Covid-19 Sentry

Contents

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

From Preprints

• Defective efferocytosis as a predictor of COVID-19 mortality -
  COVID-19 is a generally benign coronavirus disease that can spread rapidly, except for those with a group of risk factors. Since the pathogenesis responsible for the severity of the disease has not been clearly revealed, effective treatment alternatives has not been developed. The hallmark of the SARS-CoV-2-infected cells is apoptosis. Apoptotic cells are cleared through a sterile process defined as efferocytosis by professional and nonprofessional phagocytic cells. The disease would be rapidly brought under control in the organism that can achieve effective efferocytosis, which is also a kind of innate immune response. In the risk group, the efferocytic process is defective. By the addition of the apoptotic cell load associated with SARS-COV-2 infection, failure to achieve efferocytosis of dying cells can initiate secondary necrosis that is a highly destructive process. Uncontrolled inflammation and coagulation abnormalities caused by secondary necrosis reason in various organ failures, lung in particular, which are responsible for the poor prognosis. Following the short and simplified information, this opinion paper aims to present possible treatment options that can control the severity of COVID-19 by detailing the mechanisms that can cause defective efferocytosis.
  🖺 Full Text HTML: Defective efferocytosis as a predictor of COVID-19 mortality
• The Role of Values in Coping with Health and Economic Threats of COVID-19 -
  The current research examined the role of values in guiding people’s responses to COVID-19. Results from an international study involving 115 countries (N = 61,490) suggest that health and economic threats of COVID-19 evoke different values, with implications for controlling and coping with the pandemic. Specifically, health threats evoked prioritization of communal values related to caring for others and belonging, whereas economic threats predicted prioritization of agentic values focused on competition and achievement. Concurrently and over time, prioritizing communal values over agentic values was associated with enactment of prevention behaviors that reduce virus transmission, motivations to help others suffering from the pandemic, and positive attitudes toward outgroup members. These results, which were generally consistent across individual and national levels of analysis, suggest that COVID-19 threats may indirectly shape important responses to the pandemic through their influence on people’s prioritization of communion and agency. Theoretical and practical implications are discussed.
  🖺 Full Text HTML: The Role of Values in Coping with Health and Economic Threats of COVID-19
• Prosocial behavior promotes positive emotion during the COVID-19 pandemic -
  The COVID-19 pandemic has raised concerns about humans’ physical and mental well-being. In response, there has been an urgent “call to action” for psychological interventions that enhance positive emotion and psychological resilience. Prosocial behavior has been shown to effectively promote well-being, but is this strategy effective during a pandemic when ongoing apprehension for personal safety could acutely heighten self-focused concern? In two online pre-registered experiments (N =1,623) conducted during the early stage of pandemic (April 2020), we examined this question by randomly assigning participants to engage in other- or self-beneficial action. For the first time, we manipulated whether prosocial behavior was related to the source of stress (COVID-19): participants purchased COVID-19-related (personal protective equipment, PPE) or COVID-19-unrelated items (food/writing supplies) for themselves or someone else. Consistent with pre-registered hypotheses, prosocial (vs. non-prosocial or proself) behavior led to higher levels of self-reported positive affect, empathy and social connectedness. Notably, we also found that psychological benefits were larger when generous acts were unrelated to COVID-19 (vs. related to COVID-19). When prosocial and proself spending involved identical COVID-19 PPEs items, prosocial behavior’s benefits were detectable only on empathy and social connectedness, but not on post-task positive affect. These findings suggest that while there are boundary conditions to be considered, generous action offers one strategy to bolster well-being during the pandemic.
  🖺 Full Text HTML: Prosocial behavior promotes positive emotion during the COVID-19 pandemic
• Determinants of early antibody responses to COVID-19 mRNA vaccines in exposed and naive healthcare workers -

  Background Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naive adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS- CoV-2 and what other factors affect responsiveness. Methods We measured IgA, IgG and IgM levels against SARS-CoV-2 spike

19. and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. Findings Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS- CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects. A second dose in pre- exposed did not increase antibody levels. Smoking and comorbidities were associated with lower neutralization and antibody levels. Among fully vaccinated, 6.3% breakthroughs were detected up to 189 days post-vaccination. Among pre- exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. Interpretation Our data support administering a single-dose in pre-exposed healthy individuals. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year.
    🖺 Full Text HTML: Determinants of early antibody responses to COVID-19 mRNA vaccines in exposed and naive healthcare workers

• Autoantibodies against IL-1-receptor-antagonist in multisystem inflammatory syndrome in children -

  Multisystem inflammatory syndrome in children (MIS-C or PIMS) is a rare but serious complication after an infection with SARS-CoV-2. A possible involvement of pathogenetically relevant autoantibodies has been discussed. Recently neutralizing autoantibodies against anti-inflammatory receptor antagonists progranulin (PGRN) and IL-1-receptor antagonist (IL-1-Ra) were discovered in adult patients with critical COVID-19. Plasma of an index case with severe PIMS/MIS-C was analyzed for autoantibodies against IL-1-Ra and PGRN. The study was extended by a case series of 12 additional patients. In addition to ELISA for of antibodies, IL-1-Ra plasma levels were determined and IL-1-Ra was analyzed by Western-blot and isoelectric focusing. Functional activity of the autoantibodies was examined in vitro with IL-1beta reporter assays. Antibodies against IL-1-Ra could be detected in 10 of 13 (76.9%) patients with PIMS/MIS-C, but not in controls. In contrast to critical COVID-19 in adults, no IL-1-Ra antibodies of the IgM class were detected in PIMS/MIS-C. IL-1-Ra-antibodies exclusively belonged to IgG1. No antibodies directed against PGRN were detected. Western blots and ELISA showed a concomitant reduction of free IL-1-Ra plasma levels in the presence of IL-1-Ra-antibodies. The antibodies inhibited IL-1-Ra function in IL-1beta reporter cell assays. Notably, an additional, hyperphosphorylated, transiently occurring atypical isoform of IL-1-Ra was observed in all IL-1-Ra autoantibody-positive patients. To conclude, IL-1-Ra autoantibodies were observed in high frequency in children with PIMS/MIS-C. They may represent a diagnostic and pathophysiologically relevant marker for PIMS/MIS-C. Their generation is likely to be triggered by an atypical, hyperphosphorylated isoform of IL-1-Ra.

  🖺 Full Text HTML: Autoantibodies against IL-1-receptor-antagonist in multisystem inflammatory syndrome in children
• Comprehensive Evaluation of COVID-19 Patient Short- and Long-term Outcomes: Disparities in Healthcare Utilization and Post-Hospitalization Outcomes -

  Abstract Background: Understanding risk factors for short- and long-term COVID-19 outcomes have implications for current guidelines and practice. We study whether early identified risk factors for COVID-19 persist one year later and through varying disease progression trajectories. Methods: This was a retrospective study of 6,731 COVID-19 patients presenting to Michigan Medicine between March 10, 2020 and March 10, 2021. We describe disease progression trajectories from diagnosis to potential hospital admission, discharge, readmission, or death. Outcomes pertained to all patients: rate of medical encounters, hospitalization-free survival, and overall survival, and hospitalized patients: discharge versus in-hospital death and readmission. Risk factors included patient age, sex, race, body mass index, and 29 comorbidity conditions. Results: Younger, non-Black patients utilized healthcare resources at higher rates, while older, male, and Black patients had higher rates of hospitalization and mortality. Diabetes with complications, coagulopathy, fluid and electrolyte disorders, and blood loss anemia were risk factors for these outcomes. Diabetes with complications, coagulopathy, fluid and electrolyte disorders, and blood loss were associated with lower discharge and higher inpatient mortality rates. Conclusions: This study found differences in healthcare utilization and adverse COVID-19 outcomes, as well as differing risk factors for short- and long-term outcomes throughout disease progression. These findings may inform providers in emergency departments or critical care settings of treatment priorities, empower healthcare stakeholders with effective disease management strategies, and aid health policy makers in optimizing allocations of medical resources.

  🖺 Full Text HTML: Comprehensive Evaluation of COVID-19 Patient Short- and Long-term Outcomes: Disparities in Healthcare Utilization and Post-Hospitalization Outcomes
• The statistical analysis of daily data associated with different parameters of the New Coronavirus COVID-19 pandemic in Georgia and their two-week interval prediction in summer 2021 -

  The lockdown introduced in Georgia on November 28, 2020 brought positive results. There were clearly positive tendencies in the spread of COVID-19 to February - first half of March 2021. However, in April-May 2021 there was a significant deterioration in the epidemiological situation. From June to August 2021, the epidemiological situation with Covid-19 in Georgia became very difficult. In this work results of the next statistical analysis of the daily data associated with New Coronavirus COVID-19 infection of confirmed (C), recovered (R), deaths (D) and infection rate (I) cases of the population of Georgia in the period from June 01, 2021 to August 31, 2021 are presented. It also presents the results of the analysis of two-week forecasting of the values of C, D and I. As earlier, the information was regularly sent to the National Center for Disease Control & Public Health of Georgia and posted on the Facebook page https://www.facebook.com/Avtandil1948/. The analysis of data is carried out with the use of the standard statistical analysis methods of random events and methods of mathematical statistics for the non-accidental time-series of observations. In particular, the following results were obtained. Georgia9s ranking in the world for Covid-19 monthly mean values of infection and deaths cases in summer 2021 (per 1 million population) was determined. Among 159 countries with population ≥ 1 million inhabitants in August 2021 Georgia was in the 1 place on new infection cases and on Death. A comparison between the daily mortality from Covid-19 in Georgia in summer 2021 with the average daily mortality rate in 2015-2019 shows, that the largest share value of D from mean death in 2015-2019 was 66.0 % (26.08.2021 and 31.08.2021), the smallest 6.0 % (09.07.2021). The statistical analysis of the daily and decade data associated with coronavirus COVID-19 pandemic of confirmed, recovered, deaths cases and infection rate of the population of Georgia are carried out. Maximum daily values of investigation parameters are following: C = 6208 (17.08.2021), R = 6177 (29.08.2021), D = 79 (26.08.2021 and 31.08.2021), I = 13.0 % (17.08.2021). Maximum mean decade values of investigation parameters are following: C = 5019 (2 Decade of August 2021), R = 4822 (3 Decade of August 2021), D = 69 (3 Decade of August 2021), I = 10.88 % (2 Decade of August 2021). It was found that as with September 2020 to February 2021 and in spring 2021 [7,8], from June to August 2021 the regression equations for the time variability of the daily values of C, R and D have the form of a tenth order polynomial. Mean values of speed of change of confirmed -V(C), recovered - V(R), deaths - V(D) and infection rate V(I) coronavirus-related cases in different decades of months in the summer 2021 were determined. Maximum mean decade values of investigation parameters are following: V(C) = +134 cases/day (1 Decade of August 2021), V(R) = +134 cases/day (2 Decade of August 2021), V(D) = +2.4 cases/day (3 Decade of August 2021), V(I) = + 0.25 %/ day (1 decades of August 2021). Cross-correlations analysis between confirmed COVID-19 cases with recovered and deaths cases shows, that the maximum effect of recovery is observed 19 days after infection (RC=0.95), and deaths - after 16 and 18 days (RC=0.94). In Georgia in the summer 2021, the duration of the impact of the delta variant of the coronavirus on people (recovery, mortality) could be up to two months. Comparison of real and calculated predictions data of C, D and I in Georgia are carried out. It was found that in summer 2021 two-week daily and mean two-week real values of C, D and I practically fall into the 67% - 99.99% confidence interval of these predicted values. With September 1, 2021, it is started monthly forecasting of C, D and I values. As earlier, the comparison of data about C and D in Georgia (GEO) with similar data in Armenia (ARM), Azerbaijan (AZE), Russia (RUS), Turkey (TUR) and in the World (WRL) is also carried out.

  🖺 Full Text HTML: The statistical analysis of daily data associated with different parameters of the New Coronavirus COVID-19 pandemic in Georgia and their two-week interval prediction in summer 2021
• Four-week forecasts of COVID-19 epidemic trajectories in South Africa, Chile, Peru and Brazil: a model evaluation -

  Introduction From the beginning of the COVID-19 pandemic, epidemiological models have been used in a number of ways to aid governments and organizations in efficient planning of resources and decision making. These models have elucidated important epidemiological transmission parameters, in addition to making short-term projections. Methods We constructed a compartmental mathematical model for the transmission, detection and prevention of SARS-CoV-2 infections for regions where Anglo American has mining operations. We fitted the model to publicly available data and used it to make short-term projections. Finally, we evaluated how the model performed by comparing short-term projections to actual confirmed cases, retrospectively. Findings The average forecast errors for four-week-ahead projections ranged between 1% and 8% in all the countries and regions considered in this study. All but one region had more than 75% of the true values falling within the range of four-week-ahead projections. The quality of the projections improved with time as expected due to increased historical data. Conclusion Our model produced four-week forecasts with a sufficiently high level of accuracy to guide operational and strategic planning for business continuity and COVID-19 responses in Anglo American mining sites.

  🖺 Full Text HTML: Four-week forecasts of COVID-19 epidemic trajectories in South Africa, Chile, Peru and Brazil: a model evaluation
• Street images classification according to COVID-19 risk in Lima, Peru: A convolutional neural networks analysis -

  Background: During the COVID-19 pandemic, convolutional neural networks (CNNs) have been used in clinical medicine (e.g., to classify chest X-rays for COVID-19 diagnosis). Whether CNNs could also inform the epidemiology of COVID-19 analysing street images has been understudied, though it could identify high-risk places and relevant features of the built environment. We trained CNNs to classify bus stops (Lima, Peru) into moderate or extreme COVID-19 risk. Methods: We used five images per bus stop. The outcome label (moderate or extreme) for each bus stop was extracted from the local transport authority. We used transfer learning and updated the output layer of five CNNs: NASNetLarge, InceptionResNetV2, Xception, ResNet152V2, and ResNet101V2. We chose the best performing network which was further tuned to increase performance. Results: There were 1,788 bus stops (1,173 moderate and 615 extreme), totalling 8,940 images. NASNetLarge outperformed the other CNNs except in the recall metric for the extreme label: 57% versus 59% in NASNetLarge and ResNet152V2, respectively. NASNetLarge was further tuned and reached: training loss of 0.50; training accuracy of 75%; precision, recall and F1 score for the moderate label of 80%, 83% and 82%, respectively; these metrics for the extreme label were 65%, 51% and 63%. Conclusions: CNNs has the potential to accurately classify street images into levels of COVID-19 risk. In addition to applications in clinical medicine, CNNs and street images could also advance the epidemiology of COVID-19 at the population level.

  🖺 Full Text HTML: Street images classification according to COVID-19 risk in Lima, Peru: A convolutional neural networks analysis
• Incidence of COVID-19 reinfection among Midwestern healthcare employees -

  Importance: Given the overwhelming worldwide rate of infection and the disappointing pace of vaccination, addressing reinfection is critical. Understanding reinfection, including protection longevity after natural infection, will allow us to better know the prospect of herd immunity, which hinges on the assumption that natural infection generates sufficient, protective immunity. The primary aim of this paper is to provide data on SARS-CoV-2 reinfection over a 10-month period. Objective: The primary objective of this study is to establish the incidence of reinfection of COVID-19 among healthcare employees who experienced a prior COVID-19 infection. Design: This observational cohort study followed a convenience sample of 2,625 participants who experienced a COVID-19 infection for subsequent COVID-19 infection. Setting: Healthcare employees were recruited across a large Midwestern healthcare system. Positive PCR test results were administered and recorded by the system-affiliated lab serving Illinois and Wisconsin. Participants: Adult healthcare system employees who enrolled in a research study focused on SARS-CoV-2 antibodies (N = 16,357) and had at least one positive PCR test result between March 1, 2020 and January 10, 2021 were included (N = 2,625). Exposure: Positive PCR test for SARS-CoV-2 Main Outcome(s) and Measure(s): The primary outcome is incidence of COVID-19 reinfection, defined by current CDC guidelines (i.e. subsequent COVID-19 infection ≥ 90 days from prior infection). COVID-19 recurrence, defined as subsequent COVID-19 infection after prior infection irrespective of time, is also described. Results: Of 2,625 participants who experienced at least one COVID-19 infection during the 10-month study period, 156 (5.94%) experienced reinfection and 540 (20.57%) experienced recurrence after prior infection. Median days were 126.50 (105.50-171.00) to reinfection and 31.50 (10.00-72.00) to recurrence. Incidence rate of COVID-19 reinfection was 0.35 cases per 1,000 person-days, with participants working in COVID-clinical and clinical units experiencing 3.77 and 3.57 times, respectively, greater risk of reinfection relative to those working in non-clinical units. Incidence rate of COVID-19 recurrence was 1.47 cases per 1,000 person-days. Conclusions and Relevance: This study supports the consensus that COVID-19 reinfection, defined as subsequent infection ≥ 90 days after prior infection, is rare, even among a sample of healthcare workers with frequent exposure.

  🖺 Full Text HTML: Incidence of COVID-19 reinfection among Midwestern healthcare employees
• Elevated plasma levels of CXCL16 in severe COVID-19 patients -

  Genome-wide association studies have recently identified 3p21.31, with lead variant pointing to the CXCR6 gene, as the strongest thus far reported susceptibility risk locus for severe manifestation of COVID-19. In order the determine its role, we measured plasma levels of Chemokine (C‐X‐C motif) ligand 16 (CXCL16) in the plasma of COVID-19 hospitalized patients. CXCL16 interacts with CXCR6 promoting chemotaxis or cell adhesion. The CXCR6/CXCL16 axis mediates homing of T cells to the lungs in disease and hyper-expression is associated with localised cellular injury. To characterize the CXCR6/CXCL16 axis in the pathogenesis of severe COVID-19, plasma concentrations of CXCL16 collected at baseline from 115 hospitalized COVID-19 patients participating in ODYSSEY COVID-19 clinical trial were assessed together with a set of controls. We report elevated levels of CXCL16 in a cohort of COVID-19 hospitalized patients. Specifically, we report significant elevation of CXCL16 plasma levels in association with severity of COVID-19 (as defined by WHO scale) (P-value<0.02). Our current study is the largest thus far study reporting CXCL16 levels in COVID-19 hospitalized patients (with whole-genome sequencing data available). The results further support the significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19 and warrants further studies to understand which patients would benefit most from targeted treatments.

  🖺 Full Text HTML: Elevated plasma levels of CXCL16 in severe COVID-19 patients
• Low dose prime and delayed boost can improve COVID-19 vaccine efficacies by increasing B cell selection stringency in germinal centres -

  The efficacy of COVID-19 vaccines appears to depend in complex ways on the vaccine dosage and the interval between the prime and boost doses. Unexpectedly, lower dose prime and longer prime-boost intervals have yielded higher efficacies in clinical trials. To elucidate the origins of these effects, we developed a stochastic simulation model of the germinal centre (GC) reaction and predicted the antibody responses elicited by different vaccination protocols. The simulations predicted that a lower dose prime could increase the selection stringency in GCs due to reduced antigen availability, resulting in the selection of GC B cells with higher affinities for the target antigen. The boost could relax this selection stringency and allow the expansion of the higher affinity GC B cells selected, improving the overall response. With a longer dosing interval, the decay in the antigen with time following the prime could further increase the selection stringency, amplifying this effect. The effect remained in our simulations even when new GCs following the boost had to be seeded by memory B cells formed following the prime. These predictions offer a plausible explanation of the observed paradoxical effects of dosage and dosing interval on vaccine efficacy. Tuning the selection stringency in the GCs using prime-boost dosages and dosing intervals as handles may help improve vaccine efficacies.

  🖺 Full Text HTML: Low dose prime and delayed boost can improve COVID-19 vaccine efficacies by increasing B cell selection stringency in germinal centres
• Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2 -
  Despite the appearance of variant SARS-CoV-2 viruses with altered receptor-binding or antigenic phenotypes, traditional methods for detecting adaptive evolution from sequence data do not pick up strong signals of positive selection. Here, we present a new method for identifying adaptive evolution on short evolutionary time scales with densely-sampled populations. We apply this method to SARS-CoV-2 to perform a comprehensive analysis of adaptively- evolving regions of the genome. We find that spike S1 is a focal point of adaptive evolution, but also identify positively-selected mutations in other genes that are sculpting the evolutionary trajectory of SARS-CoV-2. Protein- coding mutations in S1 are temporally-clustered and, in 2021, the ratio of nonsynonymous to synonymous divergence in S1 is more than 4 times greater than in the equivalent influenza HA1 subunit.
  🖺 Full Text HTML: Rapid and parallel adaptive mutations in spike S1 drive clade success in SARS-CoV-2
• Phylogenetic evidence for asparagine to aspartic acid protein editing of N-glycosylated SARS-CoV-2 viral proteins by NGLY1 deglycosylation/deamidation suggests an unusual vaccination strategy -
  Many viral proteins, including multiple SARS-CoV-2 proteins, are secreted via the endoplasmic reticulum, and viral particles are assembled and exported in ER-associated replication compartments. Viral coat proteins such as the SARS- CoV-2 Spike protein are N-glycosylated at NxS/T sites as they enter the ER. N-glycosylated sites in many eukaryotic proteins are deglycosylated by the NGLY1/PNG-1 deglycosylation enzyme which also deamidates the N-glycosylated asparagine to aspartic acid, thus editing the target protein sequence. Proteomic analysis of mammalian cell lines has revealed deamidation of many host N-glycosylated asparagines to aspartic acid by NGLY1/PNG-1 on peptides that are presented by mammalian HLA for immune surveillance. The key client protein for NGLY1/PNG-1 deglycosylation and N to D protein editing was revealed by genetic analysis of C. elegans proteasome regulation to be the intact endoplasmic reticulum-transiting SKN-1A transcription factor. Strikingly, an analysis of cancer cell genetic dependencies for growth revealed that the mammalian orthologue of SKN-1A, NRF1 (also called NFE2L1) is required by a highly correlated set of cell lines as NGLY1/PNG-1, supporting that NGLY1/PNG-1 and NRF1 act in the same pathway. NGLY1/PNG-1 edits N-glycosylated asparagines on the intact SKN-1 protein as it is retrieved by ERAD from the ER to in turn activate the transcription of target proteasomal genes. The normal requirement for NGLY1/PNG-1 editing of SKN-1A can be bypassed by a genomic substituion of N to D in four NxS/T N-glycosylation motifs of SKN-1A. Thus NGLY1/PNG-1-mediated N to D protein editing is more than a degradation step for the key client protein for proteasomal homeostasis in C. elegans or tumor growth in particular mammalian cell lines, SKN-1A/NRF1. In addition, such N to D substitutions in NxS/T N-glycosylation motifs occur in evolution: N to D substitutions are observed in phylogenetic comparisons of SKN-1A between nematode species that diverged hundreds of millions of years ago or of the vertebrate NRF1 between disparate vertebrates. Genomic N to D mutations bypass the many steps in N-glycosylation in the ER and deglycosylation-based editing of N to D, perhaps based on differences in the competency of divergent species for various N-glycosylation or deglycosylation steps. We surveyed the N-glycosylation sites in coronavirus proteins for such phylogenetic evidence for N to D protein editing in viral life cycles, and found evidence for preferential N to D residue substitutions in NxS/T N-glycosylation sites in comparisons of the genome sequences of hundreds of coronaviruses. This suggests that viruses use NGLY1/PNG-1 in some hosts, for example humans, to edit particular N-glycosylated residues to aspartic acid, but that in other hosts, often in bats, an N to D substitution mutation in the virus genome is selected. Single nucleotide mutations in Asp or Asn codons can produce viruses with N to D or D to N substitutions that might be selected in different animal hosts from the population of viral variants produced in any previous host. NGLY1/PNG-1 has been implicated in viral immunity in mammalian cell culture, favoring this hypothesis. Because of the phylogenetic evidence that the NGLY1/PNG-1 editing of protein sequences has functional importance for SKN-1A/NRF1 and viruses, and because most immunization protocols do not address the probable editing and functional importance of N-glycosylated aspargines to aspartic acid in normal viral infections, we suggest that immunization with viral proteins engineered to substitute D at genomically encoded NxS/T sites of N-glycosylated viral proteins that show a high frequency of N to D substitution in viral phylogeny may enhance immunological response to peptide antigens. Such genomically-edited peptides would not require ER-localization for N-glycosylation or other cell compartment localization for NGLY1/PNG-1 N to D protein editing. In addition, such N to D edited protein vaccines could be produced in bacteria since N-glycosylation and deglycosylation which do not occur in bacteria would no longer be required to immunize with a D-substituted peptide. Bacterially-expressed vaccines would be much lower cost and with fewer failure modes than attenuated viral vaccines or recombinant animal viruses produced in chicken eggs, mammalian tissue culture cells, or delivered by mRNA vectors to the patient directly. Because N to D edited peptides are clearly produced by NGLY1/PNG-1, and may be and presented by mammalian HLA, such peptides may more robustly activate T-cell killing or B-cell maturation to mediate more robust viral immunity.
  🖺 Full Text HTML: Phylogenetic evidence for asparagine to aspartic acid protein editing of N-glycosylated SARS-CoV-2 viral proteins by NGLY1 deglycosylation/deamidation suggests an unusual vaccination strategy
• Exposures to different SARS-CoV-2 spike variants elicit neutralizing antibody responses with differential specificity towards established and emerging strains -

  The wide spectrum of SARS-CoV-2 variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of the immune response to different spike protein versions. Here, we compare the neutralization of variants of concern, including B.1.617.2 (Delta) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing one or more spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization. These findings contribute to understanding the relationship between exposures and antibody responses and may inform booster vaccination strategies.

  🖺 Full Text HTML: Exposures to different SARS-CoV-2 spike variants elicit neutralizing antibody responses with differential specificity towards established and emerging strains

From Clinical Trials

• High-dose Intravenous Vitamin C (HDIVC) as Adjuvant Therapy in Critical Patients With Positive COVID-19. A Pilot Randomized Controlled Dose-comparison Trial. - Condition:   Covid19
  Interventions:   Drug: High doses of intravenous vitamin C;   Drug: Dextrose 500 mL
  Sponsor:   Hugo Galindo
  Not yet recruiting

• Developing and Testing a COVID-19 Vaccination Acceptance Intervention - Condition:   COVID-19 Vaccination
  Intervention:   Behavioral: Moving to COVID-19 Vaccine Acceptance Intervention
  Sponsors:   VA Office of Research and Development;   VA Bedford Healthcare System
  Not yet recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected) - Condition:   COVID-19
  Interventions:   Drug: AZVUDINE;   Drug: AZVUDINE placebo
  Sponsors:   HRH Holdngs Limited;   GALZU INSTITUTE OF RESEARCH, TEACHING, APPLIED SCIENCE AND TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• COVID-19 Morbidity in Healthcare Workers and Vitamin D Supplementation - Condition:   COVID-19 Respiratory Infection
  Intervention:   Drug: Vitamin D
  Sponsor:   Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
  Completed

• Text Message Nudges for COVID-19 Vaccination - Condition:   Covid19
  Intervention:   Behavioral: Text message
  Sponsor:  
  Ascension South East Michigan
  Not yet recruiting

• A Pilot Study of a PhysiOthErapy-based Tailored Intervention for Long Covid - Condition:   COVID-19
  Intervention:   Behavioral: Physiotherapy
  Sponsors:  
  University of Calgary;   Alberta Health Services
  Not yet recruiting

• Quercetin in the Prevention of Covid-19 Infection - Condition:   Covid19
  Interventions:   Dietary Supplement: Quercetin;   Combination Product: Placebo
  Sponsor:   Azienda di Servizi alla Persona di Pavia
  Completed

• A Study to Evaluate Change in Viral Load After OPN-019 in Adults With COVID-19 - Condition:   Covid19
  Intervention:   Drug: OPN-019
  Sponsor:   Optinose US Inc.
  Recruiting

• Physical Activity and Smell Trainings to Help Individuals With Coronavirus Disease (COVID-19) Recover From Persistent Smell and Taste Impairments - A Pilot Study - Condition:   Covid19
  Interventions:   Behavioral: Physical activity;   Other: Smell training
  Sponsor:   Université de Montréal
  Not yet recruiting

• Phase 3 Study to Evaluate the Lot Consistency of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Biological: CoVLP formulation
  Sponsor:  
  Medicago
  Not yet recruiting

• Evaluation of the Efficacy, Safety and Immunogenicity of Inactivated COVID 19 Vaccine(TURKOVAC) in Healthy Population of 18 and 64 Years of Age (Both Inclusive):a Randomized, Double-blind, Phase IIb Clinical Trial - Condition:   Covid19
  Intervention:   Biological: Triple dose vaccination by inactivated Covid19 vaccine
  Sponsors:   Health Institutes of Turkey;   TC Erciyes University;   Kocak Farma;   Mene Research
  Not yet recruiting

• Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue - Condition:   COVID-19 Respiratory Infection
  Intervention:  
  Other: Cardiopulmonary exercise training
  Sponsor:   Louis Bherer
  Recruiting

• Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions:   COVID-19 Pneumonia;   Coronavirus Infections
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell);   Biological: COVID-19 vaccine (Vero cells)
  Sponsors:  
  National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd
  Not yet recruiting

• Abbott ID NOW COVID-19 - Conditions:   Covid19;   SARS-CoV-2 Infection
  Interventions:  
  Diagnostic Test: Buccal Swab- Copan flocked swab;   Diagnostic Test: Standard of Care COVID-19 swab
  Sponsors:   University of Calgary;   Health Canada
  Not yet recruiting

• Study to Evaluate the Efficacy and Safety of Colchicine Tablets in Patients With COVID-19 - Conditions:   Covid19;   Colchicine
  Interventions:   Drug: Colchicine Tablets;   Drug: Standard therapy
  Sponsors:   Shanghai Public Health Clinical Center;   Kunming Pharmaceuticals, Inc.
  Not yet recruiting

From PubMed

• Discovery of a Natural Product with Potent Efficacy Against SARS-CoV-2 by Drug Screening - The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide for almost 2 years. It starts from viral adherence to host cells through an interaction between spike glycoprotein 1 (S1) containing a receptor-binding domain (RBD) and human angiotensin-converting enzyme-2 (ACE2). One of the useful strategies to prevent SARS-CoV-2 infection is to inhibit the attachment of RBD to ACE2. Therefore, the current work proposed…

• Potential antiviral properties of antiplatelet agents against SARS-CoV-2 infection: an in silico perspective - SARS-CoV-2 represents the causative agent of the current pandemic (COVID-19). The drug repurposing technique is used to search for possible drugs that can bind to SARS-CoV-2 proteins and inhibit viral replication. In this study, the FDA- approved antiplatelets are tested against the main protease and spike proteins of SARS-CoV-2 using in silico methods. Molecular docking and molecular dynamics simulation are used in the current study. The results suggest the effectiveness of vorapaxar,…

• Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells - The outbreak of COVID-19 has remained uncontained with urgent need for robust therapeutics. We have previously reported sex difference of COVID-19 for the first time indicating male predisposition. Males are more susceptible than females, and more often to develop into severe cases with higher mortality. This predisposition is potentially linked to higher prevalence of cigarette smoking. Nonetheless, we found for the first time that cigarette smoking extract (CSE) had no effect on angiotensin…

• Tinospora cordifolia (Willd.) Miers: Protection mechanisms and strategies against oxidative stress-related diseases - CONCLUSIONS: Our findings indicate that the pharmacological properties displayed by T. cordifolia back up its conventional uses. Antimicrobial, antiviral, antioxidant, anticancer, anti-inflammatory, antimutagenic, antidiabetic, nephroprotective, gastroprotective, hepatoprotective, and cardioprotective activities were all demonstrated in T. cordifolia stem extracts. To validate pharmacodynamic targets, further research is needed to evaluate the molecular mechanisms of the known compounds against…

• SARS-CoV-2 3C-like protease antagonizes interferon-beta production by facilitating the degradation of IRF3 - The prevalence of SARS-CoV-2 is a great threat to global public health. However, the relationship between the viral pathogen SARS-CoV-2 and host innate immunity has not yet been well studied. The genome of SARS-CoV-2 encodes a viral protease called 3C-like protease. This protease is responsible for cleaving viral polyproteins during replication. In this investigation, 293T cells were transfected with SARS-CoV-2 3CL and then infected with Sendai virus (SeV) to induce the RIG-I like receptor…

• Potential role of flavonoids against SARS-CoV-2 induced diarrhea - COVID-19, caused by the SARS-CoV-2 virus, can lead to massive inflammation in the gastrointestinal tract causing severe clinical symptoms. SARS-CoV-2 infects lungs after binding its spike proteins with alveolar angiotensin-converting enzyme 2 (ACE2), and it also triggers inflammation in the gastrointestinal tract. SARS-CoV-2 invades the gastrointestinal tract by interacting with Toll-like receptor-4 (TLR4) that induces the expression of ACE2. The influx of ACE2 facilitates cellular binding of…

• Diverse effects of clarithromycin and proposal of its clinical application for treating COVID-19 as a repurposing drug - Outbreak of SARS-CoV-2 has been declared a pandemic, which is a serious threat to human health. The disease was named coronavirus disease 2019 (COVID-19). Until now, several vaccines and a few drugs have been approved for the prevention and treatment for COVID-19. Recently, the effect of some macrolides including clarithromycin (CAM) on COVID-19 has attracted attention. CAM is known to have diverse effects including immunomodulatory and immunosuppressive effects, autophagy inhibition, steroid…

• Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro - Effective vaccines are slowing the COVID-19 pandemic, but SARS-CoV-2 will likely remain an issue in the future making it important to have therapeutics to treat patients. There are few options for treating patients with COVID-19. We show probenecid potently blocks SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Furthermore, we demonstrate that plasma concentrations up to 50-fold higher than the protein binding adjusted IC(90) value are achievable for 24 h…

• Decreased HD-MIR2911 absorption in human subjects with the SIDT1 polymorphism fails to inhibit SARS-CoV-2 replication - No abstract

• Potential of herbal products in prevention and treatment of COVID-19. Literature review - The COVID-19 epidemic is the greatest pandemic that human kind experienced for decades, with high morbidity and mortality. Despite recent development of vaccines there is still many severe cases of COVID-19. Unfortunately there is still no standardized therapies and treatment of severe cases is very challenging. The aim of this study is to indicate if herbs administered alone or as a complementary therapy could be used as prophylaxis or treatment of SARS-CoV-2 infection. Over 85% of patients…

• Supporting newly graduated medical doctors in managing COVID-19: An evaluation of a Massive Open Online Course in a limited-resource setting - INTRODUCTION: Newly graduated medical doctors in their internships are positioned to strengthen the front line in combating COVID-19. We developed a Massive Open Online Course (MOOC) to equip them with adequate knowledge for COVID-19 management. This paper aims to analyze the MOOC and evaluate participant satisfaction and increase in knowledge after completing the course.

• Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19 - Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is associated with procoagulant endothelial…

• Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode - Rupintrivir targets the 3C cysteine proteases of the picornaviridae family, which includes rhinoviruses and enteroviruses that cause a range of human diseases. Despite being a pan-3C protease inhibitor, rupintrivir activity is extremely weak against the homologous 3C-like protease of SARS-CoV-2. In this study, the crystal structures of rupintrivir were determined bound to enterovirus 68 (EV68) 3C protease and the 3C-like main protease (M^(pro)) from SARS-CoV-2. While the EV68 3C…

• Remdesivir and EIDD-1931 Interact with Human Equilibrative Nucleoside Transporters 1 and 2: Implications for Reaching SARS-CoV-2 Viral Sanctuary Sites - Equilibrative nucleoside transporters (ENTs) are present at the blood-testis barrier (BTB), where they can facilitate antiviral drug disposition to eliminate a sanctuary site for viruses detectable in semen. The purpose of this study was to investigate ENT-drug interactions with three nucleoside analogs remdesivir, molnupiravir and its active metabolite, EIDD-1931 and four non-nucleoside molecules repurposed as antivirals for COVID-19. The study used 3D pharmacophores for ENT1 and ENT2…

• Identifying FDA-approved drugs with multimodal properties against COVID-19 using a data-driven approach and a lung organoid model of SARS-CoV-2 entry - CONCLUSIONS: Small clinical studies reported that general statin use, and specifically, atorvastatin use, are associated with protective effects against COVID-19. Our study corroborrates these findings and supports the investigation of atorvastatin in larger clinical studies. Ultimately, our framework demonstrates one promising way to fast-track the identification of compounds for COVID-19, which could similarly be applied when tackling future pandemics.

From Patent Search

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

• SARS-COV-2 BINDING PROTEINS - - link

• COVID-19胸部CT图像识别方法、装置及电子设备 - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像，并针对胸部CT图像的特点，构建新冠肺炎CT识别网络，对该网络进行训练得到COVID‑19胸部CT图像识别模型，并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子，减少冗余参数；采用并行结构连接方式，实现多尺度特征融合、降低模型复杂度；采用下采样方式，使用最大模糊池化以减少锯齿效应，保持信号的平移不变性；采用通道混洗操作，减少参数量与计算量，提高分类准确率，引入坐标注意力机制，使空间坐标信息与通道信息被关注，抑制不重要的信息，以解决资源匹配问题。 - link

• A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link

• IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link

• 一种脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂 - 本发明属于基因治疗技术领域，具体涉及一系列脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂。本发明提供的具有式（I）结构的化合物，可与其它脂质化合物共同制备脂质载体，展现出pH响应性，对核酸药物的包封效率高，大大提升了核酸药物在体内的递送效率；而且，可根据核酸药物需要富集的器官而选用特定结构的脂质化合物作为脂质载体，具有良好的市场应用前景。 - link