Covid-19 Sentry

Contents

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

From Preprints

• Minor intron containing genes: Achilles’ heel of viruses? -
  The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the world’s unpreparedness to deal with the emergence of novel pathogenic viruses, pointing to the urgent need to identify targets for broad-spectrum antiviral strategies. Here, we report that proteins encoded by Minor Intron-containing Genes (MIGs) are significantly enriched in datasets of cellular proteins that are leveraged by SARS-CoV-2 and other viruses. Pointing to a general gateway for viruses to tap cellular machinery, MIG-encoded proteins (MIG-Ps) that react to the disruption of the minor spliceosome are most important points of viral attack, suggesting that MIG-Ps may pan-viral drug targets. While contemporary anti-viral drugs shun MIG-Ps, we surprisingly found that anti-cancer drugs that have been repurposed to combat SARS-CoV-2, indeed target MIG-Ps, suggesting that such genes can potentially be tapped to efficiently fight viruses.
  🖺 Full Text HTML: Minor intron containing genes: Achilles’ heel of viruses?
• Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response -
  The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-{gamma}) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.
  🖺 Full Text HTML: Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response
• Reproducibility of spatial summation of pain effect during COVID-19 pandemic -
  The ongoing COVID-19 pandemic has led to many restrictions affecting the research conduct. The purpose of this study was to reproduce the previously observed spatial summation of pain effect (SSp) using non-laboratory procedures and commercial equipment. An additional aim was to measure the association between expectation and SSp for the first time. The Cold Pressor Task (CPT) was used to induce SSp. Healthy participants (N=68) immersed their non-dominant hands (divided into 5 segments) into cold water (Cold Pressor Task). Two conditions were used 1) gradual hand immersion (ascending condition) and 2) gradual hand withdrawal (descending condition). Pain intensity was measured on a Visual Analogue Scale (VAS). The influence of psychological factors, such as the volunteer’s expectation of pain intensity, on the actual perception of pain were also measured on a VAS. Results showed significant SSp (p < 0.001), reproduced with non-laboratory equipment in a home-based set-up. Furthermore, two novel findings were observed: i) spatial summation increased with the increase in exposure to the noxious stimulus (p < 0.001), ii) there was a significant correlation between expectation and perceived pain, indicating that pain expectations can contribute to SSp. Results showed that SSp is shaped by a mixture of excitatory and inhibitory mechanisms and is influenced by the sensitization of the nociceptive system. Moreover, spatial summation is influenced by expectation. This study proposes a new feasible way to induce SSp using a home-based set-up using the CPT during COVID-19.
  🖺 Full Text HTML: Reproducibility of spatial summation of pain effect during COVID-19 pandemic
• CiDRE+ M2c macrophages hijacked by SARS-CoV-2 cause COVID-19 severity -
  Infection of the lungs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin I converting enzyme 2 (ACE2) receptor induces a type of systemic inflammation known as a cytokine storm. However, the precise mechanisms involved in severe coronavirus disease 2019 (COVID-19) pneumonia are unknown. Here, we show that interleukin-10 (IL-10) changed normal alveolar macrophages into ACE2-expressing M2c-type macrophages that functioned as spreading vectors for SARS-CoV-2 infection. The depletion of alveolar macrophages and blockade of IL-10 attenuated SARS-CoV-2 pathogenicity. Furthermore, genome-wide association and quantitative trait locus analyses identified novel mRNA transcripts in human patients, COVID-19 infectivity enhancing dual receptor (CiDRE), which has unique synergistic effects within the IL-10-ACE2 system in M2c-type macrophages. Our results demonstrate that alveolar macrophages stimulated by IL-10 are key players in severe COVID-19. Collectively, CiDRE expression levels are potential risk factors that predict COVID-19 severity, and CiDRE inhibitors might be useful as COVID-19 therapies.
  🖺 Full Text HTML: CiDRE+ M2c macrophages hijacked by SARS-CoV-2 cause COVID-19 severity
• SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks -
  With new daily discoveries about the long-term impacts of COVID-19 there is a clear need to develop in vitro models that can be used to better understand the pathogenicity and impact of COVID-19. Here we demonstrate the utility of developing a model of endothelial dysfunction that utilizes induced pluripotent stem cell-derived endothelial progenitors encapsulated in collagen hydrogels to study the effects of COVID-19 on the endothelium. We found that treating these cell-laden hydrogels with SARS-CoV-2 spike protein resulted in a significant decrease in the number of vessel-forming cells as well as vessel network connectivity. Following treatment with the anti-inflammatory drug dexamethasone, we were able to prevent SARS-CoV-2 spike protein-induced endothelial dysfunction. In addition, we confirmed release of inflammatory cytokines associated with the COVID-19 cytokine storm. In conclusion, we have demonstrated that even in the absence of immune cells, we are able to use this 3D in vitro model for angiogenesis to reproduce COVID-19 induced endothelial dysfunction seen in clinical settings.
  🖺 Full Text HTML: SARS-CoV-2 spike protein induces endothelial dysfunction in 3D engineered vascular networks
• Mask-wearing increased after a government recommendation: A natural experiment in the U.S. during the COVID-19 pandemic -
  On April 3 2020, the U.S. Centers for Disease Control and Prevention (CDC) recommended that all Americans wear face masks to prevent the spread of COVID-19. The announcement came during the fielding of a large, nationally-representative survey (N = 3,933) of Americans’ COVID-19-related knowledge, attitudes, and behaviors, providing an opportunity to measure the impact of the CDC’s recommendation on public reported mask wearing and buying behavior. The study found significant increases in reported mask wearing (+12 percentage points) and mask buying (+7 points). These findings indicate the speed with which government recommendations can affect the adoption of protective behaviors by the public. The results demonstrate the importance of national leadership and communication during a public health crisis.
  🖺 Full Text HTML: Mask-wearing increased after a government recommendation: A natural experiment in the U.S. during the COVID-19 pandemic
• Validity of energy social research during and after COVID-19: challenges, considerations, and responses -
  Measures to control the spread of coronavirus disease 2019 (COVID-19) are having unprecedented impacts on people’s lives around the world. In this paper, we argue that those conducting social research in the energy domain should give special consideration to the internal and external validity of their work conducted during this pandemic period. We set out a number of principles that researchers can consider to give themselves and research users greater confidence that findings and recommendations will still be applicable in years to come. Largely grounded in existing good practice guidance, our recommendations include collecting and reporting additional supporting contextual data, reviewing aspects of research design for vulnerability to validity challenges, and building in longitudinal elements where feasible. We suggest that these approaches also bring a number of opportunities to generate new insights. However, we caution that a more systemic challenge to validity of knowledge produced during this period may result from changes in the kinds of social research that it is practicable to pursue.
  🖺 Full Text HTML: Validity of energy social research during and after COVID-19: challenges, considerations, and responses
• Social norms motivate COVID-19 preventive behaviors -
  In this working paper, we used a large national survey of American adults (N = 3,933) to estimate the effect of perceived social norms among friends and family (i.e., how often friends and family perform preventive behaviors, and whether they think it is important for the respondent to do so) on people’s own COVID-19 preventive behaviors. We found that perceived norms within these close relationships are often strongly associated with the adoption of preventive behavior–in some cases more than doubling the odds that an individual will engage in a given behavior.
  🖺 Full Text HTML: Social norms motivate COVID-19 preventive behaviors
• Americans’ Risk Perceptions and Emotional Responses to COVID-19, April 2020 -
  Drawing on a scientific national survey (N = 3,933; including 3,188 registered voters), this report describes Americans’ risk perceptions and emotional responses to COVID-19 to inform the public health community, policymakers, and the public.
  🖺 Full Text HTML: Americans’ Risk Perceptions and Emotional Responses to COVID-19, April 2020
• A gateway conspiracy? Belief in COVID-19 conspiracy theories prospectively predicts greater conspiracist ideation -
  A primary focus of research on conspiracy theories has been understanding the psychological characteristics that predict people’s level of conspiracist ideation. However, the dynamics of conspiracist ideation—i.e., how such tendencies change over time—are not well understood. To help fill this gap in the literature, we used data from longitudinal studies conducted during the COVID-19 pandemic. We find that greater belief in COVID-19 conspiracy theories at baseline predicts both greater endorsement of a novel real-world conspiracy theory involving voter fraud in the 2020 American Presidential election (Study 1) and increases in generic conspiracist beliefs over a period of several months (Studies 1 and 2). Thus, engaging with real-world conspiracy theories appears to act as a gateway, leading to more general increases in conspiracist ideation. Beyond enhancing our knowledge of conspiracist ideation, this work highlights the importance of fighting the spread of conspiracy theories.
  🖺 Full Text HTML: A gateway conspiracy? Belief in COVID-19 conspiracy theories prospectively predicts greater conspiracist ideation
• Modelling the epidemiological implications for SARS-CoV-2 of Christmas household bubbles in England -

  The emergence of SARS-CoV-2 saw severe detriments to public health being inflicted by COVID-19 disease throughout 2020. In the lead up to Christmas 2020, the UK Government sought an easement of social restrictions that would permit spending time with others over the Christmas period, whilst limiting the risk of spreading SARS-CoV-2. In November 2020, plans were published to allow individuals to socialise within `Christmas bubbles9 with friends and family. This policy involved a planned easing of restrictions in England between 23-27 December 2020, with Christmas bubbles allowing people from up to three households to meet throughout the holiday period. We estimated the epidemiological impact of both this and alternative bubble strategies that allowed extending contacts beyond the immediate household. We used a stochastic individual-based model for a synthetic population of 100,000 households, with demographic and SARS-CoV-2 epidemiological characteristics comparable to England as of November 2020. We evaluated five Christmas bubble scenarios for the period 23-27 December 2020, assuming our populations of households did not have symptomatic infection present and were not in isolation as the eased social restrictions began. Assessment comprised incidence and cumulative infection metrics. We tested the sensitivity of the results to a situation where it was possible for households to be in isolation at the beginning of the Christmas bubble period and also when there was lower adherence to testing, contact tracing and isolation interventions. We found that visiting family and friends over the holiday period for a shorter duration and in smaller groups was less risky than spending the entire five days together. The increases in infection from greater amounts of social mixing disproportionately impacted the eldest. We provide this account as an illustration of a real-time contribution of modelling insights to a scientific advisory group, the Scientific Pandemic Influenza Group on Modelling, Operational sub-group (SPI-M-O) for the Scientific Advisory Group for Emergencies (SAGE) in the UK, during the COVID-19 pandemic. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”.

  🖺 Full Text HTML: Modelling the epidemiological implications for SARS-CoV-2 of Christmas household bubbles in England
• Fifteen Years of India’s NREGA: Employer of the Last Resort? -
  For the last decade, India’s National Rural Employment Guarantee Act (NREGA, 2005) has been the world’s largest public works programme. This legal entitlement provided employment to 28 percent of rural Indian households in 2019-20. After the COVID-19 pandemic, NREGA is increasingly emerging as an invaluable employer of the last resort. However, longitudinal data of its implementation in the last fifteen years reveals distinctive trends. On the one hand, since inception NREGA has rendered greater benefit to women and marginalised communities. But on the other, since 2014, the right-wing Bharatiya Janata Party (BJP)-led government has reduced NREGA coverage compared to its implementation during the previous Indian National Congress (INC)-led United Progressive Alliance (UPA) coalition which had enacted the legislation. Nevertheless, in light of the pandemic and based on from international experiences, there is an urgent need for expansion of the employment guarantee.
  🖺 Full Text HTML: Fifteen Years of India’s NREGA: Employer of the Last Resort?
• Understanding change in COVID-19 vaccination intention with network analysis of longitudinal data from Dutch adults -
  Prior research into the relationship between attitudes and vaccination intention is predominantly cross sectional and therefore does not provide insight into directions of relations. During the COVID-19 vaccines development and enrollment phase, we studied the temporal dynamics of COVID-19 vaccination intention in relation to attitudes toward COVID-19 vaccines and the pandemic, vaccination in general, social norms and trust. The data are derived from a longitudinal survey study with Dutch participants from a research panel (N = 744; six measurements between December 2020 and May 2021; age 18 – 84 years [M = 53.32]) and analyzed with vector-autoregression network analyses. While cross-sectional results indicated that vaccination intention was relatively strongly related to attitudes toward the vaccines, results from temporal analyses showed that vaccination intention mainly predicted other vaccination-related variables and to a lesser extent was predicted by variables. We found a weak predictive effect from social norm to vaccination intention that was not robust. This study underlines the challenge of stimulating uptake of new vaccines developed during pandemics, and the importance of examining directions of effects in research into vaccination intention.
  🖺 Full Text HTML: Understanding change in COVID-19 vaccination intention with network analysis of longitudinal data from Dutch adults
• A psychological network approach to attitudes and preventive behaviors during pandemics: A COVID-19 study in the United Kingdom and the Netherlands -
  Preventive behaviors are crucial to prevent spread of the coronavirus causing COVID-19. We adopted a complex psychological systems approach to obtain a descriptive account of the network of attitudes and behaviors related to COVID-19. A survey study (N = 1022) was conducted with subsamples from the United Kingdom (n = 502) and the Netherlands (n = 520). The results highlight the importance of people’s support for, and perceived efficacy of, the measures and preventive behaviors. This also applies to the perceived norm of family and friends adopting these behaviors. The networks in both countries were largely similar but also showed notable differences. The interplay of psychological factors in the networks is also highlighted, resulting in our appeal to policymakers to take complexity and mutual dependence of psychological factors into account. Future research should study effects of interventions aimed at these factors, including effects on the network, to make causal inferences.
  🖺 Full Text HTML: A psychological network approach to attitudes and preventive behaviors during pandemics: A COVID-19 study in the United Kingdom and the Netherlands
• Immune responses of the third dose of AZD1222 vaccine or BNT162b2 mRNA vaccine after two doses of CoronaVac vaccines against Delta and Omicron variants -

  Summary. Half-dose AZD1222 or BNT162b2 boosters maintained immunogenicity and safety, and were non-inferior to full doses. All doses elicited high immunogenicity and best with extended post-CoronaVac primary-series intervals (120-180 days) and high-transmissibility Omicron. Methods. At 60-to-<90, 90-to-<120, or 120-to-180 days (intervals) post-CoronaVac primary-series, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, and followed up at day-28, -60 and -90. Vaccination-induced immunogenicity to Ancestral, Delta and Omicron BA.1 strains were evaluated by assessing anti-spike (anti-S), anti-nucleocapsid antibodies, pseudovirus neutralization (PVNT), micro-neutralization titers, and T-cells assays. Descriptive statistics and non-inferiority cut-offs were reported as geometric mean concentration (GMC) or titer (GMT) and GMC/GMT ratios comparing baseline to day-28 and day-90 seroresponses, and different intervals post-CoronaVac primary-series. Omicron immunogenicity was only evaluated in full-dose recipients. Findings. No serious or severe vaccine-related safety events occurred. All assays and intervals showed non-inferior immunogenicity between full-doses and half-doses. However, full-dose vaccines and/or longer, 120-to-180-day intervals substantially improved immunogenicity (in GMC measured by anti-S assays or GMT measured by PVNT50; p <0.001). Within platforms and regardless of dose or platform, seroconversions were over 97%, and over 90% for pseudovirus neutralizing antibodies, but similar against the SARS-CoV-2 strains. Immunogenicity waned more quickly with half-doses than full-doses between day 60-to-90 follow-ups, but remained high against Ancestral or Delta strains. Against Omicron, the day-28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines. Interpretation. Combining heterologous schedules, fractional dosing, and extended post-second dose intervals, broadens population-level protection and prevents disruptions, especially in resource-limited settings. Funding. Funding was provided by the Program Management Unit for Competitiveness Enhancement (PMU-C) National research, National Higher Education, Science, Research and Innovation Policy Council, Thailand through Clinixir Ltd.

  🖺 Full Text HTML: Immune responses of the third dose of AZD1222 vaccine or BNT162b2 mRNA vaccine after two doses of CoronaVac vaccines against Delta and Omicron variants

From Clinical Trials

• The Efficacy and Safety of TADIOS as an Adjuvant Therapy in Patients Diagnosed With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: TADIOS;   Drug: Placebo
  Sponsor:   Helixmith Co., Ltd.
  Completed

• COVID-19 iCura SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Device: iCura COVID-19 Antigen Rapid Home Test;   Diagnostic Test: RT-PCR Test
  Sponsors:   EDP Biotech;   Paragon Rx Clinical, Inc.;   iCura Diagnostics, LLC
  Recruiting

• FMT for Post-acute COVID-19 Syndrome - Conditions:   Post-Acute COVID19 Syndrome;   COVID-19
  Intervention:   Procedure: Faecal Microbiota Transplantation
  Sponsor:   Chinese University of Hong Kong
  Recruiting

• Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia - Condition:   COVID-19
  Intervention:   Drug: DILTIAZEM TEVA 60 mg or placebo
  Sponsors:   Hospices Civils de Lyon;   Signia Therapeutics
  Not yet recruiting

• Research on Community Based ATK Test Study to Control Spread of COVID-19 in Migrant Community - Condition:   COVID-19 Pandemic
  Intervention:   Device: STANDARD Q COVID-19 Ag Test
  Sponsor:   University of Oxford
  Active, not recruiting

• Safety and Immunogenicity of COVID-19 Vaccine in Population Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: low-dose LYB001;   Biological: Recombinant COVID-19 Vaccine (CHO Cell);   Biological: high-dose LYB001
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.
  Recruiting

• The Efficacy and Safety of BioBlock® Intranasally Administered Virus-Neutralizing Bovine Colostrum Nasal Spray in Preventing of COVID-19 (Coronavirus Disease-19) Infection in Healthy Volunteer Individuals - Condition:   SARS CoV 2 Infection
  Intervention:   Biological: BioBlock® antiviral nasal spray
  Sponsor:   Chemi-Pharm AS
  Recruiting

• Safety, Tolerability, and Immunogenicity of Trivalent Coronavirus Vaccine Candidate VBI-2901a - Conditions:   COVID-19;   Coronavirus Infections
  Intervention:   Biological: VBI-2901a
  Sponsor:   VBI Vaccines Inc.
  Not yet recruiting

• Understanding the Impact of Death Conditions Linked to the COVID-19 Crisis on the Grieving Process in Bereaved Families - Condition:   Psychological Disorder
  Intervention:   Other: Qualitative research interview
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• 3EO Health SARS-CoV-2 OTC At Home Test - Condition:   COVID-19 Pandemic
  Intervention:   Diagnostic Test: In Vitro
  Sponsor:   3EO Health
  Not yet recruiting

• Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial - Conditions:   HIV;   Organ Transplantation;   Lymphoma, Non-Hodgkin;   Chronic Lymphocytic Leukemia;   Multiple Myeloma;   COVID-19 Vaccines
  Interventions:   Biological: BNT162b2;   Biological: mRNA-1273;   Biological: NVX-COV2373
  Sponsors:   Bayside Health;   Monash University
  Not yet recruiting

• PAPR: PAP + MBSR for Front-line Healthcare Provider COVID-19 Related Burnout - Conditions:   Depression;   Burnout, Professional
  Interventions:   Drug: Psilocybin;   Behavioral: Mindfulness-Based Stress Reduction (MBSR)
  Sponsors:   University of Utah;   Heffter Research Institute;   Usona Institute
  Not yet recruiting

• Physiology of Long COVID and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity - Condition:   Post-acute Sequelae of SARS-CoV-2 Infection
  Intervention:   Behavioral: Exercise
  Sponsor:   University of Colorado, Denver
  Not yet recruiting

• Scaling Well-Being for Educators During COVID-19 - Conditions:   Anxiety;   Depression
  Intervention:   Behavioral: Healthy Minds Program Foundations Training
  Sponsors:   University of Wisconsin, Madison;   Chan Zuckerberg Initiative
  Not yet recruiting

• A Cohort Study of COVID-19 mRNA Vaccine, Bivalent in Participants in China - Condition:   SARS-CoV-2
  Interventions:   Biological: SARS-CoV-2 mRNA Vaccine, Bivalent Low dose;   Biological: SARS-CoV-2 mRNA Vaccine, Bivalent High dose;   Drug: Placebo
  Sponsors:   AIM Vaccine Co., Ltd.;   Ningbo Rongan Biological Pharmaceutical Co. Ltd;   First Affiliated Hospital Bengbu Medical College
  Not yet recruiting

From PubMed

• Reducing delayed transfer of care in older people: A qualitative study of barriers and facilitators to shorter hospital stays - CONCLUSION: Poor quality and availability of information, and poor communication, inhibit effective transfer of care. Communication is fundamental to patient-centred care and even more important in discharge models characterized by limited assessments and quicker discharge. Interventions at the service level and targeted patient information about what to expect in discharge assessments and after discharge could help to address poor communication and support for improving discharge of older…

• RNA-dependent RNA polymerase (RdRp) natural antiviral inhibitors: a review - Viral diseases are the cause of many global epidemics, leading to deaths, affecting the quality of life of populations, and impairing public health. The limitations in the treatment of viral diseases and the constant resistance to conventional antiviral treatments encourage researchers to discover new compounds. In this perspective, this literature review presents isolated molecules and extracts of natural products capable of inhibiting the activity of the nonstructural protein that acts as the…

• Novel α-aminophosphonate derivates synthesis, theoretical calculation, Molecular docking, and in silico prediction of potential inhibition of SARS-CoV-2 - Using the Density Functional Theory approach and in silico docking, the current study analyzes the inhibitory role of a novel α-aminophosphonate derivative against SARS-CoV-2 major protease (Mpro) and RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. FT-IR, UV-Vis, and NMR (1H, 13C, 31P) approaches were used to produce and confirm the novel α-aminophosphonate derivative. The quantum chemical parameters were detremined, and the reactivity of the synthesized molecule was discussed using DFT at…

• Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients - The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2^(nd) dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6…

• Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2 - Three directly acting antivirals (DAAs) demonstrated substantial reduction in COVID-19 hospitalizations and deaths in clinical trials. However, these agents did not completely prevent severe illness and are associated with cases of rebound illness and viral shedding. Combination regimens can enhance antiviral potency, reduce the emergence of drug-resistant variants, and lower the dose of each component in the combination. Concurrently targeting virus entry and virus replication offers…

• Correction for Zhao et al., “Gasdermin D Inhibits Coronavirus Infection by Promoting the Noncanonical Secretion of Beta Interferon” - No abstract

• Crystal structure of the Rho-associated coiled-coil kinase 2 inhibitor belumosudil bound to CK2α - The small molecule belumosudil was initially identified as a selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2) and has recently been approved for the treatment of graft-versus-host disease. However, recent studies have shown that many of the phenotypes displayed upon treatment with belumosudil were due to CK2α inhibition. CK2α is in itself a very promising therapeutic target for a range of conditions and has recently been put forward as a potential treatment for COVID-19….

• IL-4 receptor blockade is a global repressor of naïve B cell development and responses in a dupilumab-treated patient - Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naïve B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in…

• Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines - SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth…

• Case report: Refractory intestinal Behçet’s syndrome successfully treated with tofacitinib: A report of four cases - Behçet’s syndrome (BS) is a chronic form of relapsing multisystem vasculitis, characterized by recurrent oral and genital ulcers. Intestinal BS is a special type of BS. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BS, and punched-out ulcers can be observed in the intestine or esophagus. At present, there is no recognized radical treatment for intestinal BS. Glucocorticoids and immunosuppressants are currently the main drugs used to improve the condition. Although it…

• Searching for potential inhibitors of SARS-COV-2 main protease using supervised learning and perturbation calculations - Inhibiting the biological activity of SARS-CoV-2 Mpro can prevent viral replication. In this context, a hybrid approach using knowledge- and physics-based methods was proposed to characterize potential inhibitors for SARS-CoV-2 Mpro. Initially, supervised machine learning (ML) models were trained to predict a ligand-binding affinity of ca. 2 million compounds with the correlation on a test set of R = 0.748 ± 0.044 . Atomistic simulations were then used to refine the outcome of the ML model….

• Emotions and Incivility in Vaccine Mandate Discourse: Natural Language Processing Insights - CONCLUSIONS: The results suggest that our multidimensional approach to incivility is a promising alternative to understanding and intervening in the psychological processes underlying uncivil vaccine discourse. Understanding specific emotions that can increase or decrease incivility such as anxiety, anger, and sadness can enable researchers and public health professionals to develop effective interventions against uncivil vaccine discourse. Given the need for real-time monitoring and automated…

• Potent Virustatic Polymer-Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo - Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanoparticles that mimic functional components of host cell membranes, yielding multivalent nanomimics that act by directly binding to varied pathogens. Nanomimic blood circulation time was prolonged by reformulating polymer-lipid hybrids. Femtomolar concentrations of the polymer nanomimics…

• A genetically encoded BRET-based SARS-CoV-2 M^pro protease activity sensor - The main protease, M^(pro), is critical for SARS-CoV-2 replication and an appealing target for designing anti-SARS-CoV-2 agents. Therefore, there is a demand for the development of improved sensors to monitor its activity. Here, we report a pair of genetically encoded, bioluminescence resonance energy transfer (BRET)-based sensors for detecting M^(pro) proteolytic activity in live cells as well as in vitro. The sensors were generated by sandwiching peptides containing the M^(pro) N-terminal…

• Effectiveness of Remdesivir in Comparison with Five Approved Antiviral Drugs for Inhibition of RdRp in Combat with SARS-CoV-2 - The treatment of COVID-19 disease has been one of the most critical essential concerns of researchers in recent years. One of the most exciting and potential therapeutic targets for SARS-CoV-2 therapy progression is RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication throughout host cells. According to some research, Remdesivir suppresses RdRp. The nucleoside medication remdesivir has been authorized under an Emergency Use Authorization to treat COVID-19. Given the role…

From Patent Search