Covid-19 Sentry

Contents

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

From Preprints

• Infection Prevention and Control in Residential Aged Care Facilities In and Out of Recent Pandemics: A Scoping Review Protocol -
  Abstract Background The longstanding problem of infection prevention and control (IPC) in residential aged care facilities (RACFs) has been highlighted and seriously exacerbated by the COVID-19 pandemic. The risk of severe illness and death from COVID-19 among aged care residents is increased by age, comorbidities and the congregate living arrangements, which often also function as healthcare settings. Implementation of IPC practices are intended to protect residents and staff from infectious disease risks, but can also impact on other dimensions of wellbeing and safety. Objectives To identify evidence of effective IPC strategies in RACFs and their impacts on resident or staff safety or wellbeing, during both ‘business as usual’ and infectious disease outbreaks. Methods We will search relevant databases for original research articles, published in 2000 or later, that examine (1) IPC measures and/or (2) infectious disease outbreaks in (3) in residential aged care settings, whilst (4) considering resident and/or staff wellbeing and/or safety. Following Preferred Reporting of Systematic Review and Meta-Analysis for Scoping Reviews (PRISMA-SCR) and consultation with a university librarian, we have devised a search strategy for review of relevant key articles. One author customised the search strategy for each database (CINAHL, Embase, Cochrane, MEDLINE, Scopus and Web of Science) and reviewed each term before inclusion. After deletion of duplicates, 2-4 reviewers will screen references by title and abstract, then review full texts of selected articles. Items included will be charted with respect to publication details and quality assessment performed. Results will be grouped according to thematic contributions. Results Systematic searches began at the end of 2021 and data extraction will progress in early 2022, followed by data analyses and writing. Anticipated conclusions Implementation of IPC practices in RACFs must balance effectiveness, feasibility, and wellbeing and safety of residents and staff. This review will summarise, and identify gaps in, evidence for how best to protect residents and staff from infection in long term aged care settings. Support Partial financial support for this project has been provided by the Sydney Institute for Infectious Diseases, University of Sydney.
  🖺 Full Text HTML: Infection Prevention and Control in Residential Aged Care Facilities In and Out of Recent Pandemics: A Scoping Review Protocol
• Exploring psychosocial impacts of COVID-19 mandates in children with and without autism spectrum disorder -
  Children with autism spectrum disorder (ASD) are particularly at risk for adverse psychosocial consequences as a result of unexpected challenges such as the COVID-19 pandemic. These children experience a higher prevalence of depression and anxiety, difficulties with cognitive flexibility, and a reduction in support services during the pandemic. Higher executive function (EF) has been previously found to be protective against negative mental health outcomes. Here we probed the psychosocial impacts of pandemic responses in children with ASD by relating pre-pandemic (EF) measures with mental health outcomes measured several months into the pandemic. We found that pre-existing inhibition and shift difficulties measured by the Behavior Rating Inventory of Executive Function predicted higher risk of anxiety symptoms, with shift difficulties also predicting elevated depressive symptoms during the pandemic. These findings are critical for promoting community recovery and maximizing clinical preparedness to support children at increased risk for adverse psychosocial outcomes.
  🖺 Full Text HTML: Exploring psychosocial impacts of COVID-19 mandates in children with and without autism spectrum disorder
• Pin-pointing the key hubs in the IFN-gamma pathway responding to SARS-CoV-2 infection -

  Interferon gamma may be a potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-gamma pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2 positive and negative patients, we identified IFN-gamma-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1 and JAK2 in COVID-19 positive vs. negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient9s viral load. Expression of MX1, MX2, ISG15 and OAS1 (4 well-known IFN-stimulated genes (ISGs)) displayed upregulation in COVID-19 positive vs. negative patients. Integrative analyses showcased higher levels of ISGs which were associated with increased viral load and STAT1/JAK2 expression. Confirmation of ISGs up-regulation was performed in vitro using the A549 lung cell line treated with Poly(I:C), a synthetic analog of viral double-stranded RNA; and in different pulmonary human cell lines and ferret tracheal biopsies infected with SARS-CoV-2. A pre-clinical murine model of coronavirus infection confirmed findings displaying increased ISGs in the liver and lungs from infected mice. Altogether, these results demonstrate the role of IFN-gamma and ISGs in response to SARS-CoV-2 infection, highlighting alternative druggable targets that can boost the host response.

  🖺 Full Text HTML: Pin-pointing the key hubs in the IFN-gamma pathway responding to SARS-CoV-2 infection
• Cervical cancer screening improvements with self- sampling during the COVID-19 pandemic -

  Background<br />At the onset of the COVID-19 pandemic cervical screening in the capital region of Sweden was cancelled for several months. A series of measures to preserve and improve the cervical screening under the circumstances were instituted, including a switch to screening with HPV self-sampling to enable screening in compliance with social distancing recommendations.<br />Methods<br />We describe the major changes implemented, which were i) nationwide implementation of HPV screening ii) switch to primary self-sampling instead of clinician sampling iii) implementation of HPV screening in all screening ages and iv) combined HPV vaccination and HPV screening in the cervical screening program.<br />Results<br />A temporary government regulation allowed primary self-sampling with HPV screening in all ages. In the Stockholm region, 330,000 self-sampling kits were sent to the home address of screening-eligible women, instead of an invitation to clinician sampling. A dramatic increase in population test coverage was seen (from 75% to 85% in just one year). In addition, a national campaign for faster elimination of cervical cancer with concomitant screening and vaccination for women in ages 23- 28 was launched.<br />Conclusions<br />The COVID-19 pandemic necessitated major changes in the cervical cancer preventive strategies, where it can already be concluded that the strategy with organised primary self-sampling for HPV has resulted in a major improvement of population test-coverage.<br />Funding<br />Funded by the Swedish Association 44 of Local Authorities and Regions, the Swedish Cancer Society, the European Union’s Horizon 2020 Research and Innovation Program, the Swedish government and the Stockholm county.

  🖺 Full Text HTML: Cervical cancer screening improvements with self- sampling during the COVID-19 pandemic
• Lost in pandemic time: A phenomenological analysis of temporal disorientation during the Covid-19 crisis -
  People have experienced many forms of temporal disorientation during the Covid-19 crisis. For this study, we collected a rich corpus of reports on the multifaceted experiences of disorientation during the pandemic. In this paper, we study the resulting corpus using a descriptive approach. We identify six emerging themes: temporal rift; temporal vertigo; impoverished time; tunnel vision; spatial and social scaffolding of time; suspended time. We offer a phenomenological analysis of each of the themes. Based on the phenomenological analysis, we draw a key distinction between episodic and existential forms of temporal disorientation, and we argue that the Covid-19 crisis is best conceptualised as a period of suspended time.
  🖺 Full Text HTML: Lost in pandemic time: A phenomenological analysis of temporal disorientation during the Covid-19 crisis
• Bereavement during lockdown: The potential impact of COVID-19 restrictions on grief and post-traumatic stress disorder in a Turkish population -
  The current study examined whether perceived disruption to bereavement via suppression of sociocultural death rite traditions could be linked to core bereavement and post-traumatic stress disorder (PTSD) symptoms in Turkish individuals who lost their close relatives to COVID-19. The sample included patients who consulted the clinic, presenting with self-reported bereavement issues related to coping, sleep, and eating, as well as individuals who sought general grief counselling. Participants (n=52) completed a Demographic Information and Bereavement Experience (DIBEF) form with items probing participants’ demographics, experience of attending rituals, and receiving social support. The final item inquired the rating of perceived disruption to bereavement due to COVID-19 restrictions (perceived disruption score-PDS). The Core Bereavement Items (CBI) scale and the Post-traumatic Stress Disorder Checklist-Civilian Version (PCL-C) were also used to measure symptomology. The results revealed that 92.3% of the participants did not receive condolence visitors, 98.1% did not get to say goodbye, and 78.8% were unable to practice their religious duties. Regression analysis suggested that PDS was a significant predictor of the CBI scores while it was not associated with PCL-C scores. The potential role of perceived disruption to bereavement in aggravating the grief response is discussed regarding the dual process model of coping with bereavement. Health authorities should thus introduce additional support mechanisms such as technology-based grief counselling, tailored to cultural values and individual needs. Relevant bodies should also ensure the accessibility of virtual platforms through which individuals could connect with others and participate in rituals during future pandemics or other humanitarian crises.
  🖺 Full Text HTML: Bereavement during lockdown: The potential impact of COVID-19 restrictions on grief and post-traumatic stress disorder in a Turkish population
• Specific pandemic-related worries predict higher attention-related errors and negative affect independent of trait anxiety -
  Recent surveys have revealed a rise in anxiety levels, in response to the COVID-19 pandemic. Based on cognitive-emotional models of anxiety, we predict this increase may be underpinned by pandemic-related worry (PRW), characterised by repetitive negative thinking about pandemic-specific outcomes. We also predicted that PRW would occupy limited capacity cognitive resources required for attentional control, needed for the regulation of worry. We developed a novel instrument to measure the contents of PRW, and to explore its independent relationship with cognitive functioning and negative affect. A five-factor model of PRW was identified in Study 1 (N = 255) and validated in Study 2 (N = 382). In Study 2, regression analyses revealed that worries about the declining quality of life and the probability of COVID-19 infection were the strongest predictors of attention and memory-related errors. We also found that attention-related errors partially mediated the positive relationship between PRW and negative affect. Importantly, all analyses remained significant when controlling for recalled pre-pandemic trait anxiety and worry, suggesting that the relationships reflected elevated anxiety even in those with low levels of trait anxiety. The findings suggest that to support psychological wellbeing in the wake of the COVID-19 pandemic, support should target specific PRWs.
  🖺 Full Text HTML: Specific pandemic-related worries predict higher attention-related errors and negative affect independent of trait anxiety
• COVID-19 vaccine effectiveness against mortality and risk of death from other causes after COVID-19 vaccination, the Netherlands, January 2021- January 2022 -

  Background: We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk in non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. Methods: National registries of causes of death, COVID-19 vaccination and long-term care reimbursements were linked by a unique identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 8 weeks following a first, second or booster dose, adjusting for birth year, sex and country of origin. Results: VE against COVID-19 mortality was >90% for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80% at 7-8 months post-primary series for most groups, and around 60% for elderly receiving a high level of long-term care and for people aged 90+ years. The risk of non-COVID-19 mortality was lower or similar in the 8 weeks following a first booster dose compared to no vaccination, first or second dose, respectively, for all age and long-term care groups. Conclusion: COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was seen at the population level.

  🖺 Full Text HTML: COVID-19 vaccine effectiveness against mortality and risk of death from other causes after COVID-19 vaccination, the Netherlands, January 2021- January 2022
• Learning from pre-pandemic data to forecast viral antibody escape -
  From early detection of variants of concern to vaccine and therapeutic design, pandemic preparedness depends on identifying viral mutations that escape the response of the host immune system. While experimental scans are useful for quantifying escape potential, they remain laborious and impractical for exploring the combinatorial space of mutations. Here we introduce a biologically grounded model to quantify the viral escape potential of mutations at scale. Our method - EVEscape - brings together fitness predictions from evolutionary models, structure-based features that assess antibody binding potential, and distances between mutated and wild-type residues. Unlike other models that predict variants of concern based on newly observed variants, EVEscape has no reliance on recent community prevalence, and is applicable before surveillance sequencing or experimental scans are broadly available. We validate EVEscape predictions against experimental data on H1N1, HIV and SARS-CoV-2, including data on immune escape. For SARS-CoV-2, we show that EVEscape anticipates mutation frequency, strain prevalence, and escape mutations. Drawing from GISAID, we provide continually updated escape predictions for all current strains of SARS-CoV-2.
  🖺 Full Text HTML: Learning from pre-pandemic data to forecast viral antibody escape
• A linear DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain elicits protective immunity in domestic cats -
  Since its first detection in China in late 2019, SARS-CoV-2, the etiologic agent of COVID-19 pandemic, has infected a wide range of animal species, especially mammals, all over the world. Indeed, as reported by the American Veterinary Medical Association, besides human-to-human transmission, human-to-animal transmission has been observed in some wild animals and pets, especially in cats. With animal models as an invaluable tool in the study of infectious diseases combined with the fact that the intermediate animal source of SARS-CoV-2 is still unknown, researchers have demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species. Here, we show results from a randomized Phase I/II clinical study conducted in domestic cats to assess safety and immunogenicity of a linear DNA (linDNA) vaccine encoding the RBD domain of SARS-CoV-2. No significant adverse events occurred and both RBD-specific binding/neutralizing antibodies and T cells were detected. These findings demonstrate the safety and immunogenicity of a genetic vaccine against COVID-19 administered to cats and strongly support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans.
  🖺 Full Text HTML: A linear DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain elicits protective immunity in domestic cats
• Durability of the Neutralizing Antibody Response to mRNA Booster Vaccination Against SARS-CoV-2 BA.2.12.1 and BA.4/5 Variants -
  The recent emergence of the SARS-CoV-2 BA.4/5 and BA.2.12.1 variants has led to rising COVID-19 case numbers and concerns over the continued efficacy of mRNA booster vaccination. Here we examine the durability of neutralizing antibody (nAb) responses against these SARS-CoV-2 Omicron subvariants in a cohort of health care workers 1-40 weeks after mRNA booster dose administration. Neutralizing antibody titers fell by ~1.5-fold 4-6 months and by ~2.5-fold 7-9 months after booster dose, with average nAb titers falling by 11-15% every 30 days, far more stable than two dose induced immunity. Notably, nAb titers from booster recipients against SARS-CoV-2 BA.1, BA.2.12.1, and BA.4/5 variants were ~4.7-, 7.6-, and 13.4-fold lower than against the ancestral D614G spike. However, the rate of waning of booster dose immunity was comparable across variants. Importantly, individuals reporting prior infection with SARS-CoV-2 exhibited significantly higher nAb titers compared to those without breakthrough infection. Collectively, these results highlight the broad and stable neutralizing antibody response induced by mRNA booster dose administration, implicating a significant role of virus evolution to evade nAb specificity, versus waning humoral immunity, in increasing rates of breakthrough infection.
  🖺 Full Text HTML: Durability of the Neutralizing Antibody Response to mRNA Booster Vaccination Against SARS-CoV-2 BA.2.12.1 and BA.4/5 Variants
• Estimating the time-varying reproduction number for COVID-19 in South Africa during the first four waves using multiple measures of incidence for public and private sectors across four waves -

  Objectives We aimed to quantify transmission trends in South Africa during the first four waves of the COVID-19 pandemic using estimates of the time-varying reproduction number (R) and to compare the robustness of R estimates based on three different data sources and using data from public and private sector service providers. Methods We estimated R from March 2020 through April 2022, nationally and by province, based on time series of rt-PCR-confirmed cases, hospitalizations, and hospital-associated deaths, using a method which models daily incidence as a weighted sum of past incidence. We also estimated R separately using public and private sector data. Results Nationally, the maximum case-based R following the introduction of lockdown measures was 1.55 (CI: 1.43-1.66), 1.56 (CI: 1.47-1.64), 1.46 (CI: 1.38-1.53) and 3.33 (CI: 2.84-3.97) during the first (Wuhan-Hu), second (Beta), third (Delta), and fourth (Omicron) waves respectively. Estimates based on the three data sources (cases, hospitalisations, deaths) were generally similar during the first three waves but cases-based estimates were higher during the fourth wave. Public and private sector R estimates were generally similar except during the initial lockdowns and in case-based estimates during the fourth wave. Discussion Agreement between R estimates using different data sources during the first three waves suggests data from any of these sources could be used in early stages of a future pandemic. High R estimates for Omicron relative to earlier waves is interesting given a high level of exposure pre-Omicron. The agreement between public and private sector R estimates highlights the fact that clients of the public and private sectors did not experience two separate epidemics, except perhaps to a limited extent during the strictest lockdowns during the first wave.

  🖺 Full Text HTML: Estimating the time-varying reproduction number for COVID-19 in South Africa during the first four waves using multiple measures of incidence for public and private sectors across four waves
• Years of Life Lost in the US During the COVID-19 Pandemic, March 2020 to October 2021 -

  Background Given a downward age shift in COVID-19-involved deaths observed during the COVID-19 pandemic, we sought to estimate years of life lost (YLL) associated with leading causes of US death during the first 20 months of the pandemic. Findings Despite 4796 fewer COVID-19 deaths in Jan-Oct 2021 than in Mar-Dec 2020, the number of YLL due to COVID-19 increased by 1,159,761, from 4,474,186 to 5,633,947 (a 25.9% increase). YLL per COVID-19 death increased from 12.8 in 2020 to 16.3 in 2021, a 27.7% increase. YLL per death did not change by more than 2.3% for any other cause. Interpretation Increased YLL per COVID-19 death in 2021 result from younger-age COVID-19 mortality, contributing to a marked increase in YLL from this preventable cause of death at a later stage of the pandemic despite advancements in vaccines in treatments.

  🖺 Full Text HTML: Years of Life Lost in the US During the COVID-19 Pandemic, March 2020 to October 2021
• Early COVID-19 Pandemic Response in Western Visayas, Philippines -

  The COVID-19 pandemic has burdened the public health system in the Philippines since January 2020. In Western Visayas (Region 6), Philippines, issues have been raised on the limitations of the government’s response on testing, contact tracing, and augmentation of healthcare facilities. Using data from the Western Visayas - Regional Epidemiologic Surveillance Unit (WV - RESU) from March 20 – June 20, 2020, the following observations were made: 1) Of the 6 provinces, Iloilo had the highest % tests done per capita which may be linked to the presence of the only regional COVID-19 testing facility in the province at that time, 2) There were delays in the overall processing times for specimens from Antique and Negros Occidental which may be linked to transport logistics and/or laboratory processing, 3) Contact tracing and testing were de-linked – tracing was adequate (3,420/3,503, 97.63%), but less than 50% of these (1,668/3,420) were tested, 4) Hospital and quarantine facility capacities were still adequate, but their utilization rates needed to be monitored continuously for further augmentation, if needed. This data shows the challenges of establishing a pandemic response in one of the regions in the Philippines.

  🖺 Full Text HTML: Early COVID-19 Pandemic Response in Western Visayas, Philippines
• Active safety surveillance of COVID-19 mRNA vaccines in children aged 5-15 years in Australia -

  AusVaxSafety (the Australian active safety surveillance system) used SMS/email delivered surveys to actively solicit the short-term (within first 3 days after vaccination) adverse event profile of mRNA COVID-19 vaccines in children (aged 5-15 years) by age, dose, brand and pre-existing comorbidity. 392,268 survey responses for children aged 5-15 who received a COVID-19 vaccine between July 2021 and May 2022 (211,994 following BNT162b2 10mcg in children aged 5-11 years, 173,329 following BNT162b2 30mcg and 6,945 following mRNA-1273 100mcg in adolescents aged 12-15 years) were analysed. Adverse event rates were higher following dose 2 and 3 compared to dose 1 after all vaccines and highest following dose 2 of mRNA-1273 in 12-15 years. Fever was low in the youngest children (5 years old, any dose; 1,090/26,181 (4%)). Medical review rates remained low (0.3% overall) and impact on daily activities was also low (7% overall). No self-reported cases of myocarditis or pericarditis were identified. Ongoing active safety surveillance of lower dose mRNA vaccines in children under 5 years old is required to better understand safety as the vaccines roll out into this population age-group.

  🖺 Full Text HTML: Active safety surveillance of COVID-19 mRNA vaccines in children aged 5-15 years in Australia

From Clinical Trials

• Puerto Rico COVID-19 Vaccine Uptake Study - Condition:   COVID-19
  Intervention:   Other: Educational intervention
  Sponsors:   University of Puerto Rico;   National Institutes of Health (NIH);   National Institute on Minority Health and Health Disparities (NIMHD)
  Recruiting

• Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity - Condition:   COVID-19
  Intervention:   Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors
  Sponsor:   Central Hospital, Nancy, France
  Not yet recruiting

• Beta-glucans for Hospitalised Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MC 3x3;   Drug: Placebo
  Sponsors:   Concentra Educacion e Investigación Biomédica;   Wohlstand Pharmaceutical
  Not yet recruiting

• A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa - Condition:   COVID-19
  Intervention:   Drug: Molnupiravir 200 mg
  Sponsors:   University of Witwatersrand, South Africa;   Bill and Melinda Gates Foundation
  Not yet recruiting

• **NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Placebo;   Drug: Experimental drug
  Sponsor:   Medesis Pharma SA
  Recruiting

• Safety and Immunogenicity of Recombinant COVID-19 Vaccine (Sf9 Cell) as a Booster - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: Recombinant COVID-19 Vaccine (Sf9 Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsor:   WestVac Biopharma Co., Ltd.
  Recruiting

• Safety and Immunogenicity of Recombinant COVID-19 Variant Vaccine (Sf9 Cell) as a Booster - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: Recombinant COVID-19 variant Vaccine (Sf9 Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: mRNA COVID-19 vaccine (Moderna);   Biological: Viral Vector COVID-19 vaccine (AstraZeneca)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention - Condition:   Post-acute COVID-19 Syndrome
  Intervention:   Behavioral: PACS Coping and Recovery (PACS-CR) Intervention
  Sponsor:   VA Office of Research and Development
  Not yet recruiting

• Mineralocorticoid Use in COVID-19 Patients - Conditions:   COVID-19;   ARDS
  Intervention:   Drug: Fludrocortisone Acetate 0.1 MG
  Sponsor:   Ain Shams University
  Completed

• An Observer-blind, Cohort Randomized, Exploratory Phase 3 Study to Evaluate the Safety and Immunogenicity of Recombinant Covid-19 Vaccine, mRNA Covid-19 Vaccine and Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine as 4th Dose in Individuals Primed/ Boosted With Various Regimens - Condition:   COVID-19
  Interventions:   Biological: AstraZeneca/Fiocruz;   Biological: Pfizer/Wyeth;   Biological: Clover SCB-2019
  Sponsors:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation;   University of Oxford
  Not yet recruiting

• Xanthohumol as an Adjuvant Therapy in Critically Ill COVID-19 Patients - Condition:   COVID-19 Respiratory Infection
  Intervention:   Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/
  Sponsor:   Medical University of Lublin
  Suspended

• A Clinical Trial of Immuno-bridging Between Different Manufacture Scales of Recombinant COVID-19 Vaccine (Sf9 Cell) - Conditions:   COVID-19;   SARS-CoV-2 Pneumonia
  Intervention:   Biological: Recombinant COVID-19 vaccine (Sf9 cell)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects - Condition:   COVID-19
  Intervention:   Combination Product: Delcetravir dry powder inhaler
  Sponsor:   Esfam Biotech Pty Ltd
  Not yet recruiting

• Physiotherapy for Persistent COVID-19 Disease Using Aerobic Exercise - Conditions:   COVID-19;   Genetic Predisposition to Disease
  Interventions:   Device: Experimental;   Genetic: Control
  Sponsors:   Universidad Francisco de Vitoria;   Universidad Rey Juan Carlos
  Completed

• Passive Antibodies Against COVID-19 With EVUSHELD in Vaccine Non-responsive CLL - Conditions:   Chronic Lymphocytic Leukemia;   COVID-19
  Intervention:   Biological: EVUSHELD
  Sponsors:   Sunnybrook Health Sciences Centre;   AstraZeneca
  Not yet recruiting

From PubMed

• SARS-CoV-2 triggers pericyte-mediated cerebral capillary constriction - The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7). In brain slices from hamster, which has an ACE2 sequence similar to human ACE2, angiotensin II evoked a small pericyte-mediated capillary constriction via AT1 receptors, but evoked a large constriction when the SARS-CoV-2 receptor binding domain (RBD, original Wuhan…

• Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV‑2 papain-like protease - The coronavirus papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for viral polypeptide cleavage and the deISGylation of interferon-stimulated gene 15 (ISG15), which enable it to participate in virus replication and host innate immune pathways. Therefore, PLpro is considered an attractive antiviral drug target. Here, we show that parthenolide, a germacrane sesquiterpene lactone, has SARS-CoV-2 PLpro inhibitory activity. Parthenolide…

• PTP1B inhibitors protect against acute lung injury and regulate CXCR4 signaling in neutrophils - Acute lung injury (ALI) can cause acute respiratory distress syndrome (ARDS), a lethal condition with limited treatment options and currently a common global cause of death due to COVID-19. ARDS secondary to transfusion-related ALI (TRALI) has been recapitulated preclinically by anti-MHC-I antibody administration to LPS-primed mice. In this model, we demonstrate that inhibitors of PTP1B, a protein tyrosine phosphatase that regulates signaling pathways of fundamental importance to homeostasis and…

• Secondary metabolites of Livistona decipiens as potential inhibitors of SARS-CoV-2 - In late December 2019, a pandemic coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread all over the globe. One of the promising therapeutic techniques of viral infection is to search for enzyme inhibitors among natural phytochemicals using molecular docking to obtain leads with the least side effects. The COVID-19 virus main protease (M^(pro)) is considered as an attractive target due to its pivotal role in controlling viral transcription and replication. Metabolic profiling of…

• Endothelial Cells as a Key Cell Type for Innate Immunity: A Focused Review on RIG-I Signaling Pathway - The vascular endothelium consists of a highly heterogeneous monolayer of endothelial cells (ECs) which are the primary target for bacterial and viral infections due to EC’s constant and close contact with the bloodstream. Emerging evidence has shown that ECs are a key cell type for innate immunity. Like macrophages, ECs serve as sentinels when sensing invading pathogens or microbial infection caused by viruses and bacteria. It remains elusive how ECs senses danger signals, transduce the signal…

• Application of green synthesised copper iodide particles on cotton fabric-protective face mask material against COVID-19 pandemic - Microorganisms cause variety of diseases that constitutes a severe threat to mankind. Due to the upsurge of many infectious diseases, there is a high requirement and demand for the development of safety products finished with antimicrobial properties. The study involves the antimicrobial activity of natural cotton coated with copper iodide capped with Hibiscus rosa-sinensis L. flower extract (CuI-FE) which is rich in anthocyanin, cyanidin-3-sophoroside by ultrasonication method. The coated and…

• The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative…

• Detection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR - An easily implementable serological assay to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies is urgently needed to better track herd immunity, vaccine efficacy and vaccination rates. Herein, we report the Split-Oligonucleotide Neighboring Inhibition Assay (SONIA) which uses real-time qPCR to measure the ability of neutralizing antibodies to block binding between DNA-barcoded viral spike protein subunit 1 and the human angiotensin-converting…

• SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells - Patients with COVID-19 have high prevalence of albuminuria which is used as a marker of progression of renal disease and is associated with severe COVID-19. We hypothesized that SARS-CoV-2 spike protein (S protein) could modulate albumin handling in proximal tubule epithelial cells (PTECs) and, consequently contribute to the albuminuria observed in patients with COVID-19. In this context, the possible effect of S protein on albumin endocytosis in PTECs was investigated. Two PTEC lines were used:…

• A new circular RNA-encoded protein BIRC6-236aa inhibits transmissible gastroenteritis virus (TGEV)-induced mitochondrial dysfunction - Transmissible gastroenteritis virus (TGEV), a member of the coronavirus family, is the pathogen responsible for transmissible gastroenteritis, which results in mitochondrial dysfunction in host cells. Previously, we identified 123 differentially-expressed (DE) circular RNAs (circRNAs) from the TGEV-infected porcine intestinal epithelial cell line jejunum 2 (IPEC-J2). Previous bioinformatics analysis suggested that, of these, circBIRC6 had the potential to regulate mitochondrial function….

• Discovery of potent benzoxaborole inhibitors against SARS-CoV-2 main and dengue virus proteases - The RNA viruses SARS-CoV-2 and dengue pose a major threat to human health worldwide and their proteases (M^(pro); NS2B/NS3) are considered as promising targets for drug development. We present the synthesis and biological evaluation of novel benzoxaborole inhibitors of these two proteases. The most active compound achieves single-digit micromolar activity against SARS-CoV-2 M^(pro) in a biochemical assay. The most active substance against dengue NS2B/NS3 protease has submicromolar activity in…

• Angiotensin-Converting Enzyme 2 Potentiates SARS-CoV-2 Infection by Antagonizing Type I Interferon Induction and Its Down-Stream Signaling Pathway - The innate interferon (IFN) response constitutes the first line of host defense against viral infections. It has been shown that IFN-I/III treatment could effectively contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. However, how SARS-CoV-2 survives through the innate antiviral mechanism remains to be explored. Our study uncovered that human angiotensin-converting enzyme 2 (ACE2), identified as a primary receptor for SARS-CoV-2 entry, can disturb the…

• A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human…

• New Perspectives on Antimicrobial Agents: Molnupiravir and Nirmatrelvir/Ritonavir for Treatment of COVID-19 - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged to cause pandemic respiratory disease in the past 2 years, leading to significant worldwide morbidity and mortality. At the beginning of the pandemic, only nonspecific treatments were available, but recently two oral antivirals have received emergency use authorization from the U.S. Food and Drug Administration for the treatment of mild to moderate coronavirus disease (COVID-19). Molnupiravir targets the viral polymerase…

• Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells - Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the…

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