Covid-19 Sentry

Contents

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

From Preprints

• Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease -
  SARS-CoV-2 is the causative agent of COVID-19. The highly conserved viral NSP15 endoribonuclease, NendoU, is a key enzyme involved in viral immune evasion, and a promising target for the development of new classes antivirals. Yet, the broad variety of recognition sequences, complex assembly and kinetics, and lack of structural complexes hamper the development of new competitive or allosteric inhibitors for this target. In here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index of 2. By using cryo-EM in distinct pH’s combined with X-ray crystallography and structural analysis, we demonstrate the potential for NendoU to shift between open and closed states, and assembly in larger supramolecular entities, which might serve as a mechanism of self-regulation. Further, we report results from our large fragment screening campaign against NendoU, revealing multiple new allosteric sites for the development of new inhibitors.
  🖺 Full Text HTML: Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease
• Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19 -

  Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19. Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality. Results: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41-0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo). Conclusions: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality. Trial registration: ClinicalTrials.gov (NCT04593940).

  🖺 Full Text HTML: Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19
• Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis -
  Objectives: Our objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics. Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear. Methods: Autopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue. Results: We observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels. Conclusions: Our results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis and endothelial activation as key drivers of cardiovascular events during COVID-19.
  🖺 Full Text HTML: Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis
• Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against Omicron -
  The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the antibodies’ epitopes and genotypes. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their binding patterns. We found that the epitopes of one class of antibodies were significantly less affected by Omicron mutations than other classes. Binding and virus neutralization experiments show that such antibodies can effectively inhibit the immune escape of Omicron. Cryo-EM results show that this class of antibodies utilizes a conserved mechanism to neutralize SARS-CoV-2. Our results greatly help us deeply understand the impact of Omicron mutations. At the same time, it also provides guidance and insights for developing Omicron antibodies and vaccines.
  🖺 Full Text HTML: Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against Omicron
• SARS-CoV-2 Uses Nonstructural Protein 16 to Evade Restriction by IFIT1 and IFIT3 -
  Understanding the molecular basis of innate immune evasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important consideration for designing the next wave of therapeutics. Here, we investigate the role of the nonstructural protein 16 (NSP16) of SARS-CoV-2 in infection and pathogenesis. NSP16, a ribonucleoside 2’-O methyltransferase (MTase), catalyzes the transfer of a methyl group to mRNA as part of the capping process. Based on observations with other CoVs, we hypothesized that NSP16 2’-O MTase function protects SARS-CoV-2 from cap-sensing host restriction. Therefore, we engineered SARS-CoV-2 with a mutation that disrupts a conserved residue in the active site of NSP16. We subsequently show that this mutant is attenuated both in vitro and in vivo, using a hamster model of SARS-CoV-2 infection. Mechanistically, we confirm that the NSP16 mutant is more sensitive to type I interferon (IFN-I) in vitro. Furthermore, silencing IFIT1 or IFIT3, IFN-stimulated genes that sense a lack of 2’-O methylation, partially restores fitness to the NSP16 mutant. Finally, we demonstrate that sinefungin, a methyltransferase inhibitor that binds the catalytic site of NSP16, sensitizes wild-type SARS-CoV-2 to IFN-I treatment. Overall, our findings highlight the importance of SARS-CoV-2 NSP16 in evading host innate immunity and suggest a possible target for future antiviral therapies.
  🖺 Full Text HTML: SARS-CoV-2 Uses Nonstructural Protein 16 to Evade Restriction by IFIT1 and IFIT3
• Zymosan-induced leukocyte and cytokine changes in pigs: a new model for streamlined drug testing against severe COVID-19 -
  Injection of 0.1 mg/kg zymosan in pigs i.v. elicited transient hemodynamic disturbance within minutes, without major blood cell changes. In contrast, infusion of 1 mg/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This change was followed by a transient granulopenia with a trough at 1 h, and then, up to about 6 h, a major granulocytosis, resulting in a 3-4-fold increase of neutrophil-to-lymphocyte ratio (NLR). In parallel with the changes in WBC differential, qRT-PCR and ELISA analyses showed increased transcription and/or release of inflammatory cytokines and chemokines into blood, including IL-6, TNF-, CCL-2, CXCL-10, and IL-1RA. The expression of IL-6 peaked at already 1.5-2.5 h, and we observed significant correlation between lymphopenia and IL-6 gene expression. While these changes are consistent with zymosan’s known stimulatory effect on both the humoral and cellular arms of the innate immune system, what gives novel clinical relevance to the co-manifestation of above hemodynamic, hematological, and immune changes is that they represent independent bad prognostic indicators in terminal COVID-19 and other diseases involving cytokine storm. Thus, within a 6 h experiment, the model enables consecutive reproduction of a symptom triad that is characteristic of late-stage COVID-19. Given the limitations of modeling cytokine storm in animals and effectively treating severe COVID-19, the presented relatively simple large animal model may advance the R&D of drugs against these conditions. One of these disease markers (NLR), obtained from a routine laboratory endpoint (WBC differential), may also enable streamlining the model for high throughput drug screening.
  🖺 Full Text HTML: Zymosan-induced leukocyte and cytokine changes in pigs: a new model for streamlined drug testing against severe COVID-19
• Nanobodies for the treatment of SARS-CoV-2 in animals: a meta-analysis -
  This meta-analysis aimed to find the effect of variable domain of heavy-chain antibodies (VHHs) for the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in animals. The databases of the PubMed, China National Knowledge Infrastructure (CNKI), Wan fang data, Cochrane Library, and Embase were searched for articles published before August 2022 on the protective effects of VHHs in animals. The articles retrieved were screened using inclusion and exclusion criteria. The data were analyzed using Review Manager 5.4. Six articles were selected from 667 articles based on the inclusion and exclusion criteria in VHHs. A forest plot showed that VHHs could offer protection against SARS-CoV-2 infection in animals [Mantel-Haenszel (MH) = 172.94, 95% confidence interval (CI) = (43.96, 678.42), P < 0.00001]. There was almost no heterogeneity in this study (I2 = 0). A funnel plot showed that the bias of the data analysis was small. This is a special meta-analysis proved that VHHs could treat and prevent SARS-CoV-2 in animals.
  🖺 Full Text HTML: Nanobodies for the treatment of SARS-CoV-2 in animals: a meta-analysis
• High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike -
  Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All COVID-19 vaccines in the US encode spike with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering prefusion-stabilized spike immunogens involve tedious experimental work and heavily rely on structural information. Here, we established a systematic and unbiased method of identifying mutations that concomitantly improve expression and stabilize the prefusion conformation of the SARS-CoV-2 spike. Our method integrated a fluorescence-based fusion assay, mammalian cell display technology, and deep mutational scanning. As a proof-of-concept, this method was applied to a region in the S2 domain that includes the first heptad repeat and central helix. Our results revealed that besides K986P and V987P, several mutations simultaneously improved expression and significantly lowered the fusogenicity of the spike. As prefusion stabilization is a common challenge for viral immunogen design, this work will help accelerate vaccine development against different viruses.
  🖺 Full Text HTML: High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike
• A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta -
  Clinically licensed COVID-19 vaccines ameliorate viral infection by inducing vaccinee production of neutralizing antibodies that bind to the SARS-CoV-2 Spike protein to inhibit viral cellular entry (Walsh et al., 2020; Baden et al., 2021), however the clinical effectiveness of these vaccines is transitory as viral variants arise that escape antibody neutralization (Tregoning et al., 2021; Willett et al., 2022). Vaccines that solely rely upon a T cell response to combat viral infection could be transformational because they can be based on highly conserved short peptide epitopes that hold the potential for pan-variant immunity, but a T cell vaccine has not been shown to be sufficient for effective antiviral prophylaxis. Here we show that a mRNA-LNP vaccine based on highly conserved short peptide epitopes activates a CD8+ and CD4+ T cell response that prevents mortality in HLA-A*02:01 transgenic mice infected with the SARS-CoV-2 Beta variant of concern (B.1.351). The T cell vaccine produced 5.5 times more CD8+ T cell infiltration of the lungs in response to infection when compared to the Pfizer-BioNTech Comirnaty(R) vaccine. The T cell vaccine did not produce neutralizing antibodies, and thus our results demonstrate that SARS-CoV-2 viral infection can be controlled by a T cell response alone. Our results suggest that further study is merited for pan-variant T cell vaccines, and that T cell vaccines may be relevant for individuals that cannot produce neutralizing antibodies or to help mitigate Long COVID.
  🖺 Full Text HTML: A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta
• PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application -
  The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had and still has a considerable impact on global public health. One of the characteristics of SARS-CoV-2 is a surface homotrimeric spike protein, the primary responsible for the host immune response upon infection. Here we show the preclinical studies of a broad protective SARS-CoV-2 subunit vaccine developed from our Trimer Domain platform using the Delta spike protein, from antigen design to purification, vaccine evaluation and manufacturability. The prefusion trimerized Delta spike protein, PF-D-Trimer, was highly expressed in Chinese hamster ovary (CHO) cells, purified by a rapid one-step anti-Trimer Domain monoclonal antibody immunoaffinity process and prepared as a vaccine formulation with an adjuvant. The immunogenicity studies demonstrated that this vaccine candidate induces robust immune responses in mouse, rat and Syrian hamster models. It also protects K18-hACE2 transgenic mice in a homologous virus challenge. The neutralizing antibodies induced by this vaccine display a cross-reactive capacity against the ancestral WA1 and Delta variants as well as different Omicron, including BA.5.2. The Trimer Domain platform was proven to be a key technology in the rapid production of the PF-D-Trimer vaccine and may be crucial to accelerate the development of updated versions of SARS-CoV-2 vaccines.
  🖺 Full Text HTML: PF-D-Trimer, a broadly protective SARS-CoV-2 subunit vaccine: immunogenicity and application
• Impact of cross-coronavirus immunity in post-acute sequelae of COVID-19 -

  Beyond the unpredictable acute illness caused by SARS-CoV-2, one-fifth of infections unpredictably result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie post-acute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus or the dysregulation of immunity. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2 or other pathogen specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2 and a panel of endemic pathogens or routine vaccine antigens using Systems Serology in a cohort of patients with pre-existing rheumatic disease who either developed or did not develop PASC. A distinct humoral immune response was observed in individuals with PASC. Specifically, individuals with PASC harbored less inflamed and weaker Fc-receptor binding anti-SARS-CoV-2 antibodies and a significantly expanded and more inflamed antibody response against endemic Coronavirus OC43. Individuals with PASC, further, generated more avid IgM responses and developed an expanded inflammatory OC43 S2-specific Fc-receptor binding response, linked to cross reactivity across SARS-CoV-2 and common coronaviruses. These findings implicate previous common Coronavirus imprinting as a marker for the development of PASC.

  🖺 Full Text HTML: Impact of cross-coronavirus immunity in post-acute sequelae of COVID-19
• Markers of blood-brain barrier disruption increase early and persistently in COVID-19 patients with neurological manifestations -

  Background: Coronavirus disease 2019 (COVID-19) leads to peripheral and central disorders, frequently with neurological implications. Blood-brain barrier disruption (BBBd) has been hypothesized as a mechanisms in the acute phase. We tested whether markers of BBBd, brain injury and inflammation could help identify a blood signature for disease severity and neurological complications. Methods: Biomarkers of BBBd (MMP-9, GFAP), neuronal damage (NFL) and inflammation (PPIA, IL-10, TNFα) were measured by SIMOA, AlphaLISA and ELISA, in two COVID-19 patient cohorts with high disease severity (ICU Covid; n=79) and neurological complications (NeuroCovid; n=78), and in two control groups with no COVID-19 history: healthy subjects (n=20) and patients with amyotrophic lateral sclerosis (ALS; n=51). Results: Biomarkers of BBBd and neuronal damage were high in COVID-19 patients, with levels similar to or higher than in ALS. NeuroCovid patients had lower levels of PPIA but higher levels of MMP-9 than ICU Covid patients. There was evidence of different temporal dynamics in ICU Covid compared to NeuroCovid patients with PPIA and IL-10 levels highest in ICU Covid patients in the acute phase. In contrast, MMP-9 was higher in the acute phase in NeuroCovid patients, with severity-dependency in the long term. We also found clear severity-dependency of NFL and GFAP. Conclusions: The overall picture points to an increased risk of neurological complications in patients with high levels of biomarkers of BBBd. Our observations may provide hints for therapeutic approaches mitigating BBBd to reduce the neurological damage in the acute phase and potential dysfunction in the long term.

  🖺 Full Text HTML: Markers of blood-brain barrier disruption increase early and persistently in COVID-19 patients with neurological manifestations
• Impact of sample clarification by size exclusion on virus detection and diversity in wastewater-based epidemiology -

  The use of wastewater-based epidemiology (WBE) for early detection of virus circulation and response during the SARS-CoV-2 pandemic increased interest in and use of virus concentration protocols that are quick, scalable, and efficient. One such protocol involves sample clarification by size fractionation using either low-speed centrifugation to produce a clarified supernatant or membrane filtration to produce an initial filtrate depleted of solids, eukaryotes and bacterial present in wastewater (WW), followed by concentration of virus particles by ultrafiltration of the above. While this approach has been successful in identifying viruses from WW, it assumes that majority of the viruses of interest should be present in the fraction obtained by ultrafiltration of the initial filtrate, with negligible loss of viral particles and viral diversity. We used WW samples collected in a population of ~700,000 in southwest USA between October 2019 and March 2021, targeting three non-enveloped viruses (enteroviruses [EV], canine picornaviruses [CanPV], and human adenovirus 41 [Ad41]), to evaluate whether size fractionation of WW prior to ultrafiltration leads to appreciable differences in the virus presence and diversity determined. We showed that virus presence or absence in WW samples in both portions (filter trapped solids [FTS] and filtrate) are not consistent with each other. We also found that in cases where virus was detected in both fractions, virus diversity (or types) captured either in FTS or filtrate were not consistent with each other. Hence, preferring one fraction of WW over the other can undermine the capacity of WBE to function as an early warning system and negatively impact the accurate representation of virus presence and diversity in a population.

  🖺 Full Text HTML: Impact of sample clarification by size exclusion on virus detection and diversity in wastewater-based epidemiology
• Sharp reductions in COVID-19 case fatalities and excess deaths in Peru in close time conjunction, state-by-state, with ivermectin treatments -
  On May 8, 2020, Peru’s Ministry of Health approved ivermectin (IVM) for the treatment of COVID-19. A drug of Nobel Prize-honored distinction, IVM has been safely distributed in 3.7 billion doses worldwide since 1987. It has exhibited major, statistically significant reductions in case mortality and severity in 11 clinical trials for COVID-19, three with randomized controls. The indicated biological mechanism of IVM is the same as that of antiviral antibodies generated by vaccines—binding to SARS-CoV-2 viral spike protein, blocking viral attachment to host cells. Mass distributions of IVM for COVID-19 treatments, inpatient and outpatient, were conducted in different timeframes with local autonomy in the 25 states (departamentos) of Peru. These treatments were conducted early in the pandemic’s first wave in 24 states, in some cases beginning even a few weeks before the May 8 national authorization, but delayed four months in Lima. Analysis was performed using Peruvian public health data for all-cause deaths and for COVID-19 case fatalities, as independently tracked for ages 60 and above. These daily figures were retrieved and analyzed by state. Case incidence data were not analyzed due to variations in testing methods and other confounding factors. These clinical data associated with IVM treatments beginning in different time periods, April through August 2020, in each of 25 Peruvian states, spanning an area equivalent to that from Denmark to Italy and Greece in Europe or from north to south along the US, with a total population of 33 million, provided a rich source for analysis. For the 24 states with early IVM treatment (and Lima), excess deaths dropped 59% (25%) at +30 days and 75% (25%) at +45 days after day of peak deaths. Case fatalities likewise dropped sharply in all states but Lima, yet six indices of Google-tracked community mobility rose over the same period. For nine states having mass distributions of IVM in a short timeframe through a national program, Mega-Operación Tayta (MOT), excess deaths at +30 days dropped by a population-weighted mean of 74%, each drop beginning within 11 day after MOT start. Extraneous causes of mortality reductions were ruled out. These sharp major reductions in COVID-19 mortality following IVM treatment thus occurred in each of Peru’s states, with such especially sharp reductions in close time conjunction with IVM treatments in each of the nine states of operation MOT. Its safety well established even at high doses, IVM is a compelling option for immediate, large scale national deployments as an interim measure and complement to pandemic control through vaccinations.
  🖺 Full Text HTML: Sharp reductions in COVID-19 case fatalities and excess deaths in Peru in close time conjunction, state-by-state, with ivermectin treatments
• Impact of COVID-19 pandemic on the incidence of suicidal behaviors: a retrospective analysis of integrated electronic health records in a 7.5-million population -

  The COVID-19 pandemic has caused a remarkable psychological overwhelming and increase of stressors that may trigger suicidal behaviors. However, its impact on the rate of suicidal behaviors has been poorly reported. We conducted a population-based retrospective analysis of all suicidal behaviors attended in healthcare centers of Catalonia (North-East Spain; 7.5-million inhabitants), between January 2017 and June 2022. We retrieved data from the episode, including an assessment of suicide risk and the individual9s socioeconomic and clinical characteristics. Data were summarized yearly and for the periods before and after the onset of the COVID-19 pandemic in Spain in March 2020. The analysis included 26,458 episodes of suicidal behavior (21,920 individuals); of them, 16,414 (62.0%) were a suicide attempt. The monthly moving average ranged between 300 and 400 episodes until July 2020, and progressively increased to over 600 episodes monthly. In the post-pandemic period, suicidal ideation increased at the expense of suicidal attempts. Cases showed a lower suicide risk; the percentage of females and younger individuals increased, whereas the prevalence of classical risk factors, such as living alone or lacking family network and a history of psychiatric diagnosis, decreased. In summary, suicidal behaviors have increased during the COVID-19 pandemic, with more episodes of suicidal ideations without attempt and younger and lower risk profiles.

  🖺 Full Text HTML: Impact of COVID-19 pandemic on the incidence of suicidal behaviors: a retrospective analysis of integrated electronic health records in a 7.5-million population

From Clinical Trials

• Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19 - Condition:   COVID-19
  Interventions:   Other: Olfactory training with essential oils;   Other: Olfactory training with fragrance-free oils
  Sponsor:   Ditte Gertz Mogensen
  Recruiting

• 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 Fourth Dose Study in Australia - Condition:   COVID-19
  Interventions:   Biological: Tozinameran;   Biological: Elasomeran;   Biological: Bivalent Pfizer-BioNTech;   Biological: Bivalent Moderna
  Sponsors:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   The Peter Doherty Institute for Infection and Immunity
  Not yet recruiting

• Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg;   Biological: BNT162b4 5 µg;   Biological: BNT162b4 10 µg;   Biological: BNT162b4 15 µg
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• Trial of 2nd Booster Dose of COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Other: Invitation to get a 2nd booster dose of COVID-19 vaccine
  Sponsor:   Norwegian Institute of Public Health
  Not yet recruiting

• PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PBI-0451;   Drug: Placebo
  Sponsor:   Pardes Biosciences, Inc.
  Recruiting

• Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AD17002 + Formulation buffer;   Biological: Placebo
  Sponsors:   Advagene Biopharma Co. Ltd.;   Gadjah Mada University
  Not yet recruiting

• Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents - Condition:   COVID-19
  Interventions:   Behavioral: Community-based Health Education based on core intervention package;   Behavioral: Health Information Sharing Group
  Sponsors:   The Hong Kong Polytechnic University;   Food and Health Bureau, Hong Kong
  Recruiting

• Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia - Conditions:   Olfactory Disorder;   COVID-19
  Intervention:   Drug: Simvastatin
  Sponsors:   Washington University School of Medicine;   Duke University
  Not yet recruiting

• 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

• Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations - Condition:   COVID-19
  Intervention:   Behavioral: Active Intervention Group
  Sponsor:   Pennington Biomedical Research Center
  Not yet 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

• Cardiopulmonary Rehabilitation in Post-acute COVID-19 Syndrome - Condition:   Post Acute COVID-19 Syndrome
  Interventions:   Other: Cardiopulmonary rehabilitation;   Other: Health education
  Sponsor:   Taipei Medical University Shuang Ho Hospital
  Not yet recruiting

• Evaluation of the Efficacy of Mouth Rinses With Commercial Mouthwashes to Decrease Viral Load in Saliva in COVID-19 Patients - Condition:   covid19
  Interventions:   Drug: Lacer Clorhexidina Colutorio;   Drug: Lacer Clorhexidine 0.20% Colutorio;   Drug: Gingilacer Encías Delicadas Colutorio;   Drug: Distilled water
  Sponsors:   Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana;   Hospital Universitario Fundación Jiménez Díaz;   Hospital Universitario Infanta Elena
  Completed

• Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of COVID-19 Positive Patients - Conditions:   Covid19;   Hydrogen-oxygen Gas;   AMS-H-03
  Interventions:   Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03;   Device: the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen)
  Sponsor:   Ruijin Hospital
  Active, not recruiting

From PubMed

• Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence - Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19),…

• CLL-050 Induction of Neutralizing Antibodies in Chronic Lymphocytic Leukemia Patients After SARS-CoV-2 mRNA Vaccination: A Monocentric Experience - CONCLUSIONS: Only around half of vaccinated CLL patients acquire detectable anti-RBD and neutralizing antibodies, according to our findings. Furthermore, we discovered a substantial difference in the rates of detectable anti-SARS-CoV-2 antibodies between patients who were treatment-naïve/in clinical remission and those on CLL-directed treatment. The persistence and burden of disease represent a surrogate of vaccine failure, probably due to the persistence of immune dysfunction.

• SARS-CoV-2 ORF3a inhibits cGAS-STING-mediated autophagy flux and antiviral function - Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS-STING-mediated innate immunity are essential for the host defense against viruses. Recent studies have reported that SARS-CoV-2 infection, responsible for the COVID-19 pandemic, triggers cGAS-STING activation. cGAS-STING activation can trigger IRF3-type I interferon (IFN) and autophagy-mediated antiviral activity. Although viral evasion of STING-triggered IFN-mediated antiviral function has been well studied, studies concerning viral…

• Preventing SARS-CoV-2 Infection Using Anti-spike Nanobody-IFN-β Conjugated Exosomes - CONCLUSION: Exosomes conjugated with nanobody-IFN-β may provide potential benefits in the treatment of COVID-19 because of the cooperative anti-viral effects of the anti-spike nanobody and the IFN-β.

• Semisynthetic teicoplanin derivatives with dual antimicrobial activity against SARS-CoV-2 and multiresistant bacteria - Patients infected with SARS-CoV-2 risk co-infection with Gram-positive bacteria, which severely affects their prognosis. Antimicrobial drugs with dual antiviral and antibacterial activity would be very useful in this setting. Although glycopeptide antibiotics are well-known as strong antibacterial drugs, some of them are also active against RNA viruses like SARS-CoV-2. It has been shown that the antiviral and antibacterial efficacy can be enhanced by synthetic modifications. We here report the…

• An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension - The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants and breakthrough infections despite available coronavirus disease 2019 (COVID-19) vaccines calls for antiviral therapeutics. The application of soluble angiotensin converting enzyme 2 (ACE2) as a SARS-CoV-2 decoy and reduce cell bound ACE2-mediated virus entry is limited by a short plasma half-life. This work presents a recombinant human albumin ACE2 genetic fusion (rHA-ACE2) to increase the plasma…

• The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses - Genome-wide screens are powerful approaches to unravel regulators of viral infections. Here, a CRISPR screen identifies the RNA helicase DDX42 as an intrinsic antiviral inhibitor of HIV-1. Depletion of endogenous DDX42 increases HIV-1 DNA accumulation and infection in cell lines and primary cells. DDX42 overexpression inhibits HIV-1 infection, whereas expression of a dominant-negative mutant increases infection. Importantly, DDX42 also restricts LINE-1 retrotransposition and infection with other…

• Remdesivir in treating hospitalized patients with COVID-19: A renewed review of clinical trials - Since December 2019, COVID-19 has spread across the world almost through 2.5 years. As of 16 June 2022, the cumulative number of confirmed cases of COVID-19 worldwide has reached 542.62 million, and the death toll has risen to 6.33 million. With the increasing number of deaths, it is urgent to find effective treatment drugs. Remdesivir, an investigational broad-spectrum antiviral drug produced by Gilead has been shown to inhibit SARS-CoV-2, in vitro and in vivo. This review is aimed to analyze…

• Zinc-finger antiviral protein-mediated inhibition of porcine epidemic diarrhea virus growth is antagonized by the coronaviral nucleocapsid protein - Coronaviruses have long posed a major threat not only to human health but also to agriculture. Outbreaks of an animal coronavirus such as porcine epidemic diarrhea virus (PEDV) can cause up-to-100% mortality in suckling piglets, resulting in devastating effects on the livestock industry. Understanding how the virus evades its host’s defense can help us better manage the infection. Zinc-finger antiviral protein (ZAP) is an important class of host antiviral factors against a variety of viruses,…

• Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et) - CONCLUSIONS: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19.

• mRNA vaccination drives differential mucosal neutralizing antibody profiles in naïve and SARS-CoV-2 previously-infected individuals - Two doses of BNT162b2 mRNA vaccine induces a strong systemic SARS-CoV-2 specific humoral response. However, SARS-CoV-2 airborne transmission makes mucosal immune response a crucial first line of defense. Therefore, we characterized SARS-CoV-2-specific IgG responses induced by BNT162b2 vaccine, as well as IgG responses to other pathogenic and seasonal human coronaviruses in oral fluid and plasma from 200 UK healthcare workers who were naïve (N=62) or previously infected with SARS-CoV-2 (N=138)…

• Beta receptor blocker therapy for the elderly in the COVID-19 era - When the coronavirus disease 2019 (COVID-19) pandemic spread globally from the Hubei region of China in December 2019, the impact on elderly people was particularly unfavorable. The mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was highest in older individuals, in whom frailty and comorbidities increased susceptibility to severe forms of COVID-19. Unfortunately, in older patients, the course of COVID-19 was often characterized by significant…

• Visible Light-Mediated Photoactivated Sulfur Quantum Dots as Heightened Antibacterial Agents - The need for antimicrobial or antibacterial fabric has increased exponentially in recent past years, especially after the outbreak of the SARS-CoV-2 pandemic. Several studies have been conducted, and the primary focus is the development of simple, automated, performance efficient and cost-efficient fabric for disposable and frequent-use items such as personal protective materials. In this regard, we have explored the light-driven antibacterial activity of water-soluble Sdots for the first time….

• Design of a Structurally Novel Multipotent Drug Candidate by the Scaffold Architecture Technique for ACE-II, NSP15, and M^pro Protein Inhibition: Identification and Isolation of a Natural Product to Prevent the Severity of Future Variants of Covid 19 and a Colorectal Anticancer Drug - Scaffold architecture in the sectors of biotechnology and drug discovery research include scaffold hopping and molecular modelling techniques and helps in searching for potential drug candidates containing different core structures using computer-based software, which greatly aids medicinal and pharmaceutical chemistry. Going ahead, the computational method of scaffold architecture is thought to produce new scaffolds, and the method is capable of helping search engines toward producing new…

• Tailored lipopeptide surfactants as potentially effective drugs to treat SARS-CoV-2 infection - Finding effective drugs to treat SARS-CoV-2 infection as a complementary step to the extensive vaccination is of the great importance to overcome the current pandemic situation. It has been shown that some bio-active unsaturated fatty acids such as Arachidonic Acid (AA) can reduce the infection severity and even destroy the virus by disintegration of the virus lipid envelope. On the other hand, it has been reported that several designed peptides with an activity similar to the angiotensin…

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