Covid-19 Sentry

Contents

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

From Preprints

• A social media-based framework for quantifying temporal changes to wildlife viewing intensity: Case study of sea turtles before and during COVID-19 -
  Documenting how human pressure on wildlife changes over time is important to minimise potential adverse effects through implementing appropriate management and policy actions; however, obtaining objective measures of these changes and their potential impacts is often logistically challenging, particularly in the natural environment. Here, we developed a modular stochastic model that infers the ratio of actual viewing pressure on wildlife in consecutive time periods (years) using social media, as this medium is widespread and easily accessible. Pressure was calculated from the number of times individual animals appeared in social media in pre-defined time windows, accounting for time-dependent variables that influence them (e.g. number of people with access to social media). Formulas for the confidence intervals of viewing pressure ratios were rigorously developed and validated, and corresponding uncertainty was quantified. We applied the developed framework to calculate changes to wildlife viewing pressure on loggerhead sea turtles (Caretta caretta) at Zakynthos island (Greece) before and during the COVID-19 pandemic (2019-2021) based on 2646 social media entries. Our model ensured temporal comparability across years of social media data grouped in time window sizes, by correcting for the interannual increase of social media use. Optimal sizes for these windows were delineated, reducing uncertainty while maintaining high time-scale resolution. The optimal time window was around 7-days during the peak tourist season when more data were available in all three years, and >15 days during the low season. In contrast, raw social media data exhibited clear bias when quantifying changes to viewing pressure, with unknown uncertainty. The framework developed here allows widely-available social media data to be used objectively when quantifying temporal changes to wildlife viewing pressure. Its modularity allowed viewing pressure to be quantified for all data combined, or subsets of data (different groups, situations or locations), and could be applied to any site supporting wildlife exposed to tourism.
  🖺 Full Text HTML: A social media-based framework for quantifying temporal changes to wildlife viewing intensity: Case study of sea turtles before and during COVID-19
• mRNA-based vaccines against SARS-CoV-2 do not stimulate interferon stimulatory gene expression in individuals affected by Aicardi Goutieres Syndrome. -
  The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses threats to individuals with rare disease, in part because so little is known about the impact of COVID-19 infection and vaccination safety in rare disease populations. Of particular concern, given the overlap in disease manifestations and interferon dysregulation, are a group of heritable autoinflammatory conditions called type I interferonopathies. The most common of these, Aicardi Goutieres Syndrome (AGS), is caused by altered nucleic acid metabolism and sensing, resulting in additional concerns surrounding the use of mRNA vaccination approaches. To determine whether mRNA vaccines induce an interferon response in AGS, we applied mRNA SARS-CoV-2 vaccines to whole blood samples and assessed internalization and interferon signaling gene expression responses to the mRNA. In all cases (11 AGS and 11 control samples), interferon signatures did not significantly increase from baseline, regardless of baricitinib treatment status in the AGS subjects, and were even decreased, when using codon optimized SARS-CoV-2 di-proline modified spike sequence (S2P). Internalization of S2P in human dendritic cells was verified by Western Blot, and in control and AGS blood cells was verified by Luciferase activity. Although numbers of tested samples in this rare disease are small, based on these findings, we suggest that COVID vaccination is unlikely to directly stimulate the interferon signaling gene expression in AGS patients via response to mRNA internalization. The in vitro nature of this study cannot exclude an exaggerated interferon response to spike protein production at a systemic level in individuals with a primary heritable interferonopathy. In the context of continued SARS-CoV-2 spread in the community, we do not recommend withholding vaccination in this rare disease group. However, we recommend that vaccinations for AGS patients are provided in a controlled setting with appropriate observation and used with caution in individuals with prior vaccine associated adverse events.
  🖺 Full Text HTML: mRNA-based vaccines against SARS- CoV-2 do not stimulate interferon stimulatory gene expression in individuals affected by Aicardi Goutieres Syndrome.
• Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates -
  Despite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
  🖺 Full Text HTML: Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates
• Parameter Estimation for a Modified SEIR Model of the COVID-19 Dynamics in the Philippines using Genetic Algorithm -

  The Philippines has been under a series of different levels of community quarantine and this affected the dynamics of the COVID-19 spread in the country. Predicting the trajectory has been an interest of various research groups. To provide a more efficient method to estimate the parameters of the Age-Stratified, Quarantine-modified SEIR model with Nonlinear Incidence Rates (ASQ-SEIR-NLIR) other than the shooting method, a genetic algorithm approach is explored. By defining constraints for each parameter, the algorithm arrived at an acceptable optimal value for each parameter. The experiment is done on two regions of interest: the Philippines (country-level) and Quezon City, Metro Manila (city-level). The ASQ-SEIR-NLIR model, using the parameters generated by the genetic algorithm, is able to produce an average trajectory compared to the actual data, which may be deemed noisy. The dynamics of the COVID-19 spread between Quezon City and average country level is compared, showing that the city population is being exposed to the virus at a much faster rate than the country average and may have more asymptomatics not getting tested than the country average. Given the average trajectory, the peak daily infection projection is way lower at 0.0823% of the country population for the country projection and 0.1494% of the Quezon City population for the city projection, which is below than previous literature estimates of 3-10%.

  🖺 Full Text HTML: Parameter Estimation for a Modified SEIR Model of the COVID-19 Dynamics in the Philippines using Genetic Algorithm
• COMPARISON OF SARS-COV-2 WUHAN AND ALPHA VARIANTS: CLINICAL AND LABORATORY HIGHLIGHTS -

  Since December 2019, after the declaration of new cases regarding novel coronavirus disease, many variants have emerged as a consequence of the viral evolution. Though the SARS-CoV-2 variants have been studied for molecular basis, the clinical and pathologic disparities of them have been understood inadequately. The aim of this research was to figure out the differences between the SARS-CoV-2 Alpha (B1.1.7) variant and the classical Wuhan groups on the clinical basis and laboratory results of the COVID-19 patients who had positive PCR test. The study was done retrospectively inclusive of epidemiological, laboratory data and clinical symptoms of patients who were admitted to the emergency service between February 15 and March 15, 2021 and had positive COVID-19 PCR test results. Though there was no statistically significant difference in symptoms between SARS-CoV-2 Alpha variant and classical variant (Wuhan type) groups; C-reactive protein (CRP), lymphocyte and leukocyte counts were statistically significantly higher in the Wuhan type group; prothrombin time (PT), International Normalized Ratio (INR) and serum creatinine values were statistically significantly higher in the Alpha group. Studies such as ours that investigate both the clinical features and laboratory data of SARS-CoV-2 variants will close the knowledge gaps, so better decisions may be made by health policy makers. Additional studies in this area will increase the understanding of the topic.

  🖺 Full Text HTML: COMPARISON OF SARS-COV-2 WUHAN AND ALPHA VARIANTS: CLINICAL AND LABORATORY HIGHLIGHTS
• Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study -

  The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

  🖺 Full Text HTML: Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study
• Comprehensive analysis of pathways in Coronavirus 2019 (COVID-19) using an unsupervised machine learning method -
  The World Health Organization (WHO) introduced “Coronavirus disease 19” or “COVID19” as a novel coronavirus in March 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the fast discovery of effective treatments to fight this worldwide crisis. Artificial intelligence and bioinformatics analysis pipelines can assist with finding biomarkers, explanations, and cures. Artificial intelligence and machine learning methods provide powerful infrastructures for interpreting and understanding the available data. On the other hand, pathway enrichment analysis, as a dominant tool, could help researchers discover potential key targets present in biological pathways of host cells that are targeted by SARS-CoV-2. In this work, we propose a two-stage machine learning approach for pathway analysis. During the first stage, four informative gene sets that can represent important COVID-19 related pathways are selected. These “representative genes” are associated with the COVID-19 pathology. Then, two distinctive networks were constructed for COVID-19 related signaling and disease pathways. In the second stage, the pathways of each network are ranked with respect to some unsupervised scorning method based on our defined informative features. Finally, we present a comprehensive analysis of the top important pathways in both networks.
  🖺 Full Text HTML: Comprehensive analysis of pathways in Coronavirus 2019 (COVID-19) using an unsupervised machine learning method
• COVID-19 lockdown reveals fish density may be much higher in marine reserves -
  Marine reserves generally allow ecotourism to offer an alternative income to fishing. However, we need to assess its impact on wildlife to make this activity sustainable. The COVID-19 lockdown provided a unique opportunity to evaluate wildlife diversity in the absence of human activity. In a Mexican reserve, we monitored fish assemblages before, during, and just after the lockdown. We show that ecotourism activities alter the behavior of fishes by finding a 2.5-fold density rise during the lockdown. We suggest that the noise pollution generated by the numerous recreational vessels is a significant factor of perturbation. In the absence of noise pollution, some fishes may be bolder (less hidden) and others can come back to the reserve from usually quieter areas (e.g., deeper waters). Our results represent a great worldwide incentive to improve the health of marine reserves by establishing concrete measures in managing plans to mitigate noise pollution.
  🖺 Full Text HTML: COVID-19 lockdown reveals fish density may be much higher in marine reserves
• Impact of the COVID-19 pandemic on Infant Feeding Practices in the U.S.: Food Insecurity, Supply Shortages, and Deleterious Feeding Practices -
  The COVID-19 pandemic drastically increased food insecurity among U.S. households, however, little is known about how infants, who rely primarily on human milk and/or infant formula, were impacted. We conducted an online survey with U.S. caregivers of infants (<2 years) (N=319) to assess how the COVID-19 pandemic impacted breastfeeding, formula-feeding, and household ability to obtain infant-feeding supplies and lactation support (68% mothers; 66% white; 8% living in poverty). Results suggest that the COVID-19 pandemic had a greater negative impact on formula-feeding families, largely due to formula shortages and financial strain. We found 31% of formula-feeding families indicated they experienced various challenges to obtaining formula, citing the following top three reasons: formula was sold out (20%), had to travel to multiple stores (21%), or too expensive (8%). In response, 33% of formula-feeding families reported resorting to potentially harmful feeding practices such as diluting formula with extra water (12%) or cereal (10%), preparing smaller bottles (8%), or feeding left-over/expired formula (11%). Only 15% of breastfeeding families reported feeding difficulties directly as a result of the pandemic—15% were reluctant to obtain lactation support and 9% weaned early. In fact, 51% of breastfeeding families reported increased provision of human milk to infants due to perceived benefits for the infant’s immune system (37%), ability to work remotely/stay home (31%), or concerns about money (8%) or formula shortages (8%). To protect infants from malnutrition in future crises, our results underscore the need for policies to support breastfeeding families and ensure equitable access to infant formula.
  🖺 Full Text HTML: Impact of the COVID-19 pandemic on Infant Feeding Practices in the U.S.: Food Insecurity, Supply Shortages, and Deleterious Feeding Practices
• How Should COVID-19 Vaccines be Distributed between the Global North and South? A Discrete Choice Experiment in Six European Countries -

  Background: The global distribution of COVID-19 vaccinations remains highly unequal. We examine public preferences in six European countries regarding the allocation of COVID-19 vaccines between the Global South and Global North. Methods: We conducted online discrete choice experiments with adult participants in France (n=766), Germany (n=1964), Italy (n=767), Poland (n=670), Spain (n=925), and Sweden (n=938). Respondents were asked to decide which one of two candidates, who varied along four attributes: age, mortality risk, employment, and living in a low- or high-income country, should receive the vaccine first. We analysed the relevance of each attribute in allocation decisions using a conditional logit regression. Results: Across countries, respondents selected candidates with a high mortality and infection risk, irrespective of whether the candidate lived in their own country. All else equal, respondents in Italy, France, Spain, and Sweden gave priority to a candidate from a low-income country, whereas German respondents were significantly more likely to choose the candidate from their own country. Female, younger, and more educated respondents were more favourable of an equitable vaccine distribution. Conclusions: Given these preferences for global solidarity, European governments should promote vaccine transfers to poorer world regions.

  🖺 Full Text HTML: How Should COVID-19 Vaccines be Distributed between the Global North and South? A Discrete Choice Experiment in Six European Countries
• Epitope Mapping of SARS-CoV-2 Spike Protein Reveals Distinguishable Antibody Binding Activity of Vaccinated and Infected Individuals. -
  A multitude of studies have attempted to characterize the antibody response of individuals to the SARS-CoV-2 virus on a linear peptide level by utilizing peptide microarrays. These studies have helped to identify epitopes that have potential to be used for diagnostic tests to identify infected individuals, however the immunological responses of individuals who have received the currently available mRNA vaccines have not been characterized. We aimed to identify linear peptides of the SARS-CoV-2 spike protein that elicited high IgA or IgG binding activity and compare the immunoreactivity of infected individuals to those who received recommended doses of either the Moderna mRNA-1273 or Pfizer BNT162b2 vaccines by utilizing peptide microarrays. Our results revealed peptide epitopes of significant IgG binding among recently infected individuals, many of which are located near functional domains implicated in the high infectivity of SARS-CoV-2. Vaccinated individuals were found to have less intense antibody binding activity than those acutely infected, yet novel markers of IgG binding were identified in the vaccinated group.
  🖺 Full Text HTML: Epitope Mapping of SARS-CoV-2 Spike Protein Reveals Distinguishable Antibody Binding Activity of Vaccinated and Infected Individuals.
• Evaluation of anti-spike glycoprotein antibody and neutralizing antibody response of different vaccine platforms. A protocol of systematic review and meta-analysis of COVID-19 vaccine clinical trial studies -

  Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. SARS-CoV-2 transmit among the people fast and infected thousands of people daily around the world. Because of rapid transmission of SARS-CoV-2 among the people, there is an urgent need to prevent people from infection or hospitalization and control the disease. Methods: We will search electronic databases such as PubMed, Web of Science, Cochrane (CENTRAL), Scopus, Google scholar, the key journals (vaccine and vaccines). Moreover, trial registry including clinicalTrials.gov, WHO ICTRP, and ISRCTN will be searched. We will only select all clinical trial studies in any phases of evaluation (i.e. phase I, II, II, IV). For anti-spike glycoprotein antibody (IgG) response and neutralizing antibody response, we will report Ratio of Geometric Mean (RoGM), Ratio of Mean (RoM) or standardized mean difference (SMD) depends on type of articles. Discussion: Various vaccine platforms have been developed to increase the resistance to the SARS-CoV2 virus and reduce hospitalization and mortality rates. The comprehensive data gathering and analysis of results will guide scientists about the best available evidence. Moreover, the current study results may indicate which of the vaccine platforms are more effective and safe for COVID-19.

  🖺 Full Text HTML: Evaluation of anti-spike glycoprotein antibody and neutralizing antibody response of different vaccine platforms. A protocol of systematic review and meta-analysis of COVID-19 vaccine clinical trial studies
• Sequence Proven Reinfections with SARS-CoV-2 at a Large Academic Center -

  Increased reinfection rates with SARS-CoV-2 have recently been reported, with some locations basing reinfection on a second positive PCR test at least 90 days after initial infection. We investigated sequencing and clinical data on the 750 patients (920 samples) we identified with these criteria. The median time between tests was 377 days, and 724 (79%) of the post 90-day positives were collected after the emergence of the Omicron variant in November 2021. Successful sequencing occurred in 127 of 231 attempted samples, spiked during the Omicron surge and showed higher median days from initial infection compared to failed sequences (median 398 days compared to 276 days, p<0.0005). A total of 122 (98%) patients showed evidence of reinfection, 45 of which had sequence proven reinfection and 77 had inferred reinfections (later sequence showed a clade that was not circulating when the patient was initially infected). Children accounted for only 4% of reinfections. 43 (96%) of 45 infections with sequence proven reinfection were caused by the Omicron variant, 41 (91%) were symptomatic, 32 (71%), were vaccinated prior to the second infection, and 6 (13%) were Immunosuppressed. Only 2 (4%) were hospitalized, and both had underlying conditions.

  🖺 Full Text HTML: Sequence Proven Reinfections with SARS-CoV-2 at a Large Academic Center
• Reduced Exercise Capacity, Chronotropic Incompetence, Inflammation and Symptoms in Post-Acute COVID-19 -

  BACKGROUND Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring. METHODS In the Long-Term Impact of Infection with Novel Coronavirus (LIINC) Cohort, we performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection. We used logistic and linear regression to compare those with and without cardiopulmonary symptoms (dyspnea, chest pain, palpitations) adjusting for confounders. RESULTS One hundred twenty individuals were studied, among whom 46 participants (unselected for symptom status) had at least one advanced test performed at median 17 months (IQR 15-18). Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), smaller RV volume and stroke volume and higher extracellular volume were present among those with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/15 (87%) participants with reduced exercise capacity (<85% predicted) reported cardiopulmonary symptoms or fatigue (p=0.008). Adjusted peak VO2 was 2.7 ml/kg/min lower among those with cardiopulmonary symptoms (95%CI -6.9 to 1.5; p=0.20) or -11% predicted (95%CI -27 to 5, p=0.17). Including fatigue along with cardiopulmonary symptoms, the adjusted difference in peak VO2 was -5.9 ml/kg/min (-9.6 to -2.3; p=0.002) or -21% predicted (-35 to -7; p=0.006). Chronotropic incompetence was the primary abnormality among 9/15 with reduced peak VO2. Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Those with chronotropic incompetence had higher hsCRP, lower heart rate recovery, and lower heart rate variability suggestive of autonomic dysfunction. CONCLUSIONS Reduced exercise capacity and reduced heart rate response to exercise, and hsCRP are associated with persistent cardiopulmonary symptoms more than 1 year following COVID-19. Chronic inflammation and autonomic dysfunction may underlie cardiopulmonary PASC.

  🖺 Full Text HTML: Reduced Exercise Capacity, Chronotropic Incompetence, Inflammation and Symptoms in Post-Acute COVID-19
• Assessment of the humoral response to the homologous Gam-COVID-Vac (Sputnik V) or heterologous Sputnik V/mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in dialysis patients. -

  Introduction: The humoral response to vaccines is the most used tool to evaluate the protection against SARS- CoV-2 infection. Dialysis patients are a high-risk population and have a reduced immune response to vaccination. Objective: To assess the humoral response to homologous Gam-COVID-Vac (Sputnik V) and heterologous Sputnik V/mRNA-1273 (Moderna) vaccination in dialysis patients. Methods: SARS-CoV-2 anti-spike IgG (RBD) concentration was estimated 3-16 weeks after complete vaccination. Reactogenicity was evaluated until day 7 by patients self-reported side events. Results: 107 participants were enrolled [n=84 homologous (SpV/SpV), n=23 heterologous (SpV/Mod)]. Median (IQR) age was 64 (50-75) years old and 79 (73.8%) were male. Additionally, 19 (22.6%) of the SpV/SpV and 4 (17.4%) of the SpV/Mod group had a prior confirmed SARS-CoV-2 infection (p=0.589). In the overall population, 103 patients reached seroconversion (96.3%). Anti-S-RBD IgG median titers (IQR) were higher in the heterologous [1222 (288-5680) BAU/mL] than in the homologous scheme [447 (100-1551) BAU/mL], p=0.022. In a linear model adjusted for age and gender, previous SARS-COV-2 infection (B: 1944.3; CI95: 1136.2-2753.4; p<0.001), and SpV/Mod vaccination scheme (B: 1241.5; CI95: 420.39-2062.6; p=0.003) were independently associated with anti-S-RBD levels. Finally, a higher frequency of adverse effects was associated with the heterologous scheme, although they were well tolerated by all individuals. Conclusion: The present study provides evidence that the homologous SpV/SpV and heterologous SpV/Mod schemes showed good efficacy and safety under dialysis conditions. These results could be useful for future vaccination strategies, especially aimed at this risk group.

  🖺 Full Text HTML: Assessment of the humoral response to the homologous Gam-COVID-Vac (Sputnik V) or heterologous Sputnik V/mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in dialysis patients.

From Clinical Trials

• The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)
  Sponsors:   University of California, Irvine;   Hudson Valley Healing Arts Center
  Not yet recruiting

• Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents - Condition:   COVID-19
  Interventions:   Drug: STI-9199;   Drug: Placebo
  Sponsor:  
  Sorrento Therapeutics, Inc.
  Not yet recruiting

• A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above - Condition:   COVID-19
  Intervention:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Shulan (Hangzhou) Hospital
  Recruiting

• Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above - Condition:   COVID-19
  Interventions:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:  
  China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Hunan Provincial Center for Disease Control and Prevention
  Recruiting

• Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19 - Condition:   COVID-19
  Intervention:   Radiation: [18F]DPA-714 positron emission tomography (PET) scan
  Sponsors:   Amsterdam UMC, location VUmc;   ZonMw: The Netherlands Organisation for Health Research and Development
  Enrolling by invitation

• Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation - Condition:   COVID-19
  Intervention:   Drug: Palbociclib
  Sponsor:   biotx.ai GmbH
  Active, not recruiting

• Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo
  Sponsor:   CanSino Biologics Inc.
  Not yet recruiting

• Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo
  Sponsor:   CanSino Biologics Inc.
  Not yet recruiting

• THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: AAHI-SC2 Vaccine;   Biological: AAHI- SC3 Vaccine;   Biological: EUA or approved vaccine
  Sponsor:   ImmunityBio, Inc.
  Recruiting

• To Evaluate SSD8432/Ritonavir in Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SSD8432 dose;   Drug: SSD8432 placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• A Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19 - Condition:   COVID-19
  Intervention:   Biological: DXP604
  Sponsor:  
  Wuhan Institute of Biological Products Co., Ltd
  Not yet recruiting

• Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study - Condition:   COVID-19
  Interventions:   Drug: SSD8432 dose1;   Drug: SSD8432 dose2;   Drug: SSD8432Placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell);   Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsors:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Wuhan Institute of Biological Products Co., Ltd;   The University of Hong Kong
  Not yet recruiting

• Immunogenicity and Safety of Booster Immunization of COVID-19 Vaccine (Vero Cell), Inactivated (Omicron Variant) in Healthy People Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: COVID-19 Vaccine (Vero cell), Inactivated (Omicron variant);   Biological: COVID-19 Vaccine (Vero cell), Inactivated (CZ strain)
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• To Evaluate SSD8432/ Ritonavir in Adults With COVID-19 - Condition:   COVID-19 Patients
  Interventions:   Drug: SSD8432 dose 1/Ritonavir;   Drug: SSD8432 dose 2/Ritonavir
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Recruiting

From PubMed

• HDAC Inhibition as Potential Therapeutic Strategy to Restore the Deregulated Immune Response in Severe COVID-19 - The COVID-19 pandemic has had a devastating impact worldwide and has been a great challenge for the scientific community. Vaccines against SARS-CoV-2 are now efficiently lessening COVID-19 mortality, although finding a cure for this infection is still a priority. An unbalanced immune response and the uncontrolled release of proinflammatory cytokines are features of COVID-19 pathophysiology and contribute to disease progression and worsening. Histone deacetylases (HDACs) have gained interest in…

• Intranasal Delivery of Thermostable Subunit Vaccine for Cross-Reactive Mucosal and Systemic Antibody Responses Against SARS-CoV-2 - Despite the remarkable efficacy of currently approved COVID-19 vaccines, there are several opportunities for continued vaccine development against SARS-CoV-2 and future lethal respiratory viruses. In particular, restricted vaccine access and hesitancy have limited immunization rates. In addition, current vaccines are unable to prevent breakthrough infections, leading to prolonged virus circulation. To improve access, a subunit vaccine with enhanced thermostability was designed to eliminate the…

• Importance of Influenza Anti-Hemagglutinin Antibodies During the SARS-CoV-2 Pandemic in the 2019/2020 Epidemic Season in Poland - BACKGROUND The aim of this study was to determine the level of anti-hemagglutinin antibodies in the serum of recovered patients during the SARS-CoV-2 pandemic in the 2019/2020 epidemic season in Poland, and the course of COVID-19. MATERIAL AND METHODS The material for the study consisted of the sera of COVID-19 convalescents obtained from the following 9 Regional Blood Donation and Blood Supply Centers located in 8 voivodeships. The hemagglutination inhibition reaction assay (HAI) using 8 viral…

• Nanocomposites of Graphene Oxide-Silver Nanoparticles for Enhanced Antibacterial Activity: Mechanism of Action and Medical Textiles Coating - The resistance of microorganisms to antibiotics is a crucial problem for which the application of nanomaterials is among a growing number of solutions. The aim of the study was to create a nanocomposite (composed of graphene oxide and silver nanoparticles) with a precise mode of antibacterial action: what enables textiles to be coated in order to exhibit antibacterial properties. A characterization of nanomaterials (silver nanoparticles and graphene oxide) by size distribution, zeta potential…

• Ginkgolic acid and anacardic acid are reversible inhibitors of SARS-CoV-2 3-chymotrypsin-like protease - Because of the emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different regions of the world, the battle with infectious coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been seesawing. Therefore, the identification of antiviral drugs is of particular importance. In order to rapidly identify inhibitors for SARS-CoV-2 3-chymotrypsin-like protease (3CL^(pro)), an enzyme essential for viral replication, we combined the fluorescence polarization (FP)…

• Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro - A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic…

• SARS-CoV-2 Omicron sublineages show comparable cell entry but differential neutralization by therapeutic antibodies - The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified-BA.1, BA.2, and BA.3-and BA.2 exhibits increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-mediated inhibition. Here, we show that BA.1, BA.2, and BA.3 enter and fuse target cells with similar efficiency and in an ACE2-dependent manner. However,…

• Inhibition of IRAK4 dysregulates SARS-CoV-2 spike protein-induced macrophage inflammatory and glycolytic reprogramming - Escalated innate immunity plays a critical role in SARS-CoV-2 pathology; however, the molecular mechanism is incompletely understood. Thus, we aim to characterize the molecular mechanism by which SARS-CoV-2 Spike protein advances human macrophage (Mϴ) inflammatory and glycolytic phenotypes and uncover novel therapeutic strategies. We found that human Mϴs exposed to Spike protein activate IRAK4 phosphorylation. Blockade of IRAK4 in Spike protein-stimulated Mϴs nullifies signaling of IRAK4, AKT,…

• ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), continues to cause significant morbidity and mortality in the ongoing global pandemic. Understanding the fundamental mechanisms that govern innate immune and inflammatory responses during SARS-CoV-2 infection is critical for developing effective therapeutic strategies. While IFN-based therapies are generally expected to be beneficial during viral infection, clinical trials…

• Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice - Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was…

• Circulatory Exosomes from COVID-19 Patients Trigger NLRP3 Inflammasome in Endothelial Cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces inflammatory response, cytokine storm, venous thromboembolism, coagulopathy, and multiple organ damage. Resting endothelial cells prevent coagulation, control blood flow, and inhibit inflammation. However, it remains unknown how SARS-CoV-2 induces strong molecular signals in distant cells for immunopathogenesis. In this study, we examined the consequence of human endothelial cells, microvascular endothelial cells…

• Antiviral Activity of Selected Lamiaceae Essential Oils and Their Monoterpenes Against SARS-Cov-2 - This study presents the very first report on the in vitro antiviral activity of selected essential oils of Lamiaceae plant species and their monoterpenes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nineteen essential oils were obtained by hydrodistillation of dried plant material, and their monoterpene profiles were determined. In addition, the exact concentrations of each monoterpene that were found at a significant level were defined. Both essential oils and their…

• Ivermectin as a possible treatment for COVID-19: a review of the 2022 protocols - Ivermectin is a safe and effective drug in humans and has been approved for use in numerous parasitic infections for over 50 years. In addition, many studies have already shown its antiviral activity. Ivermectin is generally well tolerated, with no indication of central nervous system-associated toxicity at doses up to 10 times the highest FDA- approved dose of 200 µg/kg. The in vitro results of ivermectin for reducing SARS-CoV-2 viral load are promising and show that Ivermectin kills SARS-CoV-2…

• Feasibility analysis and mechanism exploration of Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) against COVID-19 - Introduction. As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for…

• Mutations in Porcine Epidemic Diarrhea Virus nsp1 Cause Increased Viral Sensitivity to Host Interferon Responses and Attenuation In Vivo - Coronavirus (CoV) nonstructural protein 1 (nsp1) inhibits cellular gene expression and antagonizes interferon (IFN) response. Porcine epidemic diarrhea virus (PEDV) infects pigs and causes high mortality in neonatal piglets. We hypothesized that a recombinant PEDV carrying mutations at the conserved residues N93 and N95 of nsp1 induces higher IFN responses and is more sensitive to IFN responses, leading to virus attenuation. We mutated PEDV nsp1 N93 and N95 to A93 and A95 to generate the…

From Patent Search