Covid-19 Sentry

Contents

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

From Preprints

• Unique amino acid substitution in RBD region of SARS-CoV-2 Omicron XAY.2 -
  We attempted to explain the rare mutation at the receptor binding domain of the spike protein in the XAY.2 variant of SARS-CoV-2 from the perspective of hydrophobic interactions. We propose that decreasing hydrophobicity at position 446 and 486 of the RBD region of the spike protein might affect the infectivity of SARS-CoV-2. We also estimated the probable mutations at the 446 and 486 position the virus may acquire, leading to a decreased hydrophobicity.
  🖺 Full Text HTML: Unique amino acid substitution in RBD region of SARS-CoV-2 Omicron XAY.2
• The Ecology of Viruses in Urban Rodents with a Focus on SARS-CoV-2 -
  Wild animals are naturally infected with a range of viruses, some of which may be zoonotic for humans. During the human COIVD pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this we have sampled rats (Rattus norvegicus) and mice (Apodemus sylvaticus) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralisation ability, that are consistent with rats being exposed to SARS-CoV-2 and / or exposed to other viruses that result in cross-reactive antibodies.
  🖺 Full Text HTML: The Ecology of Viruses in Urban Rodents with a Focus on SARS-CoV-2
• Bivalent mRNA vaccine improves antibody-mediated neutralization of many SARS-CoV-2 Omicron lineage variants -
  The early Omicron lineage variants evolved and gave rise to diverging lineages that fueled the COVID-19 pandemic in 2022. Bivalent mRNA vaccines, designed to broaden protection against circulating and future variants, were authorized by the U.S. Food and Drug Administration (FDA) in August 2022 and recommended by the U.S. Centers for Disease Control and Prevention (CDC) in September 2022. The impact of bivalent vaccination on eliciting neutralizing antibodies against homologous BA.4/BA.5 viruses as well as emerging heterologous viruses needs to be analyzed. In this study, we analyze the neutralizing activity of sera collected after a third dose of vaccination (2-6 weeks post monovalent booster) or a fourth dose of vaccination (2-7 weeks post bivalent booster) against 10 predominant/recent Omicron lineage viruses including BA.1, BA.2, BA.5, BA.2.75, BA.2.75.2, BN.1, BQ.1, BQ.1.1, XBB, and XBB.1. The bivalent booster vaccination enhanced neutralizing antibody titers against all Omicron lineage viruses tested, including a 10-fold increase in neutralization of BQ.1 and BQ.1.1 viruses that predominated in the U.S. during the last two months of 2022. Overall, the data indicate the bivalent vaccine booster strengthens protection against Omicron lineage variants that evolved from BA.5 and BA.2 progenitors.
  🖺 Full Text HTML: Bivalent mRNA vaccine improves antibody-mediated neutralization of many SARS-CoV-2 Omicron lineage variants
• Effects of Variants of Concern Mutations on the Force-Stability of the SARS-CoV-2:ACE2 Interface and Virus Transmissibility -
  Viruses mutate under a variety of selection pressures, allowing them to continuously adapt to their hosts. Mutations in SARS-CoV-2 have shown effective evasion of population immunity and increased affinity to host factors, in particular to the cellular receptor ACE2. In the dynamic environment of the respiratory tract, the question arises, if not only affinity, but also force-stability of the SARS-CoV-2:ACE2 bond, initiating infection of host cells, might be a selection factor for mutations. Here, we use magnetic tweezers (MT) to study the effect of amino acid substitutions in variants of concern (VOCs) on RBD:ACE2 bond kinetics with and without external load using a previously established assay. Matching bulk-affinity measurements determined in literature, we find higher affinity for all VOCs compared to wt. In contrast to that, Alpha is the only VOC markedly different from the wild type showing higher mechanical resilience under force. Investigating the RBD:ACE2 interactions with molecular dynamics simulations, we were able to rationalize the mechanistic molecular origins of this increase in force-stability. Our study emphasizes the diversity of contributions to the assertiveness of variants and establishes force-stability as one of several factors for fitness. Understanding fitness-advantages opens the possibility for prediction of likely mutations allowing rapid adjustment of therapeutics, vaccination, and intervention measures.
  🖺 Full Text HTML: Effects of Variants of Concern Mutations on the Force-Stability of the SARS-CoV-2:ACE2 Interface and Virus Transmissibility
• Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern -
  The high mutation rate of SARS-CoV-2 leads to emergence of several variants, some of which are resistant to vaccines and drugs targeting viral elements. Targeting host dependency factors, cell proteins required for viral replication, would help avoid resistance. However, whether different SARS-CoV-2 variants induce conserved cell responses and exploit the same core host factors is still unclear. We compared three variants of concern and observed that the host transcriptional response was conserved, differing only in kinetics and magnitude. By CRISPR screening we identified the host genes required for infection by each variant: most of the identified genes were shared by multiple variants, both in lung and colon cells. We validated our hits with small molecules and repurposed FDA-approved drugs. All drugs were highly effective against all tested variants, including delta and omicron, new variants that emerged during the study. Mechanistically, we identified ROS production as a pivotal step in early virus propagation. Antioxidant drugs, such as N-acetyl cysteine (NAC), were effective against all variants both in human lung cells, and in a humanised mouse model. Our study strongly supports the immediate use of available antioxidant drugs, such as NAC, as a general and effective anti-COVID-19 approach.
  🖺 Full Text HTML: Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern
• Vaccine effectiveness of primary and booster COVID-19 vaccinations against SARS-CoV-2 infection in the Netherlands from 12 July 2021 to 6 June 2022: a prospective cohort study -

  Introduction - Monitoring of COVID-19 vaccine effectiveness (VE) is needed to inform vaccine policy. We estimated VE of primary vaccination, and first and second booster vaccination, against SARS-CoV-2 infection overall, and in four risk groups defined by age and medical risk condition, in the Delta and Omicron BA.1/BA.2 periods. Methods - VASCO is an ongoing prospective cohort study among vaccinated and unvaccinated Dutch adults. The primary endpoint was a self-reported positive SARS-CoV-2 test during 12 July 2021-6 June 2022. Participants with a prior SARS-CoV-2 infection, based on a positive test or serology, were excluded. We used Cox proportional hazard models with vaccination status as time-varying exposure and adjustment for age, sex, educational level, and medical risk condition. We stratified by Delta and Omicron BA.1/BA.2 periods, risk group, and time since vaccination. Results - 37,170 participants (mean age 57 years) were included. In the Delta period, VE <6 weeks after primary vaccination was 80% (95%CI 69-87) and decreased to 71% (65-77) after 6 months. VE increased to 96% (86-99) shortly after the first booster vaccination. In the Omicron period these estimates were 46% (22-63), 25% (8-39) and 57% (52-62), respectively. VE was 50% (34-62) <6 weeks after a second booster vaccination in participants aged ≥60 years. For the Omicron period, an interaction term between vaccination status and risk group significantly improved the model (p<0.001), with generally lower VEs for those with a medical risk condition. Conclusions - Our results show the benefit of booster vaccinations against infection, also in risk groups, although the additional protection wanes quite rapidly.

  🖺 Full Text HTML: Vaccine effectiveness of primary and booster COVID-19 vaccinations against SARS-CoV-2 infection in the Netherlands from 12 July 2021 to 6 June 2022: a prospective cohort study
• SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 Antigen Self Tests -

  Widespread use of over-the-counter rapid diagnostic tests for SARS-CoV-2 has led to a decrease in availability of clinical samples for viral genomic surveillance. As an alternative sample source, we evaluated RNA isolated from BinaxNOW swabs stored at ambient temperature for SARS-CoV-2 rRT-PCR and full viral genome sequencing. 81 of 103 samples (78.6%) yielded detectable RNA, and 46 of 57 samples (80.7 %) yielded complete genome sequences. Our results illustrate that SARS-CoV-2 RNA extracted from used Binax test swabs provides an important opportunity for improving SARS-CoV-2 genomic surveillance, evaluating transmission clusters, and monitoring within-patient evolution.

  🖺 Full Text HTML: SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 Antigen Self Tests
• Differential COVID-19 mortality in the United States: Patterns, causes and policy implications -

  A “two Americas” narrative emerged in the summer of 2021: one with high demand for COVID-19 vaccines, and a second with widespread vaccine hesitancy and opposition to mask mandates.  But our analysis of excess mortality shows that the U.S. has been a divided nation at least since the start of the pandemic.  Through April, 2022, there were 1,335,292 excess deaths associated with COVID-19, 37% more than reported as such.  After the first wave, death rates in the South were more than double those in the Northeast; 45% of deaths were in the South, with 38% of the population.  While some regard vaccination and other measures as matters of personal choice, the population impact is striking.  If every region had the same mortality rate as the lowest regional rate in each period, more than 418,763 COVID-19 deaths were “avoidable,” more than half (58%) in the South and almost half before vaccines were available.  These results show that population-based COVID-19 policies can still play an important role in protecting those most vulnerable to severe disease and death and reducing the spread of the virus. This example illustrates the importance of excess mortality measures as part of a comprehensive surveillance system.  Official mortality counts rely on complete recording of COVID-19 as a cause of death, but COVID-19 deaths are under reported for many reasons.  Indeed, the proportion of COVID-19 deaths reported as such varied markedly over time, and from 67% in the West to 87% the Northeast.  In 2022, some regions cut back on testing making it harder to see a re-emergence of COVID-19 in those places.  More extensive surveillance based on wastewater testing and other means that do not depend on testing are needed to get a more accurate picture. Excess mortality estimates are more tenuous years beyond the pre-pandemic period.

  🖺 Full Text HTML: Differential COVID-19 mortality in the United States: Patterns, causes and policy implications
• Effectiveness of inactivated COVID-19 vaccines against SARS-CoV-2 infections among healthcare personnel in Pakistan: a test-negative, case-control study. -

  Objective: During the COVID-19 pandemic, several vaccines that were efficacious in randomized controlled trials (RCTs) were authorized for mass vaccination. In developing countries, inactivated vaccines were widely administered. While inactivated vaccines have been deemed effective in reducing disease severity, for healthcare personnel (HCPs), effectiveness against COVID-19 infections is also essential to reduce the risk to vulnerable patients and ensure a stable healthcare workforce. In addition, there are limited studies examining effectiveness of inactivated vaccines against emerging SARS-CoV-2 variants in real-world settings. We aimed to estimate the effectiveness of inactivated vaccines (BBIBP-CorV and CoronaVac) against RT-PCR-confirmed COVID-19 infections among HCPs in the setting of emerging SARS-CoV-2 variants in Pakistan. Design, setting and participants: A retrospective matched test-negative case-control analysis of existing data of HCPs at a private healthcare system in Pakistan. Methods: HCPs tested between April 1 and September 30, 2021, were included. Each case was matched to two to six controls by the date of the RT-PCR test (± 7 days) to reduce bias. We compared demographics, reasons for testing, and vaccination status between cases and controls using chi-square for categorical variables and t-test for continuous-level data. The odds of getting a PCR-confirmed SARS-COV-2 infection were calculated using conditional logistic regression, after adjusting for age, gender, and work area. Vaccine effectiveness (VE) was calculated as percent VE using (1-OR)*100. Results: Inactivated vaccines were ineffective against COVID-19 infections ≥ 14 days after receiving the first dose [VE: 20% (95% CI: -10, 41; p=0.162)]. The vaccines showed modest effectiveness ≥ 14 days after the second dose against COVID-19 infections [VE: 33% (95% CI: 11, 50; p=0.006)], and symptomatic COVID-19 infections [VE: 36% (95% CI: 10, 54; p=0.009)]. Conclusions: Inactivated vaccines show modest effectiveness against COVID-19 infections in the setting of emerging VOCs. This builds a strong case for boosters and/or additional vaccination.

  🖺 Full Text HTML: Effectiveness of inactivated COVID-19 vaccines against SARS-CoV-2 infections among healthcare personnel in Pakistan: a test-negative, case-control study.
• Research on the mental health status of frontline medical staff during the normalization of the COVID-19 pandemic -

  Objective: This study aimed to investigate the relationship between personality characteristics and psychological health of hospitals’ frontline medical staff and provide a basis and reference for targeted psychological health education for frontline medical staff and for the staff of related departments to formulate relevant policies. Methods:The self-evaluation scale of symptoms (SCL-90) was used to investigate the mental health status of 150 first-line medical staff in Zhejiang Province in response to the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Results: The average scores of SCL-90 and somatization, obsessive-compulsive, depression, anxiety, hostility, terror, and psychotic factors were significantly higher than those of the normal sample in the first-aid medical staff of Aihu Hubei. The degree of influence on the mental health status of the frontline medical staff in service in Hubei is as follows, from high to low: the degree of suspicion that they may have been infected when new coronavirus pneumonia-related symptoms occur, the degree of fear of being infected and thus bring the infection to their families, and whether they have received a medical check-up recently, as well as a high level of education (both P<0.05). C onclu sion: The psychological health level of the frontline medical staff is lower than the national norm. In the context of the increasing number of confirmed cases and the new type of coronavirus pneumonia in the absence of any specific curative treatments, the frontline medical staff is under great psychological pressure. It is necessary to institute targeted mental health promotion to relieve the psychological pressure endured by the frontline medical staff, promote their physical and mental health, and better respond to the pandemic in China.

  🖺 Full Text HTML: Research on the mental health status of frontline medical staff during the normalization of the COVID-19 pandemic
• Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: Results from the COViK study -

  Purpose: COViK - a prospective hospital-based multicenter case-control study in Germany - aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. Methods: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. Results: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95% CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. Conclusion: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.

  🖺 Full Text HTML: Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: Results from the COViK study
• The importance of increasing primary vaccinations against COVID-19 in Europe -

  In the European Union, mass vaccination against COVID-19 staved off the strict restrictions that had characterized early epidemic response. Now, vaccination campaigns are focusing on booster doses, and primary vaccinations have all but halted. Still, 52 million European adults are unvaccinated. We investigated if reaching the still unvaccinated population in future vaccination campaigns would substantially decrease the current burden of COVID-19, which is substantial. We focused on vaccination homophily, whereby those who are unvaccinated are mostly in contact with other unvaccinated, making COVID-19 circulation easier. We quantified vaccination homophily and estimated its impact on COVID-19 circulation. We used an online survey of 1,055,286 people from 22 European countries during early 2022. We computed vaccination homophily as the association between reported vaccination status and perceived vaccination uptake among one9s own social contacts, using a case-referent design and a hierarchical logistic model. We used this information in an analysis of the COVID-19 reproduction ratio to determine the impact of vaccine homophily in transmission. Vaccination homophily was present and strong everywhere: the average odds ratio of being vaccinated for a 10-percentage-point increase in coverage among contacts was 1.66 (95% CI=(1.60, 1.72)). Homophily was positively associated with the strictness of COVID-19-related restrictions in 2020 (Pearson=0.49, p-value=0.03). In the countries studied, 12%-to-18% of the reproduction ratio would be attributable to vaccine homophily. Reducing vaccination homophily may curb the reproduction ratio substantially even to the point of preventing recurrent epidemic waves. In addition to boosting those already vaccinated, increasing primary vaccination should remain a high priority in future vaccination campaigns, to reduce vaccination homophily: this combined strategy may decrease COVID-19 burden.

  🖺 Full Text HTML: The importance of increasing primary vaccinations against COVID-19 in Europe
• HostSeq : A Canadian Whole Genome Sequencing and Clinical Data Resource -

  HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

  🖺 Full Text HTML: HostSeq : A Canadian Whole Genome Sequencing and Clinical Data Resource
• Macrophages only sense infectious SARS-CoV-2 when they express sufficient ACE2 to permit viral entry, where rapid cytokine responses then limit viral replication. -
  Macrophages are key cellular contributors to COVID-19 pathogenesis. Whether SARS-CoV-2 can enter macrophages, replicate and release new viral progeny remains controversial. Similarly, whether macrophages need to sense replicating virus to drive cytokine release is also unclear. Macrophages are heterogeneous cells poised to respond to their local microenvironment, and accordingly, the SARS-CoV-2 entry receptor ACE2 is only present on a subset of macrophages at sites of human infection. Here, we use in vitro approaches to investigate how SARS-CoV-2 interacts with ACE2-negative and ACE2-positive human macrophages and determine how these macrophage populations sense and respond to SARS-CoV-2. We show that SARS-CoV-2 does not replicate within ACE2-negative human macrophages and does not induce pro-inflammatory cytokine expression. By contrast, ACE2 expression in human macrophages permits SARS-CoV-2 entry, replication, and virion release. ACE2-expressing macrophages sense replicating virus to trigger pro-inflammatory and anti-viral programs that limit virus release. These combined findings resolve several controversies regarding macrophage-SARS-CoV-2 interactions and identify a signaling circuit by which macrophages sense SARS-CoV-2 cell entry and respond by restricting viral replication.
  🖺 Full Text HTML: Macrophages only sense infectious SARS-CoV-2 when they express sufficient ACE2 to permit viral entry, where rapid cytokine responses then limit viral replication.
• Epi-Clock: A sensitive platform to help understand pathogenic disease outbreaks and facilitate the response to future outbreaks of concern. -

  The lack of virus fossilization precludes any references or ancestors for inferring evolutionary processes, and viruses have no cell structure, metabolism, or space to reproduce outside host cells. Most mutations yielding high pathogenicity become removed from the population, but adaptive mutations could be epidemically transmitted and fixed in the population. Therefore, determining how viruses originated, how they diverged and how an infectious disease was transmitted are serious challenges. To predict potential epidemic outbreaks, we tested our strategy, Epi-Clock, which applies the ZHU algorithm on different SARS-CoV-2 datasets before outbreaks to search for real significant mutational accumulation patterns correlated with the outbreak events. We imagine that specific amino acid substitutions are triggers for outbreaks. Surprisingly, some inter-species genetic distances of Coronaviridae were shorter than the intra-species distances, which may represent the intermediate states of different species or subspecies in the evolutionary history of Coronaviridae. The insertions and deletions of whole genome sequences between different hosts were separately associated with new functions or turning points, clearly indicating their important roles in the host transmission and shifts of Coronaviridae. Furthermore, we believe that non-nucleosomal DNA may play dominant roles in the divergence of different lineages of SARS-CoV-2 in different regions of the world because of the lack of nucleosome protection. We suggest that strong selective variation among different lineages of SARS-CoV-2 is required to produce strong codon usage bias, significantly appear in B.1.640.2 and B.1.617.2 (Delta). Interestingly, we found that an increasing number of other types of substitutions, such as those resulting from the hitchhiking effect, have accumulated, especially in the pre-breakout phase, even though some previous substitutions were replaced by other dominant genotypes. From most validations, we could accurately predict the potential pre-phase of outbreaks with a median interval of 5 days before. Using our pipeline, users may review updated information on the website https://bioinfo.liferiver.com.cn with easy registration.

  🖺 Full Text HTML: Epi-Clock: A sensitive platform to help understand pathogenic disease outbreaks and facilitate the response to future outbreaks of concern.

From Clinical Trials

• Efficacy and Safety of Jaktinib in Patients With COVID-19 Pneumoia - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Jaktinib;   Drug: Placebo
  Sponsor:   First Affiliated Hospital of Zhejiang University
  Not yet recruiting

• Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: Traditional Chinese Medicine Formulation;   Other: Placebo Treatment
  Sponsor:   First Affiliated Hospital Xi’an Jiaotong University
  Not yet recruiting

• Study of SHEN26 Capsule in Patients With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SHEN26 dose 1;   Drug: SHEN26 dose 2;   Drug: SHEN26 placebo
  Sponsor:   Shenzhen Kexing Pharmaceutical Co., Ltd.
  Recruiting

• Efficacy and Safety of Anti-COVID-19 Antibody SA58 Nasal Spray to Prevent Infection in High-risk Populations - Condition:   COVID-19
  Intervention:   Drug: SA58 Nasal Spray
  Sponsor:   Sinovac Life Sciences Co., Ltd.
  Recruiting

• Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People - Condition:   COVID-19
  Interventions:   Drug: SA58 Nasal Spray;   Drug: Placebo
  Sponsors:   Sinovac Life Sciences Co., Ltd.;   Beijing Ditan Hospital
  Recruiting

• Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines - Condition:   COVID-19
  Interventions:   Biological: CoronaVac/CoronaVac;   Biological: CoronaVac/BNT162b2
  Sponsor:   Institut Pasteur de Tunis
  Completed

• Immunogenicity and Safety of COVID-19 Vaccine as a Booster Vaccination in Population Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Vaccine (CHO Cell) LYB001;   Biological: ZF2001
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.
  Not yet recruiting

• Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: FB2001;   Drug: FB2001 placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Recruiting

• A Study of Positive Emotions With Long COVID-19 - Condition:   Post-Acute COVID-19 Syndrome
  Intervention:   Behavioral: Microdosing of mindfulness
  Sponsor:   University of California, Davis
  Not yet recruiting

• Efficacy and Safety of the Anti-COVID-19 Antibody SA55 for Injection in Patients With Hematological Malignancies Who Are Persistently Positive for COVID-19 - Conditions:   Hematological Malignancy;   COVID-19
  Intervention:   Biological: Anti-COVID-19 Antibody SA55 for Injection
  Sponsor:   Beijing Boren Hospital
  Recruiting

• A Vaccine Booster (GEO-CM04S1) for the Prevention of COVID-19 in Patients With Chronic Lymphocytic Leukemia - Conditions:   Chronic Lymphocytic Leukemia;   COVID-19 Infection
  Interventions:   Procedure: Biospecimen Collection;   Biological: mRNA COVID-19 Vaccine;   Biological: Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1
  Sponsors:   City of Hope Medical Center;   National Cancer Institute (NCI)
  Not yet recruiting

• Sars-COV-2 Immunity in immunoCOmpromised Populations - Conditions:   SARS CoV 2 Infection;   COVID-19
  Intervention:   Diagnostic Test: Humoral immunity
  Sponsors:   Maria Goossens;   Université Libre de Bruxelles;   Institute of Tropical Medicine, Belgium;   Mensura EDPB;   Erasme hospital
  Not yet recruiting

• The Effect of Motivational Interviewing on the Adherence to Medication of Patients With COVID-19 Diagnosed at Home - Condition:   Drug Compliance
  Intervention:   Behavioral: motivational interview
  Sponsor:   Saglik Bilimleri Universitesi Gulhane Tip Fakultesi
  Completed

• Qigong for Post Acute Sequelae of COVID-19 Infection - Condition:   Long COVID
  Intervention:   Behavioral: External Qigong
  Sponsor:   University of California, Davis
  Recruiting

• Safety, Tolerability and Pharmacokinetic Characteristics Evaluation on GST-HG171 Tablets - Condition:   COVID-19
  Interventions:   Drug: GST-HG171;   Drug: placebo of GST-HG171
  Sponsor:   Fujian Akeylink Biotechnology Co., Ltd.
  Recruiting

From PubMed

• The nanomolar affinity of C-phycocyanin from virtual screening of microalgal bioactive as potential ACE2 inhibitor for COVID-19 therapy - The global pandemic of COVID-19 caused by SARS-CoV-2 has caused more than 400 million infections with more than 5.7 million deaths worldwide, and the number of validated therapies from natural products for treating coronavirus infections needs to be increased. Therefore, the virtual screening of bioactive compounds from natural products based on computational methods could be an interesting strategy. Among many sources of bioactive natural products, compounds from marine organisms, particularly…

• Delivery of siRNAs against MERS-CoV in Vero and HEK-293 cells: A comparative evaluation of transfection reagents - CONCLUSION: Based on the results and data analysis, it is concluded that the use of two different transfection reagents was significantly effective. But the Lipofectamine™ 2000 was found to be a better transfection reagent than the JetPRIME^(R) for the delivery of siRNAs in both cell lines.

• Polypropylene nanoplastic exposure leads to lung inflammation through p38-mediated NF-κB pathway due to mitochondrial damage - CONCLUSIONS: These results suggest that PP stimulation may contribute to inflammation pathogenesis via the p38 phosphorylation-mediated NF-κB pathway as a result of mitochondrial damage.

• Overcoming Pharmaceutical Bottlenecks for Nucleic Acid Drug Development - ConspectusThe outbreak of the coronavirus disease 2019 (COVID-19) pandemic and swift approval of two mRNA vaccines have put nucleic acid therapeutics in the spotlight of both the scientific community and the general public. Actually, in addition to mRNAs, multiple nucleic acid therapeutics have been successively commercialized over the past few years. The rapid development of nucleic acid drugs not only demonstrates their superior potency but also marks a new era of the field. Compared with…

• DDQ/Fe(NO₃)₃-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2 - In the present study, we herein report a DDQ-catalyzed new protocol for the synthesis of substituted 3-acylindoles. Being a potential system for virtual hydrogen storage, introduction of catalytic DDQ in combination with Fe(NO(3))(3)·9H(2)O and molecular oxygen as co-catalysts offers a regioselective oxo-functionalization of C-3 alkyl-/aryllidine indolines even with scale-up investigations. Intermediate isolation, their spectroscopic characterization, and the density functional theory…

• A knowledge-based protein-protein interaction inhibition (KPI) pipeline: an insight from drug repositioning for COVID-19 inhibition - The inhibition of protein-protein interactions (PPIs) by small molecules is an exciting drug discovery strategy. Here, we aimed to develop a pipeline to identify candidate small molecules to inhibit PPIs. Therefore, KPI, a Knowledge-based Protein-Protein Interaction Inhibition pipeline, was introduced to improve the discovery of PPI inhibitors. Then, phytochemicals from a collection of known Middle Eastern antiviral herbs were screened to identify potential inhibitors of key PPIs involved in…

• SARS-CoV-2 Harnesses Host Translational Shutoff and Autophagy To Optimize Virus Yields: the Role of the Envelope (E) Protein - The SARS-CoV-2 virion is composed of four structural proteins: spike (S), nucleocapsid (N), membrane (M), and envelope (E). E spans the membrane a single time and is the smallest, yet most enigmatic of the structural proteins. E is conserved among coronaviruses and has an essential role in virus-mediated pathogenesis. We found that ectopic expression of E had deleterious effects on the host cell as it activated stress responses, leading to LC3 lipidation and phosphorylation of the translation…

• ‘Building back better’ or sustaining the unsustainable? The climate impacts of Bank of England QE in the Covid-19 pandemic - The environmental impacts of monetary policy received academic attention after the 2008 financial crisis and the ‘market neutral’ quantitative easing policies that followed. This article examines the Bank of England’s Corporate Covid Financing Facility (CCFF) and the Asset Purchasing Facility (APF) between June 2020 and June 2021 to assess whether the Bank’s response to the COVID-19 pandemic was aligned with the transition to sustainability. The data indicates that the Bank of England’s monetary…

• Inhibition of SARS-CoV2 viral infection with natural antiviral plants constituents: an in-silico approach - CONCLUSION: The phytoconstituents were found to hinder the early stages of infection, such as absorption and penetration, while ivermectin prevented the passage of genetic material from the cytoplasm to the nucleus. Additional research involving living tissues and clinical trials are suggested to corroborate the computational findings.

• Plant production of high affinity nanobodies that block SARS-CoV-2 spike protein binding with its receptor, human angiotensin converting enzyme - Nanobodies^(®) (V(HH) antibodies), are small peptides that represent the antigen binding domain, V(HH) of unique single domain antibodies (heavy chain only antibodies, HcAb) derived from camelids. Here, we demonstrate production of V(HH) nanobodies against the SARS-CoV-2 spike proteins in the solanaceous plant Nicotiana benthamiana through transient expression and their subsequent detection verified through western blot. We demonstrate that these nanobodies competitively inhibit binding between…

• Methotrexate inhibition of SARS-CoV-2 entry, infection and inflammation revealed by bioinformatics approach and a hamster model - CONCLUSIONS: We demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.

• A review of Janus kinase inhibitors for the treatment of Covid-19 pneumonia - CONCLUSION: Thus, the development of molecular targeted drugs with elucidated pathological mechanisms may aid in controlling Covid-19 infection.

• Oral antiviral treatments for COVID-19 during severe connective tissue disease flares: report of two cases - Antiviral therapies targeting SARS-CoV-2 replication change the course of COVID-19. The European Medicines Agency (EMA) has approved a nirmatrelvir/ritonavir combination that inhibits the main protease of the virus. Molnupiravir, an RNA polymerase misdirector, is proposed by EMA in selected cases, despite still without marketing authorisation. Both are for use in mild disease with a high risk of progression to severe COVID. Patients with inflammatory rheumatic diseases under immunosuppression,…

• The Effects of Propolis on Viral Respiratory Diseases - Propolis remains an interesting source of natural chemical compounds that show, among others, antibacterial, antifungal, antiviral, antioxidative and anti-inflammatory activities. Due to the growing incidence of respiratory tract infections caused by various pathogenic viruses, complementary methods of prevention and therapy supporting pharmacotherapy are constantly being sought out. The properties of propolis may be important in the prevention and treatment of respiratory tract diseases caused…

• Triterpenic Acid Amides as Potential Inhibitors of the SARS-CoV-2 Main Protease - Although the incidence and mortality of SARS-CoV-2 infection has been declining during the pandemic, the problem related to designing novel antiviral drugs that could effectively resist viruses in the future remains relevant. As part of our continued search for chemical compounds that are capable of exerting an antiviral effect against the SARS-CoV-2 virus, we studied the ability of triterpenic acid amides to inhibit the SARS-CoV-2 main protease. Molecular modeling suggested that the compounds…

From Patent Search