Covid-19 Sentry

Contents

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

From Preprints

• Fragment-based computational design of antibodies targeting structured epitopes -
  De novo design methods hold the promise of reducing the time and cost of antibody discovery, while enabling the facile and precise targeting of specific epitopes. Here we describe a fragment-based method for the combinatorial design of antibody binding loops and their grafting onto antibody scaffolds. We designed and tested six single-domain antibodies targeting different epitopes on three antigens, including the receptor-binding domain of the SARS-CoV-2 spike protein. Biophysical characterisation showed that all designs are highly stable, and bind their intended targets with affinities in the nanomolar range without any in vitro affinity maturation. We further show that a high-resolution input antigen structure is not required, as our method yields similar predictions when the input is a crystal structure or a computer-generated model. This computational procedure, which readily runs on a laptop, provides the starting point for the rapid generation of lead antibodies binding to pre-selected epitopes.
  🖺 Full Text HTML: Fragment- based computational design of antibodies targeting structured epitopes
• The AstraZeneca affair. A litmus test of information disorder in the Italian hybrid media ecosystem -
  In this paper we seek to demonstrate how a variety of information disorder phenomena comes to be at the intersection of legacy and social media interaction. To do so, we collected more than 750.000 tweets and 30.000 news articles related to the adoption of AstraZeneca vaccine in Italy for a period of six months (1st January 2021 - 30th June 2021). Initially, using timestamps of publications and tweets, we tracked the pace of public debate. Then, using a mixed methods approach, we investigated Twitter reaction during the climax of attention toward AstraZeneca. Acting as a litmus test, our study reveals three different but intertwined information disorder phenomena: first, the vaccine debate exhibit a flat progression with few condensed peaks of attention (acceleration phenomenon); second, the two main peaks that involve both journalistic coverage and Twitter discussion generate from news of suspect deaths related to AstraZeneca (sensationalisation phenomenon); and finally, the report of suspect deaths news by mainstream media accounts on Twitter correlates with a polarized and ideological reaction of the connected publics (fragmentation phenomenon). These results highlight how a direct implication of the hybrid media ecosystem’s actual configuration could be a resistance in the formation of a public arena capable of sustaining a prolonged and effective debate, particularly with respect to controversial societal issues such as those related to the covid-19 vaccination campaign.
  🖺 Full Text HTML: The AstraZeneca affair. A litmus test of information disorder in the Italian hybrid media ecosystem
• Vaccine effectiveness against SARS-CoV-2 infection and COVID-19-related hospitalization with the Alpha, Delta and Omicron SARS-CoV-2 variants: a nationwide Danish cohort study -

  Background The continued occurrence of more contagious SARS-CoV-2 variants and waning immunity over time require ongoing re-evaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in two age groups (12-59 and 60 years or above) of two and three vaccine doses (BNT162b2 mRNA or mRNA-1273 vaccine) by time since vaccination against SARS-CoV-2 infection and COVID-19-related hospitalization in an Alpha, Delta and Omicron dominated period. Methods A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19-related hospitalization with the Alpha, Delta and Omicron variants. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all residents in Denmark aged 12 years or above (18 years or above for the analysis of three doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021) and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated using Cox proportional hazard regression models with adjustments for age, sex and geographical region. Vaccination status was included as a time-varying exposure. Findings In the oldest age group, VE against infection after two doses was 91.0% (95% CI: 88.5; 92.9) for the Alpha variant, 82.2% (95% CI: 75.3; 87.1) for the Delta variant and 39.9% (95% CI: 26.4; 50.9) for the Omicron variant 14-30 days since vaccination. The VE waned over time and was 71.5% (95% CI: 54.7; 82.8), 49.8% (95% CI: 46.5; 52.8) and 4.7% (95% CI: 0.2; 8.9) >120 days since vaccination against the three variants, respectively. Higher estimates were observed after the third dose with VE estimates against infection of 86.0% (Delta, 95% CI: 83.3; 88.3) and 57.6% (Omicron, 95% CI: 55.8; 59.4) 14-30 days since vaccination. Among both age groups, VE against COVID-19-related hospitalization 14-30 days since vaccination with two or three doses was 94.8% or above for the Alpha and Delta variants, whereas among the youngest age group, VE estimates against the Omicron variant after two and three doses were 62.4% (95% CI: 46.3; 73.6) and 89.8% (95% CI: 87.9; 91.3), respectively. Conclusions Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19-related hospitalization with the Alpha and Delta variants with protection waning over time. Two vaccine doses provided only limited protection against SARS-CoV-2 infection and COVID-19-related hospitalization with the Omicron variant. The third vaccine dose substantially increased the protection against Delta and Omicron.

• Uncovering the structural flexibility of SARS-CoV-2 glycoprotein spike variants -
  The severe acute respiratory syndrome CoV-2 rapidly spread worldwide, causing a pandemic. After a period of evolutionary stasis, a set of SARS-CoV-2 mutations has arisen in the spike, the leading glycoprotein at the viral envelope and the primary antigenic candidate for vaccines against the 2019 CoV disease (COVID-19). Here, we present comparative biochemical data of the glycosylated full-length ancestral and D614G spike together with three other highly transmissible strains classified by the World Health Organization as variants of concern (VOC): beta, gamma, and delta. By showing that only D614G early variant has less hydrophobic surface exposure and trimer persistence at mid- temperatures, we place D614G with features that support a model of temporary fitness advantage for virus spillover worldwide. Further, during the SARS-CoV-2 adaptation, the spike accumulates alterations leading to less structural rigidity. The decreased trimer stability observed for the ancestral and the gamma strain and the presence of D614G uncoupled conformations mean higher ACE-2 affinities when compared to the beta and delta strains. Mapping the energetic landscape and flexibility of spike variants is necessary to improve vaccine development.
  🖺 Full Text HTML: Uncovering the structural flexibility of SARS-CoV-2 glycoprotein spike variants
• Compellingly high SARS-CoV-2 susceptibility of Golden Syrian hamsters suggests multiple zoonotic infections of pet hamsters during the COVID-19 pandemic -
  Golden Syrian hamsters (Mesocricetus auratus) are used as a research model for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Millions of Golden Syrian hamsters are also kept as pets in close contact to humans. To determine the minimum infective dose (MID) for assessing the zoonotic transmission risk, and to define the optimal infection dose for experimental studies, we orotracheally inoculated hamsters with SARS-CoV-2 doses from 1105 to 110-4 tissue culture infectious dose 50 (TCID50). Body weight and virus shedding were monitored daily. 110-3 TCID50 was defined as the MID, and this was still sufficient to induce virus shedding at levels up to 102.75 TCID50/ml, equaling the estimated MID for humans. Virological and histological data revealed 1102 TCID50 as the optimal dose for experimental infections. This compellingly high susceptibility resulting in productive infections in Golden Syrian hamsters needs to be considered also as a source of SARS-CoV-2 infections in humans.
  🖺 Full Text HTML: Compellingly high SARS-CoV-2 susceptibility of Golden Syrian hamsters suggests multiple zoonotic infections of pet hamsters during the COVID-19 pandemic
• Emergence of new subgenomic mRNAs in SARS-CoV-2 -
  Two mutations occurred in SARS-CoV-2 early during the COVID-19 pandemic that have come to define circulating virus lineages: first a change in the spike protein (D614G) that defines the B.1 lineage and second, a double substitution in the nucleocapsid protein (R203K, G204R) that defines the B.1.1 lineage, which has subsequently given rise to three Variants of Concern: Alpha, Gamma and Omicron. While the latter mutations appear unremarkable at the protein level, there are dramatic implications at the nucleotide level: the GGG[->]AAC substitution generates a new Transcription Regulatory Sequence (TRS) motif, driving SARS-CoV-2 to express a novel subgenomic mRNA (sgmRNA) encoding a truncated C-terminal portion of nucleocapsid (N.iORF3), which is an inhibitor of type I interferon production. We find that N.iORF3 also emerged independently within the Iota variant, and further show that additional TRS motifs have convergently evolved to express novel sgmRNAs; notably upstream of Spike within the nsp16 coding region of ORF1b, which is expressed during human infection. Our findings demonstrate that SARS-CoV-2 is undergoing evolutionary changes at the functional RNA level in addition to the amino acid level, reminiscent of eukaryotic evolution. Greater attention to this aspect in the assessment of emerging strains of SARS-CoV-2 is warranted.
  🖺 Full Text HTML: Emergence of new subgenomic mRNAs in SARS-CoV-2
• Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle- immunized mice -
  The COVID-19 pandemic continues to threaten human health worldwide, as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around K417 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values that range from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on a broadly neutralizing chimeric antibody to create K-RBD-hAb-62, which still retains excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.
  🖺 Full Text HTML: Broadly neutralizing antibodies against Omicron variants of SARS-CoV-2 derived from mRNA-lipid nanoparticle-immunized mice
• Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model -
  Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS CoV-2 variants could improve COVID-19 control. We compared monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S protein, primarily in a transgenic mouse model and a Wistar rat model. The low-dose bivalent mRNA vaccine contained half the mRNA of each respective monovalent vaccine, but induced comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, specific CD4+ and CD8+ responses, and fully protected transgenic mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduced viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized Wistar rats also contained neutralizing antibodies against the B.1.1.529 (Omicron BA.1) variant. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins is a feasible approach for increasing the potency of vaccines against emerging and co-circulating SARS-CoV-2 variants.
  🖺 Full Text HTML: Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model
• Targeting SARS-CoV-2 infection through CAR-T like bispecific T cell engagers incorporating ACE2 -
  Despite advances in antibody treatments and vaccines, COVID-19 caused by SARS-CoV-2 infection remains a major health problem resulting in excessive morbidity and mortality and the emergence of new variants has reduced the effectiveness of current vaccines. Here, as a proof-of-concept we engineered primary CD8 T cells to express SARS-CoV-2 Spike protein-specific CARs, using extracellular region of ACE2, and demonstrated their highly specific and potent cytotoxicity towards Spike-expressing target cells. To improve on this concept as a potential therapeutic, we developed a bispecific T cell engager combining ACE2 with an anti-CD3 scFv (ACE2-Bite) to target infected cells and the virus. Similar to CAR-T cell approach, ACE2-Bite endowed cytotoxic cells to selectively kill Spike-expressing targets. Furthermore, ACE2-Bite neutralized the pseudoviruses of SARS-CoV, SARS-CoV-2 wild-type and variants including Delta and Omicron, as a decoy protein. Remarkably, ACE2-Bite molecule showed a higher binding and neutralization affinity to Delta and Omicron variants compared to SARS-CoV-2 wild-type Spike proteins, suggesting the potential of this approach as a variant-proof, therapeutic strategy for future SARS-CoV-2 variants, employing both humoral and cellular arms of the adaptive immune response.
  🖺 Full Text HTML: Targeting SARS-CoV-2 infection through CAR-T like bispecific T cell engagers incorporating ACE2
• 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.
• High neutralizing activity against Omicron BA.2 can be induced by COVID-19 mRNA booster vaccination -

  The VOC of SARS-CoV-2, Omicron (BA.1, BA.1.1, BA.2, or BA.3), is associated with an increased risk of reinfection. BA.2 has become the next dominant variant worldwide. Although BA.2 infection has been shown to be mild illness, its high transmissibility will result in high numbers of cases. In response to the surge of Omicron BA.1 cases, booster vaccination was initiated in many countries. But there is limited evidence regarding the effectiveness of a booster vaccination against BA.2. We collected blood samples from 84 physicians at Kobe University Hospital, Japan, in January 2022 ~7 months after they had received two BNT162b2 vaccinations and ~2 weeks after their booster vaccination. We performed a serum neutralizing assay against BA.2 using authentic virus. Although most of the participants had no or a very low titer of neutralizing antibody against BA.2 at 7 months after two BNT162b2 vaccinations, the titer increased significantly at 2 weeks after the booster vaccination.

  🖺 Full Text HTML: High neutralizing activity against Omicron BA.2 can be induced by COVID-19 mRNA booster vaccination
• Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Infection Caused by the SARS-CoV-2 Omicron Variant in People with a Prior SARS-CoV-2 Infection -

  Importance: The benefit of primary and booster vaccination in people who experienced prior SARS-CoV-2 infection remains unclear. Objective: To estimate the effectiveness of a primary (two-dose) and booster (third dose) vaccination against Omicron infection among previously infection people. Design: Test-negative case-control study. Setting: Yale New Haven Health System facilities serving southern Connecticut communities. Participants: Vaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022. Exposure: COVID-19 mRNA primary and booster vaccination. Main Outcomes and Measures: We conducted two analyses, each with an outcome of Omicron BA.1 variant infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary vaccination during the period before and during booster eligibility (14-149 and ≥150 days, respectively, after 2nd dose) and of booster vaccination (≥14 days after booster dose). To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people. Results: Overall, 10,676 cases and 119,397 controls were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 6.1% and 7.8% had a prior infection. The effectiveness of primary vaccination 14-149 days after 2nd dose was 36.1% (95% CI, 7.1-56.1%) and 28.5% (95% CI, 20.0-36.2%) for people with and without prior infection, respectively. The effectiveness of booster vaccination was 45.8% (95% CI, 20.0-63.2%) and 56.9% (95% CI, 52.1-61.2%) in people with and without prior infection, respectively. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (95% CI, 0.56-1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (95% CI, 0.46-0.56). Conclusions and Relevance: Primary vaccination provided significant but limited protection against Omicron BA.1 infection among people with and without prior infection. While booster vaccination was associated with additional protection in people without prior infection, it was not associated with additional protection among people with prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.

  🖺 Full Text HTML: Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Infection Caused by the SARS-CoV-2 Omicron Variant in People with a Prior SARS-CoV-2 Infection
• Wastewater to clinical case (WC) ratio of COVID-19 identifies insufficient clinical testing, onset of new variants of concern and population immunity in urban communities -

  Clinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the extant and anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) is likely to have greater value as an important diagnostic tool to inform public health. As the widespread adoption of WWS is relatively new at the scale employed for COVID-19, interpretation of data, including the relationship to clinical cases, has yet to be standardized. An in-depth analysis of the metrics derived from WWS is required for public health units/agencies to interpret and utilize WWS-acquired data effectively and efficiently. In this study, the SARS-CoV-2 wastewater signal to clinical cases (WC) ratio was investigated across seven different cities in Canada over periods ranging from 8 to 21 months. Significant increases in the WC ratio occurred when clinical testing eligibility was modified to appointment-only testing, identifying a period of insufficient clinical testing in these communities. The WC ratio decreased significantly during the emergence of the Alpha variant of concern (VOC) in a relatively non-immunized community9s wastewater (40-60% allelic proportion), while a more muted decrease in the WC ratio signaled the emergence of the Delta VOC in a relatively well-immunized community9s wastewater (40-60% allelic proportion). Finally, a rapid and significant decrease in the WC ratio signaled the emergence of the Omicron VOC, likely because of the variant9s greater effectiveness at evading immunity, leading to a significant number of new reported clinical cases, even when vaccine- induced community immunity was high. The WC ratio, used as an additional monitoring metric, complements clinical case counts and wastewater signals as individual metrics in its ability to identify important epidemiological occurrences, adding value to WWS as a diagnostic technology during the COVID-19 pandemic and likely for future pandemics.

• Information Dissemination and the COVID-19 Pandemic: The Relationship between Different Information Sources and Symptoms of Psychopathology -
  The 2020-2021 COVID-19 pandemic has added to the mental health strain on individuals and groups across the world. Viral mitigation protocols and viral spread affect millions every day, but to widely different degrees. How individuals gather information about the pandemic might have an effect on levels of mental distress in the population. In this cross-sectional and representative study of the adult population of Norway, findings suggest that information gathered through newspapers and social media are the information pathways with the strongest association to symptoms of anxiety, depression and health anxiety with small to medium effect sizes. However, avoiding information about the pandemic had larger effect sizes related to symptoms of psychopathology than acquiring information about the pandemic from any source. The results suggest that to reach those who avoid pandemic news is an important goal, both to ensure the population as a whole gets relevant information regarding current viral mitigation protocols, that may in turn alleviate stress, and thus reduce the likelihood of viral transmission. The spread of pandemic misinformation on social media and the internet must be buffered, and successful interventions against misinformation may affect the mental health of the population.
  🖺 Full Text HTML: Information Dissemination and the COVID-19 Pandemic: The Relationship between Different Information Sources and Symptoms of Psychopathology
• Changes of LipoxinA4 Levels Following Early Hospital Management of Patients with Non-Severe COVID-19: A Pilot Study -

  LipoxinA4 (LXA4) is an anti-inflammatory biomarker participating in the active process of inflammation resolution, which is suggested to be effective on infectious and inflammatory diseases like COVID-19. In this study, we hypothesized that LXA4 levels may increase following COVID-19 treatment and are even more accurate than commonly used inflammatory markers such as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and ferritin. To test this hypothesis, a pilot study was conducted with 31 adult hospitalized patients with non-severe COVID-19. LXA4 levels were measured at the baseline and 48-72 hours later. Accordingly, ESR and CRP levels were collected on the first day of hospitalization. Moreover, the maximum serum ferritin levels were collected during the five days. LXA4 levels significantly increased at 48-72 hours compared to the baseline. ESR, CRP, and ferritin levels were positively correlated with the increased LXA4. In contrast, aging was shown to negatively correlate with the increased LXA4 levels. LXA4 may be known as a valuable marker to assess the treatment response among non-elderly patients with non-severe COVID-19. Furthermore, LXA4 could be considered as a potential treatment option under inflammatory conditions. Further studies are necessary to clarify LXA4 role in COVID-19 pathogenesis, as well as the balance between such pro-resolving mediators and inflammatory parameters.

  🖺 Full Text HTML: Changes of LipoxinA4 Levels Following Early Hospital Management of Patients with Non-Severe COVID-19: A Pilot Study

From Clinical Trials

• Clinical Performance Evaluation of the Bio-Self™ COVID-19 Antigen Home Test - Condition:   COVID-19
  Interventions:   Device: Bio-Self COVID-19 Antigen Home Test;   Device: Standard of Care COVID-19 Test;   Diagnostic Test: RT-PCR Test
  Sponsors:   BioTeke USA, LLC;   CSSi Life Sciences
  Not yet recruiting

• Functional Capacity in Patients Post Mild COVID-19 - Condition:   COVID-19
  Intervention:   Device: Cardiopulmonary exercise test (CPET)
  Sponsor:   Rambam Health Care Campus
  Recruiting

• Circuit Training Program in Post COVID-19 Patients - Condition:   COVID-19
  Interventions:   Other: Circuit Training Exercise Program;   Other: Aerobic Training Exercise Program
  Sponsor:   Riphah International University
  Recruiting

• The Effect of Home-based Rehabilitation Program After COVID-19 Infection - Condition:   COVID-19
  Interventions:   Behavioral: Add-on telerehabilitation and home-based rehabilitation;   Behavioral: Home-based rehabilitation alone
  Sponsor:  
  National Taiwan University Hospital
  Recruiting

• A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine in Population Aged ≥18 Years - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Biological: SCTV01E;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: mRNA-1273
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years. - Condition:   COVID-19
  Interventions:   Biological: 1 Nebulized inhalation for booster groups;   Biological: 2 Nebulized inhalation for booster groups;   Biological: 3 Nebulized inhalation for booster groups;   Biological: 4 Nebulized inhalation for booster groups;   Biological: 5 Intramuscular injection for booster groups;   Biological: 6 Intramuscular injection for booster groups;   Biological: 7 Intramuscular injection for booster groups;   Biological: 8 Intramuscular injection for booster groups;   Biological: 9 Intramuscular injection for booster groups;   Biological: 10 Intramuscular injection for booster groups;   Biological: 11 Nebulized inhalation for booster groups;   Biological: 12 Nebulized inhalation for booster groups;   Biological: 13 Nebulized inhalation for booster groups;   Biological: 14 Nebulized inhalation for booster groups;   Biological: 15 Intramuscular injection for booster groups;   Biological: 16 Intramuscular injection for booster groups;   Biological: 17 Intramuscular injection for booster groups;   Biological: 18 Intramuscular injection for booster groups;   Biological: 19 Intramuscular injection for booster groups;   Biological: 20 Intramuscular injection for booster groups;   Biological: 21 Nebulized inhalation for primary groups;   Biological: 22 Nebulized inhalation for primary groups;   Biological: 23 Nebulized inhalation for primary groups;   Biological: 24 Nebulized inhalation for primary groups
  Sponsor:  
  Seventh Medical Center of PLA General Hospital
  Not yet recruiting

• Non-inferiority Trial on Treatments in Early COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Sotrovimab;   Drug: Tixagevimab Cilgavimab;   Drug: Nirmatrelvir Ritonavir
  Sponsors:   Azienda Ospedaliera Universitaria Integrata Verona;   Agenzia Italiana del Farmaco;   Azienda Sanitaria-Universitaria Integrata di Udine
  Recruiting

• Neutralizing Power of Anti-SARS-CoV-2 (Anti-COVID-19) Serum Antibodies - Conditions:   COVID-19;   SARS CoV 2 Infection
  Intervention:  
  Other: Collection of biological samples
  Sponsor:   Centre Hospitalier Régional d’Orléans
  Not yet recruiting

• Immunogenicity and Safety Study of Recombinant Two-Component COVID-19 Vaccine (CHO Cell)(ReCOV) - Condition:   COVID-19
  Interventions:   Biological: Recombinant two-component COVID-19 vaccine (CHO cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated
  Sponsor:   Jiangsu Rec- Biotechnology Co., Ltd.
  Not yet recruiting

• Immunogenicity，Safety and Cross - Immune Response With the Strains of the Booster Immunization Using an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Biological: Inactivated COVID-19 Vaccine
  Sponsor:   Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Interleukine 6 (IL6) Assay for Predicting Failure of Spontaneous Breathing in Patients With COVID-19 Acute Respiratory Distress Syndrome - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Interventions:  
  Biological: IL6 assessment;   Biological: CRP and PCT assessment
  Sponsor:  
  Centre Hospitalier Henri Duffaut - Avignon
  Recruiting

• A Single Arm Phase-IV Study to Determine Reactogenicity and Immunogenicity of Delayed COVID-19 Vaccine Schedule in Children - Conditions:   Vaccine Reaction;   COVID-19;   Children, Only
  Intervention:  
  Biological: BNT162b2 Pfizer-BioNTech/Comirnaty
  Sponsors:   KK Women’s and Children’s Hospital;   Duke- NUS Graduate Medical School
  Recruiting

• Establishing Immunogenicity and Safety of Needle-free Intradermal Delivery of mRNA COVID-19 Vaccine - Conditions:   Vaccination; Infection;   COVID-19
  Interventions:  
  Device: solid microneedle skin patch;   Drug: mRNA-1273
  Sponsor:   Leiden University Medical Center
  Recruiting

• Bivalirudin Versus Enoxaparin in Critically Ill COVID-19 Patients - Conditions:   Acute Respiratory Failure;   SARS CoV 2 Infection;   Anticoagulants
  Interventions:  
  Drug: Enoxaparin Sodium;   Drug: Bivalirudin
  Sponsor:   University Magna Graecia
  Not yet recruiting

From PubMed

• A Novel Needle-free Microjet Drug Injector Using Er:YAG LASER: A Completely New Concept of Trans-Dermal Drug Delivery System - CONCLUSION: This study showed that a novel needle-free microjet injector using Er:YAG LASER can introduce beneficial, liquid, aesthetic drugs into the papillary dermal layer (depth of 300um) with minimal epidermal damage. This article is protected by copyright. All rights reserved.

• Safety Learning in Anxiety, Pavlovian Conditioned Inhibition and COVID Concerns - Experimental studies of fear conditioning have identified the effectiveness of safety signals in inhibiting fear and maintaining fear-motivated behaviors. In fear conditioning procedures, the presence of safety signals means that the otherwise expected feared outcome will not now occur. Differences in the inhibitory learning processes needed to learn safety are being identified in various psychological and psychiatric conditions. However, despite early theoretical interest, the role of…

• Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of COVID-19 - Corona virus is quickly spreading around the world. The goal of viral management is to disrupt the virus’s life cycle, minimize lung damage, and alleviate severe symptoms. Numerous strategies have been used, including repurposing existing antivirals or drugs used in previous viral outbreaks. One such strategy is to repurpose FDA-approved kinase inhibitors that are potential chemotherapeutic agents and have demonstrated antiviral activity against a variety of viruses, including MERS, SARS-CoV-1,…

• Methylene blue in management of COVID19 - CONCLUSION: No statistically significant difference in outcome measures like Spo2, duration of hospital stay or inflammatory markers. A general trend of fall in inflammatory markers and O2 requirements in group receiving methylene blue but this difference was not consistantly statistically significant.

• Antibody Profiling in COVID-19 Patients with Different Severities by Using Spike Variant Protein Microarrays - The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants….

• Porcine Epidemic Diarrhea Virus nsp7 Inhibits Interferon-Induced JAK-STAT Signaling through Sequestering the Interaction between KPNA1 and STAT1 - Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic enteric coronavirus that causes high mortality in piglets. Interferon (IFN) responses are the primary defense mechanism against viral infection; however, viruses always evolve elaborate strategies to antagonize the antiviral action of IFN. Previous study showed that PEDV nonstructural protein 7 (nsp7), a component of the viral replicase polyprotein, can antagonize ploy(I:C)-induced type I IFN production. Here, we found that PEDV nsp7…

• Does government intervention affect CO₂ emission reduction effect of producer service agglomeration? Empirical analysis based on spatial Durbin model and dynamic threshold model - Achieving carbon peak and carbon neutrality is an inherent requirement for countries to promote green recovery and transformation of the global economy after the COVID-19 pandemic. As “a smoke-free industry,” producer services agglomeration (PSA) may have significant impacts on CO(2) emission reduction. Therefore, based on the nightlight data to calculate the CO(2) emissions of 268 cities in China from 2005 to 2017, this study deeply explores the impact and transmission mechanism of PSA on CO(2)…

• Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm - Background. Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease , attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine…

• Receptor binding domain of SARS-CoV-2 is a functional αv-integrin agonist - Among the novel mutations distinguishing SARS-CoV-2 from similar respiratory coronaviruses is a K403R substitution in the receptor-binding domain (RBD) of the viral spike (S) protein within its S1 region. This amino acid substitution occurs near the angiotensin-converting enzyme 2 (ACE2)-binding interface and gives rise to a canonical RGD adhesion motif that is often found in native extracellular matrix proteins, including fibronectin. In the present study, the ability of recombinant S1-RBD to…

• The Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness - During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A,…

• Hippo Signaling Pathway Activation during SARS-CoV-2 Infection Contributes to Host Antiviral Response - SARS-CoV-2, responsible for the COVID-19 pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of…

• Different HMGCR-inhibiting statins vary in their association with increased survival in patients with COVID-19 - BACKGROUND: In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. Here we explored the possibility that different statins might differ in their ability to exert protective effects based on computational predictions.

• Virucidal activity and mechanism of action of cetylpyridinium chloride against SARS-CoV-2 - CONCLUSIONS: Our results suggest that CPC inhibits the interaction between S protein and ACE2, and thus, reduces infectivity of SARS-CoV-2 and suppresses viral adsorption.

• Synthesis and biological evaluation of 2-benzylaminoquinazolin-4(3H)-one derivatives as a potential treatment for SARS-CoV-2 - Despite the continuing global crisis caused by coronavirus disease 2019 (COVID-19), there is still no effective treatment. Therefore, we designed and synthesized a novel series of 2-benzylaminoquinazolin-4(3H)-one derivatives and demonstrated that they are effective against SARS-CoV-2. Among the synthesized derivatives, 7-chloro-2-(((4-chlorophenyl)(phenyl)methyl)amino)quinazolin-4(3H)-one (Compound 39) showed highest anti-SARS-CoV-2 activity, with a half-maximal inhibitory concentration value…

• Mitoxantrone modulates a heparan sulfate-spike complex to inhibit SARS-CoV-2 infection - Spike-mediated entry of SARS-CoV-2 into human airway epithelial cells is an attractive therapeutic target for COVID-19. In addition to protein receptors, the SARS-CoV-2 spike (S) protein also interacts with heparan sulfate, a negatively charged glycosaminoglycan (GAG) attached to certain membrane proteins on the cell surface. This interaction facilitates the engagement of spike with a downstream receptor to promote viral entry. Here, we show that Mitoxantrone, an FDA- approved topoisomerase…

From Patent Search