Covid-19 Sentry

Contents

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

From Preprints

• Is Fostamatinib a possible drug for COVID-19? – A computational study -
  COVID-19 has turned out to be a global pandemic within a very short period since its first origin in China in December 2019. With the gradual increase in the mortality rate all over the world, there is an urgent need for an effectual drug. Though no clinically approved vaccine or drug is available until now but scientists are trying hard to identify potential antivirals to this new coronavirus. Several drugs like hydroxychloroquine, remdesivir, azithromycin etc. are put under evaluation in more than 300 clinical trials for the treatment of COVID-19. Few of them already show encouraging results. The main agent of disease progression of COVID-19 is SARS-CoV2/nCoV, which is believed to have ~89% genetic resemblance with SARSCoV, a coronavirus responsible for the massive outbreak in 2003. With this hypothesis, a recently developed in silico Human-nCoV network and potential COVID-19 spreader proteins, have been derived from the Human-SARS-CoV protein interactions using SIS model and fuzzy thresholding, followed by a potential FDA drugs target based validation. We then perform a two-way analysis to identify the potential drug targets of COVID-19. In the first analysis, we identify the complete list of FDA drugs for the 37 level 1 and 4948 level 2 spreader proteins in this network followed by the application of a consensus strategy. In the second analysis, the same consensus strategy is applied but on a curated overlapping set of key genes identified from COVID-19 symptoms, risk factors and clinical outcome. The applied consensus strategy in both the analysis reveals that Fostamatinib, a FDA approved drug, has the highest drug consensus score both in level 1 and level 2. Further analysis reveals that Fostamatinib also targets CYP3A4, a level 2 spreader protein and the most common target for most of the potential COVID-19 drugs. A subsequent docking study also reveals that Fostamatinib has also the highest docking score with respect to 6LU7, the crystal structure of COVID-19 main protease in complex with an inhibitor N3, in comparison to other potential drugs like hydroxychloroquine, remdesivir, favipiravir and darunavir. Our computational study suggests that Fostamatinib may also be considered as one of the potential candidates for further clinical trials in pursuit to counter the spread of COVID-19.
  🖺 Full Text HTML: Is Fostamatinib a possible drug for COVID-19? – A computational study
• Knowledge, attitude and practices related to COVID-19 among medical students in Pakistan: A web-based survey -
  In the times of the COVID-19 pandemic, it is necessary for the medical students to have knowledge about the features of the disease, how the disease is transmitted, and protective measures to contain the COVID-19. This study was conducted to evaluate knowledge, attitude, and practices related to COVID-19 in Pakistani medical students. We conducted a web-based survey from March 29 to May 10, 2020, utilizing an online platform. Medical students from 1 st to 5th professional years in medical colleges across the country were requested to participate. The questionnaire consisting of 31 items were circulated online using different social media channels to collect the required information. Proportions for categorical variables were tested using the Chi-square test or Fisher’s exact tests. A total of 344 medical students responded, and their overall knowledge about COVID-19 was 88.86 %. Nearly 31.0% of participants were involved in awareness projects regarding COVID-19 in the community and 84.6% of participants were willing to volunteer in healthcare crises. The percentage of the medical students who opted lockdown/curfew to be a better solution for curbing disease transmission was 94.2% while 95.9% of them believed social distancing can prevent the transmission. The average rate of practicing correct preventive measures among the respondents was 93.25%. The study showed sufficient knowledge, the crucial practice of preventive measures regarding COVID-19, and unveiled a profoundly assertive attitude of the medical students of Pakistan toward the current health crises. More regular awareness and educational programs for medical students related to the COVID-19 can boost and update their current knowledge.
  🖺 Full Text HTML: Knowledge, attitude and practices related to COVID-19 among medical students in Pakistan: A web-based survey
• Analysis of amino acid change dynamics reveals SARS-CoV-2 variant emergence -
  Since its emergence in late 2019, the diffusion of SARS-CoV-2 is associated with the evolution of its viral genome. The co-occurrence of specific amino acid changes, collectively named ‘virus variant’, requires scrutiny (as variants may hugely impact the agent’s transmission, pathogenesis, or antigenicity); variant evolution is studied using phylogenetics. Yet, never has this problem been tackled by digging into data with ad hoc analysis techniques. Here we show that the emergence of variants can in fact be traced through data-driven methods, further capitalizing on the value of large collections of SARS-CoV-2 sequences. For all countries with sufficient data, we compute weekly counts of amino acid changes, unveil time-varying clusters of changes with similar - rapidly growing - dynamics, and then follow their evolution. Our method succeeds in timely associating clusters to variants of interest/concern, provided their change composition is well characterized. This allows us to detect variants’ emergence, rise, peak, and eventual decline under competitive pressure of another variant. Our early warning system, exclusively relying on deposited sequences, shows the power of big data in this context, and concurs to calling for the wide spreading of public SARS-CoV-2 genome sequencing for improved surveillance and control of the COVID-19 pandemic.
  🖺 Full Text HTML: Analysis of amino acid change dynamics reveals SARS-CoV-2 variant emergence
• A drug candidate for treating adverse reactions caused by pathogenic antibodies inducible by COVID-19 virus and vaccines -
  In a previous study, we reported that certain anti-spike antibodies of COVID-19 and SARS-CoV viruses can have a pathogenic effect through binding to sick lung epithelium cells and misleading immune responses to attack self-cells. We termed this new pathogenic mechanism Antibody Dependent Auto-Attack (ADAA). This study explores a drug candidate for prevention and treatment of such ADAA-based diseases. The drug candidate is a formulation comprising N-acetylneuraminic acid methyl ester (NANA-Me), an analog of N-acetylneuraminic acid. NANA-Me acts through a unique mechanism of action (MOA) which is repairment of the missing sialic acid on sick lung epithelium cells. This MOA can block the antibody binding to sick cells, which are vulnerable to pathogenic antibodies. Our in vivo data showed that the formulation significantly reduced the sickness and deaths caused by pathogenic anti-spike antibodies. Therefore, the formulation has the potential to prevent and treat the serious conditions caused by pathogenic antibodies during a COVID-19 infection. In addition, the formulation has potential to prevent and treat the adverse reactions of COVID-19 vaccines because the vaccines can induce similar antibodies, including pathogenic antibodies. The formulation will be helpful in increasing the safety of the vaccines without reducing the vaccine efficacy. Compared to existing antiviral drugs, the formulation has a unique MOA of targeting receptors, broad spectrum of indications, excellent safety profile, resistance to mutations, and can be easily produced.
  🖺 Full Text HTML: A drug candidate for treating adverse reactions caused by pathogenic antibodies inducible by COVID-19 virus and vaccines
• Development Of The Inactivated QazCovid-In Vaccine: Protective Efficacy Of The Vaccine In Syrian Hamsters -
  In March 2020, the first cases of human coronavirus infection COVID-19 were registered in Kazakhstan. We isolated the SARS-CoV-2 virus from the clinical material from the patients. Subsequently, a whole virion inactivated candidate vaccine, QazCovid-in, was developed based on this virus. To obtain the vaccine, a virus grown in Vero cell culture was used, which was inactivated with formaldehyde, purified, concentrated, sterilized by filtration, and then sorbed on aluminum hydroxide gel particles. The formula virus and adjuvant in buffer saline solution was used as a vaccine. The safety and protective effectiveness of the developed vaccine was studied on Syrian hamsters. The results of the studies showed the absolute safety of the candidate vaccine on the Syrian hamsters. When studying the protective effectiveness, the developed vaccine with an immunizing dose of 5 mcg/dose of a specific antigen protected animals from wild virus at a dose of 104.5 TCID50/ml. The candidate vaccine formed virus-neutralizing antibodies in vaccinated hamsters in titers from 3.3 {+/-} 1.45 log2 to 7.25 {+/-} 0.78 log2, which were retained for 6 months (observation period) in the indicated titers. The candidate vaccine suppressed the replication of the wild virus in the body of vaccinated hamsters, protected against the development of acute pneumonia and ensured 100% survival of the animals. At the same time, no replicative virus was isolated from the lungs of vaccinated animals. At the same time, a virulent virus was isolated from the lungs of unvaccinated animals in relatively high titers, reaching 4.5 {+/-} 0.7 lg TCID50/ml. After challenge infection, 100% of unvaccinated hamsters became ill with clinical signs (stress state, passivity, tousled coat, decreased body temperature and body weight, and the development of acute pneumonia), of which 25 {+/-} 5% were fatal. The findings paved the way for testing the candidate vaccine in humans in clinical trials.
  🖺 Full Text HTML: Development Of The Inactivated QazCovid-In Vaccine: Protective Efficacy Of The Vaccine In Syrian Hamsters
• Probing remdesivir nucleotide analogue insertion to SARS-CoV-2 RNA dependent RNA polymerase in viral replication -
  Remdesivir (RDV) prodrug can be metabolized into a triphosphate form nucleotide analogue (RDV-TP) to bind and insert into the active site of viral RNA dependent RNA polymerase (RdRp) to further interfere with the viral genome replication. In this work, we computationally studied how RDV-TP binds and inserts to the SARS-CoV-2 RdRp active site, in comparison with natural nucleotide substrate adenosine triphosphate (ATP). To do that, we first constructed atomic structural models of an initial binding complex (active site open) and a substrate insertion complex (active site closed), based on high-resolution cryo-EM structures determined recently for SARS-CoV-2 RdRp or non-structural protein (nsp) 12, in complex with accessory protein factors nsp7 and nsp8. By conducting all-atom molecular dynamics simulation with umbrella sampling strategies on the nucleotide insertion between the open and closed state RdRp complexes, our studies show that RDV-TP can bind comparatively stabilized to the viral RdRp active site, as it primarily forms base stacking with the template Uracil nucleotide (at +1), which is under freely fluctuations and supports a low free energy barrier of the RDV-TP insertion (~ 1.5 kcal/mol). In comparison, the corresponding natural substrate ATP binds to the RdRp active site in Watson-Crick base pairing with the template nt, and inserts into the active site with a medium low free energy barrier (~ 2.6 kcal/mol), when the fluctuations of the template nt are well quenched. The simulations also show that the initial base stacking of RDV-TP with the template can be particularly stabilized by motif B-N691, S682, and motif F-K500 with the sugar, base, and the template backbone, respectively. Although the RDV-TP insertion can be hindered by motif-F R555/R553 interaction with the triphosphate, the ATP insertion seems to be facilitated by such interactions. The inserted RDV-TP and ATP can be further distinguished by specific sugar interaction with motif B-T687 and motif-A D623, respectively.
  🖺 Full Text HTML: Probing remdesivir nucleotide analogue insertion to SARS-CoV-2 RNA dependent RNA polymerase in viral replication
• Peter Chew “Logical Science” System For Epidemics(Covid-19) -
  Abstract Background: Lessons must be learned from the mistakes of the Covid pandemic. As we have seen, some countries are facing persistently high rates of covid-19 infection, but some countries such as China and South Korea can address the covid-19 problem when their country faces a surge in covid-19. This indicates that some countries facing persistently high infections may have used the wrong strategy, leaving them facing persistently high infections. The study will analyse what have been the main mistake since the Covid pandemic. Then create a system to solve the problem so that it can be used in future pandemic. Methods: Peter Chew’s “Logical Science” system focuses on logical review. The main purpose of the logical review part is to determine whether the guidelines are false. For non-medical treatment guidelines, if the logical review part determines that the guidelines are not false, real-world evidence is needed to determine whether the guidelines are correct. Similar to Mathematical Induction, The goal of the base case is to determine whether the statement (rule, formula, etc.) is false. If the sentence is not false, you need to continue to the second case, the inductive step determines whether the sentence (rule, formula, etc.) is true. Results: Using Peter Chew’s “Logical Science” system, we can find wrong guidelines earlier. It can prevent continued practice of wrong guidelines, leading to persistently high infections. As we have seen, Director-general of the Chinese Canter for Disease Control and Prevention (CDC), George Gao said that in his view, a big mistake in the United States and Europe is that people do not wear masks. Therefore, early detection of wrong guidelines is important to reduce high infection rates. In fact, the important lesson we can learn from China’s response to the covid-19 surge is that China will not wait for study evidence to apply non-medical prevention, such as Wuhan compulsory wearing masks on January 22, 2020. Conclusions: Prevention is better than cure. Instead of creating new medical treatment or vaccine for viruses or mutant viruses, it is better to create a system to prevent the spread of pandemic viruses. As we have seen, China and South Korea managed to solve the covid-19 surge in their countries without using vaccines in 2020. Therefore, the epidemic prevention system must be able to detect any wrong guidelines faster to prevent the use of the wrong guidelines from causing widespread spread of the virus. For pandemics, waiting for research evidence to implement non-medical prevention strategies is a big mistake, because the prime time to reduce the spread of the virus has been missed. It takes time to generate research evidence, and follow-up peer review also takes time, so the process of peer review research evidence allows the virus to spread widely, and some mutations may occur, making virus prevention more difficult to deal with.
  🖺 Full Text HTML: Peter Chew “Logical Science” System For Epidemics(Covid-19)
• Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine -
  The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need of 20 billion vaccine doses to fully vaccinate the world population. To reach this goal, the manufacturing and logistic processes should be affordable to all countries, irrespectively of economical and climatic conditions. Outer membrane vesicles (OMVs) are bacterial-derived vesicles that can be engineered to incorporate heterologous antigens. Given the inherent adjuvanticity, such modified OMVs can be used as vaccine to induce potent immune responses against the associated protein. Here we show that OMVs engineered to incorporate peptides derived from the receptor binding motif (RBM) of the spike protein from SARS-CoV-2 elicit an effective immune response in immunized mice, resulting in the production of neutralizing antibodies. The immunity induced by the vaccine is sufficient to protect K18-hACE2 transgenic mice from intranasal challenge with SARS-CoV-2, preventing both virus replication in the lungs and the pathology associated with virus infection. Furthermore, we show that OMVs can be effectively decorated with RBM peptides derived from a different genetic variant of SARS-CoV-2, inducing a similarly potent neutralization activity in vaccinated mice. Altogether, given the convenience associated with ease of engineering, production and distribution, our results demonstrate that OMV-based SARS-CoV-2 vaccines can be a crucial addition to the vaccines currently available.
  🖺 Full Text HTML: Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine
• TNF-α levels in respiratory samples are associated with SARS-CoV-2 infection. -
  Purpose: Increased serum levels of IL-6 and TNF-alpha have been proposed as biomarkers for COVID-19 progression. However, the role and the implication of these cytokines in SARS-CoV-2 infection remain controversial. The aim of this study was to measure levels of IL-6 and TNF-alpha in swab samples from individuals with symptoms compatible with COVID-19 and analyze their association with SARS-CoV-2 presence. Methods: SARS-CoV-2 detection was performed using the CDC (USA) real-time RT-PCR primers, probes and protocols. Cytokine concentrations were measured using commercial reagents based on enzyme linked immunosorbent assay (ELISA). Results: TNF-alpha median levels were greater in COVID19 (+) symptomatic group (5.88 (1.36 - 172.1) pg/ml) compared to COVID19 (-) symptomatic individuals (2.87 (1.45 - 69.9) pg/ml) (p=0.0003). No significant differences were shown in IL-6 median values between COVID-19 (+) and (-) symptomatic patients (5.40 (1.7 - 467) pg/ml and 6.07 (1.57 - 466.6) pg/ml respectively). In addition, increased TNF-alpha; levels (greater than 10 pg/ml), but not IL-6, were associated with SARS-CoV-2 presence (OR= 5.7; p=0.006; 95% CI= 1,551 to 19,11). Conclusions: IL-6 concentration showed high levels in swabs from some symptomatic patients, suggesting the presence of immune response at viral entry site. However, IL-6 levels were independent from SARS-CoV-2 presence and viral load, individual’s age and gender. On the contrary, TNF-alpha evaluation confirmed the presence of inflammatory response but mostly related to COVID-19. More studies are required in order to characterize the cytokine profile expressed at the site of infection of SARS-CoV-2 and its implications in disease outcomes.
  🖺 Full Text HTML: TNF-α levels in respiratory samples are associated with SARS-CoV-2 infection.
• Indications that Stockholm has reached herd immunity, given limited restrictions, against several variants of SARS- CoV-2 -

  “When COVID-19 cases go up, public compliance with restrictions is poor, when cases go down, public compliance is good.” In this article, we question this explanation and show that relatively low levels of sero-prevalence helps to keep cases down. In other words, the herd-immunity threshold appears to be much lower than previously thought. We construct a mathematical model taking pre-immunity, antibody waning and more infectious variants of concern into consideration, thereby providing a theoretical framework in which the cases in Stockholm county can be fully predicted without relying on neither oscillations in restrictions (and public compliance thereof) nor vaccination roll-out. We also show that it is very difficult to match the data from Stockholm without including pre-immunity, or, which turns out to be equivalent, great variations in susceptibility.

  🖺 Full Text HTML: Indications that Stockholm has reached herd immunity, given limited restrictions, against several variants of SARS-CoV-2
• Transmission of SARS-CoV-2 into and within immigrant households. Nation-wide registry-study from Norway -

  Background: Minority ethnic groups and immigrants have been hit disproportionally hard by COVID-19 in many developed countries, including Norway. Most transmissions of SARS-CoV-2 occur in households. Methods: Using individual- level registry data of all Norwegian residents we compared infections across all multi-person households. A household with at least one member born abroad was defined as an immigrant household. For the subset of households where at least one person tested positive for SARS-CoV-2 from August 1st 2020 to May 1st 2021, we calculated secondary attack rates (SARs) as the percent of other household members testing positive within 14 days after the first household member tested positive. Logistic regression model was used to adjust for sex, age, household composition and geography. Results: Among all multi-person households in Norway (n=1 421 642), immigrant households (n=341 604) comprised more members on average (3.2) than households with only Norwegian-born members (2.8). The share of immigrant households where at least one member had been tested, was 56% (vs 49% in the households with only Norwegian-born members), and the share where at least one member was infected was 3.7% (vs 1.4% in households with only Norwegian-born members). Secondary attack rates were higher in immigrant (32%) than Norwegian-born households (20%). Results differed considerably by country of birth, with secondary attack rates particularly high in households from Syria, Iraq, Turkey, and Pakistan, also after adjustment for sex, age, household composition and geography. Conclusion: SARS-CoV-2 is more frequently introduced into multi-person immigrant households than into households with only Norwegian-born members, and transmission within the household occurs more frequently in immigrant households. The results are likely related to living conditions, family composition or differences in social interaction, emphasizing the need to prevent introduction of SARS-CoV-2 into these vulnerable households.

  🖺 Full Text HTML: Transmission of SARS-CoV-2 into and within immigrant households. Nation-wide registry-study from Norway
• Mode of Presentation and Outcomes of COVID-19 Cases in a Tertiary Hospital in Nigeria -

  Coronavirus disease 2019 (COVID-19) has spread across the globe with its consequent human and economic challenges. To achieve effective control of the pandemic, efforts need to be holistic and global. Understanding patients demographics and clinical characteristics will assist in the control of the infection. However, there is a paucity of studies on the clinical presentation of COVID-19 patients from Nigeria and indeed Africa. Thus, this retrospective case series evaluated the medical records of COVID-19 patients admitted in a tertiary hospital in Nigeria. Patients demographics, and other clinical variables were assessed and presented. Data of 14 patients with complete records were included in the study. Most of the patients (78.6%) were males and the mean age of the study participants is 63.5 years (SD; 11.5). The commonest presenting symptoms were fever (93%), cough (71.4%), and dyspnoea (57.1%). At presentation, 13 patients had coexisting diseases while 8 (57.0%) patients had moderate disease and the remaining 6 (43.0%) had severe cases. After management, 1 patient died, two were referred and 11 recovered and were discharged alive. Thus, this study has identified advanced age, male gender, and comorbidity as increased risk factors for hospitalisation. The patient survival outcome in this study was also good.

  🖺 Full Text HTML: Mode of Presentation and Outcomes of COVID-19 Cases in a Tertiary Hospital in Nigeria
• Pre-immunity: the Schrodinger’s cat of immunology -

  Early 2020, catastrophic consequences of COVID-19 was predicted in the do-nothing scenario, based on mathematical models for epidemiology. As data began to emerge, several scientists noted that growth did not seem exponential, as the models predicted, leading to speculations of pre-existing immunity or immunological dark matter to explain this pattern. On the other hand, reports of choir-rehearsals infecting most members seemed to refute this, and the topic remained inconclusive. We provide a mathematical theory in which both observations are true; on a population level, pre-immunity exists, on an individual level, it doesn9t. This theory demonstrates that established formulas relating e.g. R0 and the herdimmunity threshold are wrong. We derive new mathematical formulas, which applies to any virus whose transmission dynamics is associated with large individual variability in susceptibility to the infection. Contrary to great variability in infectivity, which we show has no bearing on the mathematical modeling, variability in susceptibility actually manifests itself as pre-immunity on a macroscopic scale, thus making pre-immunity a necessity for accurate mathematical modeling.

  🖺 Full Text HTML: Pre-immunity: the Schrodinger’s cat of immunology
• Heterologous immunisation with vector vaccine as prime followed by mRNA vaccine as boost leads to humoral immune response against SARS-CoV-2, which is comparable to that according to a homologous mRNA vaccination scheme -

  Background: The humoral immune response after primary immunisation with a SARS-CoV-2 vector vaccine (AstraZeneca AZD1222, ChAdOx1 nCoV-19, Vaxzevria) followed by an mRNA vaccine boost (BioNTech, BNT162b2; Moderna, m-1273) was examined and compared with the antibody response after homologous vaccination schemes (AZD1222/AZD1222 or BNT162b2/BNT162b2). Methods: Sera from 59 vaccinees were tested for SARS-CoV-2 immunoglobulin G (IgG) and virus- neutralising antibodies (VNA) with four IgG assays, a surrogate neutralisation test (sVNT) and a Vero cell-based neutralisation test (cVNT) before and after heterologous (n=31 and 42) or homologous booster vaccination (AZD1222/AZD1222, n=8/9; BNT162b2/BNT162b2, n=8/8). The strength of IgG binding to separate SARS-CoV-2 antigens was measured as avidity. Results: After the first vaccination, prevalence of IgGs antibodies directed against (trimeric) SARS-CoV-2 spike (S)- protein and its receptor-binding domain (RBD) varied from 55-95 % (AZD1222) to 100% (BNT162b2), depending on the vaccine used and the SARS-CoV-2 antigen used. The booster vaccination resulted in 100 percent seroconversion and appearance of highly avid IgG as well as VNA against a SARS-CoV-2 variant of concern (alpha; B.1.1.7) used as antigen in the cVNT. The results of the sVNT basically agree with those of our in-house cVNT, but the sVNT seems to overestimate non- and weakly virus-neutralizing titres. The mean IgG and VNA titres were higher after heterologous vaccination compared to the homologous AZD1222 scheme. Conclusions: The heterologous SARS-CoV-2 vaccination leads to a strong antibody response with anti-SARS-CoV-2 IgG and VNA titres at a level comparable to that of a homologous BNT162b2 vaccination scheme. Irrespectively of the chosen immunisation regime, highly avid IgG antibodies can be detected just two weeks after the second vaccine dose indicating the development of a robust humoral immunity.

  🖺 Full Text HTML: Heterologous immunisation with vector vaccine as prime followed by mRNA vaccine as boost leads to humoral immune response against SARS-CoV-2, which is comparable to that according to a homologous mRNA vaccination scheme
• T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire -

  AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T-cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 280 unique vaccine recipients aged 18-85 years who enrolled in the phase 2/3 COV002 trial. Total spike-specific CD4+ T cell helper type 1 (Th1) and CD8+ T-cell responses were significantly increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T-cell receptor (TCR) β ; sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for the AZD1222-induced CD4+ and CD8+ T-cell responses. Overall, AZD1222 vaccination induced a robust, polyfunctional Th1-dominated T-cell response, with broad CD4+ and CD8+ T-cell coverage across the SARS-CoV-2 spike protein.

  🖺 Full Text HTML: T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire

From Clinical Trials

• COVID-19 Vaccinations With a Sweepstakes - Condition:   Covid19
  Intervention:   Behavioral: Philly Vax Sweepstakes
  Sponsors:  
  University of Pennsylvania;   Philadelphia Department of Public Health
  Active, not recruiting

• Covid-19 Virtual Recovery Study - Condition:   Covid19
  Interventions:   Behavioral: Strength RMT;   Behavioral: Strength RMT and nasal breathing;   Behavioral: Endurance RMT;   Behavioral: Endurance RMT and nasal breathing;   Behavioral: Low dose RMT
  Sponsor:   Mayo Clinic
  Not yet recruiting

• A Study of PF-07321332/Ritonavir in Nonhospitalized High Risk Adult Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Ritonavir;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents - Condition:   Covid19 Vaccine
  Interventions:   Biological: MVC-COV1901(S protein with adjuvant);   Biological: MVC-COV1901(Saline)
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine;   Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   CanSino Biologics Inc.
  Not yet recruiting

• Efficacy of Amantadine Treatment in COVID-19 Patients - Condition:   Patients With Moderate or Severe COVID-19
  Intervention:   Drug: Amantadine
  Sponsors:   Noblewell;   Medical Research Agency (ABM);   Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
  Recruiting

• Covid-19 Patients Management During Home Isolation - Condition:   Covid19
  Interventions:   Procedure: Oxygen therapy and physical therapy;   Device: Oxygen therapy
  Sponsor:   Cairo University
  Recruiting

• A Different Use of The Aerosol Box in COVID-19 Patients; Internal Jugular Vein Cannulation - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: Internal jugular vein cannulation
  Sponsor:   Bakirkoy Dr. Sadi Konuk Research and Training Hospital
  Completed

• Reconditioning Exercise for COVID-19 Patients Experiencing Residual sYmptoms - Condition:   Covid19
  Intervention:   Other: Exercise Therapy
  Sponsor:  
  Wake Forest University Health Sciences
  Not yet recruiting

• Lipid Emulsion Infusion and COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: SMOFlipid;   Other: 0.9% saline
  Sponsor:   Assiut University
  Recruiting

• Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition:   Covid19
  Intervention:   Drug: cholecalciferol 6 lakh IU
  Sponsor:  
  Postgraduate Institute of Medical Education and Research
  Not yet recruiting

• Immunogenicity and Safety of an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: 23-valent pneumococcal polysaccharide vaccine;   Biological: Inactivated Hepatitis A Vaccine
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Phase 1 Intranasal Parainfluenza Virus Type 5-SARS CoV-2 S Vaccine in Healthy Adults - Condition:   Covid19
  Interventions:   Biological: CVXGA1 low dose;   Biological: CVXGA1 high dose
  Sponsor:   CyanVac LLC
  Not yet recruiting

• Coenzyme Q10 as Treatment for Long Term COVID-19 - Conditions:   Covid19;   Long Term Covid19
  Interventions:   Drug: Coenzyme Q10;   Drug: Placebo
  Sponsors:   Aarhus University Hospital;   University of Aarhus;   Pharma Nord
  Recruiting

• Effect of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With Best Standard of Care for the Treatment of Hospitalized COVID-19 Patients and Continued Treatment Following Discharge - Condition:   COVID-19
  Intervention:   Device: NovoTTF-100L
  Sponsor:   NovoCure GmbH
  Completed

From PubMed

• Drug repurposing against SARS-CoV-2 receptor binding domain using ensemble-based virtual screening and molecular dynamics simulations - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused worldwide pandemic and is responsible for millions of worldwide deaths due to -a respiratory disease known as COVID-19. In the search for a cure of COVID-19, drug repurposing is a fast and cost-effective approach to identify anti-COVID-19 drugs from existing drugs. The receptor binding domain (RBD) of the SARS-CoV-2 spike protein has been a main target for drug designs to block spike protein binding to ACE2 proteins. In this…

• Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan - Healthy aging is accompanied by reduced cognitive control and widespread alterations in the underlying brain networks; but the extent to which large-scale functional networks in older age show reduced specificity across different domains of cognitive control is unclear. Here we use cov-STATIS (a multi-table multivariate technique) to examine similarity of functional connectivity during different domains of cognitive control-inhibition, initiation, shifting, and working memory-across the adult…

• A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma - INTRODUCTION: Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known.

• Autoimmune- and complement-mediated hematologic condition recrudescence following SARS-CoV-2 vaccination - A variety of autoimmune disorders have been reported after viral illnesses and specific vaccinations. Cases of de novo immune thrombocytopenia (ITP) have been reported after SARS-CoV-2 vaccination, although its effect on preexisting ITP has not been well characterized. In addition, although COVID-19 has been associated with complement dysregulation, the effect of SARS-CoV-2 vaccination on preexisting complementopathies is poorly understood. We sought to better understand SARS-CoV-2…

• SSRIs: Applications in inflammatory lung disease and implications for COVID-19 - Selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory properties that may have clinical utility in treating severe pulmonary manifestations of COVID-19. SSRIs exert anti-inflammatory effects at three mechanistic levels:

1. inhibition of proinflammatory transcription factor activity, including NF-κB and STAT3; (b) downregulation of lung tissue damage and proinflammatory cell recruitment via inhibition of cytokines, including IL-6, IL-8, TNF-α, and IL-1β; and (c) direct…

• Cationic Compounds with SARS-CoV-2 Antiviral Activity and their Interaction with OCT/MATE Secretory Transporters - In the wake of the COVID-19 pandemic, drug repurposing has been highlighted for rapid introduction of therapeutics. Proposed drugs with activity against SARS-CoV-2 include compounds with positive charges at physiological pH, making them potential targets for the organic cation (OC) secretory transporters of kidney and liver, i.e., the basolateral Organic Cation Transporters, OCT1 and OCT2; and the apical Multidrug And Toxin Extruders, MATE1 and MATE2-K. We selected several compounds proposed to…

• COVID-19 diagnosis and testing in pediatric heart transplant recipients - Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of…

• Determination of camostat and its metabolites in human plasma - preservation of samples and quantification by a validated UHPLC-MS/MS method - CONCLUSIONS: A methodology was developed that preserves camostat and GBPA in plasma samples and provides accurate and sensitive quantification of camostat, GBPA and GBA by UHPLC-MS/MS.

• Accurate Bulk Quantitation of Droplet Digital Polymerase Chain Reaction - Droplet digital PCR provides superior accuracy for nucleic acid quantitation. The requirement of microfluidics to generate and analyze the emulsions, however, is a barrier to its adoption, particularly in low resource settings or clinical laboratories. Here, we report a novel method to prepare ddPCR droplets by vortexing and readout of the results by bulk analysis of recovered amplicons. We demonstrate the approach by accurately quantitating SARS-CoV-2 sequences using entirely bulk processing…

• Strategies to target SARS-CoV-2 entry and infection using dual mechanisms of inhibition by acidification inhibitors - Many viruses utilize the host endo-lysosomal network for infection. Tracing the endocytic itinerary of SARS-CoV-2 can provide insights into viral trafficking and aid in designing new therapeutic strategies. Here, we demonstrate that the receptor binding domain (RBD) of SARS-CoV-2 spike protein is internalized via the pH-dependent CLIC/GEEC (CG) endocytic pathway in human gastric-adenocarcinoma (AGS) cells expressing undetectable levels of ACE2. Ectopic expression of ACE2 (AGS-ACE2) results in…

• Role of L-Arginine in Nitric Oxide Synthesis and Health in Humans - As a functional amino acid (AA), L-arginine (Arg) serves not only as a building block of protein but also as an essential substrate for the synthesis of nitric oxide (NO), creatine, polyamines, homoarginine, and agmatine in mammals (including humans). NO (a major vasodilator) increases blood flow to tissues. Arg and its metabolites play important roles in metabolism and physiology. Arg is required to maintain the urea cycle in the active state to detoxify ammonia. This AA also activates cellular…

• Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay - The SARS-CoV-2 Receptor Binding Domain (RBD) is both the principal target of neutralizing antibodies, and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate how this assay can be…

• Tocilizumab as a Treatment for ‘Cytokine Storm Syndrome’ in COVID-19: A Case Report - Coronavirus disease 19 (COVID-19) which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been a problem worldwide, particularly due to the high rate of transmission and wide range of clinical manifestations. Acute respiratory distress syndrome (ARDS) and multiorgan failure are the most common events observed in severe cases and can be fatal. Cytokine storm syndrome emerges as one of the possibilities for the development of ARDS and multiorgan failure in severe cases…

• Catalytic Dyad Residues His41 and Cys145 Impact the Catalytic Activity and Overall Conformational Fold of the Main SARS-CoV-2 Protease 3-Chymotrypsin-Like Protease - Coronaviruses are responsible for multiple pandemics and millions of deaths globally, including the current pandemic of coronavirus disease 2019 (COVID-19). Development of antivirals against coronaviruses, including the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) responsible for COVID-19, is essential for containing the current and future coronavirus outbreaks. SARS-CoV-2 proteases represent important targets for the development of antivirals because of their role in the…

• Pulmonary Covid Fibrosis a New Pharmaceutic Approach - CONCLUSIONS: This study proposes to inhibit phosphodiesterase by vasodilatation of the pulmonary vascular bed and the MUC1 over expression by interleukin6, the Sildenafil with the SGLT2 and N-Acetylcysteine.

From Patent Search

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• SARS-CoV-2 anti-viral therapeutic - - link

• 一种基于联邦学习的多用户协同训练人流统计方法及系统 - 本发明提供一种基于联邦学习的多用户协同训练人流统计方法，旨在利用联邦学习框架搭建一个新颖的人群计数模型，达到让多用户多设备同时训练的目的。各个客户端利用图像数据集对图像分类网络进行本地训练以获取本地模型；在各经过至少一次本地训练后，中心服务器从客户端获取本地模型的权值及附加层参数并进行聚合处理；中心服务器利用聚合处理后的权值及附加层参数更新全局模型，并将聚合处理后的权值参数及附加层参数返回给各个客户端；各个客户端利用中心服务器返回的权值以及ground truth值进行贝叶斯估计，计算loss值，并利用返回的权值参数及附加层参数更新本地模型；重复执行直至所有客户端的loss值均收敛，则完成人流统计全局模型和本地模型的训练。 - link

• A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link

• 新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域，具体而言，提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒，具体包括（a）或（b）两种方案：（a）示踪物标记的RBD三聚体抗原，包被在固体支持物上的ACE2，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；（b）示踪物标记的ACE2，包被在固体支持物上的RBD三聚体抗原，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；其中，RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度，提升阳性样本平均发光强度，缩短检测时间。 - link

• 一种检测SARS-CoV-2的引物组合物及其应用 - 本发明涉及一种检测SARS‑CoV‑2的引物组合物及其应用。所述引物组合物包括SEQ ID NO:1~SEQ ID NO:12所示的核酸序列。本发明利用所述引物组合物进行逆转录巢式PCR，并结合Sanger测序，能够快速、准确地获取SARS‑CoV‑2基因信息，从而能够实现快速检测SARS‑CoV‑2以及判断SARS‑CoV‑2突变株，且具备良好的准确性、灵敏度、特异性以及重复性。 - link

• 基于多重荧光定量PCR技术的新冠病毒突变序列检测技术及其应用 - 本发明提供一种基于多重荧光定量PCR技术的新冠病毒突变类型检测技术及其应用。本发明主要基于荧光定量PCR技术针对目前S基因重要突变类型，如序列位置23403，序列变化A>G、序列位置23063，序列变化A>T、序列位置22812‑22813，序列变化AG>GA、序列位置23012，序列变化G>A进行单管或多管多重检测。其试剂盒可以很好的鉴别目前流行的D614G、N501Y、K417N、E484K重要突变株且特异性好，对新冠病毒的突变监测具有十分积极的意义。 - link

• 基于荧光定量PCR技术的新冠病毒新型核酸突变检测技术及其应用 - 本发明提供一种基于荧光定量PCR技术的新冠病毒新型核酸突变检测技术及其应用。本发明主要基于荧光定量PCR技术针对目前S基因新突变‑双重变异（E484Q和L452R突变）进行检测。本发明提供的试剂盒可以很好的鉴别E484Q和L452R突变，对新冠病毒的新突变快速监测具有十分积极的意义。 - link