Covid-19 Sentry

Contents

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

From Preprints

• Pandemic Fatigue: Measurement, Correlates, and Consequences -
  In response to the COVID-19 pandemic, governments and health authorities worldwide have both recommended and mandated various health-protective behaviors to contain the spread of the virus and ultimately save lives. Despite strong public support for these measures overall, several countries have over the course of the pandemic witnessed a gradual decrease in adherence to recommended health-protective behaviors—a trend that has been attributed to the dawn and rise of pandemic fatigue. In absence of a clear conceptualization and psychometrically validated measure of pandemic fatigue, however, this claim remains highly speculative as the observed decrease in public adherence might very well be driven by a myriad of different factors in- or excluding pandemic fatigue. Tackling this issue and relying on quota- representative repeated cross-sectional and panel data from Denmark and Germany (overall N = 34,582), after introducing a theoretically informed conceptualization of pandemic fatigue and a corresponding brief measure with good psychometric properties, we investigate the development of pandemic fatigue over time, explore who experiences it, identify related emotions and perceptions, and shed light on the link between pandemic fatigue and adherence to various health-protective behaviors. In addition, we explore the causal impact of pandemic fatigue on people’s intention to adhere to different health- protective behaviors in a preregistered online experiment conducted with U.S. participants (N = 1,584). Taken together, our results provide much needed evidence with regard to the existence, nature, correlates, and consequences of pandemic fatigue, informative now as well as for future pandemics.
  🖺 Full Text HTML: Pandemic Fatigue: Measurement, Correlates, and Consequences
• Continuous genomic diversification of long polynucleotide fragments drives the emergence of new SARS-CoV-2 variants of concern -

  Highly transmissible or immuno-evasive SARS-CoV-2 variants have intermittently emerged and outcompeted previously circulating strains, resulting in repeated COVID-19 surges, reinfections, and breakthrough infections in vaccinated individuals. With over 5 million SARS-CoV-2 genomes sequenced globally over the last 2 years, there is unprecedented data to decipher how competitive viral evolution results in the emergence of fitter SARS-CoV-2 variants. Much attention has been directed to studying how specific mutations in the Spike protein impact its binding to the ACE2 receptor or viral neutralization by antibodies, but there is limited knowledge of a genomic signature that is shared primarily by the sequential dominant variants. Here we introduce a methodology to quantify the genome-wide distinctiveness of polynucleotide fragments of various lengths (3- to 240-mers) that constitute SARS-CoV-2 sequences (freely available at https://academia.nferx.com/GENI). Compared to standard phylogenetic distance metrics and overall mutational load, the quantification of distinctive 9-mer polynucleotides provides a higher resolution of separation between VOCs (Reference = 89, IQR: 65-108; Alpha = 166, IQR: 150-182; Beta 130, IQR: 113-147; Gamma = 165, IQR: 152-180; Delta = 234, IQR: 216-253; and Omicron = 294, IQR: 287-315). Omicron9s exceptionally high genomic distinctiveness may confer a competitive advantage over both prior VOCs (including Delta) and the recently emerged and highly mutated B.1.640.2 (IHU) lineage. Expanding on this analysis, evaluation of genomic distinctiveness weighted by intra-lineage 9-mer conservation for 1,363 lineages annotated in GISAID highlights that genomic distinctiveness has increased over time (R2=0.37) and that VOCs score significantly higher than contemporary non-VOC lineages, with Omicron among the most distinctive lineages observed till date. This study demonstrates the value of characterizing new SARS-CoV-2 variants by their genome-wide polynucleotide distinctiveness and emphasizes the need to go beyond a narrow set of mutations at known functionally or antigenically salient sites on the Spike protein. The consistently higher distinctiveness of each emerging VOC compared to prior VOCs suggests that real-time monitoring of genomic distinctiveness would aid in more rapid assessment of viral fitness.

  🖺 Full Text HTML: Continuous genomic diversification of long polynucleotide fragments drives the emergence of new SARS- CoV-2 variants of concern
• Vaccination or restriction?: COVID-19 vaccine hesitancy and vaccine passports -

  Objectives: While the development of vaccines against the novel coronavirus (COVID-19) brought the hope of establishing herd immunity, which might help end the global pandemic, vaccine hesitancy can hinder the progress towards herd immunity. In this study, we assess the determinants of vaccine hesitancy, reasons for hesitation, and effectiveness of vaccine passports in relaxing public health restrictions. Methods: Through an online survey that includes a conjoint experiment of a demographically representative sample of 5,000 Japanese adults aged 20-74, we assess the determinants of vaccine hesitancy, reasons for hesitation, and effectiveness of hypothetical vaccine passports. Results: We found that about 30% of respondents did not intend to vaccinate or have not yet decided, with major reasons for vaccine hesitancy being related to concerns about the safety and side effects of the vaccine. In line with previous findings, younger age, lower socioeconomic status, and psychological factors such as weaker COVID-19 fear were associated with vaccine hesitancy. The easing of public health restrictions such as travel, wearing face masks, and dining out at night was associated with an increase in vaccine acceptance by 4-10%. Conclusion: Vaccine hesitancy can be reduced by mitigating the concerns about vaccine safety and side effects, as well as by relaxing public health restrictions. However, the feasibility of vaccine passports needs to be sufficiently assessed, taking the ethical issues of passports and the public health impacts of the relaxation of restrictions into careful consideration.

  🖺 Full Text HTML: Vaccination or restriction?: COVID-19 vaccine hesitancy and vaccine passports
• Lineage replacement and evolution captured by the United Kingdom Covid Infection Survey -

  The Office for National Statistics COVID-19 Infection Survey is a large household-based surveillance study based in the United Kingdom. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing sequenced samples collected up until 13th November 2021. We observed four distinct sweeps or partial-sweeps, by lineages B.1.177, B.1.1.7/Alpha, B.1.617.2/Delta, and finally AY.4.2, a sublineage of B.1.617.2, with each sweeping lineage having a distinct growth advantage compared to their predecessors. Evolution was characterised by steady rates of evolution and increasing diversity within lineages, but with step increases in divergence associated with each sweeping major lineage, leading to a faster overall rate of evolution and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly as routine PCR testing is phased out or in settings where large-scale sequencing is not feasible.

  🖺 Full Text HTML: Lineage replacement and evolution captured by the United Kingdom Covid Infection Survey
• Autophagy and evasion of immune system by SARS-CoV-2. Structural features of the Non-structural protein 6 from Wild Type and Omicron viral strains interacting with a model lipid bilayer. -
  The viral cycle of SARS-CoV-2 is based on a complex interplay with the cellular machinery, which is mediated by specific proteins eluding or hijacking the cellular defense mechanisms. Among the complex pathways called by the viral infection autophagy is particularly crucial and is strongly influenced by the action of the non-structural protein 6 (Nsp6) interacting with the endoplasmic reticulum membrane. Importantly, differently from other non-structural proteins Nsp6 is mutated in the recently emerged Omicron variant, suggesting a possible different role of autophagy. In this contribution we explore, for the first time, the structural property of Nsp6 thanks to long-time scale molecular dynamic simulations and machine learning analysis, identifying the interaction patterns with the lipid membrane. We also show how the mutation brought by the Omicron variant may indeed modify some of the specific interactions, and more particularly help anchoring the viral protein to the lipid bilayer interface.
  🖺 Full Text HTML: Autophagy and evasion of immune system by SARS-CoV-2. Structural features of the Non-structural protein 6 from Wild Type and Omicron viral strains interacting with a model lipid bilayer.
• Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2 -
  The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In the present work, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC50) values between 0.41 M and 66 M. In addition, eight compounds inhibited PLpro with IC50 ranging from 1.7 M to 46 M. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.
  🖺 Full Text HTML: Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2
• Radiological follow-up of adults hospitalised with pneumonia and SARS-CoV-2 infection, in Bristol UK, during the COVID19 pandemic -

  For patients with pneumonia and COVID19 repeating chest radiography is recommend in current British Thoracic Society (BTS) guidelines. Over two distinct time periods during the COVID19 pandemic (Aug-Dec 2020, Jun-Aug 2021) we undertook an audit of 829 patients hospitalised with infective radiological change (pneumonia=481, COVID19=348). 654/829 patients (79%) required radiological follow-up under BTS guideline criteria. 414/654 (63%) were planned, 322/654 (49%) occurred and, of patients receiving radiological follow-up, most occurred within BTS timelines (86%). Further audits should be conducted to ensure BTS guidelines adherence, to avoid delay in diagnosing underlying malignancy or chronic lung disease.

  🖺 Full Text HTML: Radiological follow-up of adults hospitalised with pneumonia and SARS-CoV-2 infection, in Bristol UK, during the COVID19 pandemic
• COVID-19-Associated Hospitalizations Among Children Less Than 12 Years of Age in the United States -

  Objectives: To describe the characteristics, healthcare resource use and costs associated with initial hospitalization and readmissions among pediatric patients with COVID-19 in the US. Methods: Hospitalized pediatric patients, 0-11 years of age, with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) were selected from 1 April 2020 through 30 September 2021 in the US Premier Healthcare Database Special Release (PHD SR). Patient characteristics, hospital length of stay (LOS), in-hospital mortality, hospital costs, hospital charges, and COVID-19-associated readmission outcomes were evaluated and stratified by age groups (0-4, 5-11), four COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage, and three sequential calendar periods. Sensitivity analyses were performed using the US HealthVerity claims database and restricting the analyses to primary discharge code. Results: Among 4,573 hospitalized pediatric patients aged 0-11 years, 68.0% were 0-4 years and 32.0% were 5-11 years, with a mean (median) age of 3.2 (1) years; 56.0% were male, and 67.2% were covered by Medicaid. Among the overall study population, 25.7% had immunocompromised condition(s), 23.1% were admitted to the ICU and 7.3% received IMV. The mean (median) hospital LOS was 4.3 (2) days, hospital costs and charges were $14,760 ($6,164) and $58,418 ($21,622), respectively; in-hospital mortality was 0.5%. LOS, costs, charges, and in- hospital mortality increased with ICU admission and/or IMV usage. In total, 2.1% had a COVID-19-associated readmission. Study outcomes appeared relatively more frequent and/or higher among those 5-11 than those 0-4. Results using the HealthVerity data source were generally consistent with main analyses. Limitations: This retrospective administrative database analysis relied on coding accuracy and inpatient admissions with validated hospital costs. Conclusions: These findings underscore that children aged 0-11 years can experience severe COVID-19 illness requiring hospitalization and substantial hospital resource use, further supporting recommendations for COVID-19 vaccination.

  🖺 Full Text HTML: COVID-19-Associated Hospitalizations Among Children Less Than 12 Years of Age in the United States
• The Role of Theory of Truth in Countering Hoaxes Regarding Covid-19 -
  Indonesia is one of the countries experiencing the COVID-19 pandemic. This causes anxiety for the Indonesian people which makes information about COVID-19 becomes crucial. Objective: This research was conducted with the aim of studying philosophical theories that can play a role in the process of testing information in warding off hoaxes about COVID-19. Researchers want to know whether the theory of philosophy of science can be of assistance to the public in recognizing and rejecting hoax news about COVID-19. Methods: The research was conducted using a descriptive verification method with a qualitative approach. The data from this study were taken from interviews and secondary data was taken by studying the literature. Interview data were taken with the target respondents, namely people in Surabaya with an age range of 25-40 years or what is often referred to as generation Y or millennials. The criteria for determining the number of respondents were taken until the researcher found a saturated sample. Meanwhile, the literature study data consists of 2 books, 37 articles, 1 website, and 1 report on the results of a national survey. Results: This study found 5 types of theory of truth, namely coherence theory, correspondence theory, pragmatic theory, consensus theory, and performative theory, each of which has a use in identifying hoaxes around COVID-19. Research Recommendation: Further research needs to be conducted which can test the actual practice of applying truth theories in countering hoaxes in the community at a certain scale. Limitations: This research has little chance of being applied by some Indonesians, given their low level of digital literacy and willingness to seek information.
  🖺 Full Text HTML: The Role of Theory of Truth in Countering Hoaxes Regarding Covid-19
• Evaluation of Commercial Anti-SARS-CoV-2 Neutralizing Antibody Assays in seropositive subjects -

  The virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMerieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of

80. However, the performances of YHLO and bioMerieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.
    🖺 Full Text HTML: Evaluation of Commercial Anti-SARS-CoV-2 Neutralizing Antibody Assays in seropositive subjects

• Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients -

  Importance: Data on the humoral and cellular immune response to primary and booster SARS-CoV-2 vaccination in immunosuppressed patients is limited. Objective: To determine humoral and cellular response to primary and booster vaccination in immunosuppressed patients and identify variables associated with poor response. Design: Retrospective observational cohort study. Setting: Large healthcare system in Northern California. Participants: This study included patients fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) who underwent clinical testing for anti-SARS-SoV-2 S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon gamma release assay (IGRA) from January 1, 2021 through November 15, 2021. A cohort of 18 immunocompetent volunteer healthcare workers were included as reference. No participants had a prior diagnosis of SARS-CoV-2 infection. Exposure(s): Immunosuppressive diseases and therapies. Main Outcome(s) and Measure(s): Humoral and cellular SARS-CoV-2 vaccine response as measured by anti-S1 IgG and SARS-CoV-2 IGRA, respectively, after primary and booster vaccination. Results: 496 patients (54% female; median age 50 years) were included in this study. Among immunosuppressed patients after primary vaccination, 62% (261/419) had positive anti-S1 IgG and 71% (277/389) had positive IGRA. After booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Immunosuppressive factors associated with low rates of humoral response after primary vaccination included anti-CD20 monoclonal antibodies (n=48, P<.001), sphingosine 1-phsophate (S1P) receptor modulators (n=11, P<.001), mycophenolate (n=78, P=.002), and B cell lymphoma (n=55, P=.004); those associated with low rates of cellular response included S1P receptor modulators (n=11, P<.001) and mycophenolate (n=69, P<.001). Of patients who responded poorly to primary vaccination, 16% (4/25) with hematologic malignancy or primary immunodeficiency developed a significantly increased humoral response after the booster dose, while 52% (14/27) with solid malignancy, solid organ transplantation, or autoimmune disease developed an increased response (P=.009). Only 5% (2/42) of immunosuppressed patients developed a significantly increased cellular response following the booster dose. Conclusions and Relevance: Cellular vaccine response rates were higher than humoral response rates in immunosuppressed individuals after primary vaccination, particularly among those undergoing B cell targeting therapies. However, humoral response can be increased with booster vaccination, even in patients on B cell targeting therapies.

  🖺 Full Text HTML: Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients
• Virtually the same? Evaluating the effectiveness of remote undergraduate research experiences -
  In-person undergraduate research experiences (UREs) promote students’ integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration. To address this, we investigated indicators of scientific integration for students who participated in remote life science URE programs in summer 2020. We found that these students experienced gains in their scientific self-efficacy and scientific identity similar to results reported for in-person UREs. We also found that these students perceived high benefits and low costs of doing research at the outset of their programs, and their perceptions did not change despite the remote circumstances. Yet, their perceptions differed by program, indicating that programs differentially affected students’ perceptions of the costs of doing research. Finally, we observed that students with prior research experience made greater gains in self-efficacy and identity, as well as in their perceptions of the alignment of their values with those of the scientific community, in comparison to students with no prior research experience. This finding suggests that additional programming may be needed for undergraduates with no prior experience to benefit from remote research.
  🖺 Full Text HTML: Virtually the same? Evaluating the effectiveness of remote undergraduate research experiences
• Fully Vaccinated and Boosted Patients Requiring Hospitalization for COVID-19: an Observational Cohort Analysis -

  Objective: Real-world data on the effectiveness of boosters against COVID-19, especially as new variants continue to emerge, is limited. It is our objective to assess demographic, clinical, and outcome variables of patients requiring hospitalization for severe SARS-CoV-2 infection comparing fully vaccinated and boosted (FV&B) and unvaccinated (UV) patients. Methods: This multicenter observational cohort analysis compared demographic, clinical, and outcome variables in FV&B and UV adults hospitalized for COVID-19. A sub-analysis of FV&B patients requiring intensive care (ICU) care versus non-ICU care was performed to describe and analyze common symptom presentations, initial vital signs, initial laboratory workup, and pertinent medication use in these two groups. Results: Between August 12th, 2021 and December 6th, 2021, 4,571 patient encounters had a primary diagnosis of COVID-19 and required inpatient treatment at an acute-care hospital system in Southeastern Michigan. Of the 4,571 encounters requiring hospitalization, 65(1.4%) were FV&B and 2,935(64%) were UV. FV&B individuals were older (74 [67, 81] vs 58 [45, 70]; p <0.001) with a higher proportion of immunocompromised individuals (32.3% vs 10.4%; p<0.001). Despite a significantly higher baseline risk of in-hospital mortality in the FV&B group compared to the UV (Elixhauser 16 vs 8 (p <0.001)), there was a trend toward lower in-hospital mortality (7.7% vs 12.1%; p=0.38) among FV&B patients. Other severe outcomes followed this same trend, with 7.7% of FV&B vs 11.1% UV patients needing mechanical ventilation and 4.6% vs 10.6% of patients needing vasopressors in each group, respectively (p=0.5 and 0.17). Conclusions: Fully vaccinated and boosted individuals requiring hospital-level care for breakthrough COVID-19 tended to have less severe outcomes despite appearing to be higher risk at baseline when compared to unvaccinated individuals during the same time period. Specifically, there was a trend that FV&B group had lower rates of mechanical ventilation, use of vasopressors, and in-hospital mortality. As COVID-19 continues to spread, larger expansive trials are needed to further identify risk factors for severe outcomes among the FV&B population.

  🖺 Full Text HTML: Fully Vaccinated and Boosted Patients Requiring Hospitalization for COVID-19: an Observational Cohort Analysis
• SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein -
  SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD- dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.
  🖺 Full Text HTML: SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein
• SARS-CoV-2 Infection of Microglia Elicits Pro-inflammatory Activation and Apoptotic Cell Death -
  Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes various neurological symptoms in coronavirus disease 2019 (COVID-19) patients. The most dominant immune cells in the brain are microglia. Yet, the relationship between neurological manifestations, neuroinflammation, and host immune response of microglia to SARS-CoV-2 has not been well characterized. Here, we report that SARS-CoV-2 can directly infect human microglia, eliciting M1-like pro-inflammatory responses, followed by cytopathic effects. Specifically, SARS-CoV-2 infected human microglial clone 3 (HMC3), leading to inflammatory activation and cell death. RNA-seq analysis also revealed that ER stress and immune responses were induced in the early and apoptotic processes in the late phase of viral infection. SARS-CoV-2-infected HMC3 showed the M1 phenotype and produced pro-inflammatory cytokines such as interleukin (IL)-1{beta}, IL-6, and tumour necrosis factor (TNF-), but not the anti-inflammatory cytokine IL-10. After this pro-inflammatory activation, SARS-CoV-2 infection promoted both intrinsic and extrinsic death receptor-mediated apoptosis in HMC3. Using K18-hACE2 transgenic mice, murine microglia were also infected by intranasal inoculation of SARS-CoV-2. This infection induced the acute production of pro-inflammatory microglial IL- 6 and TNF- and provoked a chronic loss of microglia. Our findings suggest that microglia are potential mediators of SARS-CoV-2-induced neurological problems and, consequently, can be targets of therapeutic strategies against neurological diseases in COVID-19 patients.
  🖺 Full Text HTML: SARS-CoV-2 Infection of Microglia Elicits Pro-inflammatory Activation and Apoptotic Cell Death

From Clinical Trials

• Phase III Study of Novaferon in Non-hospitalized Adult Patients With Mild COVID-19 - Condition:   Covid19
  Interventions:   Biological: Novaferon;   Biological: Placebo
  Sponsors:   Genova Inc.;   Tokyo Shinagawa Hospital
  Recruiting

• Human COVID-19 Immunoglobulin (COVID-HIG) Therapy for COVID-19 Patients - Condition:   COVID-19
  Interventions:   Biological: Human COVID-19 immunoglobulin (pH4) for intravenous injection;   Drug: Placebo
  Sponsors:   Sinopharm Wuhan Plasma-derived Biotherapies Co., Ltd.;   China National Biotec Group Company Limited;   Beijing Tiantan Biological Products Co., Ltd.
  Not yet recruiting

• A Telemedicine Brief Mindfulness Intervention in Post-COVID-19 - Condition:   Post COVID-19
  Intervention:   Other: Mindfulness
  Sponsors:  
  Fondazione Don Carlo Gnocchi Onlus;   Catholic University of the Sacred Heart
  Recruiting

• Immunogenicity and Safety of a Booster Dose of the SpikoGen COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant;   Biological: Saline placebo
  Sponsors:   Cinnagen;   Vaxine Pty Ltd
  Active, not recruiting

• Quality of Life and Lung Function on Post Covid-19 Patient - Condition:   COVID-19
  Intervention:   Other: breathing exercise, Aerobic exercises
  Sponsor:   Qassim University
  Recruiting

• A Safety, Tolerability, and Efficacy Study of IBI314 in Mild to Moderate Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Biological: IBI314(low dose);   Biological: IBI314(high dose);   Biological: IBI314(medium dose);   Other: Placebo
  Sponsor:  
  Innovent Biologics (Suzhou) Co. Ltd.
  Not yet recruiting

• PTX-COVID19-B, an mRNA Humoral Vaccine, Intended for Prevention of COVID-19 in a General Population. This Study is Designed to Demonstrate the Safety, Tolerability, and Immunogenicity of PTX-COVID19-B in Comparison to the Pfizer- BioNTech COVID-19 Vaccine. - Condition:   Covid19 Vaccine
  Interventions:   Biological: PTX-COVID19-B;   Biological: Pfizer- BioNTech COVID-19 vaccine;   Biological: Placebo
  Sponsor:   Providence Therapeutics Holdings Inc.
  Active, not recruiting

• CONFIDENT: Supporting Long-term Care Workers During COVID-19 - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccine Confidence
  Interventions:  
  Behavioral: Dialogue-Based Webinar;   Behavioral: Social Media Website;   Other: Enhanced Usual Practice
  Sponsors:   Dartmouth-Hitchcock Medical Center;   National Association of Health Care Assistants;   Institute for Healthcare Improvement;   East Carolina University
  Not yet recruiting

• Multicenter Double Blind, Parallel-group Phase 2/3 Trial, to Study Raloxifene in Adult COVID-19 Patients. - Condition:   SARS CoV 2 Infection
  Interventions:   Drug: Raloxifene;   Other: Placebo
  Sponsor:   Dompé Farmaceutici S.p.A
  Completed

• Safety & Immunogenicity of Booster SARS-CoV-2 Vaccine (Vero Cell) - Condition:   COVID-19
  Intervention:   Biological: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated
  Sponsor:   PT. Kimia Farma (Persero) Tbk
  Not yet recruiting

• Spa Rehabilitation, Antioxidant and Bioenergetic Supportive Treatment of Patients With Post-Covid-19 Syndrome - Condition:   COVID-19 Respiratory Infection
  Interventions:   Dietary Supplement: ubiquinol (reduced coenzyme Q10);   Other: mountain spa rehabilitation;   Diagnostic Test: 2x14 ml of peripheral blood collected in a tube with anticoagulant
  Sponsors:   Comenius University;   Sanatórium of Dr. Guhr, n.o.
  Completed

• Symptom-based Rehabilitation Compared to Usual Care in Post-COVID - a Randomized Controlled Trial - Conditions:   COVID-19;   Long-COVID
  Interventions:   Other: symptom-focused rehabilitation;   Other: usual care
  Sponsors:   Schön Klinik Berchtesgadener Land;   Bavarian State Office for Health and Food Safety;   Praxis im Zentrum Erlangen;   Pneumologen Lichterfelde Berlin;   Pneumopraxis Marburg;   COVID ambulance Philipps-University Marburg;   Pneumologie Elisenhof Munich;   COVID ambulance Pneumology LMU Munich;   COVID ambulance psychology LMU Munich;   University Clinic Augsburg;   COVID ambulance Schön Klinik Schönau
  Not yet recruiting

• Study to Evaluate the Effect of Nicotinamide Mononucleotide (NMN) As an Adjuvant to Standard of Care (SOC) On Fatigue Associated With COVID-19 Infection - Condition:   COVID-19 Infection
  Interventions:   Other: Nicotinamide Mononucleotide;   Other: Nicotinamide Mononucleotide with L-Leucine;   Other: Placebo
  Sponsor:  
  Vedic Lifesciences Pvt. Ltd.
  Recruiting

• The Effectiveness of RPSG Intervention for Nurses During the COVID-19 - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Interventions:   Behavioral: RPSG;   Behavioral: AVMBM
  Sponsor:   National Taiwan University Hospital
  Not yet recruiting

• Safety, Reactogenicity, and Immunogenicity Study of Heterologous Booster Vaccination of a SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) - Condition:   COVID-19 (Healthy Volunteers)
  Interventions:   Biological: SARS-CoV-2 Recombinant Protein Nanoparticle Vaccine (GBP510) (RBD of SARS-CoV-2 25ug / dose) Adjuvanted with AS03;   Other: Normal saline
  Sponsors:   Korea University Guro Hospital;   Korean Center for Disease Control and Prevention
  Not yet recruiting

From PubMed

• Antiviral drugs : Potent agents, promising therapies for COVID-19 and therapeutic limitations - Antiviral drugs inhibit viral replication by interaction with specific elements of the viral replication cycle. Directly acting antiviral agents have revolutionized the therapeutic options for chronic infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Pharmacological developments constantly improve therapeutic and prophylactic options for diseases caused by herpes viruses, which is of particular relevance for immunocompromised patients. While…

• Structures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2 - Background: Administration of potent anti-receptor-binding domain (RBD) monoclonal antibodies has been shown to curtail viral shedding and reduce hospitalization in patients with SARS-CoV-2 infection. However, the structure-function analysis of potent human anti-RBD monoclonal antibodies and its links to the formulation of antibody cocktails remains largely elusive. Methods: Previously, we isolated a panel of neutralizing anti-RBD monoclonal antibodies from convalescent patients and showed their…

• Case Report: Clinical Management of a Patient With Metastatic Non-Small Cell Lung Cancer Newly Receiving Immune Checkpoint Inhibition During Symptomatic COVID-19 - Effects of initiation of programmed-death-protein 1 (PD1) blockade during active SARS-CoV-2 infection on antiviral immunity, COVID-19 course, and underlying malignancy are unclear. We report on the management of a male in his early 40s presenting with highly symptomatic metastatic lung cancer and active COVID-19 pneumonia. After treatment initiation with pembrolizumab, carboplatin, and pemetrexed, the respiratory situation initially worsened and high-dose corticosteroids were initiated due to…

• Activation of Sphingomyelinase-Ceramide-Pathway in COVID-19 Purposes Its Inhibition for Therapeutic Strategies - Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA- approved drugs. Here, we report…

• Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach - The four Janus kinase (JAK) proteins and seven signal transducer and activator of transcription (STAT) transcription factors mediate intracellular signal transduction downstream of cytokine receptors, which are implicated in the pathology of autoimmune, allergic and inflammatory diseases. Development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders. JAK inhibitors…

• COVID-19: from the structure and replication cycle of SARS-CoV-2 to its disease symptoms and treatment - In December 2019, a small number of cases of pneumonia of unknown origin were recognized in the city of Wuhan, China. Soon, the disease, whose etiological factor was recognized as a coronavirus SARS-CoV-2, had spread across the world. The resulting CoV-associated diseases were classified by the WHO as COVID-19, and a pandemic was declared in March 2020. By 25 November 2021, there have been nearly 256.8 million of confirmed cases of COVID-19 around the world, including 5.17 million deaths. This…

• Repurposing of FDA-approved drugs as potential inhibitors of the SARS-CoV-2 main protease: Molecular insights into improved therapeutic discovery - With numerous infections and fatalities, COVID-19 has wreaked havoc around the globe. The main protease (Mpro), which cleaves the polyprotein to form non-structural proteins, thereby helping in the replication of SARS-CoV-2, appears as an attractive target for antiviral therapeutics. As FDA-approved drugs have shown effectiveness in targeting Mpro in previous SARS-CoV(s), molecular docking and virtual screening of existing antiviral, antimalarial, and protease inhibitor drugs were carried out…

• Activation of the MKK3-p38-MK2-ZFP36 axis by coronavirus infection restricts the upregulation of AU-rich element- containing transcripts in proinflammatory response - Coronavirus infections induce the expression of multiple proinflammatory cytokines and chemokines. We have previously shown that in cells infected with gammacoronavirus infectious bronchitis virus (IBV), interleukin 6 (IL-6) and IL-8 were drastically upregulated, and the MAP kinase p38 and the integrated stress response pathways were implicated in this process. In this study, we report that coronavirus infection activates a negative regulatory loop that restricts the upregulation of a number of…

• Cyclosporine A Inhibits Viral Infection and Release as Well as Cytokine Production in Lung Cells by Three SARS-CoV-2 Variants - In December 2019, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started spreading worldwide causing the coronavirus disease 2019 (COVID-19) pandemic. The hyperactivation of the immune system has been proposed to account for disease severity and death in COVID-19 patients. Despite several approaches having been tested, no therapeutic protocol has been approved. Given that Cyclosporine A (CsA) is well-known to exert a strong antiviral activity on several viral strains and an…

• Binding mechanism of inhibitors to SARS-CoV-2 main protease deciphered by multiple replica molecular dynamics simulations - The outbreak caused by SARS-CoV-2 has received extensive worldwide attention. As the main protease (M^(pro)) in SARS- CoV-2 has no human homologues, it is feasible to reduce the possibility of targeting the host protein by accidental drugs. Thus, M^(pro) has been an attractive target of efficient drug design for anti-SARS-CoV-2 treatment. In this work, multiple replica molecular dynamics (MRMD) simulations, principal component analysis (PCA), free energy landscapes (FELs), and the molecular…

• Identification of SARS-CoV-2 main protease inhibitors from FDA-approved drugs by artificial intelligence-supported activity prediction system - Although a certain level of efficacy and safety of several vaccine products against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been established, unmet medical needs for orally active small molecule therapeutic drugs are still very high. As a key drug target molecule, SARS-CoV-2 main protease (M^(pro)) is focused and large number of in-silico screenings, a part of which were supported by artificial intelligence (AI), have been conducted to identify M^(pro) inhibitors both…

• SARS-CoV-2 treatment effects induced by ACE2-expressing microparticles are explained by the oxidized cholesterol- increased endosomal pH of alveolar macrophages - Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but…

• Thymoquinone: A Review of Pharmacological Importance, Oxidative Stress, COVID-19, and Radiotherapy - Widely consumed worldwide, Nigella sativa (NS) is a medicinal herb commonly used in various alternative medicine systems such as Unani and Tibb, Ayurveda, and Siddha. Recommended for regular use in Tibb-e-Nabwi (Prophetic Medicine), NS is considered one of the most notable forms of healing medicine in Islamic literature. Thymoquinone (TQ), the main component of the essential oil of NS, has been reported to have many properties such as antioxidant, anti-inflammatory, antiviral, and…

• Unravelling multiple removal pathways of oseltamivir in wastewater by microalgae through experimentation and computation - Increased worldwide consumption of antiviral drugs (AVDs) amid COVID-19 has induced enormous burdens to the existing wastewater treatment systems. Microalgae-based bioremediation is a competitive alternative technology due to its simultaneous nutrient recovery and sustainable biomass production. However, knowledge about the fate, distribution, and interaction of AVDs with microalgae is yet to be determined. In this study, a concentration-determined influence of AVD oseltamivir (OT) was observed…

• The Type 2 Asthma Mediator IL-13 Inhibits SARS-CoV-2 Infection of Bronchial Epithelium - Asthma is associated with chronic changes in the airway epithelium, a key target of SARS-CoV-2. Many epithelial changes, including goblet cell metaplasia, are driven by the type 2 cytokine IL-13, but the effects of IL-13 on SARS-CoV-2 infection are unknown. We found that IL-13 stimulation of differentiated human bronchial epithelial cells (HBECs) cultured at air-liquid interface reduced viral RNA recovered from SARS-CoV-2 infected cells and decreased dsRNA, a marker of viral replication, to…

From Patent Search

• Hung Thanh Phan COVID-19 NEW SOLUTION - - link

• METHODS OF TREATING SARS-COV-2 INFECTION - - link

• 피라졸 유도체의 폐섬유증 치료제 - 본 발명은 피라졸 유도체인 하기 화학식 1의 화합물 또는 이의 약학적으로 허용가능한 염을 포함하는, 폐섬유증 치료용 약학적 조성물 또는 항바이러스제를 제공한다 <화학식 1>

(상기 화학식 1에서 R은 발명의 설명에서 정의한 바와 같다.).

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      66 - [link](https://patentscope.wipo.int/search/en/detail.jsf?docId=KR345008871)

• 一种疾病相关标志物的筛选方法、应用及试剂盒 - 本发明公开了一种疾病相关标志物的筛选方法、应用及试剂盒。筛选方法包括：使用能够结合免疫球蛋白（Ig）的物质，分别从第一批健康样本血清和患病样本血清中纯化出Ig复合物；将与Ig相结合的蛋白进行蛋白质谱测序分析，比较健康样本与患病样本的差异，找到只出现在患病样本中的差异蛋白，即为该疾病相关潜在标志物。另外还可以通过以下步骤进一步验证该潜在标志物：使用第二批健康样本和患病样本的血清（扩大病例），纯化获得Ig复合物，利用差异蛋白的特异性抗体进行进一步鉴定。该方法先从血清中获得Ig复合物（而不是全血清），再将与Ig相结合的蛋白进行蛋白质谱测序联合特异性抗体分析，能够快速有效地筛选出疾病相关标志物。 - link

• 一种慢性淋巴细胞白血病SSCR风险模型及其建立方法和应用 - 本发明提供一种慢性淋巴细胞白血病SSCR风险模型及其建立方法和应用，属于疾病预后和分子生物学技术领域。本发明采用高通量测序的慢性淋巴细胞白血病(CLL)表达谱，进一步证实CLL的异质性，验证基于CLL细胞分化的CLL患者分类，预测患者预后。本发明将CLL细胞按分化状态分为两组，并对CLL细胞分化相关基因进行鉴定。最后，选择4个最具预后意义的CLL细胞分化相关基因，建立基于CLL细胞分化相关基因的SSCR风险评分模型，经验证该风险评分模型对CLL患者总生存期及首次治疗时间预测具有良好的可靠性。该评分系统可以帮助医生根据CLL细胞分化状况预测患者的预后，选择最佳的治疗方案，具有良好的实际应用价值。 - link

• 一种流感新冠联合疫苗及其制备方法 - 本发明公开了一种流感新冠联合疫苗，包括以下质量浓度的原料：含RBD‑Fc融合蛋白的重组新冠疫苗1‑100μg/mL；含H1N1型流感病毒的流感亚单位疫苗1‑50μg/mL；含H3N2型流感病毒的流感亚单位疫苗1‑50μg/mL；含B型流感病毒的流感亚单位疫苗1‑50μg/mL；氢氧化铝溶液，其中铝离子在流感新冠联合疫苗中的终浓度为0.5‑2.0mg/mL；余量为PBS磷酸缓冲液。制备方法：称取各原料；将四种疫苗分别用PBS磷酸缓冲液稀释后与氢氧化铝溶液混合；按照等体积比例混合，即得。本发明为含铝佐剂的新型冠状病毒疫苗和含铝佐剂的流感亚单位疫苗的联合疫苗，联合后，两种抗原组分疫苗之间没有相互抑制，能很好兼容。 - link

• REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - link

• 一种瑞德西韦的合成方法 - 本发明涉及一种瑞德西韦的合成方法，包括以下步骤：将(2R,3R,4S,5R)‑2‑(4‑氨基吡咯[2,1‑f][1,2,4]三嗪‑7‑基)‑3,4‑二羟基‑5‑(羟甲基)四氢呋喃‑2‑碳腈、2,2‑二甲氧基丙烷和第一酸催化剂加入第一溶剂中，搅拌，经2,2‑二甲氧基丙烷保护邻二羟基合成中间体4，反应完毕后调碱降温；将无水氯化镁和中间体7加入反应中，通氮气流保护，搅拌均匀后滴加碱催化剂，升温搅拌，合成中间体5，反应完毕后进行提取分液；向反应中滴加第二酸催化剂，搅拌，经过后处理得到瑞德西韦粗品。本发明的三步反应均以第一溶剂为介质进行反应，仅在三步反应完成后进行后处理浓缩溶剂，减少浓缩溶剂的次数，降低工业成本。 - link

• 一种基于宏基因组学的病原微生物检测方法及装置 - 本发明公开了一种基于宏基因组学的病原微生物检测方法及装置，包括：获取待检测样本的宏基因组测序数据；对宏基因组测序数据进行预处理，得到目标数据；对目标数据进行筛选，得到目标序列；对目标序列进行聚类分析，获得待测样本的候选物种类别；将目标数据与非冗余参考基因集进行比对，并计算每个基因在单个样本中的丰度，得到待测样本的目标物种分类信息；将目标数据与病原微生物可检测数据库中的信息进行比对，获得待测样本的耐药基因和毒性元件信息；将目标物种分类信息、耐药基因和毒性元件信息，确定为待检测样本的检测结果。本发明提升了病原微生物检测适用性范围和病原检测准确性。 - link

• CONJUNTO DE ESCOBILLA Y ESCOBILLERO CON AUTOLIMPIEZA - - link