Covid-19 Sentry

Contents

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

From Preprints

• Impact of Omicron variant on the response to SARS-CoV-2 mRNA vaccination in multiple myeloma and monoclonal gammopathies -

  Multiple myeloma (MM) patients may have a reduced response to vaccination due to immunodeficiency. The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of spike variants, including the emerging Omicron one, are still unclear and have been investigated in this study in a cohort of MM patients and those with pre-malignant monoclonal gammopathies. Firstly, we have shown that MM patients with relapsed- refractory disease (MMR) had a reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 mRNA full vaccination. Interestingly, all the analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and in smoldering MM too. Moreover, lower spike-specific IL-2-producing CD4+ T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing-CD8+ T cells were found in MM patients as compared to MGUS. Finally, we found that booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. On the other hand, in MMR patients, Omicron retain a negative impact on neutralizing ability, suggesting these patients need to be considered still at risk of Omicron SARS-CoV-2 infection with a clinically relevant disease.

  🖺 Full Text HTML: Impact of Omicron variant on the response to SARS-CoV-2 mRNA vaccination in multiple myeloma and monoclonal gammopathies
• Proteomic analysis of human milk reveals nutritional and immune benefits in the colostrum from mothers with COVID-19 -
  The range of benefits breastfeeding provides neonates and infants include nutrition, improved neonatal survival, and reduced morbidity from certain diseases. It also aids maternal health by speeding postpartum recovery. However, due to concern about the risk of SARS-CoV-2 transmission and the lack of evidence of breastmilk’s protective effects against the virus, whether mothers with COVID-19 should be encouraged to breastfeed is under debate. Here, we present the results of proteomic and glycoproteomic studies of breast milk (colostrum and mature milk) from mothers with confirmed COVID-19. All colostrum samples exhibited significantly upregulated immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, and increased glycosylation levels and heterogeneity at those proteins. Such adaptive differences in milk from COVID-19 mothers tend to fade in mature milk from the same mothers one month postpartum. These results suggest the immune benefits of colostrum from mothers with COVID-19 and provide molecular- level insights that aid breastmilk feeding decisions in cases of active infection.
  🖺 Full Text HTML: Proteomic analysis of human milk reveals nutritional and immune benefits in the colostrum from mothers with COVID-19
• Protection of Hamsters Challenged with SARS-CoV-2 after Two Doses of MVC-COV1901 Vaccine Followed by a Single Intranasal Booster with Nanoemulsion Adjuvanted S-2P Vaccine -
  Intramuscular vaccines have greatly reduced hospitalization and death due to severe COVID-19. However, most countries are experiencing a resurgence of infection driven predominantly by the Delta and Omicron variants of SARS- CoV-2. In response, booster dosing of COVID-19 vaccines has been implemented in many countries to address waning immunity and reduced protection against the variants. However, intramuscular boosting fails to elicit mucosal immunity and therefore does not solve the problem of persistent viral carriage and transmission, even in patients protected from severe disease. In this study, two doses of stabilized prefusion SARS-CoV-2 spike (S-2P)-based intramuscular vaccine adjuvanted with Alum/CpG1018, MVC-COV1901, were used as a primary vaccination series, followed by an intranasal booster vaccination with nanoemulsion (NE01)-adjuvanted S-2P vaccine in a hamster model to demonstrate immunogenicity and protection from viral challenge. Here we report that this vaccination regimen resulted not only in the induction of robust immunity and protection against weight loss and lung pathology following challenge with SARS-CoV-2, but also led to increased viral clearance from both upper and lower respiratory tracts. Our findings showed that intramuscular MVC- COV1901 vaccine followed by a booster with intranasal NE01-adjuvanted vaccine promotes protective immunity against both viral infection and disease, suggesting that this immunization protocol may offer a solution in addressing a significant, unmet medical need for both the COVID-19 and future pandemics.
  🖺 Full Text HTML: Protection of Hamsters Challenged with SARS-CoV-2 after Two Doses of MVC-COV1901 Vaccine Followed by a Single Intranasal Booster with Nanoemulsion Adjuvanted S-2P Vaccine
• Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution -
  SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites–a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan- Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites, thereby shaping subsequent evolutionary change. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.
  🖺 Full Text HTML: Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
• A structural dynamic explanation for observed escape of SARS-CoV-2 BA.2 variant mutation S371L/F -
  Upon emergence, the SARS-CoV-2 Omicron sub-variant BA, was identified to have increased transmissibility and immune evasion and has since become the dominant variant worldwide. Subsequently, the Omicron sub-variant BA.2 was observed to have a growth advantage as compared to BA.13. In response to the rise of BA.1 and BA.2, scientists worldwide have raced to computationally and experimentally characterize the decreased efficacy of current vaccines and therapeutic antibodies that were designed to target the wild-type Wuhan SARS-COV-2 strain. Specifically, two recent studies by Liu et al. and Iketani et al. provide a detailed analysis of loss of potency by evaluating vaccine/convalescent sera and therapeutic antibodies against pseudotyped viruses with D614G spike proteins harboring single point mutations from the variants of concern (VOCs). This characterization of individual variant mutations improves our mechanistic understanding of RBD antigenic space, facilitating next-generation antibody and vaccine design and interpretation of future variant phenotypes.
  🖺 Full Text HTML: A structural dynamic explanation for observed escape of SARS-CoV-2 BA.2 variant mutation S371L/F
• Transcriptomic landscapes of SARS-CoV-2-infected and bystander lung cells reveal a selective upregulation of NF-κB- dependent coding and non-coding proviral transcripts -
  Detailed knowledge of cellular networks that are modulated by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to understand viral replication and host response. So far, transcriptomic analyses of interactions between SARS-CoV-2 and cells were performed on mixed populations of infected and uninfected cells or using single-cell RNA sequencing, both leading to inaccurate or low-resolution gene expression interpretations. Moreover, they generally focused on annotated messenger RNAs (mRNAs), ignoring other transcripts, such as long non-coding RNAs (lncRNAs) and unannotated RNAs. Here, we performed deep polyA+ transcriptome analyses of lung epithelial A549 cells infected with SARS-CoV-2, which were sorted based on the expression of the viral protein spike (S). To increase the sequencing depth and improve the robustness of the analysis, the samples were depleted of viral transcripts. Infection caused a massive reduction in mRNAs and lncRNAs, including transcripts coding for antiviral innate immune proteins, such as interferons (IFNs). This absence of IFN response probably explains the poor transcriptomic response of bystander cells co-cultured with spike positive (S+) ones. NF-{kappa}B and inflammatory response were among the pathways that escaped the global shutoff in S+ cells. In agreement with the RNA-seq analysis, inflammatory cytokines, but not IFNs, were produced and secreted by infected cells. Functional investigations revealed the proviral function of the NF-{kappa}B subunit p105/p50 and some of its known target genes, including IL32 and IL8, as well as the lncRNA ADIRF- AS1, which we identified as a novel NF-{kappa}B target gene. Thus, analyzing the polyA+ transcriptome of sorted populations of infected lung cells allowed unprecedented identification of cellular functions that are directly affected by infection and the recovery of coding and non-coding genes that contribute to SARS-CoV-2 replication.
  🖺 Full Text HTML: Transcriptomic landscapes of SARS- CoV-2-infected and bystander lung cells reveal a selective upregulation of NF-κB-dependent coding and non-coding proviral transcripts
• Adenosine A2A Receptor (A2AR) agonists improve survival in K28-hACE2 mice following SARS CoV-2 infection -
  Effective and available therapies for the treatment of COVID-19 disease are limited. Apadenoson is a highly potent selective anti-inflammatory adenosine A2A receptor (A2AR) agonist and potential treatment option for COVID-19 patients. Apadenoson, when administered after infection with SARS CoV-2, was found to decrease weight loss, improve clinical symptoms, reduce levels of a several proinflammatory cytokines and chemokines in bronchial lavage (BAL) fluid, and promote increased survival in K18hACE2 transgenic mice. Of note, administering apadenoson after, but not prior to Covid-19 infection, caused a rapid decrease in lung viral burden. The work presented provides the foundation for further examination of these drugs as a therapy option for COVID-19.
  🖺 Full Text HTML: Adenosine A2A Receptor (A2AR) agonists improve survival in K28-hACE2 mice following SARS CoV-2 infection
• IgG1 responses following SARS-CoV-2 infection are polyclonal and highly personalized, whereby each donor and each clone displays a distinct pattern of cross-reactivity against SARS-CoV-2 variants -
  Using a recently introduced efficient mass spectrometry-based approach we monitored in molecular detail the IgG1 clonal responses in individual donors’ IgG1 clonal responses in molecular detail, examining SARS-CoV-2 spike-protein- specific IgG1 repertoires. We monitored the plasma clonal IgG1 profiles of 8 donors (4 male and 4 female) who had recently experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we charted the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer as antigen. We observed that shortly after infection in between <0.1% to almost 10% of all IgG1 antibody molecules present in plasma did bind to the spike protein. Each donor displayed a unique plasma IgG1 repertoire, but also each donor displayed a unique and polyclonal antibody response against the SARS-CoV-2 spike-protein variants. Our analyses revealed that certain clones exhibit (alike) binding affinity towards all four tested spike- protein variants, whereas other clones displayed strong unique mutant-specific affinity. We conclude that each infected person generates a unique polyclonal response following infection, whereby some of these clones can bind multiple viral variants, whereas other clones do not display such cross-reactivity. In general, by assessing IgG1 repertoires following infection it becomes possible to identify and select fully matured human plasma antibodies that target specific antigens, and display either high specificity or cross-reactivity versus mutated versions of the antigen, which will aid in selecting antibodies that may be developed into biotherapeutics.
  🖺 Full Text HTML: IgG1 responses following SARS-CoV-2 infection are polyclonal and highly personalized, whereby each donor and each clone displays a distinct pattern of cross-reactivity against SARS-CoV-2 variants
• Late-Ensemble of Convolutional Neural Networks with Test Time Augmentation for Chest XR COVID-19 Detection -

  COVID-19, a severe acute respiratory syndrome aggressively spread among global populations in just a few months. Since then, it has had four dominant variants (Alpha, Beta, Gamma and Delta) that are far more contagious than original. Accurate and timely diagnosis of COVID-19 is critical for analysis of damage to lungs, treatment, as well as quarantine management. CT, MRI or X-rays image analysis using deep learning provide an efficient and accurate diagnosis of COVID-19 that could help to counter its outbreak. With the aim to provide efficient multi-class COVID-19 detection, recently, COVID-19 Detection challenge using X-ray is organized. In this paper, the late-fusion of features is extracted from pre-trained various convolutional neural networks and fine-tuned these models using the challenge dataset. The DensNet201 with Adam optimizer and EffecientNet-B3 are fine-tuned on the challenge dataset and ensembles the features to get the final prediction. Besides, we also considered the test time augmentation technique after the late-ensembling approach to further improve the performance of our proposed solution. Evaluation on Chest XR COVID-19 showed that our model achieved overall accuracy is 95.67%.

  🖺 Full Text HTML: Late-Ensemble of Convolutional Neural Networks with Test Time Augmentation for Chest XR COVID-19 Detection
• Reassessment of persistent symptoms, self-reported COVID-19 infection and SARS-CoV-2 serology in the SAPRIS-SERO cohort: identifying possible sub-syndromes of Long Covid. -

  Background Long Covid remains a relatively new phenomenon with emerging understanding. Estimated UK prevalence of Long Covid with three or more symptoms lasting for 12 weeks or more was 2.2% at the end of 2021. The population based French SAPRIS SERO cohort has novel information about the pattern of symptoms of Long Covid that has been obscured by controversy around the original paper. Methods Secondary analysis was used to describe and re-interpret the pattern of persistent symptoms by IgG seropositivity and self reported Long Covid in the SAPRIS-SERO survey. Participants in the cross-sectional analysis were 26823 individuals from the French population based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, the Euroimmun enzyme linked immunosorbent assay was used to detect anti SARS CoV 2 antibodies. Surveyed online between December 2020 and January 2021, participants self reported previous COVID 19 infection and physical symptoms during the previous four weeks that were new since March 2020, and had persisted for at least eight weeks. Results There was similarity of prevalence over the majority of symptoms in those self reporting COVID-19 infection, regardless of blood test result. Persistent symptoms significantly associated with self reported COVID 19 infection and common in both groups include respiratory tract symptoms and a group of symptoms that might be related to chronic fatigue, malaise or postural issues. Seropositivity for IgG antibodies did not predict symptoms independently of self reported Long Covid, except for anosmia. Conclusions There may be three common subsyndromes of Long Covid, one with persistent anosmia, another with other respiratory tract symptoms and a third, currently under researched, with symptoms relatable to chronic fatigue. Antibody tests are insufficient for case detection while Long Covid remains poorly understood.

  🖺 Full Text HTML: Reassessment of persistent symptoms, self-reported COVID-19 infection and SARS-CoV-2 serology in the SAPRIS-SERO cohort: identifying possible sub- syndromes of Long Covid.
• Changes in the quality of cancer care as assessed through performance indicators during the first wave of the COVID-19 pandemic in 2020: a Scoping Review -

  Objectives: Summarize performance indicators used in the literature to evaluate the impact of the COVID-19 pandemic on cancer care (January-June 2020), and to assess changes in the quality of care as assessed via selected indicators. Methods: Scoping review. Indicators and their reported trends were collated following the cancer care pathway. Results: Database searches retrieved 6277 articles, 838 articles met the inclusion criteria, and 135 articles were included after full-text screening, from which 917 indicators were retrieved. Indicators assessing the diagnostic process showed a decreasing trend: from 33 indicators reporting on screening, 30 (91%) signalled a decrease during the pandemic (n=30 indicators, 91%). A reduction was also observed in the number of diagnostic procedures (n=64, 58%) and in the diagnoses (n=130, 89%). The proportion of diagnoses in the emergency setting and waiting times showed an increasing trend (n=8, 89% and n=14, 56%, respectively). Nine indicators (64%) showed stability in cancer stages distribution. A decreasing trend in the proportion of earliest stage cancers was reported by 63% of indicators (n=9), and 70% (n=43) of indicators showed an increasing trend in the proportion of advanced-stage cancers. Indicators reflecting the treatment process signalled a reduction in the number of procedures: 79% (n=82) of indicators concerning surgeries, 72% (n=41) of indicators assessing trends in radiotherapy, and 93% (n=40) of indicators related to systemic therapies. Modifications in cancer treatment were frequently reported: 64% (n=195) of indicators revealed changes in treatment. Ten indicators (83%) signalled a decreasing number of hospital admissions. Conclusion: Health systems struggled to ensure continuity of cancer care. As this pandemic keeps evolving, the trends reported over the first 6 months of 2020 provide an argument to monitor these changes closely. This information needs to be transparent, standardised, and timely, allowing to monitor quality and outcomes of care during crises and inform policy responses.

  🖺 Full Text HTML: Changes in the quality of cancer care as assessed through performance indicators during the first wave of the COVID-19 pandemic in 2020: a Scoping Review
• Duration of Protection Against SARS-CoV-2 Reinfection and Associated Risk of Reinfection Assessed with Real-World Data -

  Importance: Better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection is needed. Objective: Primary: To assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection. Secondary: Evaluate the crude SARS-CoV-2 reinfection rate and associated characteristics. Design and Setting: Retrospective observational study of HealthVerity data among 144,678,382 individuals, during the pandemic era through April 2021. Participants: Individuals studied had SARS-CoV-2 molecular diagnostic or antibody index test results from February 29 through December 9, 2020, with ≥365 days of pre-index continuous closed medical enrollment, claims, or electronic health record activity. Main Outcome(s) and Measure(s): Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result. Results: Among 22,786,982 individuals with index SARS-CoV-2 laboratory test data (2,023,341 index positive), the crude rate of reinfection during follow-up was significantly lower (9.89/1,000-person years) than that of primary infection (78.39/1,000 person years). Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals (hazard ratio, 0.13; 95% CI, 0.13, 0.13). The cumulative incidence of reinfection among index-positive individuals and infection among index-negative individuals was 0.85% (95% CI: 0.82%, 0.88%) and 6.2% (95% CI: 6.1%, 6.3%), respectively, over follow-up of 375 days. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk. Conclusions and Relevance: This large US population-based study demonstrates that SARS-CoV-2 reinfection is uncommon among individuals with laboratory evidence of a previous infection. Protection from SARS-CoV-2 reinfection is stable up to one year. Reinfection risk was primarily associated with age 85+ years, comorbid immunologic conditions and living in congregate care settings; healthcare workers demonstrated a decreased reinfection risk. These findings suggest that infection induced immunity is durable for variants circulating prior to Delta.

  🖺 Full Text HTML: Duration of Protection Against SARS-CoV-2 Reinfection and Associated Risk of Reinfection Assessed with Real-World Data
• Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study -

  Background and Aims: The incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients. Methods: We identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all- cause mortality at 30 days among infected CLD patients. Results: We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days. Conclusions: In this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.

  🖺 Full Text HTML: Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study
• Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression -
  BACKGROUND: How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. The K18-hACE2 mouse model has been widely used for evaluation of new interventions for COVID-19. METHOD. Herein we use RNA-Seq data and bioinformatics approaches to compare the transcriptional responses in the SARS-CoV-2 infected lungs of K18-hACE2 mice with those seen in humans. RESULTS: Overlap in differentially expressed genes was generally poor ({approx}20-30%), even when multiple studies were combined. The overlap was not substantially improved when a second mouse model was examined wherein hACE was expressed from the mouse ACE2 promoter. In contrast, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between the species. CONCLUSION: As immunity and immunopathology are the focus of most studies, these hACE2 transgenic mouse models can thus be viewed as representative and relevant models of COVID-19.
  🖺 Full Text HTML: Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression
• POST-ACUTE SEQUELAE AND ADAPTIVE IMMUNE RESPONSES IN PEOPLE LIVING WITH HIV RECOVERING FROM SARS-COV-2 INFECTION -

  Background: Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH). Methods: We measured SARS-CoV-2 specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n=39 and n=43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing post-acute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T cell responses, as well as differences in the prevalence of PASC. Results: Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T cell responses as compared with a well-matched group of HIV- negative individuals. PWH had 70% lower relative levels of SARS-CoV-2 specific memory CD8+ T cells (p=0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2 specific CD4+ T cells (p=0.007). Higher CD4/CD8 ratio was associated with lower PD-1 expression on SARS-CoV-2 specific CD8+ T cells (0.34-fold effect, p=0.02). HIV status was strongly associated with PASC (odds ratio 4.01, p=0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms. Conclusions: We identified potentially important differences in SARS-CoV-2 specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

  🖺 Full Text HTML: POST- ACUTE SEQUELAE AND ADAPTIVE IMMUNE RESPONSES IN PEOPLE LIVING WITH HIV RECOVERING FROM SARS-COV-2 INFECTION

From Clinical Trials

• Pulmonary Rehabilitation Implemented With VR for Post-COVID-19 Patients - Condition:   COVID-19
  Intervention:   Procedure: Pulmonary Rehabilitation Program
  Sponsor:   The Opole University of Technology
  Recruiting

• Pulmonary Rehabilitation Implemented With Virtual Reality for Post-COVID-19 Patients - Condition:   COVID-19
  Intervention:   Procedure: Pulmonary rehabilitation
  Sponsor:  
  The Opole University of Technology
  Not yet recruiting

• Anti-inflammatory Drug Algorithm for COVID-19 Home Treatment - Condition:   COVID-19
  Interventions:   Drug: Recommended treatment schedule;   Drug: Usual care
  Sponsors:   Mario Negri Institute for Pharmacological Research;   Family physicians
  Not yet recruiting

• Transcranial Direct Stimulation for Persistent Fatigue Treatment Post-COVID-19 - Condition:   COVID-19
  Interventions:   Device: Active tDCS;   Device: Sham tDCS
  Sponsor:   Hospital San Carlos, Madrid
  Not yet recruiting

• Effect of Combined Use of Ivermectin and Colchicine in COVID-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Ivermectin + colchicine;   Drug: Colchicine
  Sponsor:   Ain Shams University
  Recruiting

• COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores - Condition:   COVID-19 Pneumonia
  Intervention:   Biological: Bacillus subtilis
  Sponsors:   DreamTec Research Limited;   Middle East Cell and Gene Therapy;   National Institute of Genetic Engineering and Biotechnology
  Completed

• A Phase III, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of TD0069 Capsule as a Combination Regimen With Standard Treatment for Patients With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: TD0069 hard capsule;   Drug: TD0069 Placebo
  Sponsors:   Sao Thai Duong Joint Stock Company;   Clinical Training Company
  Recruiting

• A Phase II Study of the Immunogenicity and Safety of SCTV01C in Population Aged ≥12 Years and Previously Vaccinated With Inactivated COVID-19 Vaccine - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Biological: SCTV01C;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01E in Population Aged ≥18 Years Previously Fully Vaccinated With mRNA COVID-19 Vaccine - Conditions:   COVID-19;   Sars-CoV-2 Infection
  Interventions:   Biological: SCTV01E;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E in Population Aged ≥12 Years Previously Fully Vaccinated With Inactivated COVID-19 Vaccine - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: Sinopharm inactivated COVID-19 vaccine
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SCTV01C in Population Aged ≥18 Years and Previously Fully Vaccinated With Either Inactivated or mRNA COVID-19 Vaccine or Previously Diagnosed With COVID-19 - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Nebulised Heparin in Patients With COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Unfractionated heparin
  Sponsor:   Lady Reading Hospital, Pakistan
  Not yet recruiting

• Nutrition and LOComotoric Rehabilitation in Long COVID-19 - Condition:   COVID-19
  Intervention:   Other: Intervention group
  Sponsors:  
  Universitair Ziekenhuis Brussel;   Vrije Universiteit Brussel
  Not yet recruiting

• Vale+ Tu Salud: Corner-Based Randomized Trial to Test a Latino Day Laborer Program Adapted to Prevent COVID 19 - Condition:   COVID-19
  Interventions:   Behavioral: COVID-19 Group Problem Solving;   Behavioral: Control Group-standard of care
  Sponsors:   The University of Texas Health Science Center, Houston;   National Institute on Minority Health and Health Disparities (NIMHD)
  Not yet recruiting

• BetaShield: A Phase II, Randomized Trial to Test the Effect of Povidone-iodine 0.5% as Mouthwash/Gargle on SARS- CoV-2 Load (COVID 19) as an Adjuvant Infection Control Measure in Dental Practice - Condition:   COVID-19
  Intervention:   Drug: Mouth rinse
  Sponsors:  
  University of Pennsylvania;   Purdue Pharma LP
  Recruiting

From PubMed

• Azadirachta indica A. Juss bark extract and its Nimbin isomers restrict β-coronaviral infection and replication - Emerging mutations in the SARS-CoV-2 genome pose a challenge for vaccine development and antiviral therapy. The antiviral efficacy of Azadirachta indica bark extract (NBE) was assessed against SARS-CoV-2 and m-CoV-RSA59 infection. Effects of in vivo intranasal or oral NBE administration on viral load, inflammatory response, and histopathological changes were assessed in m-CoV-RSA59-infection. NBE administered inhibits SARS-CoV-2 and m-CoV-RSA59 infection and replication in vitro, reducing…

• Imparting reusable and SARS-CoV-2 inhibition properties to standard masks through metal-organic nanocoatings - Face masks are effective response to address this havoc pandemic caused by respiratory infection virus, but they are lack of reusable, antibacterial, and antiviral abilities due to their simple filtration mechanism, bringing to a supply shortage and severe plastic pollution globally. Herein, we designed reusable, antiviral, and antibacterial masks (referred to as R2A masks) that transformed from commonly-used standard masks and household fabrics based on the polyphenol-based surface…

• The spike-ACE2 binding assay: An in vitro platform for evaluating vaccination efficacy and for screening SARS-CoV-2 inhibitors and neutralizing antibodies - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has become a worldwide pandemic, and there is a pressing need for the rapid development of novel therapeutic strategies. SARS-CoV-2 viral entry is mediated by interaction between the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein and host cellular receptor, human angiotensin converting enzyme 2 (ACE2). The lack of a high throughput screening (HTS) platform for…

• Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay - SARS-CoV-2 proteases Mpro and PLpro are promising targets for antiviral drug development. In this study, we present an antiviral screening strategy involving a novel in-cell protease assay, antiviral and biochemical activity assessments, as well as structural determinations for rapid identification of protease inhibitors with low cytotoxicity. We identified eight compounds with anti-SARS-CoV-2 activity from a library of 64 repurposed drugs and modeled at protease active sites by in silico…

• Analysis of the Neutralizing Activity of Antibodies Targeting Open or Closed SARS-CoV-2 Spike Protein Conformations - SARS-CoV-2 infection elicits a polyclonal neutralizing antibody (nAb) response that primarily targets the spike protein, but it is still unclear which nAbs are immunodominant and what distinguishes them from subdominant nAbs. This information would however be crucial to predict the evolutionary trajectory of the virus and design future vaccines. To shed light on this issue, we gathered 83 structures of nAbs in complex with spike protein domains. We analyzed in silico the ability of these nAbs to…

• Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs - The COVID-19 pandemic has evidenced the urgent need for the discovery of broad-spectrum antiviral therapies that could be deployed in the case of future emergence of novel viral threats, as well as to back up current therapeutic options in the case of drug resistance development. Most current antivirals are directed to inhibit specific viruses since these therapeutic molecules are designed to act on a specific viral target with the objective of interfering with a precise step in the replication…

• Polysaccharides and Their Derivatives as Potential Antiviral Molecules - In the current context of the COVID-19 pandemic, it appears that our scientific resources and the medical community are not sufficiently developed to combat rapid viral spread all over the world. A number of viruses causing epidemics have already disseminated across the world in the last few years, such as the dengue or chinkungunya virus, the Ebola virus, and other coronavirus families such as Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV). The…

• High-Sulfated Glycosaminoglycans Prevent Coronavirus Replication - Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are urgently needed. In this study, we characterize the antiviral effects of two high-sulfated glycosaminoglycan (GAG) derivatives against SARS-CoV-2 and bovine coronaviruses (BCoV), which are both members of the Betacoronavirus genus. The investigated…

• Comparative Investigation of Methods for Analysis of SARS-CoV-2-Spike-Specific Antisera - In light of an increasing number of vaccinated and convalescent individuals, there is a major need for the development of robust methods for the quantification of neutralizing antibodies; although, a defined correlate of protection is still missing. Sera from hospitalized COVID-19 patients suffering or not suffering from acute respiratory distress syndrome (ARDS) were comparatively analyzed by plaque reduction neutralization test (PRNT) and pseudotype-based neutralization assays to quantify…

• Sensitivity of SARS-CoV-2 Life Cycle to IFN Effects and ACE2 Binding Unveiled with a Stochastic Model - Mathematical modelling of infection processes in cells is of fundamental interest. It helps to understand the SARS-CoV-2 dynamics in detail and can be useful to define the vulnerability steps targeted by antiviral treatments. We previously developed a deterministic mathematical model of the SARS-CoV-2 life cycle in a single cell. Despite answering many questions, it certainly cannot accurately account for the stochastic nature of an infection process caused by natural fluctuation in reaction…

• In Silico Analysis and Synthesis of Nafamostat Derivatives and Evaluation of Their Anti-SARS-CoV-2 Activity - Inhibition of transmembrane serine protease 2 (TMPRSS2) is expected to block the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nafamostat, a potent TMPRSS2 inhibitor as well as a candidate for anti-SARS-CoV-2 drug, possesses the same acyl substructure as camostat, but is known to have a greater antiviral effect. A unique aspect of the molecular binding of nafamostat has been recently reported to be the formation of a covalent bond between its acyl…

• Unlike Chloroquine, Mefloquine Inhibits SARS-CoV-2 Infection in Physiologically Relevant Cells - Despite the development of specific therapies against severe acute respiratory coronavirus 2 (SARS-CoV-2), the continuous investigation of the mechanism of action of clinically approved drugs could provide new information on the druggable steps of virus-host interaction. For example, chloroquine (CQ)/hydroxychloroquine (HCQ) lacks in vitro activity against SARS-CoV-2 in TMPRSS2-expressing cells, such as human pneumocyte cell line Calu-3, and likewise, failed to show clinical benefit in the…

• Screening of Botanical Drugs against SARS-CoV-2 Entry Reveals Novel Therapeutic Agents to Treat COVID-19 - An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted global health. There is a severe lack of specific treatment options for diseases caused by SARS-CoV-2. In this study, we used a pseudotype virus (pv) containing the SARS-CoV-2 S glycoprotein to screen a botanical drug library containing 1037 botanical drugs to identify agents that prevent SARS-CoV-2 entry into the cell. Our study identified four hits, including…

• Carbohydrate Ligands for COVID-19 Spike Proteins - An outbreak of SARS-CoV-2 coronavirus (COVID-19) first detected in Wuhan, China, has created a public health emergency all over the world. The pandemic has caused more than 340 million confirmed cases and 5.57 million deaths as of 23 January 2022. Although carbohydrates have been found to play a role in coronavirus binding and infection, the role of cell surface glycans in SARS-CoV-2 infection and pathogenesis is still not understood. Herein, we report that the SARS- CoV-2 spike protein S1…

• Ferristatin II Efficiently Inhibits SARS-CoV-2 Replication in Vero Cells - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to have a significant impact on global public health. Multiple mechanisms for SARS-CoV-2 cell entry have been described; however, the role of transferrin receptor 1 (TfR1) in SARS-CoV-2 infection has received little attention. We used ferristatin II to induce the degradation of TfR1 on the surface of Vero cells and to study the consequences of such treatment on the viability of the cells and the replication of SARS-CoV-2. We…

From Patent Search

• A METHOD FOR THE TREATMENT OF COVID-19 INFECTIONS WITH PALMITOYLETHANOLAMIDE - - link

• SOCIAL NAVIGATION SYSTEM FOR MOBILE ROBOTS IN THE EMERGENCY DEPARTMENT TECHNOLOGY - The emergency department (ED) is a safety-critical environment in which healthcare workers (HCWs) are overburdened, overworked, and have limited resources, especially during the COVID-19 pandemic. One way to address this problem is to explore the use of robots that can support clinical teams, e.g., to deliver materials or restock supplies. However, due to EDs being overcrowded, and the cognitive overload HCWs experience, robots need to understand various levels of patient acuity so they avoid disrupting care delivery. In this invention, we introduce the Safety-Critical Deep Q-Network (SafeDQN) system, a new acuity-aware navigation system for mobile robots. SafeDQN is based on two insights about care in EDs: high-acuity patients tend to have more HCWs in attendance and those HCWs tend to move more quickly. We compared SafeDQN to three classic navigation methods, and show that it generates the safest, quickest path for mobile robots when navigating in a simulated ED environment. We hope this work encourages future exploration of social robots that work in safety-critical, human-centered environments, and ultimately help to improve patient outcomes and save lives. Figure 1. - link

• A SYSTEM BASED ON DEEP LEARNING FOR ANALYZING DELAYED ENHANCEMENT MAGNETIC RESONANCE IMAGING TO IDENTIFY COVID 19 AND METHOD THEREOF - The present invention discloses a system based on deep learning for analyzing delayed enhancement magnetic resonance imaging to identify COVID 19 and method thereof. The method and system include, but not limited to, a processing unit adapted to process the data based on deep learning data modelling in the magnetic resonance imaging associated with the digital image scanning system for diagnosis COVID 19 with the spatial resolution that each frame is deposited is 256 * 256, and being creating that level and vertical resolution respectively are 256 pixels (pixel), the read/write address that the read/write address of each image element, which is controlled by processing unit and forms circuit and finishes; And the data that will be stored in memory are input to a real-time microcontroller, it is characterized in that: analyze and compare by the Multi-source Information Fusion analytical system by using the real-time microcontroller to deliver the D/A changer then, digital signal is become analogue signal output. - link

• 用于体外诊断的新型冠状病毒核衣壳蛋白抗体 - 本发明提供了一种用于体外诊断的新型冠状病毒核衣壳蛋白抗体或抗原结合片段。所提供的抗体包括重链可变区和轻链可变区，重链可变区包括SEQ ID NO:11、12和13所示的CDR序列，轻链可变区包括SEQ ID NO:14、15和16所示的CDR序列。所提供的抗体用于新型冠状病毒的体外检测，具有极高的灵敏度和特异性。 - link

• 用于体外诊断的新型冠状病毒核衣壳蛋白抗体 - 本发明提供了一种用于体外诊断的新型冠状病毒核衣壳蛋白抗体或抗原结合片段。所提供的抗体包括重链可变区和轻链可变区，重链可变区包括SEQ ID NO:1、2和3所示的CDR序列，轻链可变区包括SEQ ID NO:4、5和6所示的CDR序列。所提供的抗体用于新型冠状病毒的体外检测，具有极高的灵敏度和特异性。 - link

• 新型冠状病毒抗原检测的方法和试剂盒 - 本发明提供了一种新型冠状病毒抗原检测的方法和试剂盒。试剂盒包括试剂条，试剂条包括底板，以及位于底板上的沿样品层析的方向依次相连的样品垫、胶体金垫、硝酸纤维素膜和吸水纸；胶体金垫上附着有胶体金标记的质控标记物和第二新型冠状病毒核衣壳蛋白抗体；硝酸纤维素膜上设有T线和C线，T线含有第一新型冠状病毒核衣壳蛋白抗体，C线包含与胶体金标记的质控标记物特异结合的配体；第一新型冠状病毒核衣壳蛋白抗体具有包含SEQ ID NO:1、2和3所示CDR序列的第一重链可变区和SEQ ID NO:4、5和6所示CDR序列的第一轻链可变区。所提供的试剂盒用于新型冠状病毒的体外检测，具有极高的灵敏度和特异性。 - link

• 一种特异性结合新型冠状病毒S蛋白的抗体及其应用 - 本发明涉及一种特异性结合新型冠状病毒S蛋白的抗体及其应用，属于生物技术领域。本发明提供了一种抗原，所述抗原包括氨基酸序列如SEQ ID NO.1所示的多肽，氨基酸序列如SEQ ID NO.2所示的多肽，与SEQ ID NO.1所示氨基酸序列具有80%以上同源性，且具有诱发针对SARS‑CoV‑2 S蛋白免疫反应功能的衍生多肽，和/或，与SEQ ID NO.2所示氨基酸序列具有80%以上同源性，且具有诱发针对SARS‑CoV‑2 S蛋白免疫反应功能的衍生多肽；使用所述抗原对动物进行免疫可获得能够与SARS‑CoV‑2 S蛋白特异性结合的多克隆抗体。 - link

• 检测SARS-CoV-2变异株的组合物、试剂盒、方法及其用途 - 本发明属于分子生物学检测领域；涉及SARS‑CoV‑2奥密克戎（Omicron）变异株的检测。本发明提供了包含所述组合物的试剂盒，所述组合物的用途，以及用于检测SARS‑CoV‑2变异株并分型的方法。通过检测SARS‑CoV‑2变异株S基因上的4个不同的特征功能变异位点，对奥密克戎变异株进行分型，从而在单管反应体系中同时实现SARS‑CoV‑2病毒及奥密克戎变异株分型的检测。本发明的组合物，结合荧光探针熔解曲线法，其成本低，通量高。并且操作简便，结果读取过程通过熔解峰Tm值即可以判定。检测全过程均在单管封闭条件下进行，避免了由于样本间交叉引起的假阳性和环境污染。 - link

• 一种用于检测病毒的试剂盒 - 本发明提供了一种用于检测病毒的试剂盒，包括裂解病毒的试剂和病毒的免疫层析检测装置，通过在试纸条上设置连接标记区域和检测区域的缓冲过渡区域，以及在卡壳盖上设置三条压住试纸条的压条，减缓样本的流速，提高样本在试纸条上的层析和过滤效果，并搭配裂解病毒的试剂，暴露出更多的抗原或者抗原位点，从而大幅提高待测物的检测灵敏度，特别是针对新型冠状病毒的裂解，可以明显提高样本中的病毒抗原浓度，从而采用特定结构的免疫荧光测试条，提高检测的最低阀值，防止漏检。 - link

• 一种用于检测病毒的试剂和试剂盒 - 本发明提供了一种用于检测病毒的试剂和试剂盒，包括裂解病毒的试剂和试纸条，通过在试纸条上设置连接标记区域和检测区域的缓冲过渡区域，减缓样本的流速，提高样本在试纸条上的层析和过滤效果，并搭配裂解病毒的试剂裂解病毒，暴露出更多的抗原或者抗原位点，从而提高检测的灵敏度。在样本中病毒量特别低的时候，希望能够获得阳性结果，就希望获得更多的抗原片段或者病毒片段，采用本发明提供的裂解液对样本进行裂解，可以明显提高样本中的病毒抗原浓度，从而采用免疫荧光测试条，提高检测的最低阀值，防止漏检，特别适用于针对新型冠状病毒的裂解。 - link