Covid-19 Sentry

Contents

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

From Preprints

• Effectiveness of mRNA COVID-19 monovalent and bivalent vaccine booster doses against Omicron severe outcomes among adults aged ≥50 years in Ontario, Canada -

  Objective: We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Methods: We used a test-negative design to estimate vaccine effectiveness (VE), with unvaccinated adults as the comparator, against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years between June 19, 2022 and January 28, 2023 stratified by time since vaccination. We explored VE by vaccine product (Moderna Spikevax ® monovalent; Pfizer-BioNTech Comirnaty® monovalent; Moderna Spikevax® BA.1 bivalent; Pfizer-BioNTech Comirnaty® BA.4/BA.5 bivalent). Results: We included 3,755 Omicron cases and 14,338 test-negative controls. For the Moderna and Pfizer-BioNTech monovalent vaccines, VE 7-29 days after vaccination was 85% (95% confidence interval [CI], 72-92%) and 88% (95%CI, 82-92%), respectively, and was 82% (95%CI, 76-87%) and 82% (95%CI, 77-86%) 90-119 days after vaccination. For the Moderna BA.1 bivalent vaccine, VE was 86% (95%CI, 82-90%) 7-29 days after vaccination and was 76% (95%CI, 66-83%) 90-119 days after vaccination. For the Pfizer-BioNTech BA.4/BA.5 bivalent vaccine, VE 7-29 days after vaccination was 83% (95%CI, 77-88%) and was 81% (95%CI 72-87%) 60-89 days after vaccination. Conclusions: Booster doses of monovalent and bivalent mRNA COVID-19 vaccines provided similar, strong initial protection against severe outcomes in community-dwelling adults aged ≥50 years in Ontario. Nonetheless, uncertainty remains around waning protection of these vaccines.

  🖺 Full Text HTML: Effectiveness of mRNA COVID-19 monovalent and bivalent vaccine booster doses against Omicron severe outcomes among adults aged ≥50 years in Ontario, Canada
• The landscape of biomedical research -
  The number of publications in biomedicine and life sciences has rapidly grown over the last decades, with over 1.5 million papers now published every year. This makes it difficult to keep track of new scientific works and to have an overview of the evolution of the field as a whole. Here we present a 2D atlas of the entire corpus of biomedical literature, and argue that it provides a unique and useful overview of the life sciences research. We base our atlas on the abstract texts of 21 million English articles from the PubMed database. To embed the abstracts into 2D, we use a large language model PubMedBERT, combined with t-SNE tailored to handle samples of our size. We use our atlas to study the emergence of the Covid-19 literature, the evolution of the neuroscience discipline, the uptake of machine learning, and the distribution of gender imbalance in academic authorship. Furthermore, we present an interactive web version of our atlas that allows easy exploration and will enable further insights and facilitate future research.
  🖺 Full Text HTML: The landscape of biomedical research
• 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
• The Impact Of COVID-19 on Health Financing in Kenya -

  Background  Sudden shocks to health systems, such as the COVID-19 pandemic may disrupt health system functions.  Health system functions may also influence the health system’s ability to deliver in the face of sudden shocks such as the COVID-19 pandemic. We examined the impact of COVID-19 on the health financing function in Kenya, and how specific health financing arrangements influenced the health systems capacity to deliver services during the COVID-19 pandemic. Methods We conducted a cross-sectional study in three purposively selected counties in Kenya using a qualitative approach. We collected data using in-depth interviews (n = 56) and relevant document reviews. We interviewed national level health financing stakeholders, county department of health managers, health facility managers and COVID-19 healthcare workers. We analysed data using a framework approach. Results Purchasing arrangements:  COVID-19 services were partially subsidized by the national government, exposing individuals to out-of-pocket costs given the high costs of these services. The National Health Insurance Fund (NHIF) adapted its enhanced scheme’s benefit package targeting formal sector groups to include COVID-19 services but did not make any adaptations to its general scheme targeting the less well-off in society. This had potential equity implications. Public Finance Management (PFM) systems: Nationally, PFM processes were adaptable and partly flexible allowing shorter timelines for budget and procurement processes. At county level, PFM systems were partially flexible with some resource reallocation but maintained centralized purchasing arrangements. The flow of funds to counties and health facilities was delayed and the procurement processes were lengthy. Reproductive and child health services: Domestic and donor funds were reallocated towards the pandemic response resulting in postponement of program activities and affected family planning service delivery. Universal Health Coverage (UHC) plans: Prioritization of UHC related activities was negatively impacted due the shift of focus to the pandemic response. Contrarily the strategic investments in the health sector were found to be a beneficial approach in strengthening the health system. Conclusions Strengthening health systems to improve their resilience to cope with public health emergencies requires substantial investment of financial and non-financial resources.  Health financing arrangements are integral in determining the extent of adaptability, flexibility, and responsiveness of health system to COVID-19 and future pandemics.

  🖺 Full Text HTML: The Impact Of COVID-19 on Health Financing in Kenya
• Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2 -
  To prevent future pandemics, it is important that we understand whether SARS-CoV-2 spilled over directly from animals to people, or indirectly in a laboratory accident. The genome of SARS-COV-2 contains a peculiar pattern of unique restriction endonuclease recognition sites allowing efficient dis- and re-assembly of the viral genome characteristic of synthetic viruses. Here, we report the likelihood of observing such a pattern in coronaviruses with no history of bioengineering. We find that SARS-CoV-2 is an anomaly, more likely a product of synthetic genome assembly than natural evolution. The restriction map of SARS-CoV-2 is consistent with many previously reported synthetic coronavirus genomes, meets all the criteria required for an efficient reverse genetic system, differs from closest relatives by a significantly higher rate of synonymous mutations in these synthetic-looking recognitions sites, and has a synthetic fingerprint unlikely to have evolved from its close relatives. We report a high likelihood that SARS-CoV-2 may have originated as an infectious clone assembled in vitro.
  🖺 Full Text HTML: Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2
• Estimating COVID-19 Vaccine Protection Rates via Dynamic Epidemiological Models–A Study of Ten Countries -

  The real-world performance of vaccines against COVID-19 infections is critically important to counter the pandemics. We propose a varying coefficient stochastic epidemic model to estimate the vaccine protection rates based on the publicly available epidemiological and vaccination data. To tackle the challenges posed by the unobserved state variables, we develop a multi-step decentralized estimation procedure that uses different data segments to estimate different parameters. A B-spline structure is used to approximate the underlying infection rates and to facilitate model simulation in obtaining an objective function between the imputed and the simulation-based estimates of the latent state variables, leading to simulation-based estimation of the diagnosis rate using data in the pre-vaccine period and the vaccine effect parameters using data in the post-vaccine periods. And the time-varying infection, recovery and death rates are estimated by kernel regressions. We apply the proposed method to analyze the data in ten countries which collectively used 8 vaccines. The analysis reveals that the average protection rate of the full vaccination was at least 22% higher than that of the partial vaccination and was largely above the WHO recognized level of 50% before November 20, 2021, including the Delta variant dominated period. The protection rates for the booster vaccine in the Omicron period were also provided.

  🖺 Full Text HTML: Estimating COVID-19 Vaccine Protection Rates via Dynamic Epidemiological Models–A Study of Ten Countries
• Natural Environments, Psychosocial Health, and Health Behaviors in a Crisis – A Scoping Review of the Literature in the COVID-19 Context -
  The COVID-19 outbreak has led to major restrictions globally, affecting people’s psychosocial health and their health behaviors. Thus, the purpose of this scoping review was to summarize the available research regarding the nature-health-association in the COVID-19 context. Keywords related to natural environments and COVID-19 were combined to conduct a systematic online search in six major databases. Eligibility criteria were a) published since 2020 with data collected in the COVID-19 context b) peer-reviewed, c) original empirical data collected on human participants, d) investigated the association between natural environments and psychosocial health or health behavior, and e) English, German, or Scandinavian language. Out of 8,568 articles being obtained, we identified 82 relevant articles representing 80 unique studies. Most studies focused on adults in the general population and were predominantly conducted in the USA and Europe. Overall, the findings tentatively indicate that nature mitigates the impact of COVID-19 on psychological health and physical activity. Through thematic analysis of the extracted data, three primary themes were identified: 1) type of nature assessed, 2) psychosocial health and health behaviors investigated, and 3) heterogeneity in the nature-health relationship. Research gaps in the COVID-19 context were identified regarding I) nature characteristics that promote psychosocial health and health behaviors, II) investigations of digital and virtual nature, III) psychological constructs relating to mental health promotion, IV) health behaviors other than physical activity, V) underlying mechanisms regarding heterogeneity in the nature-health relationship based on human, nature, and geographic characteristics, and VI) research focusing on vulnerable groups. Overall, natural environments demonstrate considerable potential in buffering the impact of stressful events on a population level on mental health. However, future research is warranted to fill the mentioned research gaps and to examine the long-term effects of nature exposure during COVID-19.
  🖺 Full Text HTML: Natural Environments, Psychosocial Health, and Health Behaviors in a Crisis – A Scoping Review of the Literature in the COVID-19 Context
• Infants and young children generate more durable antibody responses to SARS-CoV-2 infection than adults -

  Since the emergence of SARS-CoV-2, research has shown that adult patients mount broad and durable immune responses to infection. However, response to infection remains poorly studied in infants/young children. In this study, we evaluated humoral responses to SARS-CoV-2 in 23 infants/young children before and after infection. We found that antibody responses to SARS-CoV-2 spike antigens peaked approximately 30 days after infection and were maintained up to 500 days with little apparent decay. While the magnitude of humoral responses was similar to an adult cohort recovered from mild/moderate COVID-19, both binding and neutralization titers to WT SARS-CoV-2 were more durable in infants/young children, with Spike and RBD IgG antibody half-life nearly 4X as long as in adults. The functional breadth of adult and infant/young children SARS-CoV-2 responses were comparable, with similar reactivity against panel of recent and previously circulating viral variants. Notably, IgG subtype analysis revealed that while IgG1 formed the majority of both adults9 and infants/young children9s response, IgG3 was more common in adults and IgG2 in infants/young children. These findings raise important questions regarding differential regulation of humoral immunity in infants/young children and adults and could have broad implications for the timing of vaccination and booster strategies in this age group.

  🖺 Full Text HTML: Infants and young children generate more durable antibody responses to SARS-CoV-2 infection than adults
• A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK -

  Vaccination rates against SARS-CoV-2 in children aged five to 11 years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection. There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to 11, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid. We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it. Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.

  🖺 Full Text HTML: A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds in the UK
• NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing -
  The blood proteome holds great promise for precision medicine but poses daunting challenges due to the low abundance of the majority of plasma proteins and the vast dynamic range across the proteome. We report the development and validation of a novel proteomic analysis technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA) - that incorporates a dual capture and release mechanism to suppress the assay background to the minimum, thus drastically improving the signal-to-noise ratio. NULISA improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level, which is enabled by antibody-conjugated DNA sequences that mediate the purification of immunocomplexes and contain target- and sample-specific barcodes for next-generation sequencing-based, highly multiplexed analysis. To demonstrate its performance and utility, we developed a 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins that demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultra-high sensitivity enabled the detection of previously difficult-to-detect but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA uniquely addresses longstanding challenges in the proteomic analysis of liquid biopsy samples and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.
  🖺 Full Text HTML: NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing
• SARS-CoV-2’s evolutionary capacity is mostly driven by host antiviral molecules -
  The COVID-19 pandemic has been characterised by sequential variant-specific waves shaped by viral, individual human and population factors. SARS-CoV-2 variants are defined by their unique combinations of mutations and there has been a clear adaptation to human infection since its emergence in 2019. Here we use machine learning models to identify shared signatures, i.e., common underlying mutational processes, and link these to the subset of mutations that define the variants of concern (VOCs). First, we examined the global SARS-CoV-2 genomes and associated metadata to determine how viral properties and public health measures have influenced the magnitude of waves, as measured by the number of infection cases, in different geographic locations using regression models. This analysis showed that, as expected, both public health measures and not virus properties alone are associated with the rise and fall of regional SARS-CoV-2 reported infection numbers. This impact varies geographically. We attribute this to intrinsic differences such as vaccine coverage, testing and sequencing capacity, and the effectiveness of government stringency. In terms of underlying evolutionary change, we used non-negative matrix factorisation to observe three distinct mutational signatures, unique in their substitution patterns and exposures from the SARS-CoV-2 genomes. Signatures 0, 1 and 3 were biased to C->T, T->C/A->G and G->T point mutations as would be expected of host antiviral molecules APOBEC, ADAR and ROS effects, respectively. We also observe a shift amidst the pandemic in relative mutational signature activity from predominantly APOBEC-like changes to an increasingly high proportion of changes consistent with ADAR editing. This could represent changes in how the virus and the host immune response interact, and indicates how SARS-CoV-2 may continue to accumulate mutations in the future. Linkage of the detected mutational signatures to the VOC defining amino acids substitutions indicates the majority of SARS-CoV-2’s evolutionary capacity is likely to be associated with the action of host antiviral molecules rather than virus replication errors.
  🖺 Full Text HTML: SARS-CoV-2’s evolutionary capacity is mostly driven by host antiviral molecules
• Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking -
  SARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.
  🖺 Full Text HTML: Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking
• Unbiased spectral cytometry immunome characterization predicts COVID-19 mRNA vaccine failure in older adults and patients with lymphoid malignancies. -

  COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, NK cells, monocytes and CD45RA+CCR7- Tγδ cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note up to 7 subsets were found within the CD45RA+CCR7- Tγδ population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV-2 mRNA vaccines.

  🖺 Full Text HTML: Unbiased spectral cytometry immunome characterization predicts COVID-19 mRNA vaccine failure in older adults and patients with lymphoid malignancies.
• Global surveillance of novel SARS-CoV-2 variants -

  Earlier global detection of novel SARS-CoV-2 variants gives governments more time to respond. However, few countries can implement timely national surveillance resulting in gaps in monitoring. The UK implemented large-scale community and hospital surveillance, but experience suggests it may be faster to detect new variants through testing UK arrivals for surveillance. We developed simulations of the emergence and importation of novel variants with a range of infection hospitalisation rates (IHR) to the UK. We compared time taken to detect the variant though testing arrivals at UK borders, hospital admissions, and the general community. We found that sampling 10 to 50% of arrivals at UK borders could confer a speed advantage of 3.5 to 6 weeks over existing community surveillance, and 1.5 to 5 weeks (depending on IHR) over hospital testing. We conclude that directing limited global capacity for surveillance to highly connected ports could speed up global detection of novel SARS-CoV-2 variants.

  🖺 Full Text HTML: Global surveillance of novel SARS-CoV-2 variants
• A cross-sectional study of the association between COVID-19 infection and psychological distress in Japanese workers -

  The COVID-19 pandemic infected many people worldwide with SARS-CoV2. Psychological distress is one of the sequelae reported to occur in many of those infected (Choutka et al., 2022). We investigated the association between personal experience of COVID-19 infection and psychological distress in Japan. A total of 18,560 persons participated in the original survey, conducted in December 2020. After excluding unreliable responses, data from 14,901 persons who participated in a follow-up survey in December 2022-were included in the analysis. Odds ratios (ORs) were estimated by univariate and multiple logistic regression analysis with history of COVID-19 infection as the independent variable and presence of psychological distress as the dependent variable. This results showed that the experience of COVID-19 infection is associated with psychological distress. Moreover, most cases of mental distress among those who experienced COVID-19 infection can be at least partly explained by a perception of unfair treatment.

  🖺 Full Text HTML: A cross-sectional study of the association between COVID-19 infection and psychological distress in Japanese workers

From Clinical Trials

• Effectiveness and Safety of Quinine Sulfate as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia ( DEAL-COVID19 ) - Condition:   COVID-19
  Interventions:   Drug: Standard of Care + Quinine Sulfate;   Drug: Standard of Care
  Sponsors:   Universitas Padjadjaran;   National Research and Innovation Agency of Indonesia;   Prodia Diacro Laboratories P.T.
  Recruiting

• Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Exosomes in Treating Chronic Cough After COVID-19 - Condition:   Long COVID-19 Syndrome
  Intervention:   Biological: MSC-derived exosomes
  Sponsors:   Huazhong University of Science and Technology;   REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.
  Recruiting

• A Nasal Treatment for COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Optate;   Drug: Placebo
  Sponsor:   Indiana University
  Not yet recruiting

• Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Adult COVID-19 Patients With Comorbidities - Condition:   COVID-19
  Interventions:   Drug: Ropeginterferon alfa-2b;   Procedure: SOC
  Sponsor:   National Taiwan University Hospital
  Not yet recruiting

• Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome - Condition:   Post-COVID-19 Syndrome
  Interventions:   Behavioral: Complementary self-help strategies in addition to treatment as usual;   Other: Treatment as usual
  Sponsor:   Universität Duisburg-Essen
  Not yet recruiting

• Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Interventions:   Other: conventional western medicine treatment;   Drug: Dexamethasone oral tablet;   Other: Traditional Chinese medicine decoction
  Sponsor:   China-Japan Friendship Hospital
  Recruiting

• Inpatient COVID-19 Lollipop Study - Conditions:   COVID-19;   Diagnostic Test
  Intervention:   Device: Lollipop
  Sponsor:   University of Wisconsin, Madison
  Not yet recruiting

• Exploring the Effect of Video Interventions on Intentions for Continued COVID-19 Vaccination - Conditions:   Vaccine Refusal;   COVID-19
  Interventions:   Behavioral: Informational Video;   Behavioral: Altruistic Video;   Behavioral: Individualistic Video
  Sponsor:   Sir Mortimer B. Davis - Jewish General Hospital
  Not yet recruiting

• Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants - Condition:   COVID19 Testing
  Interventions:   Behavioral: FABI tailored COVID-19 testing pamphlet;   Behavioral: Standard COVID-19 home-based test kit
  Sponsors:   Texas Woman’s University;   National Institutes of Health (NIH)
  Not yet recruiting

• A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized. - Condition:   SARS-CoV-2 Infection
  Interventions:   Drug: PF-07817883;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial - Conditions:   Healthy;   COVID-19;   Distress, Emotional
  Interventions:   Behavioral: RASMUS Resilience Training;   Behavioral: Progressive Muscle Relaxation
  Sponsor:   Medical University Innsbruck
  Recruiting

• Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms - Condition:   Long Covid19
  Interventions:   Drug: Testofen;   Drug: Microcrystalline cellulose
  Sponsor:   RDC Clinical Pty Ltd
  Not yet recruiting

• Rehabilitation Treatment of Patients With COVID-19 - Conditions:   Rehabilitation;   Pneumonia, Viral;   COVID-19;   Quality of Life
  Interventions:   Other: exercises;   Other: massage
  Sponsors:   I.M. Sechenov First Moscow State Medical University;   MEDSI Clinical Hospital 1, ICU
  Completed

• Addressing Vaccine Acceptance in Carceral Settings Through Community Engagement - Condition:   COVID-19
  Intervention:   Behavioral: ADVANCE Steering Committee interventions
  Sponsors:   Yale University;   National Institute on Minority Health and Health Disparities (NIMHD)
  Recruiting

• A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of the Monoclonal Antibody VYD222 in Healthy Adult Participants - Condition:   COVID-19
  Interventions:   Drug: VYD222;   Other: Placebo
  Sponsors:   Invivyd, Inc.;   Novotech (Australia) Pty Limited
  Recruiting

From PubMed

• First study on in vitro antiviral and virucidal effects of flavonoids against feline infectious peritonitis virus at the early stage of infection - CONCLUSION: Isoginkgetin interfered with FIPV replication during both post-viral infection and virucidal experiments on CRFK cells, whereas luteolin inhibited the virus after infection. These results demonstrate the potential of herbal medicine for treating FIP.

• Synthesis, antimycobacterial screening, molecular docking, ADMET prediction and pharmacological evaluation on novel pyran-4-one bearing hydrazone, triazole and isoxazole moieties: Potential inhibitors of SARS CoV-2 - The respiratory infection tuberculosis is caused by the bacteria Mycobacterium tuberculosis and its unrelenting spread caused millions of deaths around the world. Hence, it is needed to explore potential and less toxic anti-tubercular drugs. In the present work, we report the synthesis and antitubercular activity of four different (hydrazones 7-12, O-ethynyl oximes 19-24, triazoles 25-30, and isoxazoles 31-36) hybrids. Among these hybrids 9, 10, 33, and 34, displayed high antitubercular activity…

• SARS-CoV-2 infection aggravates cigarette smoke-exposed cell damage in primary human airway epithelia - CONCLUSION: Smoking led to dysregulation of host immune response and cell damage as seen in SARS-CoV-2-infected primary human airway epithelia. These findings may contribute to increased disease susceptibility with severe condition and provide a better understanding of the pathogenesis of SARS-CoV-2 infection in smokers.

• Dual action anti-inflammatory/antiviral isoquinoline alkaloids as potent naturally occurring anti-SARS-CoV-2 agents: A combined pharmacological and medicinal chemistry perspective - In the search for compounds that inhibit the SARS-CoV-2 after the onset of the COVID-19 pandemic, isoquinoline-containing alkaloids have been identified as compounds with high potential to fight the disease. In addition to having strong antiviral activities, most of these alkaloids have significant anti-inflammatory effects which are often manifested through the inhibition of a promising host-based anti-COVID-19 target, the p38 MAPK signaling pathway. In the present review, our pharmacological…

• SARS-CoV-2 Infection of Human Neurons Is TMPRSS2 Independent, Requires Endosomal Cell Entry, and Can Be Blocked by Inhibitors of Host Phosphoinositol-5 Kinase - 2019 coronavirus disease (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to respiratory illness, COVID-19 patients exhibit neurological symptoms lasting from weeks to months (long COVID). It is unclear whether these neurological manifestations are due to an infection of brain cells. We found that a small fraction of human induced pluripotent stem cell (iPSC)-derived neurons, but not astrocytes, were naturally susceptible to SARS-CoV-2….

• L-Tartaric Acid Inhibits Diminazene-induced Vasorelaxation in Isolated Rat Aorta - CONCLUSION: This investigation provides important experimental evidence of the efficacy of L-tartaric acid in inhibiting diminazene-induced vasorelaxation.

• Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19 - Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice. 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were predicted, which were…

• Discovery and characterization of the covalent SARS-CoV-2 3CL^pro inhibitors from Ginkgo biloba extract via integrating chemoproteomic and biochemical approaches - CONCLUSION: Collectively, GBE50 and some constituents in this herbal product could strongly inhibit SARS-CoV-2 3CL^(pro) in dose- and time-dependent manner. Gallocatechin and sciadopitysin were identified as potent SARS-CoV-2 3CL^(pro) inhibitors, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.

• Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral…

• Neurological damages in COVID-19 patients: Mechanisms and preventive interventions - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19) which led to neurological damage and increased mortality worldwide in its second and third waves. It is associated with systemic inflammation, myocardial infarction, neurological illness including ischemic strokes (e.g., cardiac and cerebral ischemia), and even death through multi-organ failure. At the early stage, the virus infects the lung epithelial cells and is slowly…

• The Unexpected Protective Role of Thrombosis in Sepsis-Induced Inflammatory Lung Injury Via Endothelial Alox15 - CONCLUSION: We have demonstrated that moderate levels of thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of Alox5 inhibits severe pulmonary thrombosis-induced increase of ALI. Thus, activation of ALOX15 signaling represents a promising therapeutic strategy for treatment of ARDS, especially in sub-populations of patients with thrombocytopenia and/or severe pulmonary thrombosis.

• Massively Parallel Profiling of RNA-targeting CRISPR-Cas13d - Type VI CRISPR enzymes cleave target RNAs and are widely used for gene regulation, RNA tracking, and diagnostics. However, a systematic understanding of their RNA binding specificity and cleavage activation is lacking. Here, we describe RNA c hip- h ybridized a ssociation- m apping p latform (RNA-CHAMP), a massively parallel platform that repurposes next-generation DNA sequencing chips to measure the binding affinity for over 10,000 RNA targets containing structural perturbations, mismatches,…

• Immune and ionic mechanisms mediating the effect of dexamethasone in severe COVID-19 - CONCLUSION: Our findings suggest that dexamethasone attenuates inflammatory cytokine release via Kv1.3 suppression, and this mechanism contributes to dexamethasone-mediated immunosuppression in severe COVID-19.

• Transporter Inhibition Profile for the Antivirals Tilorone, Quinacrine and Pyronaridine - Pyronaridine, tilorone and quinacrine are cationic molecules that have in vitro activity against Ebola, SARS-CoV-2 and other viruses. All three molecules have also demonstrated in vivo activity against Ebola in mice, while pyronaridine showed in vivo efficacy against SARS-CoV-2 in mice. We have recently tested these molecules and other antivirals against human organic cation transporters (OCTs) and apical multidrug and toxin extruders (MATEs). Quinacrine was found to be an inhibitor of OCT2,…

• The therapeutic effect and mechanism of parthenolide in skeletal disease, cancers, and cytokine storm - Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic…

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