Covid-19 Sentry

Contents

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

From Preprints

• Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein -
  Intranasal vaccination is an attractive strategy for preventing COVID-19 disease as it stimulates the production of multimeric secretory immunoglobulin A (IgAs), the predominant antibody isotype in the mucosal immune system, at the target site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, the evaluation of intranasal vaccine efficacy is based on the measurement of polyclonal antibody titers in nasal lavage fluid. However, how individual multimeric secretory IgA protects the mucosa from SARS-CoV-2 infection remains to be elucidated. To understand the precise contribution and molecular nature of multimeric secretory IgAs induced by intranasal vaccines, we developed 99 monoclonal IgAs from nasal mucosa and 114 monoclonal IgAs or IgGs from nonmucosal tissues of mice that were intranasally immunized with the SARS-CoV-2 spike protein. The nonmucosal IgAs exhibited shared origins and both common and unique somatic mutations with the related nasal IgA clones, indicating that the antigen-specific plasma cells in the nonmucosal tissues originated from B cells stimulated at the nasal mucosa. Comparing the spike protein binding reactivity, angiotensin-converting enzyme-2-blocking and SARS-CoV-2 virus neutralization of monomeric and multimeric IgA pairs recognizing different epitopes showed that even nonneutralizing monomeric IgA, which represents 70% of the nasal IgA repertoire, can protect against SARS-CoV-2 infection when expressed as multimeric secretory IgAs. Our investigation is the first to demonstrate the function of nasal IgAs at the monoclonal level, showing that nasal immunization can provide effective immunity against SARS-CoV-2 by inducing multimeric secretory IgAs at the target site of virus infection.
  🖺 Full Text HTML: Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein
• Analysing the performance of multilateral organizations facing major crises: Covid-19 in comparative perspective -
  The research objective is to analyse the consequences that recent crises have had for multilateral organizations, to what extent they fostered a transformation of response mechanisms and whether this transformation has contributed to strengthening the institution and improving its response to new crises. We analyse and compare the role of two specific International Organizations (IOs), the World Health Organization and the International Organization of Migration, in recent major transnational crises: the COVID-19 pandemic and the migration crisis caused by Russian aggression against Ukraine. Two complementary strands of the scientific literature are taken into account: Studies analysing the functioning and performance of IOs and the literature on crisis management. In each case study, we describe the IOs’ institutional designs and the characteristics of the policy regimes in which the IOs operate. Then we assess the response given to the crises, distinguishing between planned measures designed to provide an immediate response and resilience measures for future crises. We end with a comparative assessment of the performance of these two IOs in the face of these crises and their capacity to learn lessons from them to deal with future crises.
  🖺 Full Text HTML: Analysing the performance of multilateral organizations facing major crises: Covid-19 in comparative perspective
• DNA fragments detected in monovalent and bivalent Pfizer/BioNTech and Moderna modRNA COVID-19 vaccines from Ontario, Canada: Exploratory dose response relationship with serious adverse events. -
  Background: In vitro transcription (IVT) reactions used to generate nucleoside modified RNA (modRNA) for SARS-CoV-2 vaccines currently rely on an RNA polymerase transcribing from a DNA template. Production of modRNA used in the original Pfizer randomized clinical trial (RCT) utilized a PCR-generated DNA template (Process 1). To generate billions of vaccine doses, this DNA was cloned into a bacterial plasmid vector for amplification in Escherichia coli before linearization (Process 2), expanding the size and complexity of potential residual DNA and introducing sequences not present in the Process 1 template. It appears that Moderna used a similar plasmid-based process for both clinical trial and post-trial use vaccines. Recently, DNA sequencing studies have revealed this plasmid DNA at significant levels in both Pfizer-BioNTech and Moderna modRNA vaccines. These studies surveyed a limited number of lots and questions remain regarding the variance in residual DNA observed internationally. Methods: Using previously published primer and probe sequences, quantitative polymerase chain reaction (qPCR) and Qubit® fluorometry was performed on an additional 27 mRNA vials obtained in Canada and drawn from 12 unique lots (5 lots of Moderna child/adult monovalent, 1 lot of Moderna adult bivalent BA.4/5, 1 lot of Moderna child/adult bivalent BA.1, 1 lot of Moderna XBB.1.5 monovalent, 3 lots of Pfizer adult monovalent, and 1 lot of Pfizer adult bivalent BA.4/5). The Vaccine Adverse Events Reporting System (VAERS) database was queried for the number and categorization of adverse events (AEs) reported for each of the lots tested. The content of one previously studied vial of Pfizer COVID-19 vaccine was examined by Oxford Nanopore sequencing to determine the size distribution of DNA fragments. This sample was also used to determine if the residual DNA is packaged in the lipid nanoparticles (LNPs) and thus resistant to DNaseI or if the DNA resides outside of the LNP and is DNaseI labile. Results: Quantification cycle (Cq) values (1:10 dilution) for the plasmid origin of replication (ori) and spike sequences ranged from 18.44 - 24.87 and 18.03 - 23.83 and for Pfizer, and 22.52 – 24.53 and 25.24 – 30.10 for Moderna, respectively. These values correspond to 0.28 – 4.27 ng/dose and 0.22 - 2.43 ng/dose (Pfizer), and 0.01 -0.34 ng/dose and 0.25 – 0.78 ng/dose (Moderna), for ori and spike respectively measured by qPCR, and 1,896 – 3,720 ng/dose and 3,270 – 5,100 ng/dose measured by Qubit® fluorometry for Pfizer and Moderna, respectfully. The SV40 promoter-enhancer-ori was only detected in Pfizer vials with Cq scores ranging from 16.64 – 22.59. In an exploratory analysis, we found preliminary evidence of a dose response relationship of the amount of DNA per dose and the frequency of serious adverse events (SAEs). This relationship was different for the Pfizer and Moderna products. Size distribution analysis found mean and maximum DNA fragment lengths of 214 base pairs (bp) and 3.5 kb, respectively. The plasmid DNA is likely inside the LNPs and is protected from nucleases. Conclusion: These data demonstrate the presence of billions to hundreds of billions of DNA molecules per dose in these vaccines. Using fluorometry, all vaccines exceed the guidelines for residual DNA set by FDA and WHO of 10 ng/dose by 188 – 509-fold. However, qPCR residual DNA content in all vaccines were below these guidelines emphasizing the importance of methodological clarity and consistency when interpreting quantitative guidelines. The preliminary evidence of a dose-response effect of residual DNA measured with qPCR and SAEs warrant confirmation and further investigation. Our findings extend existing concerns about vaccine safety and call into question the relevance of guidelines conceived before the introduction of efficient transfection using LNPs. With several obvious limitations, we urge that our work is replicated under forensic conditions and that guidelines be revised to account for highly efficient DNA transfection and cumulative dosing.
  🖺 Full Text HTML: DNA fragments detected in monovalent and bivalent Pfizer/BioNTech and Moderna modRNA COVID-19 vaccines from Ontario, Canada: Exploratory dose response relationship with serious adverse events.
• De novo generation of antibody CDRH3 with a pre-trained generative large language model -
  Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies. We also build a high-precision model antigen-antibody binder (A2binder) that pairs antigen epitope sequences with antibody sequences to predict binding specificity and affinity. PALM-generated antibodies exhibit binding ability to SARS-CoV-2 antigens, including the emerging XBB variant, as confirmed through in-silico analysis and in-vitro assays. The in-vitro assays validated that PALM-generated antibodies achieve high binding affinity and potent neutralization capability against both wild-type and XBB spike proteins of SARS-CoV-2. Meanwhile, A2binder demonstrated exceptional predictive performance on binding specificity for various epitopes and variants. Furthermore, by incorporating the attention mechanism into the PALM model, we have improved its interpretability, providing crucial insights into the fundamental principles of antibody design.
  🖺 Full Text HTML: De novo generation of antibody CDRH3 with a pre-trained generative large language model
• COVID-19 stress and cognitive failures in daily life: A multilevel examination of within- and between-persons patterns -
  The COVID-19 pandemic has claimed an extremely high number of lives worldwide, causing widespread panic and stress. The current research examined whether COVID-19 stress was associated with everyday cognitive failures, using data from a seven-day daily diary study of 253 young adults in Singapore. Multilevel modelling revealed that COVID-19 stress was significantly associated with cognitive failures even after adjusting for demographic factors, both at the within-person and between-persons levels. Specifically, individuals experienced more cognitive failures on days they experienced more COVID-19 stress (as compared to their own average levels of COVID-19 stress), and individuals who experienced more COVID-19 stress overall (as compared to individuals who experienced less COVID-19 stress overall) experienced more cognitive failures in general. While a large body of work has evidenced the detrimental effects of COVID-19 stress on individuals’ well-being, the current findings provide novel insights that these stressors may negatively impact individuals’ cognitive functioning as well.
  🖺 Full Text HTML: COVID-19 stress and cognitive failures in daily life: A multilevel examination of within- and between-persons patterns
• The SHOW COVID-19 cohort: methods and rationale for examining the statewide impact of COVID-19 on the social determinants of health -

  Background: National and large city mortality and morbidity data emerged during the early years of the COVID-19 pandemic, yet statewide data to assess the impact COVID-19 had across urban and rural landscapes on subpopulations was lacking. The SHOW COVID-19 cohort was established to provide descriptive and longitudinal data to examine the influence the social determinants of health had on COVID-19 related outcomes. Methods: Participants were recruited from the 5,742 adults in the Survey of the Health of Wisconsin (SHOW) cohort who were all residents of Wisconsin, United States when they joined the cohort between 2008-2019. Online surveys were administered at three timepoints during 2020-2021. Survey topics included COVID-19 exposure, testing and vaccination, COVID-19 impact on economic wellbeing, healthcare access, mental and emotional health, caregiving, diet, lifestyle behaviors, social cohesion, and resilience. Results: A total of 2,304 adults completed at least one COVID-19 online survey, with n=1,090 completing all three survey timepoints. Non-Whites were 2-3 times more likely to report having had COVID-19 compared to Whites, females were more likely than males to experience disruptions in their employment, and those with children in the home were more likely to report moderate to high levels of stress compared to adults without children. Conclusion: Longitudinal, statewide cohorts are important for investigating how the social determinants of health affect health and well-being during the first years of a pandemic and offer insight into future pandemic preparation. The data are available for researchers and cohort is active for continued and future follow-up.

  🖺 Full Text HTML: The SHOW COVID-19 cohort: methods and rationale for examining the statewide impact of COVID-19 on the social determinants of health
• Persistent high mortality rates for Diabetes Mellitus and Hypertension after excluding deaths associated with COVID-19 in Brazil, 2020-2022 -

  Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a significant public health challenge globally, with Brazil being no exception. Excess mortality during this period reached alarming levels. Cardiovascular diseases (CVD), Systemic Hypertension (HTN), and Diabetes Mellitus (DM) were associated with increased mortality. However, the specific impact of DM and HTN on mortality during the pandemic remains poorly understood. Methods: This study analyzed mortality data from Brazil9s mortality system, covering the period from 2015 to 2022. Data included all causes of death as listed on death certificates, categorized by International Classification of Diseases 10th edition (ICD-10) codes. Population data were obtained from the Brazilian Census. Mortality ratios (MRs) were calculated by comparing death rates in 2020, 2021, and 2022 to the average rates from 2015 to 2019. Adjusted MRs were calculated using Poisson models. Results: Between 2015 and 2022, Brazil recorded a total of 11,423,288 deaths. Death rates remained relatively stable until 2019 but experienced a sharp increase in 2020 and 2021. In 2022, although a decrease was observed, it did not return to pre-pandemic levels. This trend persisted even when analyzing records mentioning DM, HTN, or CVD. Excluding death certificates mentioning COVID-19 codes, the trends still showed increases from 2020 through 2022, though less pronounced. Conclusion: This study highlights the persistent high mortality rates for DM and HTN in Brazil during the years 2020-2022, even after excluding deaths associated with COVID-19. These findings emphasize the need for continued attention to managing and preventing DM and HTN as part of public health strategies, both during and beyond the COVID-19 pandemic. There are complex interactions between these conditions and the pandemic9s impact on mortality rates.

  🖺 Full Text HTML: Persistent high mortality rates for Diabetes Mellitus and Hypertension after excluding deaths associated with COVID-19 in Brazil, 2020-2022
• 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
• MSclassifR: an R package for supervised classification of mass spectra with machine learning methods -
  MSclassifR is an R package that has been specifically designed to improve the classification of mass spectra obtained from MALDI-TOF mass spectrometry. It offers a comprehensive range of functions that are focused on processing mass spectra, identifying discriminant m/z values, and making accurate predictions. The package introduces innovative algorithms for selecting discriminating m/z values and making predictions. To assess the effectiveness of these methods, extensive tests were conducted using challenging real datasets, including bacterial subspecies of the Mycobacterium abscessus complex, virulent and avirulent phenotypes of Escherichia coli, different species of Streptococci and nasal swabs from individuals infected and uninfected with SARS-CoV-2. Additionally, multiple datasets of varying sizes were created from these real datasets to evaluate the robustness of the algorithms. The results demonstrated that the Machine Learning-based pipelines in MSclassifR achieved high levels of accuracy and Kappa values. On an in-house dataset, some pipelines even achieved more than 95% mean accuracy, whereas commercial system only achieved 62% mean accuracy. Certain methods showed greater resilience to changes in dataset sizes when constructing Machine Learning-based pipelines. These simulations also helped determine the minimum sizes of training sets required to obtain reliable results. The package is freely available online, and its open-source nature encourages collaborative development, customization, and fosters innovation within the community focused on improving diagnosis based on MALDI-TOF spectra.
  🖺 Full Text HTML: MSclassifR: an R package for supervised classification of mass spectra with machine learning methods
• Randomised clinical trials of COVID-19 vaccines are not designed to study non-specific effects on rare mortality -
  We read with interest the recently-published paper “Randomized clinical trials of COVID-19 vaccines: Do adenovirus-vector vaccines have beneficial non-specific effects?” by Benn et al. We have a range of concerns regarding the data quality and the study methodology, that call into question the key findings. The study presents the results of a meta-analysis of nine randomised controlled trials (RCTs) and concludes that there are “marked differences” in the overall mortality impact of mRNA and adenovirus vector vaccines. However the data used in this study cannot possibly support such a claim and we detail below some of the shortcomings of the methodology used in Benn et al. ’s manuscript.
  🖺 Full Text HTML: Randomised clinical trials of COVID-19 vaccines are not designed to study non-specific effects on rare mortality
• Influence of perceived threat of Covid-19 and HEXACO personality traits on toilet paper stockpiling -
  Following the fast spread of the coronavirus (Covid-19) across Europe and North America in March 2020, many people started stockpiling commodities like toilet paper. Despite the high relevance for public authorities to adequately address stockpiling behavior, empirical studies on the psychological underpinnings of toilet paper stockpiling are still scarce. In this study, we investigated the relation between personality traits, perceived threat of Covid-19, and stockpiling of toilet paper in an online survey (N = 996) across 22 countries. Results suggest that people who felt more threatened by Covid-19 stockpiled more toilet paper. Further, a predisposition towards Emotionality predicted the perceived threat of Covid-19 and affected stockpiling behavior indirectly. Finally, Conscientiousness was related to toilet paper stockpiling, such that individuals higher in Conscientiousness tended to stockpile more toilet paper. These results emphasize the importance of clear communication by public authorities acknowledging anxiety and, at the same time, transmitting a sense of control.
  🖺 Full Text HTML: Influence of perceived threat of Covid-19 and HEXACO personality traits on toilet paper stockpiling
• Forecasting regional-level COVID-19 hospitalisation in England as an ordinal variable using the machine learning method -

  Background COVID-19 causes substantial pressure on healthcare, with many healthcare systems now needing to prepare for and mitigate the consequences of surges in demand caused by multiple overlapping waves of infections. Therefore, public health agencies and health system managers also now benefit from short-term forecasts for respiratory infections that allow them to manage services better. However, the availability of easily implemented effective tools for generating precise forecasts at the individual regional level still needs to be improved. Methods We extended prior work on influenza to forecast regional COVID-19 hospitalisations in England for the period from 19th March 2020 to 31st December 2022, treating the number of hospital admissions in each region as an ordinal variable. We further developed the XGBoost model used previously to forecast influenza to enable it to exploit the ordering information in ordinal hospital admission levels. We incorporated different types of data as predictors: epidemiological data including weekly region COVID-19 cases and hospital admissions, weather conditions and mobility data for multiple categories of locations (e.g., parks, workplaces, etc). The impact of different discretisation methods and the number of ordinal levels was also considered. Results We find that the inclusion of weather data consistently increases the accuracy of our forecasts compared with models that rely only on the intrinsic epidemiological data, but only by a small amount. Mobility data brings about a more substantial increase in our forecasts. When both weather and mobility data are used in addition to the epidemiological data, the results are very similar to the model with only epidemiological data and mobility data. Conclusion Accurate ordinal forecasts of COVID-19 hospitalisations can be obtained using XGBoost and mobility data. While uniform ordinal levels show higher apparent accuracy, we recommend N-tile ordinal levels which contain far richer information.

  🖺 Full Text HTML: Forecasting regional-level COVID-19 hospitalisation in England as an ordinal variable using the machine learning method
• Socioeconomic inequalities in COVID-19 infection and vaccine uptake among children and adolescents in Catalonia, Spain -

  IMPORTANCE The relationship between socioeconomic deprivation and COVID-19 infection and vaccination among children and adolescents remains unclear. OBJECTIVE To investigate the association between deprivation and COVID-19 vaccine uptake and infection among children and adolescents before and after the vaccination rollout in Catalonia, Spain. DESIGN AND SETTING Population-based cohort study using primary care electronic health records from the Information System for Research in Primary Care. Individuals were followed 3 months before the start of the vaccination campaign in Spain and 3 months after the vaccination rollout among adolescents and children. PARTICIPANTS Children (5-11 years) and adolescents (12-15 years) with at least 1 year of prior history observation available and without missing deprivation data. EXPOSURE Deprivation, assessed using an ecological socioeconomic deprivation index (SDI) score for census tract urban areas and categorized into quintiles. MAIN OUTCOMES AND MEASURES COVID-19 infection and COVID-19 vaccination. For each outcome, we calculated cumulative incidence and crude Cox proportional-hazard models by SDI quintiles, and estimated hazard ratios (HRs) of COVID-19 infection and vaccine uptake relative to the least deprived quintile, Q1. RESULTS Before COVID-19 vaccination rollout, 290,625 children and 179,685 adolescents were analyzed. Increased HR of deprivation was associated with a higher risk of COVID-19 infection in both children (Q5: 1.55 [95% CI, 1.47 - 1.63]) and adolescents (Q5: 1.36 [95% CI, 1.29 - 1.43]). After the rollout, this pattern changed among children, with lower risk of infection in more deprived areas (Q5: 0.62 [95% CI, 0.61 - 0.64]). Vaccine uptake was higher among adolescents (72.6%) than children (44.8%), but in both age groups, non-vaccination was more common among those living in more deprived areas (39.3% and 74.6% in Q1 vs. 26.5% and 66.9% in Q5 among children and adolescents, respectively). CONCLUSIONS AND RELEVANCE In this cohort study, children and adolescents living in deprived areas were at higher risk of COVID-19 non-vaccination. Socioeconomic disparities in COVID-19 infection were also evident before vaccine rollout, with a higher infection risk in deprived areas across age groups. Our findings suggest that changes in the association between deprivation and infections among children after the vaccine rollout were likely due to testing disparities.

  🖺 Full Text HTML: Socioeconomic inequalities in COVID-19 infection and vaccine uptake among children and adolescents in Catalonia, Spain
• Addressing Label Noise for Electronic Health Records: Insights from Computer Vision for Tabular Data -

  The analysis of extensive electronic health records (EHR) datasets often calls for automated solutions, with machine learning (ML) techniques, including deep learning (DL), taking a lead role. One common task involves categorizing EHR data into predefined groups. However, the vulnerability of EHRs to noise and errors stemming from data collection processes, as well as potential human labeling errors, poses a significant risk. This risk is particularly prominent during the training of DL models, where the possibility of overfitting to noisy labels can have serious repercussions in healthcare. Despite the well-documented existence of label noise in EHR data, few studies have tackled this challenge within the EHR domain. Our work addresses this gap by adapting computer vision (CV) algorithms to mitigate the impact of label noise in DL models trained on EHR data. Notably, it remains uncertain whether CV methods, when applied to the EHR domain, will prove effective, given the substantial divergence between the two domains. We present empirical evidence demonstrating that these methods, whether used individually or in combination, can substantially enhance model performance when applied to EHR data, especially in the presence of noisy/incorrect labels. We validate our methods and underscore their practical utility in real-world EHR data, specifically in the context of COVID-19 diagnosis. Our study highlights the effectiveness of CV methods in the EHR domain, making a valuable contribution to the advancement of healthcare analytics and research.

  🖺 Full Text HTML: Addressing Label Noise for Electronic Health Records: Insights from Computer Vision for Tabular Data
• Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury -
  Background: Links between acute lung injury (ALI), infectious disease, and neurological outcomes have been frequently discussed over the past few years, especially due to the COVID-19 pandemic. Yet, much of the cross-communication between organs, particularly the lung and the brain, has been understudied. Here, we have focused on the role of neutrophils in driving changes to the brain endothelium with ensuing microglial activation and neuronal loss in a model of ALI. Methods: We have applied a three-dose paradigm of 10g/40l intranasal lipopolysaccharide (LPS) to induce neutrophilia accompanied by proteinaceous exudate in bronchoalveolar lavage fluid (BALF) in adult C57BL/6 mice. Brain endothelial markers, microglial activation, and neuronal cytoarchitecture were evaluated 24hr after the last intranasal dose of LPS or saline. C57BL/6-Ly6g(tm2621(Cre-tdTomato)Arte (Catchup mice) were used to measure neutrophil and blood-brain barrier permeability following LPS exposure with intravital 2-photon imaging. Results: Three doses of intranasal LPS induced robust neutrophilia accompanied by proteinaceous exudate in BALF. ALI triggered central nervous system pathology as highlighted by robust activation of the cerebrovascular endothelium (VCAM1, CD31), accumulation of plasma protein (fibrinogen), microglial activation (IBA1, CD68), and decreased expression of proteins associated with postsynaptic terminals (PSD-95) in the hippocampal stratum lacunosum moleculare, a relay station between the entorhinal cortex and CA1 of the hippocampus. 2-photon imaging of Catchup mice revealed neutrophil homing to the cerebral endothelium in the blood-brain barrier and neutrophil extravasation from cerebral vasculature 24hr after the last intranasal treatment. Conclusions: Overall, these data demonstrate ensuing brain pathology resulting from ALI, highlighting a key role for neutrophils in driving brain endothelial changes and subsequent neuroinflammation. This paradigm may have a considerable translational impact on understanding how infectious disease with ALI can lead to neurodegeneration, particularly in the elderly.
  🖺 Full Text HTML: Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury

From Clinical Trials

• Narrative Intervention for Long COVID-19 (NICO) - Conditions: Long COVID; Long Covid19
  Interventions: Behavioral: Narrative Intervention for Long COVID-19 (NICO)
  Sponsors: University of Colorado, Denver
  Active, not recruiting

• Immunogenicity of Concomitant Administration of COVID-19 Vaccines With Influenza Vaccines - Conditions: COVID-19; Influenza; Vaccine Reaction; Contaminant Injected
  Interventions: Biological: Omicron-containing COVID-19 vaccine; Biological: influenza vaccine
  Sponsors: Catholic Kwandong University; Korea University Guro Hospital
  Recruiting

• Inspiratory Muscle Strength Training in Post-Covid Syndrome - Conditions: Cardiovascular Abnormalities; Post-COVID-19 Syndrome; Physical Exercise
  Interventions: Other: Inspiratory muscle strength training
  Sponsors: D’Or Institute for Research and Education
  Recruiting

• Inspiratory Muscle Training in People With Long COVID- A Pilot Investigation. - Conditions: Long COVID
  Interventions: Device: PrO2
  Sponsors: University of Bath; Swansea University
  Not yet recruiting

• Home-Based Respiratory Muscle Strength Training Program for Individuals With Post-COVID-19 Persistent Dyspnea - Conditions: Post-COVID-19 Syndrome; Dyspnea
  Interventions: Device: Respiratory Muscle Strength Trainers
  Sponsors: University of South Florida
  Not yet recruiting

• Rural Tailored Communication to Promote SARS-CoV-2 Antibody Testing in Saliva - Conditions: SARS-CoV2 Infection
  Interventions: Behavioral: General SARS-CoV-2 Communication; Behavioral: Rural-Targeted SARS-CoV-2 Communication
  Sponsors: Michigan State University; National Cancer Institute (NCI); Johns Hopkins University
  Recruiting

• Cognitive Rehabilitation Therapy for COVID-19 - Conditions: Post-Acute COVID-19 Syndrome
  Interventions: Behavioral: Compensatory Cognitive Training for COVID-19; Behavioral: Holistic Cognitive Education
  Sponsors: VA Office of Research and Development
  Not yet recruiting

• COVID Rehabilitation - Conditions: Rehabilitation; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders
  Interventions: Behavioral: One day course; Behavioral: Individual follow-ups
  Sponsors: University Hospital of North Norway; University of Bergen; Oslo University Hospital; Norwegian University of Science and Technology
  Not yet recruiting

• Phase 3 Open-Label Controlled Trial of Convalescent Plasma in Early COVID-19 Infection - Conditions: Covid19
  Interventions: Drug: Convalescent Plasma; Other: Standard of Care
  Sponsors: Larkin Community Hospital
  Withdrawn

• Food Effects of GST-HG171 Tablets Combined With Ritonavir in Healthy Chinese Participants - Conditions: COVID-19 Respiratory Infection
  Interventions: Drug: GST-HG171/ritonavir; Drug: ritonavir
  Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
  Active, not recruiting

• Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments - Conditions: Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome; COVID-19; Fatigue; Fatigue Syndrome, Chronic
  Interventions: Device: Monoplace Hyperbaric Chamber (Class III medical device).
  Sponsors: Sunnybrook Health Sciences Centre
  Not yet recruiting

• Education of Medical Staff to Post Acute Covid susTained sYmptoms - Conditions: Post-acute COVID-19 Syndrome
  Interventions: Other: Training in the management of functional disorders; Other: Reimbursement of 3 long consultations
  Sponsors: Assistance Publique - Hôpitaux de Paris; ANRS, Emerging Infectious Diseases
  Not yet recruiting

• Pharmacist Management of Paxlovid eVisits - Conditions: COVID-19; Quality of Care
  Interventions: Other: Pharmacist Care; Other: AFM Pool Care
  Sponsors: Kaiser Permanente
  Not yet recruiting

• Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol - Conditions: COVID-19; Influenza
  Interventions: Other: Fact box
  Sponsors: Harding Center for Risk Literacy
  Not yet recruiting

• tDCS in the Management of Post-COVID Disorders - Conditions: Long COVID
  Interventions: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Motor Training; Behavioral: Cognitive Training
  Sponsors: Universidade Federal de Pernambuco; São Paulo State University
  Recruiting

From PubMed

• SARS-COV-2 protein NSP9 promotes cytokine production by targeting TBK1 - SARS-COV-2 infection-induced excessive or uncontrolled cytokine storm may cause injury of host tissue or even death. However, the mechanism by which SARS-COV-2 causes the cytokine storm is unknown. Here, we demonstrated that SARS-COV-2 protein NSP9 promoted cytokine production by interacting with and activating TANK-binding kinase-1 (TBK1). With an rVSV-NSP9 virus infection model, we discovered that an NSP9-induced cytokine storm exacerbated tissue damage and death in mice. Mechanistically, NSP9…

• Enhanced binding and inhibition of SARS-CoV-2 by a plant-derived ACE2 protein containing a fused mu tailpiece - Infectious diseases such as Coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) present an increasingly persistent crisis in many parts of the world. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The angiotensin-converting enzyme 2 (ACE2) is a crucial cellular receptor for SARS-CoV-2 infection. Inhibition of the interaction between SARS-CoV-2 and ACE2 has been proposed as a target for the prevention and treatment of COVID-19. We…

• Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein - SARS-CoV-2 has evolved several strategies to overcome host cell defenses by inducing cell injury to favour its replication. Many viruses have been reported to modulate the intracellular redox balance, affecting the Nuclear factor erythroid 2-Related Factor 2 (NRF2) signaling pathway. Although antioxidant modulation by SARS-CoV-2 infection has already been described, the viral factors involved in modulating the NRF2 pathway are still elusive. Given the antagonistic activity of ORF6 on several…

• Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections - Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (M^(pro)), its moderate activity in M^(pro) inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian…

• Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy - The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and…

• SIRT-1 is required for release of enveloped enteroviruses - Enterovirus D68 (EV-D68) is a re-emerging enterovirus that causes acute respiratory illness in infants and has recently been linked to Acute Flaccid Myelitis. Here, we show that the histone deacetylase, SIRT-1, is essential for autophagy and EV-D68 infection. Knockdown of SIRT-1 inhibits autophagy and reduces EV-D68 extracellular titers. The proviral activity of SIRT-1 does not require its deacetylase activity or functional autophagy. SIRT-1’s proviral activity is, we demonstrate, mediated…

• Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases? - Nitric oxide (NO), as an important gaseous medium, plays a pivotal role in the human body, such as maintaining vascular homeostasis, regulating immune-inflammatory responses, inhibiting platelet aggregation, and inhibiting leukocyte adhesion. In recent years, the rapid prevalence of coronavirus disease 2019 (COVID-19) has greatly affected the daily lives and physical and mental health of people all over the world, and the therapeutic efficacy and resuscitation strategies for critically ill…

• Protective effect of olopatadine hydrochloride against LPS-induced acute lung injury: via targeting NF-κB signaling pathway - CONCLUSION: In nutshell, inhibition of NF-κB pathway by Olo resulted in protection and reduced mortality in LPS- induced ALI and thus has potential to be used clinically to arrest disease progression in ALI/ARDS, since the drug is already in the market. However, the findings warrant further extensive studies, and also future studies can be planned to elucidate its role in COVID-19-associated ARDS or cytokine storm.

• Molecular insights and optimization strategies for the competitive binding of engineered ACE2 proteins: a multiple replica molecular dynamics study - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally, and rapid viral evolution and the emergence of new variants pose challenges to pandemic control. During infection, the spike protein of SARS-CoV-2 interacts with the human ACE2 protein via its receptor binding domain (RBD), and it is known that engineered forms of ACE2 can compete with wild-type (WT) ACE2 for binding to inhibit infection. Here, we conducted multiple replica…

• Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation - CONCLUSIONS: In this study, we delved into the antiviral properties of APL in the context of chicken macrophage (HD11) infection with IBV. Our findings confirm that andrographolide effectively inhibits apoptosis, pyroptosis, and inflammation by IBV infection. Furthermore, this inhibition was verified on chicken embryos in vivo. This inhibition suggests a substantial potential for APL as a therapeutic agent to mitigate the harmful effects of IBV on host cells.

• Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice - Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its…

• Block of the Angiotensin Pathways Affects Flow-Volume Spirometry in Patients with SARS-CoV-2 Infection - BACKGROUND: Angiotensin Converting Enzyme 2 (ACE2) is an endothelial cell receptor used by SARS-CoV- 2 virus to enter cells. Pulmonary function tests (PFTs), mainly spirometry, are the main diagnostic tools for most respiratory diseases. PFTs are mandatory for assessing the response to therapy.

• Differential specificity of SARS-CoV-2 main protease variants on peptide versus protein-based substrates - The SARS-CoV-2 main protease (M^(pro) ) holds significant importance as a biological target in combating coronaviruses due to its importance in virus replication. Considering the emergence of novel SARS-CoV-2 variants and the mutations observed in the M^(pro) sequence, we hypothesized that these mutations may have a potential impact on the protease’s specificity. To test this, we expressed M^(pro) corresponding to the original strain and variants Beta1, Beta2 and Omicron, and analyzed their…

• DHA and EPA inhibit porcine coronavirus replication by alleviating ER stress - The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted significant gaps in our mechanisms to prevent and control cross-species transmission of animal coronaviruses. Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine delta coronavirus (PDCoV) are common porcine coronaviruses with similar clinical features. In the absence of effective drugs and methods of prevention and…

• Autoantibodies against Angiotensin-converting enzyme 2 and immune molecules are associated with COVID-19 disease severity - Increased inflammation caused by SARS-CoV-2 infection can lead to severe coronavirus disease 2019 (COVID-19) and long-term disease manifestations referred to as post-acute sequalae of COVID (PASC). The mechanisms of this variable long-term immune activation are poorly defined. Autoantibodies targeting immune factors such as cytokines, as well as the viral host cell receptor, angiotensin-converting enzyme 2 (ACE2), have been observed after SARS-CoV-2 infection. Autoantibodies to immune factors…

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