Covid-19 Sentry

Contents

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

From Preprints

• Longitudinal sequencing and variant detection of SARS-CoV-2 across Southern California wastewater from April 2020 - August 2021 -

  Wastewater based epidemiology (WBE) is a useful method to detect pathogen prevalence and may serve to effectively monitor diseases at a broad scale. WBE has been used throughout the COVID-19 pandemic to track localized and population-level disease burden through the quantification of SARS-CoV-2 RNA present in wastewater. Aside from case load estimation, WBE is being used to assay viral genomic diversity and the emergence of potential SARS-CoV-2 variants. Here, we present a study in which we sequenced RNA extracted from sewage influent samples obtained from eight wastewater treatment plants representing 16 million people in Southern California over April 2020 - August 2021. We sequenced SARS-CoV-2 with two methods: Illumina Respiratory Virus Enrichment and metatranscriptomic sequencing (N = 269), and QIAseq SARS-CoV-2 tiled amplicon sequencing (N = 95). We were able to classify SARS-CoV-2 reads into lineages and sublineages that approximated several named variants across a full year, and we identified a diversity of single nucleotide variants (SNVs) of which many are putatively novel SNVs, and SNVs of unknown potential function and prevalence. Through our retrospective study, we also show that several sublineages of SARS-CoV-2 were detected in wastewater up to several months before clinical detection, which may assist in the prediction of future Variants of Concern. Lastly, we show that sublineage diversity was similar between wastewater treatment plants across Southern California, and that diversity changed by sampling month indicating that WBE is effective across megaregions. As the COVID-19 pandemic moves to new phases, and additional SARS-CoV-2 variants emerge, the ongoing monitoring of wastewater is important to understand local and population-level dynamics of the virus. Our study shows the potential of WBE to detect SARS-CoV-2 variants throughout Southern California9s wastewater and track the diversity of viral SNVs and strains in urban and suburban locations. These results will aid in our ability to monitor the evolutionary potential of SARS-CoV-2 and help understand circulating SNVs to further combat COVID-19.

  🖺 Full Text HTML: Longitudinal sequencing and variant detection of SARS-CoV-2 across Southern California wastewater from April 2020 - August 2021
• Unsupervised Machine Learning Unveil Easily Identifiable Subphenotypes of COVID-19 With Differing Disease Trajectories -

  Background: Given the clinical heterogeneity of COVID-19 infection, we hypothesize the existence of subphenotypes based on early inflammatory responses that are associated with mortality and additional complications. Methods: For this cross-sectional study, we extracted electronic health data from adults hospitalized patients between March 1, 2020 and May 5, 2021, with confirmed primary diagnosis of COVID-19 across five Johns Hopkins Hospitals. We obtained all electronic health records from the first 24h of the patient9s hospitalization. Mortality was the primary endpoint explored while myocardial infarction (MI), pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, delirium, length of stay (LOS), ICU admission and intubation status were secondary outcomes of interest. First, we employed clustering analysis to identify COVID-19 subphenotypes on admission with only biomarker data and assigned each patient to a subphenotype. We then performed Chi-Squared and Mann-Whitney-U tests to examine associations between COVID-19 subphenotype assignment and outcomes. In addition, correlations between subphenotype and pre-existing comorbidities were measured using Chi-Squared analysis. Results: A total of 7076 patients were included. Analysis revealed three distinct subgroups by level of inflammation: hypoinflammatory, intermediate, and hyperinflammatory subphenotypes. More than 25% of patients in the hyperinflammatory subphenotype died compared to less than 3% hypoinflammatory subphenotype (p<0.05). Additional analysis found statistically significant increases in the rate of MI, DVT, PE, stroke, delirium and ICU admission as well as LOS in the hyperinflammatory subphenotype. Conclusion: We identify three distinct inflammatory subphenotypes that predict a range of outcomes, including mortality, MI, DVT, PE, stroke, delirium, ICU admission and LOS. The three subphenotypes are easily identifiable and may aid in clinical decision making.

  🖺 Full Text HTML: Unsupervised Machine Learning Unveil Easily Identifiable Subphenotypes of COVID-19 With Differing Disease Trajectories
• Long-term effects of extreme smoke exposure on COVID-19: A cohort study -

  In early 2014, the Hazelwood coalmine fire covered the regional Australian town of Morwell in smoke and ash for 45 days. One of the fire9s by-products, PM_2.5, has been linked higher rates of COVID-19 infection to increased expression of the ACE2 receptor, which the COVID-19 virus uses to infect cells throughout the body. However, it is unclear whether the effect persists for years after exposure. In this study, we surveyed a cohort established prior to the pandemic to determine whether PM_2.5 from the coalmine fire increased long-term vulnerability to COVID-19 infection and severe disease. In late 2022, 612 members of the Hazelwood Health Study9s adult cohort, established in 2016/17, participated in a follow-up survey including standardised items to capture COVID-19 infections, hospitalisations, and vaccinations. Associations were evaluated in crude and adjusted logistic regression models, applying statistical weighting for survey response and multiple imputation to account for missing data, with sensitivity analyses to test the robustness of results. A total of 271 (44%) participants self-reported or met symptom criteria for at least one COVID-19 infection. All models found a positive association, with odds of infection increasing by between 4-21% for every standard deviation (12.3μg/m3) increase in mine fire-related PM_2.5 exposure. However, this was not statistically significant in any model. There were insufficient hospitalisations to examine severity (n=7; 1%). The findings were inconclusive in ruling out an effect of PM_2.5 exposure from coalmine fire on long-term vulnerability to COVID-19 infection. Given the positive association that was robust to modelling variations as well as evidence for a causal mechanism, it would be prudent to treat PM_2.5 from fire events as a risk factor for long-term COVID-19 vulnerability until more evidence accumulates.

  🖺 Full Text HTML: Long-term effects of extreme smoke exposure on COVID-19: A cohort study
• Ethnic inequalities among NHS staff in England - workplace experiences during the COVID-19 pandemic -

  Objectives. To determine how workplace experiences of NHS staff varied by ethnic group during the COVID-19 pandemic and examine how these experiences are associated with mental and physical health at the time of the study. Methods. An online Inequalities Survey was conducted by the TIDES study (Tackling Inequalities and Discrimination Experiences in health Services) in collaboration with NHS CHECK. This Inequalities Survey collected measures relating to workplace experiences (such as personal protective equipment (PPE), risk assessments, redeployments, and discrimination) as well as mental health, and physical health from NHS staff working in the 18 trusts participating with the NHS CHECK study between February and October 2021 (N=4622). Results. Regression analysis revealed that staff from Black and Mixed/Other ethnic groups had greater odds of experiencing workplace harassment (adjusted odds ratio (AOR) = 2.43 [1.56-3.78] and 2.38 [1.12-5.07], respectively) and discrimination (AOR = 4.36 [2.73-6.96], and 3.94 [1.67-9.33], respectively) compared to White British staff. Staff from black ethnic groups also had greater odds than White British staff of reporting PPE unavailability (AOR = 2.16 [1.16-4.00]). Such workplace experiences were associated with negative physical and mental health outcomes, though this association varied by ethnicity. Conversely, understanding employment rights around redeployment, being informed about, and having the ability to inform redeployment decisions were associated with lower odds of poor health outcomes. Conclusions. Structural changes to the way staff from ethnically minoritised groups are supported, and how their complaints are addressed by leaders within the NHS are urgently required to address racism and inequalities in the NHS. Policy implications. Maintaining transparency and implementing effective mechanisms for addressing poor working conditions, harassment, and discrimination is crucial in the NHS. This can be achieved through appointing a designated staff member, establishing a tracking system, and training HR managers in identifying and handling reports of racial discrimination. Incorporating diversity and inclusion considerations into professional development activities and providing staff with opportunities to actively participate in decision-making can also benefit their health. The NHS Workforce Race Equality Standard may need to broaden its scope to assess race equality effectively.

  🖺 Full Text HTML: Ethnic inequalities among NHS staff in England - workplace experiences during the COVID-19 pandemic
• Time to get attention: The effect of temporal values on health, income and happiness -
  We study the effect of people’s temporal values (habits of attending to past or future events) on their health, labour market performance and happiness. Participants’ (N=1177) data were initially collected in 2016 and then again in a follow-up study in 2020-2021. We find that habitually more attending to the future is negatively associated with diseases (heart attack; high cholesterol; diabetes; high-blood pressure; Covid19), but positively with health-related behaviour (eating vegetables and fruit; less smoking), health status (e.g., healthy weight; long life expectancy), income, hourly wage, financial satisfaction and happiness. Furthermore, such temporal values predict participants’ future situation of these aspects of well-being in 2020-2021, even after controlling for the 2016 baseline situation, IQ, self-control, patience, risk aversion and demographic information. Given that habitually attending to the past is likely to lead people to give less priority to the future compared to the past, we propose a temporal values and well-being hypothesis: Temporal values have consequences for people’s planning and behaviour, thus influencing individuals’ concurrent and longitudinal overall well-being. Our findings have strong implications for theories of time perception, measurements of temporal values, and for a better understanding of factors that influence people’s health, income, and happiness.
  🖺 Full Text HTML: Time to get attention: The effect of temporal values on health, income and happiness
• Gender Responsivity of Family Planning Cadres in Family Resilience Counseling during the Covid-19 Pandemic in Ajibarang Subdistrict -
  The Covid-19 pandemic has decreased resilience, particularly the socio-psychological aspects of many families, including the Ajibarang Subdistrict. This can be seen from the many cases of domestic violence and child marriage occurring in this part of the Banyumas Regency. In order not to continue, this condition needs to be prevented immediately through counseling activities that are appropriate in material and right on target, for both women and men. In other words, counseling must be gender-responsive. In this case, Family Planning Cadres in the village and RW levels play a vital role in helping family planning counselors take preventive measures. Therefore, it would be interesting to study the gender responsivities of family planning counselors. This study aimed to gather information about (1) the phenomenon of family resilience in their area and (2) the gender responsivity of family resilience counseling conducted in the subdistrict. By applying a descriptive qualitative approach, this study gathered data through questionnaires and direct discussions. The data were analyzed using interactive methods. The results showed that during the Covid-19 pandemic, there were a large number of divorced and married children. While counseling was provided to address this issue, the target clients were mostly females. Among the many reasons, cadres only partially understood the concept of gender and never attended training for gender-perspective counseling.
  🖺 Full Text HTML: Gender Responsivity of Family Planning Cadres in Family Resilience Counseling during the Covid-19 Pandemic in Ajibarang Subdistrict
• Determination of the factors responsible for host tropism of SARS-CoV-2-related bat coronaviruses -
  Differences in host ACE2 genes may affect the host range of SARS-CoV-2-related coronaviruses (SC2r-CoVs) and further determine the tropism of host ACE2 for the infection receptor. However, the factor(s) responsible for determining the host tropism of SC2r-CoVs, which may in part be determined by the tropism of host ACE2 usage, remains unclear. Here, we use the pseudoviruses with the spike proteins of two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and the cells expressing ACE2 proteins of eight different Rhinolophus bat species, and show that these two spikes have different tropisms for Rhinolophus bat ACE2. Through structural analysis and cell culture experiments, we demonstrate that this tropism is determined by residue 493 of the spike and residues 31 and 35 of ACE2. Our results suggest that SC2r-CoVs exhibit differential ACE2 tropism, which may be driven by adaptation to different Rhinolophus bat ACE2 proteins.
  🖺 Full Text HTML: Determination of the factors responsible for host tropism of SARS-CoV-2-related bat coronaviruses
• A scoping review on the use and acceptability of preprints -
  Background: Preprints are open and accessible scientific manuscript or report that has not been submitted to a peer reviewed journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The purpose of this scoping review was to explore the current evidence on the use and acceptability of preprints by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
  🖺 Full Text HTML: A scoping review on the use and acceptability of preprints
• The balance of risks and benefits in the COVID-19 “vaccine hesitancy” literature: An umbrella review -
  Background: “Vaccine hesitancy” (VH) has been described as a “threat to global health”, especially in the COVID-19 era. Research on VH indicates that the concerns of vaccine recipients with the balance of risks and benefits of COVID-19 vaccination, which involve safety and effectiveness considerations (hereafter “safety concerns”), are a leading driver of VH. However, what explains these concerns is underexplored. Goal: We conducted a qualitative umbrella review following PRISMA guidelines and informed by a critical perspective to examine how the safety concerns of COVID-19 vaccine recipients are addressed in the VH literature. Methods: We searched PubMed, the Epistemonikos COVID-19 platform (COVID-19 L. OVE), and the WHO Global Research on COVID-19 Database. We included 49 refereed reviews examining VH in any population involved with COVID-19 vaccination decisions for themselves or as caretakers, with no methodological, quality, temporal, or geographic restrictions, and were published in English, excluding those that authors did not identify as “systematic”. Two reviewers completed article screening and data extraction and synthesis. Thematic synthesis was used to identify themes and frequencies were calculated to assess the strength of support for themes. Disagreements were resolved through full team discussion. The protocol was registered with PROSPERO (ID CRD42022351489) and partially funded by a SSHRC grant (# 435-2022-0959). Findings: All reviews assumed that VH was a major barrier to ending the COVID-19 crisis. With vaccines assumed to be “safe and effective”, recipients’ safety concerns were downplayed. Evidence incompatible with “VH-as-a-problem”, whenever mentioned, was dismissed as “misinformation”. Informed consent was either not discussed or was presented as a potential threat to “vaccine confidence”. We observed no differences regardless of study population, methodology, or other study characteristics. Limitations are discussed. Conclusions: Neglecting or dismissing vaccine recipients’ safety concerns contributes to the problem that research on COVID-19 VH purports to address. It also undermines the implementation of informed consent, critical to ethical medical and public health research, policy, and practice. The scant attention to bioethical considerations in current COVID-19 VH research is concerning.
  🖺 Full Text HTML: The balance of risks and benefits in the COVID-19 “vaccine hesitancy” literature: An umbrella review
• SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2 -
  SARS-CoV-2 interferes with antigen presentation by downregulating MHC II on antigen presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. This downregulation of CIITA is independent of NSP5’s proteolytic activity, and rather, NSP5 delivers HDAC2 to the CIITA promoter via an IRF3-dependent mechanism. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 can limit MHC II expression, thereby delaying or weakening the subsequent adaptive immune response.
  🖺 Full Text HTML: SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2
• The airborne transmission of viruses causes tight transmission bottlenecks -
  The transmission bottleneck describes the number of viral particles that found an infection in a new host. Previous studies have used genome sequence data to suggest that transmission bottlenecks for influenza and SARS-CoV-2 involve few viral particles, but the general principles underlying these bottlenecks are not fully understood. Here we show that, across a broad range of circumstances, tight transmission bottlenecks arise as a consequence of the physical process underlying airborne viral transmission. We use a mathematical model to describe the process of infectious particles being emitted by an infected individual and inhaled by others nearby. The extent to which exposure to particles translates into infection is determined by an effective viral load, which is calculated as a function of the epidemiological parameter R0. Across multiple scenarios, including those present at a superspreading event, our model suggests that the great majority of transmission bottlenecks involve few viral particles, with a high proportion of infections being caused by a single viral particle. Our results provide a physical explanation for previous inferences of bottleneck size and predict that tight transmission bottlenecks prevail more generally in respiratory virus transmission.
  🖺 Full Text HTML: The airborne transmission of viruses causes tight transmission bottlenecks
• SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes -
  Splicing is a highly conserved, intricate mechanism intimately linked to transcription elongation, serving as a pivotal regulator of gene expression. Alternative splicing may generate specific transcripts incapable of undergoing translation into proteins, designated as unproductive. A plethora of respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), strategically manipulate the host’s splicing machinery to circumvent antiviral responses. During the infection, SARS-CoV-2 effectively suppresses interferon (IFN) expression, leading to B cell and CD8+ T cell leukopenia, while simultaneously increasing the presence of macrophages and neutrophils in patients with severe COVID-19. In this study, we integrated publicly available omics datasets to systematically analyze transcripts at the isoform level and delineate the nascent-peptide translatome landscapes of SARS-CoV-2-infected human cells. Our findings reveal a hitherto uncharacterized mechanism whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling genes, interferon-stimulated genes (ISGs), class I MHC genes, and splicing machinery genes, including IRF7, OAS3, HLA-B, and HNRNPH1. In stark contrast, cytokine and chemokine genes, such as IL6, CXCL8, and TNF, predominantly express productive (protein-coding) splicing isoforms in response to SARS-CoV-2 infection. We postulate that SARS-CoV-2 employs a previously unreported tactic of exploiting the host splicing machinery to bolster viral replication and subvert the immune response by selectively upregulating unproductive splicing isoforms from antigen presentation and antiviral response genes. Our study sheds new light on the molecular interplay between SARS-CoV-2 and the host immune system, offering a foundation for the development of novel therapeutic strategies to combat COVID-19.
  🖺 Full Text HTML: SARS-CoV-2 selectively induces the expression of unproductive splicing isoforms of interferon, class I MHC and splicing machinery genes
• The impact of COVID-19 lockdown on postpartum mothers in London, England: An online focus group study -
  Aims: The postpartum/postnatal period is widely acknowledged as a time when mothers require greater levels of support from multiple sources. However, stay-at-home orders commonly known as “lockdown” deployed in some countries to limit COVID-19 transmission reduced access to support. In England, many postpartum mothers navigated household isolation under intensive mothering and expert parenting culture. Examining the impact of lockdown may reveal strengths and weaknesses in current policy and practice, revealing opportunities to improve maternal experience and wellbeing. Subject and Methods: We conducted an online focus group involving 20 mothers living in London, England, with “lockdown babies,” following up on our earlier survey on social support and maternal wellbeing. We thematically analysed focus group transcripts, and identified key themes around Lockdown Experience and Determinants of Lockdown Experience. Results: Participants raised some positives of lockdown, including fostering connections and protection from external expectations, but also raised many negatives, including social isolation, institutional abandonment, and intense relationships within the household. Potential reasons behind variations in lockdown experience include physical environments, timing of birth, and number of children. Our findings reflect how current systems may be “trapping” some families into the male-breadwinner/female-caregiver family model, while intensive mothering and expert parenting culture may be increasing maternal stress and undermining responsive mothering. Conclusions: Facilitating partners to stay at home during the postpartum period and establishing peer/community support instead of reliance on professionals may promote positive postpartum maternal experience and wellbeing.
  🖺 Full Text HTML: The impact of COVID-19 lockdown on postpartum mothers in London, England: An online focus group study
• Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model -
  Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.
  🖺 Full Text HTML: Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model
• SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition -
  A significant proportion of patients with SARS-CoV-2 infection develop lingering symptoms for months, even years after their infection, a condition now known as Post-COVID Condition (PCC). The underlying pathophysiology of PCC is not known. The wide spectrum of symptoms encompassing various organ systems and the detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be associated with aberrant immune response to the viral antigens. Here, we studied the antibody and B cell responses to the spike protein and the RBD domain in PCC patients who experienced mild COVID-19 disease during the early stages of COVID-19 pandemic in the pre-vaccination era. Our results suggest that the immune responses to the spike antigen may be altered in those who develop PCC.
  🖺 Full Text HTML: SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

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

• Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19 - Condition:   Omicron Variant of COVID-19
  Intervention:   Drug: Nirmatrelvir/Ritonavir
  Sponsor:   Xiangao Jiang
  Completed

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

• To Evaluate the Safety and Efficacy of Meplazumab in Treatment of COVID-19 Sequelae - Condition:   COVID-19
  Interventions:   Biological: Meplazumab for injection;   Other: Normal saline
  Sponsor:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
  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

• Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes. - Condition:   COVID-19
  Interventions:   Biological: SCB-2019/Clover;   Biological: AstraZeneca/Fiocruz;   Biological: Pfizer/Wyeth
  Sponsors:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation
  Active, not 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

• 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

• 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

• 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

• Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome - Condition:   Post-COVID-19 Syndrome
  Intervention:   Dietary Supplement: PS23 heat-treated
  Sponsors:   Mackay Memorial Hospital;   Bened Biomedical Co., Ltd.
  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

• 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

From PubMed

• SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors - Virus entry into animal cells is initiated by attachment to target macromolecules located on host cells. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) trimeric spike glycoprotein targets host angiotensin converting enzyme 2 to gain cellular access. The SARS-CoV-2 glycoprotein contains a neurotoxin-like region that has sequence similarities to the rabies virus and the human immunodeficiency virus glycoproteins, as well as to snake neurotoxins, which interact with nicotinic…

• Pathological angiogenesis: mechanisms and therapeutic strategies - In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and…

• A universal fluorescence polarization high throughput screening assay to target the SAM-binding sites of SARS-CoV-2 and other viral methyltransferases - AbstractSARS-CoV-2 has caused a global pandemic with significant humanity and economic loss since 2020. Currently, only limited options are available to treat SARS-CoV-2 infections for vulnerable populations. In this study, we report a universal fluorescence polarization (FP)-based high throughput screening (HTS) assay for SAM-dependent viral methyltransferases (MTases), using a fluorescent SAM-analog, FL-NAH. We performed the assay against a reference MTase, NSP14, an essential enzyme for…

• Synthesis, cytotoxicity, and pharmacokinetic evaluations of niclosamide analogs for anti-SARS-CoV-2 - Niclosamide, an oral anthelmintic drug, could inhibit SARS-CoV-2 virus replication through autophagy induction, but high cytotoxicity and poor oral bioavailability limited its application. Twenty-three niclosamide analogs were designed and synthesized, of which compound 21 was found to exhibit the best anti-SARS-CoV-2 efficacy (EC(50) = 1.00 μM for 24 h), lower cytotoxicity (CC(50) = 4.73 μM for 48 h), better pharmacokinetic, and it was also well tolerated in the sub-acute toxicity study in…

• Characterization of the induction kinetics and antiviral functions of IRF1, ISG15 and ISG20 in cells infected with gammacoronavirus avian infectious bronchitis virus - Coronavirus infection induces a variety of cellular antiviral responses either dependent on or independent of type I interferons (IFNs). Our previous studies using Affymetrix microarray and transcriptomic analysis revealed the differential induction of three IFN-stimulated genes (ISGs), IRF1, ISG15 and ISG20, by gammacoronavirus infectious bronchitis virus (IBV) infection of IFN-deficient Vero cells and IFN-competent, p53-defcient H1299 cells, respectively. In this report, the induction kinetics…

• In-silico approaches for identification of compounds inhibiting SARS-CoV-2 3CL protease - The world has witnessed of many pandemic waves of SARS-CoV-2. However, the incidence of SARS-CoV-2 infection has now declined but the novel variant and responsible cases has been observed globally. Most of the world population has received the vaccinations, but the immune response against COVID-19 is not long-lasting, which may cause new outbreaks. A highly efficient pharmaceutical molecule is desperately needed in these circumstances. In the present study, a potent natural compound that could…

• AI-Driven Discovery of SARS-CoV-2 Main Protease Fragment-like Inhibitors with Antiviral Activity In Vitro - SARS-CoV-2 is the causative agent of COVID-19 and is responsible for the current global pandemic. The viral genome contains 5 major open reading frames of which the largest ORF1ab codes for two polyproteins, pp1ab and pp1a, which are subsequently cleaved into 16 nonstructural proteins (nsp) by two viral cysteine proteases encoded within the polyproteins. The main protease (Mpro, nsp5) cleaves the majority of the nsp’s, making it essential for viral replication and has been successfully targeted…

• Inhaled Lipid Nanoparticles Alleviate Established Pulmonary Fibrosis - Pulmonary fibrosis, a sequela of lung injury resulting from severe infection such as severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) infection, is a kind of life-threatening lung disease with limited therapeutic options. Herein, inhalable liposomes encapsulating metformin, a first-line antidiabetic drug that has been reported to effectively reverse pulmonary fibrosis by modulating multiple metabolic pathways, and nintedanib, a well-known antifibrotic drug that has been widely…

• Molecular insights into the inhibition mechanism of harringtonine against essential proteins associated with SARS-CoV-2 entry - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently posed a serious threat to global public health. Harringtonine (HT), as a small-molecule antagonist, has antiviral activity against a variety of viruses. There is evidence that HT can inhibit the SARS-CoV-2 entry into host cells by blocking the Spike protein and transmembrane protease serine 2 (TMPRSS2). However, the molecular mechanism underlying the inhibition effect of HT is largely elusive. Here, docking and all-atom…

• Neutralization of the new coronavirus by extracting their spikes using engineered liposomes - The devastating COVID-19 pandemic motivates the development of safe and effective antivirals to reduce morbidity and mortality associated with infection. We developed nanoscale liposomes that are coated with the cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Lentiviral particles pseudotyped with the spike protein of SARS-CoV-2 were constructed and used to test the virus neutralization potential of the engineered liposomes. Under…

• 3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents - Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence of cardiovascular diseases and coagulopathies that accompany cancer and COVID-19. Enzymatic assay identified novel GSK3β inhibitors in a series of 3-arylidene-2-oxindole derivatives. Considering the putative role of GSK3β in platelet activation, the most active compounds were evaluated for antiplatelet activity and antithrombotic activity. It was found that GSK3β inhibition by…

• Sphingosine Kinases Promote Ebola Virus Infection and Can Be Targeted to Inhibit Filoviruses, Coronaviruses, and Arenaviruses Using Late Endocytic Trafficking to Enter Cells - Entry of enveloped viruses in host cells requires the fusion of viral and host cell membranes, a process that is facilitated by viral fusion proteins protruding from the viral envelope. These viral fusion proteins need to be triggered by host factors, and for some viruses, this event occurs inside endosomes and/or lysosomes. Consequently, these ‘late-penetrating viruses’ must be internalized and delivered to entry-conducive intracellular vesicles. Because endocytosis and vesicular trafficking…

• Low Peripheral B-Cell Counts in Patients With Systemic Rheumatic Diseases Due to Treatment With Belimumab and/or Rituximab Are Associated With Low Antibody Responses to Primary COVID-19 Vaccination - Background: Immunosuppressive agents inhibit COVID-19 vaccine antibody (Ab) responses in patients with systemic rheumatic diseases. Rituximab may fully block Ab responses when B cells become undetected. The effect of detected but low number of B cells due to treatment with a B-cell agent (belimumab and/or rituximab) has not been established. Purpose: We sought to examine whether there is an association between a low number of B cells due to treatment with belimumab and/or rituximab and impaired…

• Impulsive Neural Control to Schedule Antivirals and Immunomodulators for COVID-19 - New SARS-CoV-2 variants escaping the effect of vaccines are an eminent threat. The use of antivirals to inhibit the viral replication cycle or immunomodulators to regulate host immune responses can help to tackle the viral infection at the host level. To evaluate the potential use of these therapies, we propose the application of an inverse optimal neural controller to a mathematical model that represents SARS-CoV-2 dynamics in the host. Antiviral effects and immune responses are considered as…

• Anti-SARS-CoV-2 Activity of Ampelozizyphus amazonicus (Saracura-Mirá): Focus on the Modulation of the Spike-ACE2 Interaction by Chemically Characterized Bark Extracts by LC-DAD-APCI-MS/MS - Traditional medicine shows several treatment protocols for COVID-19 based on natural products, revealing its potential as a possible source of anti-SARS-CoV-2 agents. Ampelozizyphus amazonicus is popularly used in the Brazilian Amazon as a fortifier and tonic, and recently, it has been reported to relieve COVID-19 symptoms. This work aimed to investigate the antiviral potential of A. amazonicus, focusing on the inhibition of spike and ACE2 receptor interaction, a key step in successful…

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