Covid-19 Sentry

Contents

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

From Preprints

• The Role of Organizational Commitment as a Mediator of Burnout Syndrome and Turnover Intention -
  Turnover intention is the tendency or intention of employees to stop working from their jobs voluntarily or move from one workplace to another according to their own choice. The purpose of this study is to investigate the effect of burnout on turnover intentions, the organizational commitment to turnover intentions, and the indirect relationship between burnout and turnover intentions through organizational commitment. This type of research is a quantitative study. The sampling in this study used probabilistic sampling using cluster sampling and simple random sampling. The study population consisted of healthcare professionals from five hospitals in Surabaya as referrals for Covid19 patients. The sample contains 100 respondents. Route analysis by the Smart PLS 2.0 program is used as a data analysis method. The results show that burnout affects turnover intentions. Burnout adversely affects an organization’s commitment, which in turn adversely affects the intent of leaving a job. In addition, the results of indirect impact tests show that organizational commitment can mediate the relationship between burnout and willingness to leave.
  🖺 Full Text HTML: The Role of Organizational Commitment as a Mediator of Burnout Syndrome and Turnover Intention
• Corruption and Demography during the COVID-19 Pandemic in Indonesia -
  COVID-19 pandemic dramatically changed the face of the world, including Indonesia. With more economic relief packages injected into public spending, corruption opportunities have risen, especially under the weakening corruption monitoring system. This article presents significant findings from the survey on the practice of corruption during the pandemic that can paint an understanding of corruption in Indonesia. Two survey rounds were conducted with respondents around Indonesia starting mid-to-end 2020, gathering 2,093 responses. The ordinary least-square (OLS) regression unveils that people who live in rural areas or spend less than the common people tend to commit or be involved in the practice of corruption. People who live in the rural areas or receive less income tend to perform corruption to close the income gap. It is also found that people with higher education levels tend to perform corruption. Higher corruption rents and broad opportunities for power abuse promote corruption in a well-educated society.
  🖺 Full Text HTML: Corruption and Demography during the COVID-19 Pandemic in Indonesia
• Steric accessibility of the N-terminus improves the titer and quality of recombinant proteins secreted from Komagataella phaffii -
  Background: Komagataella phaffii is a commonly used alternative host for manufacturing therapeutic proteins, in part because of its ability to secrete recombinant proteins into the extracellular space. Incorrect processing of secreted proteins by cells can, however, cause non-functional product-related variants, which are expensive to remove in purification and lower overall process yields. The secretion signal peptide, attached to the N-terminus of the recombinant protein, is a major determinant of the quality of the protein sequence and yield. In K. phaffii, the signal peptide from the Saccharomyces cerevisiae alpha mating factor often yields the highest secreted titer of recombinant proteins, but the quality of secreted protein can vary highly. Results: We determined that an aggregated product-related variant of the SARS-CoV-2 receptor binding domain is caused by N-terminal extension from incomplete cleavage of the signal peptide. We eliminated this variant and improved secreted protein titer up to 76% by extension of the N-terminus with a short, functional peptide moiety or with the EAEA residues from the native signal peptide. We then applied this strategy to three other recombinant subunit vaccine antigens and observed consistent elimination of the same aggregated product-related variant. Finally, we demonstrated that this benefit in quality and secreted titer can be achieved with addition of a single amino acid to the N-terminus of the recombinant protein. Conclusions: Our observations suggest that steric hindrance of proteases in the Golgi that cleave the signal peptide can cause unwanted N-terminal extension and related product variants. We demonstrated that this phenomenon occurs for multiple recombinant proteins, and can be addressed by minimal modification of the N-terminus to improve steric accessibility. This strategy will enable consistent secretion of a broad range of recombinant proteins with the highly productive alpha mating factor secretion signal peptide.
  🖺 Full Text HTML: Steric accessibility of the N-terminus improves the titer and quality of recombinant proteins secreted from Komagataella phaffii
• Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study -

  Background In early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. Methods We extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt). Findings A surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. Interpretation Our results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks.

  🖺 Full Text HTML: Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study
• Development and external validation of a deep learning-based computed tomography classification system for COVID-19 -
  Rationale: Currently available machine learning models for diagnosing COVID-19 based on computed tomography (CT) images are limited due to concerns regarding methodological flaws or underlying biases in the evaluation process. Objectives: We aimed to develop and externally validate a novel machine learning model that can classify CT image findings as positive or negative for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR). Methods: We used 3128 images from a wide variety of two-gate data sources for the development and ablation study of the machine learning model. A total of 633 COVID-19 cases and 2295 non-COVID-19 cases were included in the study. We randomly divided cases into a development set and ablation set at a ratio of 8:2. For the ablation study, we used another dataset including 150 cases of interstitial pneumonia among non-COVID-19 images. For external validation, we used 893 images from 740 consecutive patients at 11 acute care hospitals suspected of having COVID-19 at the time of diagnosis. The dataset included 343 COVID-19 patients. The reference standard was RT-PCR. Result: In ablation study, using interstitial pneumonia images, the specificity of the model were 0.986 for usual interstitial pneumonia pattern, 0.820 for non-specific interstitial pneumonia pattern, 0.400 for organizing pneumonia pattern. In the external validation study, the sensitivity and specificity of the model were 0.869 and 0.432, respectively, at the low-level cutoff, and 0.724 and 0.721, respectively, at the high-level cutoff. Conclusions: Our machine learning model exhibited a high sensitivity in external validation datasets and may assist physicians to rule out COVID-19 diagnosis in a timely manner. Further studies are warranted to improve model specificity.
  🖺 Full Text HTML: Development and external validation of a deep learning-based computed tomography classification system for COVID-19
• How do Urban Factors Control the Severity of COVID-19? -

  Human health in urban environment has emerged as a primary focus of sustainable development during the time of global pandemic caused by a severe acute respiratory syndrome due to the SARS-CoV-2 coronavirus, COVID-19. It has reshaped the world with the way our communities interact, people work, commute, and spend their leisure time. While different mitigation solutions for controlling COVID-19 virus transmission have already been established, global models that would explain and predict the impact of urban environments on the case fatality ratio CFR of COVID-19 (defined as the number of deaths divided by the number of cases over a time window) are missing. Here, with readily available data from public sources, we study the CFR of the coronavirus for 118 locations (city zip-codes, city boroughs, and cities) worldwide to identify the links between the CFR and outdoor, indoor and personal urban factors. We show that a probabilistic model, optimized on the sample of 20 districts from 4 major US cities, provides an accurate predictive tool for the CFR of COVID-19 regardless of the geographical location. When adjusted for the population, our model can be used to evaluate risk and severity of the disease at multi-geospatial scales worldwide ranging from zip-codes and neighborhoods to cities and countries for different waves of the pandemic. Our results suggest that although disease screening and vaccination policies to containment and lockdowns remain critical in controlling the spread of airborne diseases, urban factors such as population density, humidity, or order of buildings, should all be taken into consideration when identifying resources and planning targeted responses to mitigate the impact and severity of the viruses transmitted through air. We advocate the study of urban factors as a path towards facilitating timely deployment of targeted countermeasures and confinement strategies where sharing of personal information and availability of tests may be restricted or limited.

  🖺 Full Text HTML: How do Urban Factors Control the Severity of COVID-19?
• SARS-CoV-2 infection-induced immunity and the duration of viral shedding: results from a Nicaraguan household cohort study -

  Background. Much of the world’s population has been infected with SARS-CoV-2. Thus, infection-induced immunity will play a critical role in future SARS-CoV-2 transmission. We investigated the impact of immunity from prior infection on viral shedding duration and viral load.<br />Methods. We conducted a household cohort study in Managua, Nicaragua with an embedded transmission study that closely monitors participants regardless of symptom status. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity, respectively. Blood samples were collected in Feb/March and Oct/Nov 2020 and 2021, and surrounding household intensive monitoring periods. We used accelerated failure time models to compare shedding times. Participants vaccinated ≥14 days prior to infection were excluded from primary analyses.<br />Results. There were 600 RT-PCR-confirmed SARS-CoV-2 infections between May 1, 2020 and March 10, 2022 with ELISA data prior to infection. Prior infection was associated with 48% shorter shedding times, event time ratio (ETR) 0.52 (95% CI: 0.39-0.69, mean shedding: 13.7 vs 26.4 days). A 4-fold higher anti-SARS-CoV-2 spike titer was associated with 17% shorter shedding (ETR 0.83, 95% CI: 0.78-0.90). Similarly, maximum viral loads (lowest CT) were lower for previously infected individuals (mean CT 29.8 vs 28.0, p = 4.02x10^-3). Shedding was shorter in previously infected adults and children ≥10 years, but not in children 0-9 years; there was little difference in CT levels for previously infected vs naïve adults above age 60.<br />Conclusions. Prior infection-induced immunity was associated with shorter viral shedding and lower viral loads.<br />Funding: This work was supported by the National Institute for Allergy and Infectious Diseases at the National Institute of Health [award no. R01 AI120997 to A.G., and contract nos. HHSN272201400006C and 75N93021C00016 to A.G.], and a grant from Open Philanthropy.

  🖺 Full Text HTML: SARS-CoV-2 infection-induced immunity and the duration of viral shedding: results from a Nicaraguan household cohort study
• Genetic regulation of the human plasma proteome in 54,306 UK Biobank participants -
  The UK Biobank Pharma Proteomics Project (UKB-PPP) is a collaboration between the UK Biobank (UKB) and thirteen biopharmaceutical companies characterising the plasma proteomic profiles of 54,306 UKB participants. Here, we describe results from the first phase of UKB-PPP, including protein quantitative trait loci (pQTL) mapping of 1,463 proteins that identifies 10,248 primary genetic associations, of which 85% are newly discovered. We also identify independent secondary associations in 92% of cis and 29% of trans loci, expanding the catalogue of genetic instruments for downstream analyses. The study provides an updated characterisation of the genetic architecture of the plasma proteome, leveraging population-scale proteomics to provide novel, extensive insights into trans pQTLs across multiple biological domains. We highlight genetic influences on ligand-receptor interactions and pathway perturbations across a diverse collection of cytokines and complement proteins, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug target discovery by extending the genetic proxied effect of PCSK9 levels on lipid concentrations, cardio- and cerebro-vascular diseases, and additionally disentangle specific genes and proteins perturbed at COVID-19 susceptibility loci. This public-private partnership provides the scientific community with an open-access proteomics resource of unprecedented breadth and depth to help elucidate biological mechanisms underlying genetic discoveries and accelerate the development of novel biomarkers and therapeutics.
  🖺 Full Text HTML: Genetic regulation of the human plasma proteome in 54,306 UK Biobank participants
• Adjuvant Discovery via a High Throughput Screen using Human Primary Mononuclear Cells -
  Vaccines are a key biomedical intervention to prevent the spread of infectious diseases, but their efficacy can be limited by insufficient immunogenicity and nonuniform reactogenic profiles. Adjuvants are molecules that potentiate vaccine responses by inducing innate immune activation. However, there are a limited number of adjuvants in approved vaccines, and current approaches for preclinical adjuvant discovery and development are inefficient. We describe a methodology utilizing high throughput and high-content screening for novel adjuvant candidates that was used to screen a library of ~2,500 small molecules via a 384 well quantitative combined cytokine and flow cytometry immunoassay in primary human peripheral blood mononuclear cells (PBMCs) from 4 healthy adult study participants. Hits were identified based on their induction of soluble cytokine (TNF-alpha, IFN-gamma; and IL10) secretion and PBMC maturation (CD 80/86, Ox40, and HLA-DR) in at least two of the four donors screened. From an initial set of 197 compounds identified using these biomarkers-an 8.6% hit rate-we downselected to four scaffolds that demonstrated robust efficacy and potency in vitro and evaluated the top hit, vinblastine sulfate, for adjuvanticity in vivo. Vinblastine sulfate significantly enhanced murine humoral responses to recombinant SARS-CoV-2 spike protein, including a four-fold enhancement of IgG titer production when compared to treatment with the spike antigen alone. Overall, we outline a methodology for discovering immunomodulators with adjuvant potential via high-throughput screening of PBMCs in vitro that yielded a lead compound with in vivo adjuvanticity.
  🖺 Full Text HTML: Adjuvant Discovery via a High Throughput Screen using Human Primary Mononuclear Cells
• Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge rule. -
  Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved in the interaction of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with the human receptor Angiotensin-converting enzyme 2 (ACE2). As the principal computational tool, we have used the FORTE approach, capable to model proton fluctuations and computing free energies for a very large number of protein-protein systems under different physical-chemical conditions, here focusing on the RBD-ACE2 interactions. Both the wild-type and all critical variants are included in this study. From our large ensemble of extensive simulations, we obtain, as a function of pH, the binding affinities, charges of the proteins, their charge regulation capacities, and their dipole moments. In addition, we have calculated the pKas for all ionizable residues and mapped the electrostatic coupling between them. We are able to present a simple predictor for the RBD-ACE2 binding based on the data obtained for Alpha, Beta, Gamma, Delta, and Omicron variants, as a linear correlation between the total charge of the RBD and the corresponding binding affinity. This RBD charge rule should work as a quick test of the degree of severity of the coming SARS-CoV-2 variants in the future.
  🖺 Full Text HTML: Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge rule.
• It hurts your heart: frontline healthcare worker experiences of moral injury during the COVID-19 pandemic -

  Background: Moral injury is defined as the strong emotional and cognitive reactions following events which clash with someones moral code, values or expectations. During the COVID-19 pandemic, increased exposure to potentially morally injurious events (PMIEs) has placed healthcare workers (HCWs) at risk of moral injury. Yet little is known about the lived experience of cumulative PMIE exposure and how NHS staff respond to this. Objective: We sought to rectify this knowledge gap by qualitatively exploring the lived experiences and perspectives of clinical frontline NHS staff who responded to COVID-19. Methods: We recruited a diverse sample of 30 clinical frontline HCWs from the NHS CHECK study cohort, for single time point qualitative interviews. All participants endorsed at least one item on the 9-item Moral Injury Events Scale (MIES) (Nash et al., 2013) at six month follow up. Interviews followed a semi-structured guide and were analysed using reflexive thematic analysis. Results: HCWs described being routinely exposed to ethical conflicts, created by exacerbations of pre-existing systemic issues including inadequate staffing and resourcing. We found that HCWs experienced a range of mental health symptoms primarily related to perceptions of institutional betrayal as well as feeling unable to fulfil their duty of care towards patients. Conclusion: These results suggest that a multi-facetted organisational strategy is warranted to prepare for PMIE exposure, promote opportunities for resolution of symptoms associated with moral injury and prevent organisational disengagement.

  🖺 Full Text HTML: It hurts your heart: frontline healthcare worker experiences of moral injury during the COVID-19 pandemic
• COVID-19 redux: clinical, virologic, and immunologic evaluation of clinical rebound after nirmatrelvir/ritonavir -

  Clinical rebound of COVID-19 after nirmatrelvir/ritonavir treatment has been reported. We performed clinical, virologic, and immune measurements in seven patients with symptomatic rebound, six after nirmatrelvir/ritonavir treatment and one without previous treatment. There was no evidence of severe disease or impaired antibody and T-cell responses in people with rebound symptoms.

  🖺 Full Text HTML: COVID-19 redux: clinical, virologic, and immunologic evaluation of clinical rebound after nirmatrelvir/ritonavir
• Immunogenicity following two doses of BBIBP-CorV vaccine and a third booster dose with viral vector and mRNA COVID-19 vaccines against delta and omicron variants in prime immunized adults with two doses of BBIBP-CorV vaccine -

  Coronavirus disease 2019 (COVID-19) booster vaccination is being comprehensively evaluated globally due to waning immunity and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Therefore, this study aimed to evaluate antibody responses in individuals vaccinated with two doses of BBIBP-CorV vaccine and to explore the boosting effect of the different vaccine platforms in BBIBP-CorV-primed healthy adults, including viral vector vaccine (AZD122) and mRNA vaccines (BNT162b2 and mRNA-1273). The results showed that, in the BBIBP-CorV prime group, the total receptor-binding domain (RBD) immunoglobulin (Ig) and anti-RBD IgG levels waned significantly at 3 months after receiving the second dose. However, after the booster, RBD-specific binding antibody levels increased. Neutralizing antibody measured by a surrogate neutralization test showed of inhibition over 90% against the SARS-CoV-2 delta variant but less than 70% against omicron variant after the third dose on day 28. All booster vac-cines could induce the total IFN-ɣ T-cell response. The reactogenicity was acceptable and well tolerated without serious adverse events. This study supported administration of the third dose with either viral vector or mRNA vaccine for the BBIBP-CorV-primed individuals to stimulate antibody and T cell responses.

  🖺 Full Text HTML: Immunogenicity following two doses of BBIBP-CorV vaccine and a third booster dose with viral vector and mRNA COVID-19 vaccines against delta and omicron variants in prime immunized adults with two doses of BBIBP-CorV vaccine
• Misinformation in Germany during the COVID-19 pandemic: A cross-sectional survey on citizens’ perceptions and individual differences in the belief in false information -
  During the COVID-19 pandemic, citizens have been exposed to vast amounts of mis- and disinformation. This “infodemic” has undermined key behavioural and pharmacological measures to contain the pandemic—for instance, by increasing vaccine hesitancy. In a cross-sectional survey of residents of Germany, we investigated citizens’ perceptions of and ability to deal with misinformation across three Waves of data collection in 2020/21 (Ntotal = 3324). We observed three main results. First, there was a strong increase in the perceived prevalence of misinformation in classic and online media and in social interactions over the course of the pandemic. Second, some—but by no means all—respondents knew how to identify misinformation. Third, higher susceptibility to misinformation was associated with support for the far-right AFD party, reliance on tabloids, neighbours and social media for information and news, lower education, as well as migration background. To help people navigate the challenges of the infodemic, we propose a two-pronged approach, namely, to boost individuals’ abilities to discern false from accurate information, and to enrich citizens’ proximate environments (e.g., neighbourhoods with high rates of migration) with reliable, accessible and high-quality information.
  🖺 Full Text HTML: Misinformation in Germany during the COVID-19 pandemic: A cross-sectional survey on citizens’ perceptions and individual differences in the belief in false information
• Psychological Factors Shaping Public Responses to COVID-19 Digital Contact Tracing Technologies in Germany -
  Please cite the published version: Kozyreva, A., Lorenz-Spreen, P., Lewandowsky, S. et al. Psychological factors shaping public responses to COVID-19 digital contact tracing technologies in Germany. Sci Rep 11, 18716 (2021). https://doi.org/10.1038/s41598-021-98249-5 Abstract: Digital contact-tracing technologies are being used for epidemiological purposes at scale for the first time in response to the COVID-19 pandemic. This poses challenges for governments aiming at high and efficient uptake and for people weighing the advantages (e.g., public health) against the potential risks (e.g., loss of data privacy) of these unprecedented measures. Our cross-sectional survey with repeated measures across four samples in Germany (N = 4,357) focused on public perceptions of digital contact-tracing technologies and related attitudes toward privacy. We found that public acceptance of potential privacy-encroaching measures decreased over time. Levels of acceptability were high for all three hypothetical tracking apps representing a range of privacy encroachments. Intentions to download the actual tracking app (the Corona-Warn-App) that became available during our study were also high. However, this did not directly translate into actual uptake. Our results point to the crucial roles of trust in government and in the app’s security, as well as of concerns about the app’s effectiveness. A conflict between prosocial intentions and personal benefit on the one hand, and lack of trust in data security and the app’s effectiveness on the other, are at the heart of people’s decisions about whether to use digital contact-tracing technologies.
  🖺 Full Text HTML: Psychological Factors Shaping Public Responses to COVID-19 Digital Contact Tracing Technologies in Germany

From Clinical Trials

• Phase I Clinical Trial of GEN2-Recombinant COVID-19 Vaccine (CHO Cells) in Healthy People Aged 18 and Above - Condition:   COVID-19 Pneumonia
  Interventions:   Biological: Experimental Vaccine 1;   Biological: Experimental Vaccine 2;   Biological: Experimental Vaccine 3;   Biological: placebo
  Sponsors:   National Vaccine and Serum Institute, China;   Lanzhou Institute of Biological Products Co., Ltd;   Beijing Institute of Biological Products Co Ltd.
  Not yet recruiting

• COVID-19 Algorithm Treatment at Home - Condition:   COVID-19
  Interventions:   Drug: Recommended treatment schedule;   Drug: Usual care
  Sponsor:   Mario Negri Institute for Pharmacological Research
  Not yet recruiting

• Immunosuppression and COVID-19 Boosters - Condition:   COVID-19
  Interventions:   Biological: diphtheria and tetanus toxoids (adsorbed) vaccine;   Biological: COVID-19 vaccine
  Sponsors:   Kirby Institute;   Seqirus Pty Ltd, Australia;   Medical Research Future Fund (MRFF)
  Not yet recruiting

• Epidemiological Monitoring of COVID-19 Patients Hospitalized on Reunion Island - Condition:   COVID-19
  Intervention:   Other: telephone interview 24 months after hospitalization for Covid-19
  Sponsor:   Centre Hospitalier Universitaire de la Réunion
  Not yet recruiting

• Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults - Condition:   COVID-19 Vaccines
  Interventions:   Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech);   Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
  Sponsors:   Assistance Publique - Hôpitaux de Paris;   IREIVAC/COVIREIVAC Network
  Recruiting

• Immunogenicity and Safety Study of Booster Vaccine With the COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain - Condition:   COVID-19
  Intervention:   Biological: COVID-19 Vaccine (Vero Cell), Inactivated, Omicron Strain
  Sponsor:   Sinovac Biotech (Hong Kong) Limited
  Not yet recruiting

• Plerixafor in Acute Respiratory Distress Syndrome Related to COVID-19 (Phase IIb) - Conditions:   COVID-19 Acute Respiratory Distress Syndrome;   COVID-19
  Interventions:   Drug: Plerixafor 20 MG/ML [Mozobil];   Other: Placebo
  Sponsor:   4Living Biotech
  Not yet recruiting

• Effect of COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men. - Condition:   Men Infertility, Post-COVID-19
  Intervention:   Other: diagnostic test and sperm analysis
  Sponsors:   Comenius University;   GYN-FIV
  Active, not recruiting

• Calcitriol Supplementation in COVID-19 Patients - Conditions:   COVID-19;   Vitamin D Deficiency
  Intervention:   Drug: Calcitriol
  Sponsor:   RenJi Hospital
  Not yet recruiting

• Olfactory Training in COVID-19 Associated Loss of Smell - Conditions:   COVID-19;   Hyposmia
  Intervention:   Device: Sniffin’ sticks Duftquartett
  Sponsor:   Medical University Innsbruck
  Not yet recruiting

• Psychological Impact of Medical Evacuations on Families of Patients Admitted to Intensive Care Unit for Severe COVID-19 - Conditions:   COVID-19;   Stress Disorders, Post-Traumatic
  Interventions:   Other: Revised Impact of Event Scale;   Other: Hospital Anxiety and Depression scale;   Other: 36-Item Short Form Survey;   Other: satisfaction survey;   Other: semi-directed interview with trusted person on the general experience of the patient’s medical evacuation;   Other: semi-directed interview with trusted person on the general experience of hospitalization in intensive care
  Sponsor:   Centre Hospitalier Metropole Savoie
  Completed

• Effects of Telerehabilitative Aerobic and Relaxation Exercises Patients With Type 2 Diabetes With and Without COVID-19 - Conditions:   COVID-19;   Type 2 Diabetes Mellitus
  Intervention:   Other: Aerobic and Relaxation Exercises
  Sponsor:   Bozyaka Training and Research Hospital
  Active, not recruiting

• COVID-19 Vaccine Uptake Trial - Conditions:   Vaccination Refusal;   COVID-19
  Interventions:   Other: Short Message Service (SMS) + Website Link Strategy;   Other: Phone Call with Peer Strategy
  Sponsor:   Washington University School of Medicine
  Not yet recruiting

• Cardiovascular Autonomic and Immune Mechanism of Post COVID-19 Tachycardia Syndrome - Conditions:   Post-acute COVID-19 Syndrome;   Postural Tachycardia Syndrome (POTS);   Long COVID;   SARS CoV 2 Infection
  Interventions:   Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients;   Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation);   Diagnostic Test: Autonomic Symptoms assessment
  Sponsors:   Vanderbilt University Medical Center;   American Heart Association
  Recruiting

• Inhibition of Bradykinin in COVID-19 Infection With Icatibant - Condition:   SARS CoV 2 Infection
  Interventions:   Drug: Icatibant;   Drug: 0.9% Sodium Chloride Injection
  Sponsors:   Belfast Health and Social Care Trust;   Queen’s University, Belfast
  Recruiting

From PubMed

• Identification of potent inhibitors of arenavirus and SARS-CoV-2 exoribonucleases by fluorescence polarization assay - Viral exoribonucleases are uncommon in the world of RNA viruses. To date, they have only been identified in the Arenaviridae and the Coronaviridae families. The exoribonucleases of these viruses play a crucial role in the pathogenicity and interplay with host innate immune response. Moreover, coronaviruses exoribonuclease is also involved in a proofreading mechanism ensuring the genetic stability of the viral genome. Because of their key roles in virus life cycle, they constitute attractive…

• Microneedle-based Two-step Transdermal Delivery of Langerhans cell-targeting Immunoliposomes Induces a Th1-biased Immune response - Novel Coronavirus is affecting human’s life globally and vaccines are one of the most effective ways to combat the epidemic. Transcutaneous immunization based on microneedle (MN) has attracted much attention because of its painlessness, rapidity, high efficiency and good compliance. In this study, CD11c monoclonal antibody-immunoliposomes (OVA@CD11c-ILP) actively targeting to Langerhans cells (LCs) were successfully prepared and were delivered by the microchannels of skin produced by MN to…

• Synergistic interactions of repurposed drugs that inhibit Nsp1, a major virulence factor for COVID-19 - Nsp1 is one of the first proteins expressed from the SARS-CoV-2 genome and is a major virulence factor for COVID-19. A rapid multiplexed assay for detecting the action of Nsp1 was developed in cultured lung cells. The assay is based on the acute cytopathic effects induced by Nsp1. Virtual screening was used to stratify compounds that interact with two functional Nsp1 sites: the RNA-binding groove and C-terminal helix-loop-helix region. Experimental screening focused on compounds that could be…

• A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants - A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet…

• Preadmission Statin Treatment and Outcome in Patients Hospitalized With COVID-19 - Preadmission statin therapy is associated with improved outcome in patients hospitalized with COVID-19. Whether inhibition of inflammation and myocardial injury are in part responsible for this observation has not been studied. The aim of the present study was to relate preadmission statin usage to markers of inflammation, myocardial injury, and clinical outcome among patients with established atherosclerosis who were admitted with COVID-19. Adult patients with a diagnosis of coronary artery…

• Quinic and digallic acids from Pistacia atlantica Desf. leaves extracts as potent dual effect inhibitors against main protease and RNA-dependent RNA polymerase of SARS-CoV-2 - CONCLUSION: This is the first time that a group of identified compounds from Pistacia atlantica Desf. leaves is studied for their potential activity against the novel virus by inhibiting two key enzymes in its life cycle, and no further studies have been published in this context.

• Multi-Targeted Molecular Docking and Drug-Likeness Evaluation of some Nitrogen Heterocyclic Compounds Targeting Proteins Involved in Development of COVID-19 - CONCLUSION: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity.

• Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide - Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential…

• Overview of Breastfeeding Under COVID-19 Pandemic - During the global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pregnant and lactating women are at higher risk of infection. The potential of viral intrauterine transmission and vertical transmission by breastfeeding has raised wide concerns. Breastmilk is rich in nutrients that contribute to infant growth and development, and reduce the incidence rate of infant illness and death, as well as inhibit pathogens…

• Priming With Rhinovirus Protects Mice Against a Lethal Pulmonary Coronavirus Infection - Rhinoviruses (RV) have been shown to inhibit subsequent infection by heterologous respiratory viruses, including influenza viruses and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). To better understand the mechanisms whereby RV protects against pulmonary coronavirus infection, we used a native murine virus, mouse hepatitis virus strain 1 (MHV-1), that causes severe disease in the lungs of infected mice. We found that priming of the respiratory tract with RV completely prevented…

• 2-deoxy-D-glucose as India’s Response to COVID-19: A Commitment or Conceit? - 2-deoxy-d-glucose (2-DG) has recently been approved for the treatment of moderate to severe COVID-19 patients in India. Here we discuss whether this is a well-thought-out step towards the long-term management of COVID-19 or a decision taken at the spur of the moment. 2-DG, an anticancer drug, also has immunomodulatory functions. Several studies have shown 2-DG to inhibit viral replication and cytokine storm. However, these findings are mostly on cells and animal models. The clinical trial that…

• Sonic hedgehog pathway for the treatment of inflammatory diseases: implications and opportunities for future research - The Sonic hedgehog (Shh) signaling pathway is an essential pathway in the human body that plays an important role in embryogenesis and tissue homeostasis. Aberrant activation of this pathway has been linked to the development of different diseases, ranging from cancer to immune dysregulation and infections.Uncontrolled activation of the pathway through sporadic mutations or other mechanisms is associated with cancer development and progression in various malignancies, such as basal cell…

• Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial - The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease (COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect…

• Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice - With the widespread use of volatile anesthetic agents in the prolonged sedation for COVID-19 pneumonia and ARDS, there is an urgent need to investigate the effects and treatments of lengthy low-concentration inhaled anesthetics exposure on cognitive function in adults. Previous studies showed that general anesthetics dose- and exposure length-dependently induced neuroinflammatory response and cognitive decline in neonatal and aging animals. The anti-diabetes drug metformin has…

• Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure-Activity Relationships, Antiviral Activity, and X-ray Structure Determination - The main protease (M^(pro), 3CL^(pro)) of SARS-CoV-2 is an attractive target in coronaviruses because of its crucial involvement in viral replication and transcription. Here, we report on the design, synthesis, and structure-activity relationships of novel small-molecule thioesters as SARS-CoV-2 M^(pro) inhibitors. Compounds 3w and 3x exhibited excellent SARS-CoV-2 M^(pro) inhibition with k(inac)/K(i) of 58,700 M^(-1) s^(-1) (K(i) = 0.0141 μM) and 27,200 M^(-1) s^(-1) (K(i) = 0.0332 μM),…

From Patent Search