Covid-19 Sentry

Contents

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

From Preprints

• Getting Trapped in a Dead End? Trait Self-Control and Boredom Are Linked to Goal Adjustment -
  Disengaging from unattainable goals and reengaging in alternative goals is essential for effective goal pursuit; yet, surprisingly little is known about associated personality factors. Here, we focused on individual differences in self-control (domain-general self-control, if-then planning) and boredom (boredom proneness, boredom avoidance and escape tendencies). Concerning goal adjustment in everyday life (Study 1; N = 323 crowdworkers), if-then planning was associated with worse disengagement and better reengagement. While boredom proneness was associated with poorer reengagement, boredom avoidance and escape tendencies were associated with better reengagement. When goal striving was thwarted during the COVID-19 pandemic (Study 2; N = 97 students), similar associations emerged along with links to anxiety and depression. However, disengagement was no longer associated with if-then planning but instead with better self-control and higher boredom proneness. These results show differential relationships of goal disengagement and reengagement with self-control and boredom, paving the way to a better understanding of who struggles or shines when effective goal adjustment is required.
  🖺 Full Text HTML: Getting Trapped in a Dead End? Trait Self-Control and Boredom Are Linked to Goal Adjustment
• Novel Estimates Reveal Subnational Heterogeneities in Disease-Relevant Contact Patterns in the United States -
  The spread and transmission dynamics of directly transmitted airborne pathogens, such as SARS-CoV-2, are fundamentally determined by in-person contact patterns. Reliable quantitative estimates of contact patterns are critical to modeling and reducing the spread of directly transmitted infectious diseases. While national-level contact data are available in many countries, including the United States, local-level estimates of age-specific contact patterns are key since disease dynamics and public health policy vary by geography. However, collecting contact data for each state would require a very large sample and be prohibitively expensive. To overcome this challenge, we develop a flexible model to estimate age-specific contact patterns at the subnational level using national-level interpersonal contact data. Our model is based on dynamic multilevel regression with poststratification. We apply this approach to a national sample of interpersonal contact data collected by the Berkeley Interpersonal Contact Study (BICS). Results illustrate important state-level variation in levels and trends of contacts across the US.
  🖺 Full Text HTML: Novel Estimates Reveal Subnational Heterogeneities in Disease-Relevant Contact Patterns in the United States
• Generalized trust rather than perception of relational mobility correlates with nominating close friends in a social network -
  A social environment, such as relational mobility, which represents the availability of opportunities to develop new relationships in society, cultivates an individual’s psychology and social network. Generalized trust, which represents trust among people in general, is a tendency to expand individuals’ social ties in a fluid society. Using the data of 170 students, we analyzed whether an individual’s belief of generalized trust and perception of relational mobility are related to the social network. We conducted a survey to assess psychological measures and social networks under the COVID-19 pandemic for first-year university students. The analyses revealed that generalized trust was significantly associated with a higher proportion of outdegrees (i.e., the nomination of close friends) and a lower proportion of indegrees (i.e., being nominated by others). In contrast, perception of relational mobility was not significantly associated with generalized trust and any social network measures. Behavioral trust, measured using a Trust Game approximately six months later, was not significantly associated with network characteristics. The results support the argument that the belief of generalized trust functions as an adaptive psychological mechanism to expand individuals’ relationships in their social networks.
  🖺 Full Text HTML: Generalized trust rather than perception of relational mobility correlates with nominating close friends in a social network
• Assessing glucose-6-phosphate dehydrogenase (G6PD) during COVID-19 requires caution: evidence on the impact of the infection upon enzyme activity -

  Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor of severity in patients with COVID-19. In this article, we assessed the influence of G6PDd on the infection, severity, and clinical progression of patients with COVID-19. This prospective cohort study included adult participants (≥18 years old) who had clinical and/or radiological COVID-19 findings or positive RT-PCR results. Epidemiological and clinical data were extracted from electronic medical records. G6PD activity was measured in SD Biosensor STANDARD G6PD® equipment at admission and one year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms (SNPs) for G6PDd in the Brazilian Amazon s1050828, rs1050829 and rs5030868, corresponding to G6PD African A-(G202A, A376G), G6PD African A+(A376G) and G6PD Mediterranean(C563T), respectively.  Seven hundred fifty-three patients were included, of which 123 (16.3%) were G6PDd. The G6PDd group had a higher mean hemoglobin, and lower values of C-reactive protein and leukocytes at admission. There was no association between G6PDd and COVID-19 severity, considering that the frequency of G6PDd who needed to be hospitalized (1.9%) or demanding invasive mechanical ventilation (16.0%) or died (21.1%) was lower than G6PD normal patients. Only 29 out of 116 (25%) participants carried the African genotype. Out of 30 participants tested as G6PDd during disease, only 11 (36.7%) results agreed one year after discharge. In conclusion, caution must be taken when G6PDd screening in patients with acute COVID-19.

  🖺 Full Text HTML: Assessing glucose-6-phosphate dehydrogenase (G6PD) during COVID-19 requires caution: evidence on the impact of the infection upon enzyme activity
• Modelling SARS-CoV-2 spike-protein mutation effects on ACE2 binding -
  The binding affinity of the SARS-CoV-2 spike (S)-protein {Delta}{Delta}Gbind to the human membrane protein ACE2 is critical for virus function and evolution. Computational structure-based screening of new S-protein mutations for ACE2 binding lends promise to rationalize virus function directly from protein structure and ideally aid early detection of potentially concerning variants. We used a computational protocol based on cryo-electron microscopy structures of the S-protein to estimate the ACE2-binding that gave good trend agreement with experimental ACE2 affinities. We then expanded predictions to all possible S-protein mutations in 21 different S-protein-ACE2 complexes (400,000 {Delta}{Delta}Gbind data points in total), using mutation group comparisons to reduce systematic errors. We show that mutations that have arisen in major variants as a group maintain ACE2 affinity significantly more than random mutations in the total protein, at the interface, and at evolvable sites, with differences between variant mutations being small relative to these effects. Omicron mutations as a group had a modest change in binding affinity compared to mutations in other major variants. The single-mutation effects are consistent with ACE2 binding being optimized and maintained in omicron, despite increased importance of other selection pressures (antigenic drift). As epistasis, glycosylation and in vivo conditions will modulate these effects, computational predictive SARS-CoV-2 evolution remains far from achieved, but the feasibility of large-scale computation is substantially aided by using many structures and comparison of mutation groups rather than single mutation effects, which are very uncertain. Our results demonstrate substantial challenges but indicate ways to improve the quality of computer models for assessing SARS-CoV-2 mutation effects.
  🖺 Full Text HTML: Modelling SARS-CoV-2 spike-protein mutation effects on ACE2 binding
• The diversity of the glycan shield of sarbecoviruses closely related to SARS-CoV-2 -
  The animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the impact of SARS-CoV-2. Vaccines remain successful at limiting severe disease and death, however the continued emergence of SARS-CoV-2 variants, together with the potential for further coronavirus zoonosis, motivates the search for pan-coronavirus vaccines that induce broadly neutralizing antibodies. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of several sarbecovirus glycan shields. Many N-linked glycan attachment sites are shared by all sarbecoviruses, and the processing state of certain sites is highly conserved. However, there are significant differences in the processing state at several glycan sites that surround the receptor binding domain. Our studies reveal similarities and differences in the glycosylation of sarbecoviruses and show how subtle changes in the protein sequence can have pronounced impacts on the glycan shield.
  🖺 Full Text HTML: The diversity of the glycan shield of sarbecoviruses closely related to SARS-CoV-2
• Intentions to get vaccinated against Monkeypox in Healthcare workers in France and Belgium correlates with attitudes toward COVID-19 vaccination -

  Background: Front-line healthcare workers (HCWs) could be at-risk for Monkeypox infections. Vaccine hesitancy also affects HCWs and has an impact on their own attitudes toward vaccination. In the context of the exhaustion due to COVID-19 pandemic, we aimed to evaluate intentions to get vaccinated against Monkeypox in HCWs in France and Belgium. Methods: We performed a cross-sectional study (snowball sampling) using a self-administered on-line questionnaire to evaluate intentions to get vaccinated against Monkeypox in HCWs if a recommendation for HCWs vaccination was made. We compared demographics characteristics, vaccine readiness, eagerness for COVID-19 vaccine, and confidence in HCW with Chi-square tests, student-t and performed a binary regression. Results: Amon the 397 respondents, if a specific recommendation was made for HCWs vaccination against Monkeypox was made, 55.4 % will probably get the vaccine, while 79 % would accept the vaccine if recommended to the general population. COVID-19 vaccine eagerness and having concerns about Monkeypox epidemics were associated with favorable attitude toward Monkeypox vaccination in HCWs with respective adjusted odds ratio and 95 % Confidence Interval 2.5 (1.03-6.1), 2.6 (1.3-5.3). Forty-four HCWs (11 %) self-identified as at-risk for Monkeypox infections. Conclusion: Acceptance of Monkeypox vaccination in HCWs is probably moderate, HCWs are probably complacent and did not perceive the risk of Monkeypox infections in the context of professional exposure.

  🖺 Full Text HTML: Intentions to get vaccinated against Monkeypox in Healthcare workers in France and Belgium correlates with attitudes toward COVID-19 vaccination
• Antigen presentation dynamics shape the response to emergent variants like SARS-CoV-2 Omicron strain after multiple vaccinations with wild type strain -
  The Omicron variant of SARS-CoV-2 evades neutralization by most serum antibodies elicited by two doses of mRNA vaccines, but a third dose of the same vaccine increases anti-Omicron neutralizing antibodies. By combining computational modeling with data from vaccinated humans we reveal mechanisms underlying this observation. After the first dose, limited antigen availability in germinal centers results in a response dominated by B cells with high germline affinities for immunodominant epitopes that are significantly mutated in an Omicron-like variant. After the second dose, expansion of these memory cells and differentiation into plasma cells shape antibody responses that are thus ineffective for such variants. However, in secondary germinal centers, pre-existing higher affinity antibodies mediate enhanced antigen presentation and they can also partially mask dominant epitopes. These effects generate memory B cells that target subdominant epitopes that are less mutated in Omicron. The third dose expands these cells and boosts anti-variant neutralizing antibodies.
  🖺 Full Text HTML: Antigen presentation dynamics shape the response to emergent variants like SARS-CoV-2 Omicron strain after multiple vaccinations with wild type strain
• Long Covid active case finding: a co-produced community-based pilot within the STIMULATE-ICP study (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways) -

  Background and aim Long Covid is a significant public health concern with potentially negative implications for health inequalities. We know that those who are already socially disadvantaged in society are more exposed to COVID-19, experience the worst health outcomes and are more likely to suffer economically. We also know that these groups are more likely to experience stigma and discrimination and have negative healthcare experiences even before the pandemic. However, little is known about disadvantaged groups experiences of Long Covid and preliminary evidence suggests they may be under-represented in those who access formal care. We will conduct a pilot study in a defined geographical area (Camden, London, UK) to test the feasibility of a community-based approach of identifying Long Covid cases that have not been formally clinically diagnosed and have not been referred to Long Covid Specialist services. We will explore the barriers to accessing recognition, care and support, as well as experiences of stigma and perceived discrimination. Methods This protocol and study materials were co-produced with a Community Advisory Board (CAB) made up primarily of people living with Long Covid. Working with voluntary organisations, promotional material are co-developed and will be distributed in the local community with engagement from key community organisations and leaders to highlight Long Covid symptoms and invite those experiencing them to participate in the study if they are not formally diagnosed and accessing care. Awareness of Long Covid and symptoms, experiences of trying to access care, as well as stigma and discrimination will be explored through qualitative interviews with participants. Upon completion of the interviews, participants will be offered referral to the local social prescribing team to receive support that is personalised to them potentially including, but not restricted to, liaising with their primary care provider and the regional Long Covid clinic run by University College London Hospitals (UCLH). Ethics and dissemination Ethical approval has been obtained from the Faculty of Medicine Ethics Committee and Research Integrity and Governance, University of Southampton. (reference number 72400). Findings will be reported in a report and submitted for peer-reviewed publication. Definitive methods of dissemination will be decided by the CAB. Summaries of the findings will also be shared on the STIMULATE-ICP website, locally in the study area and through social media. We will specifically target policy makers and those responsible for shaping and commissioning Long Covid healthcare services and social support such as NHSE England Long Covid Group.

  🖺 Full Text HTML: Long Covid active case finding: a co-produced community-based pilot within the STIMULATE-ICP study (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)
• Phenotypic evolution of SARS-CoV-2: a statistical inference approach -

  Since its emergence in late 2019, the SARS-CoV-2 virus has spread globally, causing the ongoing COVID-19 pandemic. In the fall of 2020, the Alpha variant (lineage B.1.1.7) was detected in England and rapidly spread and outcompeted the previous lineage. Yet, very little is known about the underlying modifications of the infection process that can explain this selective advantage. Here, we try to quantify how the Alpha variant differs from its predecessor on two phenotypic traits: the transmission rate and the duration of infectiousness. To this end, we analysed the joint epidemiological and evolutionary dynamics of SARS-CoV-2 as a function of the Stringency Index, a measure of the amount of Non-Pharmaceutical Interventions. We developed a two-step approach based on a SEIR model and the analysis of a combination of epidemiological and evolutionary information. First, we infer how the Stringency Index reduces the amount of viral transmission. Secondly, based on a novel theoretical derivation of the selection gradient in a SEIR model, we infer the phenotype of the Alpha variant from the analysis of the change in its frequency and we show that its selective advantage is more likely to result from a higher transmission than from a longer infectious period.

  🖺 Full Text HTML: Phenotypic evolution of SARS-CoV-2: a statistical inference approach
• T cell responses to SARS-CoV-2 vaccination in people with multiple sclerosis differ between disease-modifying therapies -

  Immune responses in people with multiple sclerosis (pwMS) on disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators attenuate antibody responses after vaccination. Evaluation of cellular responses after vaccination is therefore of particular importance in these populations. In this study, we analysed CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy controls and pwMS on five different DMTs by flow cytometry. Although pwMS on anti-CD20 and S1PR therapies had low antibody responses after both 2 and 3 vaccine doses, T cell responses in pwMS on anti-CD20 therapies were preserved after third vaccination, even when additional anti-CD20 treatment was administered between vaccine doses 2 and 3. PwMS taking S1PR modulators had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that even in the absence of robust antibody responses vaccination can generate immune responses in pwMS.

  🖺 Full Text HTML: T cell responses to SARS-CoV-2 vaccination in people with multiple sclerosis differ between disease-modifying therapies
• Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study -

  Molnupiravir and Nirmatrelvir are the first available oral antivirals (OA) active against SARS-CoV-2. However, the trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. The purpose of this study is to provide real-life data on the efficacy and safety of OAs during the omicron surge of COVID-19 pandemic in a cohort of mostly vaccinated patients. We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy. We enrolled 257 patients. Of these, 146 (56.8%) were treated with molnupiravir and 111 (43.2%) with nirmatrelvir/ritonavir. Patients in molnupiravir group were older, had a lower body mass index, and a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir. During the 14-day follow-up, four hospitalizations were recorded (1.6%), three in molnupiravir (2.1%) and 1 in nirmatrelvir/ritonavir (0.9%) group. Only one patient (who had received molnupiravir) died. Median time-to-negativity of nasal swab was 8 days (8 days in nirmatrelvir/ritonavir vs. 10 days in molnupiravir group, p<0.01). Globally, we recorded 37 adverse drug reactions (mainly dysgeusia, diarrhea, and nausea) in 31 of 257 individuals (12.1%). Only two patients (0.8%), both receiving molnupiravir, terminated treatment due to the development of adverse drug reactions. In conclusion, during the omicron surge, in a population of mostly vaccinated patients treated with molnupiravir or nirmatrelvir/ritonavir, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were even lower than those reported in pivotal trials.

  🖺 Full Text HTML: Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study
• Correlation of patient serum IgG, IgA and IgM antigen binding with COVID-19 disease severity using multiplexed SARS-CoV-2 antigen microarray and maintained relative IgA and IgM antigen binding over time -

  Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses. Antigen glycosylation influenced antibody binding, with S glycosylation generally increasing and NP glycosylation decreasing binding. Purified antibody isotypes demonstrated a binding pattern and intensity that differed from the same isotype in the presence of other isotypes in whole serum, probably due to competition. Using purified antibody isotypes from naive Irish COVID-19 patients, we correlated antibody isotype binding to different panels of antigens with disease severity, with significance for binding to the S region S1 expressed in insect cells (S1 Sf21) for all three antibody isotypes. Assessing longitudinal response for constant concentrations of antibody isotypes for a subset of patients demonstrated that while the relative proportion of antigen-specific IgGs decreased over time for severe disease, the relative proportion of antigen-specific IgA binding remained at the same magnitude at 5 and 9 months post-first symptom onset. Further, the relative proportion of IgM binding decreased for S antigens but remained the same for NP antigens. This may support antigen specific serum IgA and IgM playing a role in maintaining longer-term protection, of importance for developing and assessing vaccine strategies. Overall, these data demonstrate the multiplexed platform as a sensitive and useful platform for expanded humoral immunity studies, allowing detailed elucidation of antibody isotypes response against multiple antigens. This approach will be useful for monoclonal antibody therapeutic studies and screening of donor polyclonal antibodies for patient infusions.

  🖺 Full Text HTML: Correlation of patient serum IgG, IgA and IgM antigen binding with COVID-19 disease severity using multiplexed SARS-CoV-2 antigen microarray and maintained relative IgA and IgM antigen binding over time
• Lessons learnt from community referral and follow up of sick young infants with Possible Severe Bacterial Infection in Turkana County, Kenya -

  Introduction: Management of possible severe bacterial infections in young infants (0-59 days) requires timely identification of danger signs and prompt administration of efficacious antibiotic treatment. The Possible Severe Bacterial Infection guidelines underscore the importance of close follow up in an outpatient basis to ensure treatment adherence and early detection of illness-related complications. The purpose of this study was to strengthen the follow up and referral of sick young infants on day 4 and 8 by introducing community-led interventions that facilitated community health volunteers to identify sick young infants, conduct community reviews, link data with responsive facilities, and refer appropriately. Methods: Six health facilities were included a a longitudinal, descriptive, mixed methods approach weaved around an initial formative context assessment and three-monthly assessments. Quantitative data was extracted from facility registers to identify gaps in follow up and referral feasibility. Qualitative data was through focus group discussions with community health volunteers and key informant interviews with frontline providers. Results: Qualitative data provided insights into key barriers and facilitators of community follow up and referral. Barriers include community socio-cultural practices, competing tasks, dysfunctional community referral pathway, drivers of common infections, and unavailability of essential commodities. Key facilitators entail indication of competency in identification of danger signs in sick young infants, presence of older women, men, and community resource persons that can leveraged on in community engagement and sensitization, and mothers are the primary decision makers in care seeking. There was increased utilization of decision support tools and an increase in the number of sick young infants managed in dispensaries. The COVID-19 pandemic however negatively impacted community follow up and referral of sick young infants. Conclusion: This study seeks to contribute evidence on strengthening PSBI community management by enhancing day 4 and day 8 follow up, review and community referral of sick young infants in Turkana, Kenya. The feasibility, adoption, and fidelity of strengthening community facility linkage through integrated communication strategies was documented, indicative of a successful community-facility linkage in dispensaries and health centers despite the effects of the COVID-19 pandemic.

  🖺 Full Text HTML: Lessons learnt from community referral and follow up of sick young infants with Possible Severe Bacterial Infection in Turkana County, Kenya
• The evolution of depressive symptomatology across three waves of the COVID-19 pandemic: A 17-month representative longitudinal study of the adult population -
  This 17-month longitudinal study on a representative sample of 4,361 Norwegian adults employs an observational ABAB design across six repeated assessments and three pandemic waves to systematically investigate the evolution of depressive symptomatology across all modifications of viral mitigation protocols (VMPs) from their onset to termination. Using Latent Change Score Models to analyze 26,166 observations, the study empirically corroborates that critical fluctuations in depressive symptomatology within and across individuals occur during the first three months of the pandemic, after which symptom profiles are predominantly consolidated throughout the pandemic period. Contrary to established belief, female sex, young age, lower education and preexisting psychiatric diagnosis only served as adequate predictors of the initial shocks to symptomatology observed during the onset of the pandemic, and did not adequately predict subsequent change observed in symptoms within and across individuals. Population-level analyses demonstrated that symptom levels increased in accordance with the presence and strictness of VMPs and were unrelated to COVID-19 incidence rates. Upon predominant termination of VMPs, population-level symptoms began declining, while large heterogeneity was present across the adult population. Detrimental long-term adversities were revealed by 10% of the adults. These individuals displayed chaotic adaptation to the pandemic and its VMPs, exhibiting substantial increases in clinical levels of symptomatology ensuing partial re-opening of society and through the remainder of the pandemic, with these deleterious symptoms projected to remain heightened ahead. Frequency of quarantine exposure was incrementally tied with increases in contemporaneously experienced and long-term depressive adversities, with information obtainment through unmonitored sources further associated with contemporaneous and long-term states of heightened symptomatology.
  🖺 Full Text HTML: The evolution of depressive symptomatology across three waves of the COVID-19 pandemic: A 17-month representative longitudinal study of the adult population

From Clinical Trials

• A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SIM0417;   Drug: Placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology - Condition:   COVID-19
  Intervention:   Other: Self-management of post COVID-19 respiratory outcomes
  Sponsor:   University of Manitoba
  Not yet recruiting

• Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Casirivimab and Imdevimab Drug Combination;   Drug: Remdesivir;   Drug: Favipiravir
  Sponsor:   Mansoura University Hospital
  Completed

• The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines - Condition:   COVID-19
  Interventions:   Biological: BCG (Bacillus Calmette-Guérin) vaccine;   Other: Placebo
  Sponsors:   Oswaldo Cruz Foundation;   University of Sao Paulo;   Federal University of Juiz de Fora
  Recruiting

• Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2) - Condition:   COVID-19
  Interventions:   Diagnostic Test: Nasal Swab;   Diagnostic Test: Nasopharyngeal swab
  Sponsor:   LumiraDx UK Limited
  Recruiting

• Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities - Condition:   COVID-19
  Interventions:   Other: Education;   Other: Motivational
  Sponsor:   University of Chicago
  Not yet recruiting

• Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults. - Condition:   COVID-19
  Intervention:   Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)
  Sponsors:   The Aurum Institute NPC;   Coalition for Epidemic Preparedness Innovations
  Recruiting

• A Study of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine - Condition:   COVID-19
  Interventions:   Biological: Adult group in immunogenicity and safety study of combined immunization;   Biological: Elderly group in immunogenicity and safety study of combined immunization;   Biological: Adult group in safety observation study of combined immunization;   Biological: Elderly group in safety observation study of combined immunization
  Sponsor:   Sinovac Biotech Co., Ltd
  Completed

• Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19 - Condition:   COVID-19 Infection
  Interventions:   Biological: Allogeneic umbilical cord mesenchymal stem cells;   Biological: Controlled normal saline
  Sponsor:   Ever Supreme Bio Technology Co., Ltd.
  Active, not recruiting

• The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients - Conditions:   COVID-19;   Vitamin D Deficiency
  Intervention:   Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion
  Sponsor:   Pauls Stradins Clinical University Hospital
  Completed

• UNAIR Inactivated COVID-19 Vaccine Phase 3 - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccines
  Interventions:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-19 Vaccine
  Sponsors:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia
  Recruiting

• Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19 - Conditions:   COVID-19;   AMS-H-03;   Hydrogen-oxygen Gas
  Interventions:   Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03;   Other: basic treatment
  Sponsor:   Shanghai Zhongshan Hospital
  Recruiting

• Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection - Conditions:   COVID-19;   Child, Only
  Intervention:   Drug: Jinzhen oral liquid or Jinhuaqinggan granules
  Sponsor:   The Affiliated Hospital of Qingdao University
  Recruiting

• COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study - Conditions:   COVID-19;   Kidney Transplant
  Intervention:   Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   PPD;   Johns Hopkins University;   Sanofi Pasteur, a Sanofi Company
  Not yet recruiting

• Smartphone Intervention for Overdose and COVID-19 - Conditions:   Substance Use Disorders;   Overdose;   COVID-19
  Intervention:   Device: iThrive WI Intervention
  Sponsors:   University of Wisconsin, Madison;   National Institute on Drug Abuse (NIDA)
  Not yet recruiting

From PubMed

• Advances in cell death mechanisms involved in viral myocarditis - Viral myocarditis is an acute inflammatory disease of the myocardium. Although many etiopathogenic factors exist, coxsackievirus B3 is a the leading cause of viral myocarditis. Abnormal cardiomyocyte death is the underlying problem for most cardiovascular diseases and fatalities. Various types of cell death occur and are regulated to varying degrees. In this review, we discuss the different cell death mechanisms in viral myocarditis and the potential interactions between them. We also explore…

• Dynamicity and persistence of severe acute respiratory syndrome coronavirus-2 antibody response after double dose and the third dose with BBV-152 and AZD1222 vaccines: A prospective, longitudinal cohort study - CONCLUSION: This year-long follow-up study found a 7- and 5-fold antibody waning in Covaxin and Covishield recipients, respectively, without any breakthrough infection history. However, individuals with booster breakthrough had mild symptoms and did not require hospital admission. The data also indicate the possible escape of omicron variants despite the presence of vaccine-induced neutralizing antibodies.

• Exploring the Impact of ACE Inhibition in Immunity and Disease - Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and is crucial in the renin-angiotensin-aldosterone system (RAAS) but also implicated in immune regulation. Intrinsic ACE has been detected in several immune cell populations, including macrophages and neutrophils, where its overexpression results in enhanced bactericidal and antitumour responses, independent of angiotensin II. With roles in antigen presentation and inflammation, the impact of ACE inhibitors must…

• Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development - COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit the…

• Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection - Porcine deltacoronavirus (PDCoV) is a recently discovered enteropathogenic coronavirus and has caused significant economic impacts on the pork industry. Although studies have partly uncovered the molecular mechanism of PDCoV-host interaction, it requires further research. In this study, we explored the roles of Stromal Antigen 2 (STAG2) in PDCoV infection. We found that STAG2-deficient cells inhibited infection with vesicular stomatitis virus (VSV) and PDCoV, whereas restoration of STAG2…

• Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-γH2AX Signaling Pathways to Foster Its Replication - DNA damage response (DDR) is an evolutionarily conserved mechanism by which eukaryotic cells sense DNA lesions caused by intrinsic and extrinsic stimuli, including virus infection. Although interactions between DNA viruses and DDR have been extensively studied, how RNA viruses, especially coronaviruses, regulate DDR remains unknown. A previous study showed that the porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the Coronaviridae family, induces DDR in infected…

• Ionophore Antibiotics Inhibit Type II Feline Coronavirus Proliferation In Vitro - Feline coronaviruses (FCoVs) infect cats worldwide and cause severe systemic diseases, such as feline infectious peritonitis (FIP). FIP has a high mortality rate, and drugs approved by the Food and Drug Administration have been ineffective for the treatment of FIP. Investigating host factors and the functions required for FCoV replication is necessary to develop effective drugs for the treatment of FIP. FCoV utilizes an endosomal trafficking system for cellular entry after binding between the…

• Evaluation of Novel Guanidino-Containing Isonipecotamide Inhibitors of Blood Coagulation Factors against SARS-CoV-2 Virus Infection - Coagulation factor Xa (fXa) and thrombin (thr) are widely expressed in pulmonary tissues, where they may catalyze, together with the transmembrane serine protease 2 (TMPRSS2), the coronaviruses spike protein (SP) cleavage and activation, thus enhancing the SP binding to ACE2 and cell infection. In this study, we evaluate in vitro the ability of approved (i.e., dabigatran and rivaroxaban) and newly synthesized isonipecotamide-based reversible inhibitors of fXa/thr (cmpds 1-3) to hinder the…

• Anti-Spike and Neutralizing Antibodies after Two Doses of COVID-19 Sinopharm/BIBP Vaccine - Host response to COVID-19 vaccines is partially evaluated through the estimation of antibody response, specifically the binding anti-spike (anti-S) and the neutralizing antibodies (nAbs) against SARS-CoV-2. Vaccine-induced humoral response affects decisions on the choice of vaccine type, vaccine acceptance, and the need for boosting. Identification of risk factors for poor antibody response helps to stratify individuals who might potentially require booster doses. The primary objective of this…

• In Vitro Evaluation and Mitigation of Niclosamide’s Liabilities as a COVID-19 Treatment - Niclosamide, an FDA-approved oral anthelmintic drug, has broad biological activity including anticancer, antibacterial, and antiviral properties. Niclosamide has also been identified as a potent inhibitor of SARS-CoV-2 infection in vitro, generating interest in its use for the treatment or prevention of COVID-19. Unfortunately, there are several potential issues with using niclosamide for COVID-19, including low bioavailability, significant polypharmacology, high cellular toxicity, and unknown…

• Neutralizing Antibody Response, Safety, and Efficacy of mRNA COVID-19 Vaccines in Pediatric Patients with Inflammatory Bowel Disease: A Prospective Multicenter Case-Control Study - The vaccination of immunocompromised children against coronavirus disease 2019 is an important public health issue. We evaluated the serological response, safety, and efficacy of the BNT162b2 vaccine in children with and without inflammatory bowel disease (IBD). A prospective, multicenter, case-control study was conducted in a pediatric population, including patients with IBD, aged 12-18 years. Clinical characteristics, safety profile, and serum samples for surrogate virus-neutralizing antibody…

• A Versatile Class of 1,4,4-Trisubstituted Piperidines Block Coronavirus Replication In Vitro - There is a clear need for novel antiviral concepts to control SARS-CoV-2 infection. Based on the promising anti-coronavirus activity observed for a class of 1,4,4-trisubstituted piperidines, we here conducted a detailed analysis of the structure-activity relationship of these structurally unique inhibitors. Despite the presence of five points of diversity, the synthesis of an extensive series of analogues was readily achieved by Ugi four-component reaction from commercially available reagents….

• Identification of a Dual Inhibitor of Secreted Phospholipase A₂ (GIIA sPLA₂) and SARS-CoV-2 Main Protease - The development of novel agents to combat COVID-19 is of high importance. SARS-CoV-2 main protease (M^(pro)) is a highly attractive target for the development of novel antivirals and a variety of inhibitors have already been developed. Accumulating evidence on the pathobiology of COVID-19 has shown that lipids and lipid metabolizing enzymes are critically involved in the severity of the infection. The purpose of the present study was to identify an inhibitor able to simultaneously inhibit both…

• Hydrophobic Alpha-Helical Short Peptides in Overlapping Reading Frames of the Coronavirus Genome - In this study, we show that the coronavirus (CoV) genome may encode many functional hydrophobic alpha-helical peptides (HAHPs) in overlapping reading frames of major coronaviral proteins throughout the entire viral genome. These HAHPs can theoretically be expressed from non-canonical sub-genomic (sg)RNAs that are synthesized in substantial amounts in infected cells. We selected and analyzed five and six HAHPs encoded in the S gene regions of severe acute respiratory syndrome coronavirus 2…

• In Silico Repurposed Drugs against Monkeypox Virus - Monkeypox is an emerging epidemic of concern. The disease is caused by the monkeypox virus and an increasing global incidence with a 2022 outbreak that has spread to Europe amid the COVID-19 pandemic. The new outbreak is associated with novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involves the use of tecovirimat. However, there is otherwise limited pharmacopoeia and research interest in monkeypox. In this…

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