Balance Acceptance and Commitment Therapy for Long COVID - Conditions: Post-COVID-19 Syndrome; Long COVID
  Interventions: Behavioral: Balance Acceptance and Commitment Therapy
  Sponsors: King’s College London
  Not yet recruiting

• Predict + Protect Study: Exploring the Effectiveness of a Predictive Health Education Intervention on the Adoption of Protective Behaviors Related to ILI - Conditions: Influenza; Influenza A; Influenza B; COVID-19; Respiratory Syncytial Virus (RSV)
  Interventions: Behavioral: ILI Predictive Alerts, Reactive Content, and Proactive Content; Behavioral: ILI Predictive Alerts, Reactive Content; Behavioral: Proactive Content; Behavioral: No Intervention
  Sponsors: Evidation Health; Biomedical Advanced Research and Development Authority
  Not yet recruiting

From PubMed

• Influenza vaccination during the 2021/22 season: A data-linkage test-negative case-control study of effectiveness against influenza requiring emergency care in England and serological analysis of primary care patients - We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1-17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2-10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50-64…

• Evaluation of molecular mechanisms of riboflavin anti-COVID-19 action reveals anti-inflammatory efficacy rather than antiviral activity - CONCLUSIONS: It is concluded that riboflavin reveals anti-inflammatory rather than antiviral activity for SARS-CoV-2 infection.

• An enhanced broad-spectrum peptide inhibits Omicron variants in vivo - The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) poses a major challenge to vaccines and antiviral therapeutics due to their extensive evasion of immunity. Aiming to develop potent and broad-spectrum anticoronavirus inhibitors, we generated A1-(GGGGS)7-HR2m (A1L35HR2m) by introducing an angiotensin-converting enzyme 2 (ACE2)-derived peptide A1 to the N terminus of the viral HR2-derived peptide HR2m through a long flexible linker,…

• Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal? - The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various…

• Genetic justification of COVID-19 patient outcomes using DERGA, a novel data ensemble refinement greedy algorithm - Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs….

• Milk Antiviral Proteins and Derived Peptides against Zoonoses - Milk is renowned for its nutritional richness but also serves as a remarkable reservoir of bioactive compounds, particularly milk proteins and their derived peptides. Recent studies have showcased several robust antiviral activities of these proteins, evidencing promising potential within zoonotic viral diseases. While several publications focus on milk’s bioactivities, antiviral peptides remain largely neglected in reviews. This knowledge is critical for identifying novel research directions…

• The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions - Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: (i) the ability to fight infections; (ii) the activation of blood coagulation or blood clot lysis systems; (iii) the activation of digestive enzymes; and (iv)…

• A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury - Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation and treatment of ARDS remains a major research focus. There are various causes of ARDS, among which pneumonia and non-pulmonary sepsis are the most common. Trauma and blood transfusion can also cause ARDS. In ARDS, the aggregation and infiltration of neutrophils in the lungs have a great influence on the development of the disease. Neutrophils regulate inflammatory responses through various…

• Unveiling the Antiviral Properties of Panduratin A through SARS-CoV-2 Infection Modeling in Cardiomyocytes - Establishing a drug-screening platform is critical for the discovery of potential antiviral agents against SARS-CoV-2. In this study, we developed a platform based on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to investigate SARS-CoV-2 infectivity, with the aim of evaluating potential antiviral agents for anti-SARS-CoV-2 activity and cardiotoxicity. Cultured myocytes of iPSC-CMs and immortalized human cardiomyocyte cell line (AC-16) were primarily characterized for the…

• Ligand-Based Design of Selective Peptidomimetic uPA and TMPRSS2 Inhibitors with Arg Bioisosteres - Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On the other hand, they are also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is involved in tissue remodeling, can increase the metastatic behavior of various cancer types when overexpressed and dysregulated. Another member of this protease class that received attention during the SARS-CoV 2 pandemic…

• Phytochemical Elucidation and Effect of Maesa indica (Roxb.) Sweet on Alleviation of Potassium Dichromate-Induced Pulmonary Damage in Rats - Maesa indica (Roxb.) Sweet is one of the well-known traditionally-used Indian plants. This plant is rich in secondary metabolites like phenolic acids, flavonoids, alkaloids, glycosides, saponins, and carbohydrates. It contains numerous therapeutically active compounds like palmitic acid, chrysophanol, glyceryl palmitate, stigmasterol, β-sitosterol, dodecane, maesaquinone, quercetin 3-rhaminoside, rutin, chlorogenic acid, catechin, quercetin, nitrendipine, 2,3-dihydroxypropyl…

• SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA - A better mechanistic understanding of virus-host dependencies can help reveal vulnerabilities and identify opportunities for therapeutic intervention. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in protein synthesis dynamics during SARS-CoV-2 (CoV2) infection. We identify specific…

• Application of a Biomimetic Nanoparticle-Based Mock Virus to Determine SARS-CoV-2 Neutralizing Antibody Levels in Blood Samples Using a Lateral Flow Assay - The presence of neutralizing antibodies against SARS-CoV-2 in blood, acquired through previous infection or vaccination, is known to prevent the (re)occurrence of outbreaks unless the virus mutates. Therefore, the measurement of neutralizing antibodies constitutes an indispensable tool in assessing an individual’s and a population’s immunity against SARS-CoV-2. For this reason, we have developed an innovative lateral flow assay (LFA) capable of detecting blood-derived neutralizing antibodies…

• Kidney organoids reveal redundancy in viral entry pathways during ACE2-dependent SARS-CoV-2 infection - With a high incidence of acute kidney injury among hospitalized COVID-19 patients, considerable attention has been focussed on whether SARS-CoV-2 specifically targets kidney cells to directly impact renal function, or whether renal damage is primarily an indirect outcome. To date, several studies have utilized kidney organoids to understand the pathogenesis of COVID-19, revealing the ability for SARS-CoV-2 to predominantly infect cells of the proximal tubule (PT), with reduced infectivity…

• Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review - The potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, the authors review the rationale and potential implications of PCSK9…

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