Covid-19 Sentry

Contents

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

From Preprints

• Between authority and common sense: development and investigation of a model explaining COVID-19 preventive behaviours -
  To protect themselves from COVID-19, people follow the recommendations of the authorities, but they also resort to placebos. To stop the virus, it is important to understand the factors underlying both types of preventive behaviour. This study examined whether our model (developed based on the Health Belief Model and the Transactional Model of Stress) can explain participation in WHO-recommended and placebo actions during the pandemic. Model was tested on a sample of 3,346 participants from Italy, Japan, Poland, Korea, Sweden, and the US. It was broadly supported: objective risk and cues to action showed both direct and indirect (through perceived threat) associations with preventive behaviours. Moreover, locus of control, decision balance, health anxiety and preventive coping moderated these relationships. Numerous differences were also found between countries. We conclude that beliefs about control over health and perceived benefits of actions are critical to the development of interventions to improve adherence to recommendations.

• The Prospective Relationship between Loneliness, Life Satisfaction, and Psychological Distress before and during the COVID-19 Pandemic in the UK -
  Background Mental wellbeing in the UK seems to have deteriorated significantly during the COVID-19 pandemic, with the rates of loneliness, life satisfaction, and psychological distress taking longer to return to the pre-pandemic levels than elsewhere. Nevertheless, there is little knowledge about the interactions between these outcomes, or the factors that played a role. Methods Longitudinal data from Understanding Society (N=3475) were used to explore the changes in loneliness, life satisfaction, and psychological distress from pre-pandemic levels (2017-19) through November 2020, the interactions between these outcomes, and the role of individual differences in the rates of change, using multivariate latent growth curve model. Results Loneliness, life satisfaction, and psychological distress deteriorated minimally between April and November 2020, compared to the pre-pandemic levels (2017-2019), while the rate of change in each outcome influenced the rate of change in the other two. Key individual (age, gender, physical health), social (number of friends) and environmental (neighbourhood quality) variables influenced baseline scores and the rates of change. Conclusion Considering significant dynamic associations between loneliness, life satisfaction, and psychological distress, we argue that interventions to tackle any one of the outcomes may have beneficial effects on others, while highlighting individual and community-level interventions to tackle loneliness.
  🖺 Full Text HTML: The Prospective Relationship between Loneliness, Life Satisfaction, and Psychological Distress before and during the COVID-19 Pandemic in the UK
• Cov2clusters: genomic clustering of SARS-CoV-2 sequences -

  Background: The COVID-19 pandemic remains a global public health concern. Advances in sequencing technologies has allowed for high numbers of SARS-CoV-2 whole genome sequence (WGS) data and rapid sharing of sequences through global repositories to enable almost real-time genomic analysis of the pathogen. WGS data has been used previously to group genetically similar viral pathogens to reveal evidence of transmission, including methods that identify distinct clusters on a phylogenetic tree. Identifying clusters of linked cases can aid in the regional surveillance and management of the disease. In this study, we present a novel method for producing stable genomic clusters of SARS-CoV-2 cases, cov2clusters, and compare the sensitivity and stability of our approach to previous methods used for phylogenetic clustering using real-world SARS-CoV-2 sequence data obtained from British Columbia, Canada, Results: We found that cov2clusters produced more stable clusters than previously used phylogenetic clustering methods when adding sequence data through time, mimicking an increase in sequence data through the pandemic. Our method also showed high sensitivity when compared to epidemiologically informed clusters. Conclusions: Our new approach allows for the identification of stable clusters of SARS-CoV-2 from WGS data. Producing high-resolution SARS-CoV-2 clusters from sequence data alone can a challenge and, where possible, both genomic and epidemiological data should be used in combination.

  🖺 Full Text HTML: Cov2clusters: genomic clustering of SARS-CoV-2 sequences
• SARS-CoV-2 Omicron disease burden in Australia following border reopening: a modelling analysis -

  Background: Countries with high COVID-19 vaccination rates have seen the SARS-CoV-2 Omicron variant result in rapidly increasing case numbers. This study evaluated the impact on the health system which may occur following introduction of the Omicron variant into Western Australia following state border reopening. We aimed to understand the effect of high vaccine coverage levels on the population health burden in the context of lower vaccine effectiveness against the Omicron variant, the impact of a third dose booster regime, and ongoing waning of vaccine-induced immunity. Originally scheduled for 5th February 2022, the Western Australian border was opened on 3rd March 2022, we also aimed to determine the impact of delaying border reopening on the COVID-19 health burden and whether the West Australian health system would be able to manage the resulting peak demand. Methods: An agent-based model was used to evaluate changes in the COVID-19 health burden resulting from different border openings, at monthly intervals. We assumed immunity was derived from vaccination with the BNT162b2 Pfizer BioNTech vaccine and waned at observed rates taken from the UK. The model was calibrated against outbreaks in two other Australian states, Queensland and South Australia, both of which were in a similar situation to Western Australia with negligible COVID-19 transmission prior to Omicron variant introduction. Age-specific infections generated by the model, together with recent UK data, permitted resulting outbreak health burden to be quantified, in particular peak ICU demand. Results: Overall population immunity in Western Australia is shown to peak and then plateau for a period of 5 months, between February and June 2022, resulting in a similar health burden if the border is reopened prior to June 2022. For an opening date of 5th March 2022, hospitalisations are predicated to peak at 510 beds, 51 of which will be in ICU, with a total of 383 deaths. If the border reopened on 5th June 2022, hospitalisations are expected to peak with 750 beds required, 75 of which would be in ICU, and a total of 478 deaths. With a total surge capacity of 52 fully staffed ICU beds, West Australian hospitals are predicted to have adequate ICU capacity for future COVID-19 demands if border reopening occurs prior to May 2022. Conclusions: Our results show that with extremely high SARS-CoV-2 vaccination rates in Western Australian, and documented vaccine-induced vaccine waning rates, the overall population immunity in Western Australia will be at its highest in the period of February 2022 to June 2022. Opening the Western Australian border prior to the end this period will result in the lowest health burden in comparison to opening in June 2022 or later. With a border reopening of 3rd March 2022 announced by the Western Australian government, our data for a 5th March 2022 opening date may be used to predict the progression of this resulting outbreak. These data show expected peak demand of 510 hospital beds, 51 of which will be in ICU, with a total of 383 deaths. With a surge capacity of 52 ICU beds, it is expected that the Western Australian hospital system will be able to handle the additional load during the peak of the wave.

  🖺 Full Text HTML: SARS-CoV-2 Omicron disease burden in Australia following border reopening: a modelling analysis
• Canadian Adolescents’ Mental Health and Substance Use during the COVID-19 Pandemic: Associations with COVID-19 Stressors -
  Objective: There have been significant concerns regarding the mental health impact of coronavirus disease 2019 (COVID-19), due to isolation, anxiety around the pandemic, and increased conflict in the home. The purpose of this study was to examine the rates of mental health problems and substance use, and to assess which COVID-19 related stressors were predictors of mental health and substance use in a large Canadian sample of adolescents, with comparisons across genders. Method: Participants (N = 809, Mage = 15.67, SD = 1.37) identified as a girl (56.2%), boy (38.7%), or trans/non-binary individual (TNBI; 5.1%) and were recruited via social media to complete an online survey. Results: A high proportion of adolescents met clinical cut-offs for depression (51%), anxiety (39%), and post-traumatic stress disorder (45%). Other mental health problems ranged from 9%-20%. Adolescents were mainly concerned with the health of family members and vulnerable populations, as well as the increased family stress at home during COVID-19. Rates of substance use were higher than expected, with over 50% of youth engaging in some form of substance use in the past 90 days, and almost 20% engaging in substance use at least once a week. TNBI and girls reported higher rates of mental health problems compared to boys. Family stress due to confinement and violence at home predicted higher rates of mental health, but not substance use problems. Conclusions: Increased rates of mental health problems and substance use necessitate targeted supports that encourage positive coping amidst the additional stresses of COVID-19.
  🖺 Full Text HTML: Canadian Adolescents’ Mental Health and Substance Use during the COVID-19 Pandemic: Associations with COVID-19 Stressors
• Peritoneal M2 macrophage-derived extracellular vesicles as natural multi-target nanotherapeutics to attenuate cytokine storm after severe infections -
  Cytokine storm is a primary cause for multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophages-derived extracellular vesicles (M2-EVs) are multi-target nanotherapeutics to resolve cytokine storm. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines. Systemically administrated M2-EVs entered major organs and were taken up by phagocytes (e.g., macrophages). M2-EVs treatment effectively reduced excessive cytokine (e.g., TNF- and IL-6) release in vitro and in vivo, thereby attenuated oxidative stress and multiple organ (lung, liver, spleen and kidney) damage in endotoxin-induced cytokine storm. Moreover, M2-EVs simultaneously inhibited multiple key proinflammatory pathways (e.g., NF-{kappa}B, JAK-STAT and p38 MAPK) by regulating complex miRNA-gene and gene-gene networks, and this effect was collectively mediated by many functional cargos (miRNAs and proteins) in EVs. In addition to the direct anti-inflammatory role, human peritoneal M2-EVs expressed angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2 spike protein, and thus could serve as nanodecoys to prevent SARS-CoV-2 pseudovirus infection in vitro. As cell-derived nanomaterials, the therapeutic index of M2-EVs can be further improved by genetic/chemical modification or loading with specific drugs. This study highlights that peritoneal M2-EVs are promising multifunctional nanotherapeutics to attenuate infectious diseases-related cytokine storm.
  🖺 Full Text HTML: Peritoneal M2 macrophage-derived extracellular vesicles as natural multi-target nanotherapeutics to attenuate cytokine storm after severe infections
• Molecular docking between human TMPRSS2 and the serine protease Kunitz-type inhibitor rBmTI-A -
  SARS-CoV-2 entrance into host cells is dependent of ACE2 receptor and viral protein S initiation by serine protease TMPRSS2. Cleavage of coronavirus protein S at the junctions Arg685/Ser686 and Arg815/Ser816 leads to the production of the S1/S2 and S2’ fragments needed for the fusion of viral and cell membranes. Studying and identifying serine protease inhibitors is an important step towards the development of candidate drugs to prevent SARS-CoV-2 infection. It has already been stablished that camostat mesylate, a serine protease inhibitor, is capable of blocking TMPRSS2 activity and prevent SARS-CoV-2 entrance into host cells. In this work, the interaction between the two domains of Kunitz-type serine protease inhibitor rBmTI-A and TMPRSS2 was studied through molecular docking. rBmTI-A domain 2 (P1 site Leu84) had the best complex results with predicted binding affinity of -12 Kcal.mol-1 and predicted dissociation constant at 25{degrees}C of 1.6 nM. The results suggest that rBmTI-A is capable of binding TMPRSS2 cleavage site at the junction Arg815/Ser816 using essentially the same residues that camostat mesylate.
  🖺 Full Text HTML: Molecular docking between human TMPRSS2 and the serine protease Kunitz-type inhibitor rBmTI-A
• Parsing the role of NSP1 in SARS-CoV-2 infection -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 (COVID-19) pandemic. Despite its urgency, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis and its ability to antagonize innate immune responses. SARS-CoV-2 leads to shutoff of cellular protein synthesis and over-expression of nsp1, a central shutoff factor in coronaviruses, inhibits cellular gene translation. However, the diverse molecular mechanisms nsp1 employs as well as its functional importance in infection are still unresolved. By overexpressing various nsp1 mutants and generating a SARS-CoV-2 mutant in which nsp1 does not bind ribosomes, we untangle the effects of nsp1. We uncover that nsp1, through inhibition of translation and induction of mRNA degradation, is the main driver of host shutoff during SARS-CoV-2 infection. Furthermore, we find the propagation of nsp1 mutant virus is inhibited specifically in cells with intact interferon (IFN) response as well as in-vivo, in infected hamsters, and this attenuation is associated with stronger induction of type I IFN response. This illustrates that nsp1 shutoff activity has an essential role mainly in counteracting the IFN response. Overall, our results reveal the multifaceted approach nsp1 uses to shut off cellular protein synthesis and uncover the central role it plays in SARS-CoV-2 pathogenesis, explicitly through blockage of the IFN response.
  🖺 Full Text HTML: Parsing the role of NSP1 in SARS-CoV-2 infection
• Immunization with recombinant accessory protein-deficient SARS-CoV-2 protects against lethal challenge and viral transmission -
  Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to a worldwide Coronavirus Disease 2019 (COVID-19) pandemic. Despite high efficacy of the authorized vaccines, protection against the surging variants of concern (VoC) was less robust. Live-attenuated vaccines (LAV) have been shown to elicit robust and long-term protection by induction of host innate and adaptive immune responses. We sought to develop a COVID-19 LAV by generating 3 double open reading frame (ORF)-deficient recombinant (r)SARS-CoV-2 simultaneously lacking two accessory open reading frame (ORF) proteins (ORF3a/ORF6, ORF3a/ORF7a, and ORF3a/ORF7b). Here, we report that these double ORF-deficient rSARS-CoV-2 have slower replication kinetics and reduced fitness in cultured cells as compared to their parental wild-type (WT) counterpart. Importantly, these double ORF-deficient rSARS-CoV-2 showed attenuation in both K18 hACE2 transgenic mice and golden Syrian hamsters. A single intranasal dose vaccination induced high levels of neutralizing antibodies against different SARS-CoV-2 VoC, and also activated viral component-specific T-cell responses. Notably, the double ORF- deficient rSARS-CoV-2 were able to protect, as determined by inhibition of viral replication, shedding, and transmission, against challenge with SARS-CoV-2. Collectively, our results demonstrate the feasibility to implement these double ORF-deficient rSARS-CoV-2 as safe, stable, immunogenic and protective LAV for the prevention of SARS-CoV-2 infection and associated COVID-19 disease.
  🖺 Full Text HTML: Immunization with recombinant accessory protein-deficient SARS-CoV-2 protects against lethal challenge and viral transmission
• C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study) -

  Abstract Background Coronavirus disease-2019 (COVID-19) symptoms can range from asymptomatic, moderate to severe manifestations that result in an overall global case fatality rate of 2-7 %. While each variant has had it challenges, and some variants are more severe than others, risk factors of severe COVID-19 are still under investigation. In this context, the host genetic predisposition is also a crucial factor to investigate. In the present study, we investigated host genotypes of the SNP rs479200 of the host EGLN1 gene, previously implicated in high altitude pulmonary edema (HAPE), some of whose symptoms such as hypoxia profoundly overlap with severe COVID-19. Methods After informed consent, 158 RT-PCR confirmed COVID-19 patients (March 2020 to June 2021) were enrolled in the study. Based on their clinical manifestations, disease severity was categorized by the clinical team. Blood samples were drawn and DNA was extracted from the clot to infer different genotypes of the SNP rs479200 of the host EGLN1 gene. PCR-RFLP analysis of the SNP rs479200 (C > T) was performed with an amplicon size of 367 bp. Various genotypes (TT, TC and CC) were assigned based on the presence/absence of a restriction site (T/GTACA) for restriction enzyme BsrGI. Allele frequencies, Hardy- Weinberg Equilibrium (HWE) and multinomial logistic regression were performed using statistical tool SPSS version 23 (IBM). Findings We observed that the severe COVID-19 category was composed of comparatively younger patients with mean age (34.9), compared to asymptomatic and moderate categories whose mean age was 49.7 and 54.3, respectively. Preponderance of males and high heterozygosity (TC) was observed across the clinical categories. Notably, the frequency of C allele (0.664) was 2-fold higher than the T allele (0.336) in severe COVID-19 patients, whereas the allele frequencies were similar in asymptomatic and moderate category of COVID-19 patients. Multinomial logistic regression showed an association of genotypes with increasing clinical severity; odds ratio (adjusted OR- 11.414 (2.564-50.812)) and (unadjusted OR- 6.214 (1.84-20.99)) for the genotype CC in severe category of COVID-19. Interestingly, the TC genotype was also found to be positively associated with severe outcome (unadjusted OR-5.816 (1.489-22.709)), indicating association of C allele in imparting the risk of severe outcome. Interpretation The study provides strong evidence that the presence of C allele of SNP (rs479200) of the EGLN1 gene associates with severity in COVID-19 patients. Thus, the presence of C allele may be a risk factor for COVID-19 severity. This study opens new avenues towards risk assessment that include EGLN1 (rs479200) genotype testing and identifying patients with C allele who might be prioritized for critical care.

  🖺 Full Text HTML: C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study)
• Lower Risk of Paediatric Inflammatory Multisystem Syndrome (PIMS-TS) with the Delta variant of SARS-CoV-2 -

  Paediatric Inflammatory Multisystem Syndrome (PIMS-TS, also known as MIS-C) typically occurs 2-6 weeks after exposure to SARS-CoV-2. Early estimates suggested a risk of PIMS-TS of 1 in 3-4000 infected children. Whether this risk is sustained with new SARS-CoV-2 variants remains unknown. We utilised prospective data from the NHS South Thames Paediatric Network (STPN), which manages all cases of PIMS-TS amongst 1.5 million children in South-East England, to assess trends over time. We compared PIMS-TS cases with two independent SARS-CoV-2 infection datasets. We used publicly available UK Health Security Agency case numbers weighted to child population distributions according to area population estimates from the Office for National Statistics (ONS). To avoid bias due to evolving testing behaviour, we also compared PIMS-TS cases to community infection rates, obtained from the ONS COVID-19 Infection Survey, which randomly selects individuals for fortnightly PCR tests. All three datasets were normalised to the peak of the Alpha wave, and plotted against time. PIMS-TS cases were plotted 40 days prior to hospitalisation, corresponding to the best fit of rising SARS-CoV-2 infection and PIMS-TS cases during the Alpha wave. Compared with the Alpha wave, we found fewer cases of PIMS-TS relative to SARS-CoV-2 infections during both initial and subsequent Delta waves. This relative reduction continued into the Omicron wave. Re-infection rates with the Alpha or Delta variants and vaccination rates were very low during the Delta wave. As a result, lower PIMS-TS rate relative to SARS-CoV-2 infections during the Delta wave is unlikely to be explained by population level immunity from prior infection or vaccination. It is most likely due to viral mutations in key antigenic epitopes responsible for triggering the hyperinflammatory response observed with PIMS- TS.

  🖺 Full Text HTML: Lower Risk of Paediatric Inflammatory Multisystem Syndrome (PIMS-TS) with the Delta variant of SARS-CoV-2
• Dual inhibition of vacuolar ATPase and TMPRSS2 is required for complete blockade of SARS-CoV-2 entry into cells -
  An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the cell-surface route or the endosomal route, respectively. In cells expressing TMPRSS2, inhibiting endosomal proteases using non-specific cathepsin inhibitors such as E64d or lysosomotropic compounds such as hydroxychloroquine fails to prevent viral entry, suggesting that the endosomal route of entry is unimportant; however, mechanism-based toxicities and poor efficacy of these compounds confound our understanding of the importance of the endosomal route of entry. Here, to identify better pharmacological agents to elucidate the role of the endosomal route of entry, we profiled a panel of molecules identified through a high throughput screen that inhibit endosomal pH and/or maturation through different mechanisms. Among the three distinct classes of inhibitors, we found that inhibiting vacuolar-ATPase using the macrolide bafilomycin A1 was the only agent able to potently block viral entry without associated cellular toxicity. Using both pseudotyped and authentic virus, we showed that bafilomycin A1 inhibits SARS- CoV-2 infection both in the absence and presence of TMPRSS2. Moreover, synergy was observed upon combining bafilomycin A1 with Camostat, a TMPRSS2 inhibitor, in neutralizing SARS-CoV-2 entry into TMPRSS2-expressing cells. Overall, this study highlights the importance of the endosomal route of entry for SARS-CoV-2 and provides a rationale for the generation of successful intervention strategies against this virus that combine inhibitors of both entry pathways.
  🖺 Full Text HTML: Dual inhibition of vacuolar ATPase and TMPRSS2 is required for complete blockade of SARS-CoV-2 entry into cells
• Understanding adherence to self-isolation in the first phase of COVID-19 response -

  Objective: To gain a better understanding of decisions around adherence to self-isolation advice during the first phase of the COVID-19 response in England. Design: A mixed-methods cross sectional study. Setting: England Participants COVID-19 cases and contacts who were contacted by Public Health England (PHE) during the first phase of the response in England (January-March 2020). Results: Of 250 respondents who were advised to self-isolate, 63% reported not leaving home at all during their isolation period, 20% reported leaving only for lower risk activities (dog walking or exercise) and 16% reported leaving for potentially higher risk, reasons (shopping, medical appointments, childcare, meeting family or friends). Factors associated with adherence to never going out included: the belief that following isolation advice would save lives, experiencing COVID-19 symptoms, being advised to stay in their room (rather than just inside), having help from outside and having regular contact by text message from PHE. Factors associated with non- adherence included being angry about the advice to isolate, being unable to get groceries delivered and concerns about losing touch with friends and family. Interviews highlighted that a sense of duty motivated people to adhere to isolation guidance and where people did leave their homes, these decisions were based on rational calculations of the risk of transmission; people would only leave their homes when they thought they were unlikely to come into contact with others. Conclusions: Measures of adherence should be nuanced to allow for the adaptations people make to their behaviour during isolation. Understanding adherence to isolation and associated reasoning during the early stages of the pandemic is an essential part of pandemic preparedness for future emerging infectious diseases.

  🖺 Full Text HTML: Understanding adherence to self- isolation in the first phase of COVID-19 response
• Nocturnal Respiratory Rate Dynamics Enable Early Recognition of Impending Hospitalizations -

  The days and weeks preceding hospitalization are poorly understood because they transpire before patients are seen in conventional clinical care settings. Home health sensors offer opportunities to learn signatures of impending hospitalizations and facilitate early interventions, however the relevant biomarkers are unknown. Nocturnal respiratory rate (NRR) is an activity-independent biomarker that can be measured by adherence-independent sensors in the home bed. Here, we report automated longitudinal monitoring of NRR dynamics in a cohort of high-risk recently hospitalized patients using non-contact mechanical sensors under patients home beds. Since the distribution of nocturnal respiratory rates in populations is not well defined, we first quantified it in 2,000 overnight sleep studies from the NHLBI Sleep Heart Health Study. This revealed that interpatient variability was significantly greater than intrapatient variability (NRR variances of 11.7 brpm2 and 5.2 brpm2 respectively, n=1,844,110 epochs), which motivated the use of patient- specific references when monitoring longitudinally. We then performed adherence-independent longitudinal monitoring in the home beds of 34 high-risk patients and collected raw waveforms (sampled at 80 Hz) and derived quantitative NRR statistics and dynamics across 3,403 patient-nights (n= 4,326,167 epochs). We observed 23 hospitalizations for diverse causes (a 30-day hospitalization rate of 20%). Hospitalized patients had significantly greater NRR deviations from baseline compared to those who were not hospitalized (NRR variances of 3.78 brpm2 and 0.84 brpm2 respectively, n= 2,920 nights). These deviations were concentrated prior to the clinical event, suggesting that NRR can identify impending hospitalizations. We analyzed alarm threshold tradeoffs and demonstrated that nominal values would detect 11 of the 23 clinical events while only alarming 2 times in non-hospitalized patients. Taken together, our data demonstrate that NRR dynamics change days to weeks in advance of hospitalizations, with longer prodromes associating with volume overload and heart failure, and shorter prodromes associating with acute infections (pneumonia, septic shock, and covid-19), inflammation (diverticulitis), and GI bleeding. In summary, adherence-independent longitudinal NRR monitoring has potential to facilitate early recognition and management of pre-symptomatic disease.

  🖺 Full Text HTML: Nocturnal Respiratory Rate Dynamics Enable Early Recognition of Impending Hospitalizations
• Broad Cross-reactive IgA and IgG Against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection -

  It is currently unclear if SARS-CoV-2 infection or mRNA vaccination can also induce IgG and IgA against common human coronaviruses (HCoVs) in lactating parents. Here we prospectively analyzed human milk (HM) and blood samples from lactating parents to measure the temporal patterns of anti-SARS-CoV-2 specific and anti-HCoV cross-reactive IgA and IgG responses. Two cohorts were analyzed: a vaccination cohort (n=30) who received mRNA-based vaccines for COVID-19 (mRNA-1273 or BNT162b2), and an infection cohort (n=45) with COVID-19 disease. Longitudinal HM and fingerstick blood samples were collected pre- and post-vaccination or, for infected subjects, at 5 time-points 14 - 28 days after confirmed diagnosis. The anti-spike(S) and anti-nucleocapsid(N) IgA and IgG antibody levels against SARS-CoV-2 and HCoVs were measured by multiplex immunoassay (mPlex-CoV). We found that vaccination significantly increased the anti-S IgA and IgG levels in HM. In contrast, while IgG levels increased after a second vaccine dose, blood and HM IgA started to decrease. Moreover, HM and blood anti-S IgG levels were significantly correlated, but anti-S IgA levels were not. SARS2 acute infection elicited anti-S IgG and IgA that showed much higher correlations between HM and blood compared to vaccination. Vaccination and infection were able to significantly increase the broadly cross-reactive IgG recognizing HCoVs in HM and blood than the IgA antibodies in HM and blood. In addition, the broader cross-reactivity of IgG in HM versus blood indicates that COVID-19 vaccination and infection might provide passive immunity through HM for the breastfed infants not only against SARS-CoV-2 but also against common cold coronaviruses.

  🖺 Full Text HTML: Broad Cross-reactive IgA and IgG Against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection

From Clinical Trials

• Effect of Bronchipret on Antiviral Immune Response in Patients With Mild COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Bronchipret
  Sponsors:   Dr. Frank Behrens;   Bionorica SE
  Recruiting

• EPIC-Peds: Study of Oral PF-07321332 (Nirmatrelvir)/Ritonavir in Nonhospitalized COVID-19 Pediatric Patients at Risk for Severe Disease - Condition:   COVID-19
  Interventions:   Drug: nirmatrelvir;   Drug: ritonavir
  Sponsor:   Pfizer
  Not yet recruiting

• Evaluating Public Health Interventions to Improve COVID-19 Testing Among Underserved Populations - Condition:   COVID-19
  Intervention:   Behavioral: Public Health Intervention Package
  Sponsors:   Kathleen Fairfield;   MaineHealth
  Not yet recruiting

• COVID-19 Serologic Strategies for Skilled Nursing Facilities - Condition:   COVID-19
  Intervention:   Other: Cohorting
  Sponsors:   NYU Langone Health;   Brown University;   National Institute on Aging (NIA)
  Recruiting

• Safety, Tolerability and Immunogenicity of Recombinant COVID-19 Vaccine Betuvax-CoV-2 - Condition:   COVID-19
  Interventions:   Biological: Betuvax-CoV-2;   Drug: Placebo
  Sponsors:   Human Stem Cell Institute, Russia;   Betuvax LLC;   CEG BIO LLC
  Active, not recruiting

• Evaluation of Full Versus Fractional Dose of COVID-19 Vaccine Given as a Booster for the Prevention of COVID 19 in Adults in Mongolia- Mongolia, Indonesia, Australia Coronavirus (MIACoV). - Condition:   COVID-19
  Interventions:   Biological: Tozinameran - Standard Dose;   Biological: Tozinameran - Fractional Dose
  Sponsors:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   PATH;   The Peter Doherty Institute for Infection and Immunity
  Not yet recruiting

• Early High-Titre Convalescent Plasma in Clinically Vulnerable Individuals With Mild COVID-19 - Condition:   COVID-19
  Interventions:   Biological: COVID-19 convalescent and vaccinated plasma;   Other: Current standard of care
  Sponsors:   Centre Hospitalier Universitaire de Besancon;   Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen;   NHS Blood and Transplant
  Not yet recruiting

• Efficacy of TCM Capsules Lian Hua Qing Wen Jiao Nang in Mild COVID-19 Patients - Condition:   COVID-19
  Interventions:   Other: TCM intervention;   Other: Placebo intervention
  Sponsor:   Singapore Chung Hwa Medical Institution
  Not yet recruiting

• Trial to Study the Efficacy and Safety of BEJO Red Ginger in COVID-19 Patients With Mild Symptoms - Condition:   COVID-19
  Interventions:   Dietary Supplement: BEJO Red Ginger Extract;   Other: Placebo
  Sponsors:   Research Center for Chemistry, National Research and Innovation Agency of Indonesia;   National Research and Innovation Agency of Indonesia;   RSDC Wisma Atlet;   PT. Bintang Toedjoe
  Recruiting

• **Safety and Immune Response of Adjuvanted SARS-CoV-2 (COVID-19) Beta Variant RBD Recombinant Protein (DoCo-Pro-RBD-1

• MF59®) and mRNA (MIPSCo-mRNA-RBD-1) Vaccines in Healthy Adults** - Condition:   SARS-CoV-2
  Interventions:   Biological: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59);   Biological: SARS-CoV-2 beta variant RBD mRNA vaccine;   Other: Normal Saline
  Sponsors:   University of Melbourne;   Southern Star Research
  Not yet recruiting

• Self-Management Interventions for Long-COVID - Condition:   COVID-19
  Interventions:   Behavioral: Education and Strategies Intervention;   Behavioral: Mindfulness Skills Intervention
  Sponsors:   Toronto Rehabilitation Institute;   Canadian Institutes of Health Research (CIHR);   University Health Network, Toronto
  Recruiting

• COVID-19 Hyper Coagulability Care by LLLT - Condition:   COVID-19 Pneumonia
  Interventions:   Radiation: Low level laser Therapy;   Other: Circulatory exercises
  Sponsor:   Cairo University
  Recruiting

• The BOOSTED (Booster Options Or Switching Tested for Effectiveness and Downsides Study) Trial (COVID-19) - Conditions:   COVID-19;   Vaccine Reaction;   COVID-19 Pandemic
  Interventions:  
  Behavioral: Moderna Booster Vaccine;   Behavioral: Pfizer Booster Vaccine
  Sponsor:  
  University of California, San Francisco
  Enrolling by invitation

• An Open-label, Randomized, Parallel-arm Study Investigating the Efficacy and Safety of Intravenous Administration of Pamrevlumab Versus Standard of Care in Patients With COVID-19 - Conditions:   COVID-19 Respiratory Infection;   COVID-19 Pneumonia;   Covid19
  Intervention:  
  Drug: Pamrevlumab
  Sponsor:   Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  Completed

• Safety, Reactogenicity, and Immunogenicity Trial of CV2CoV mRNA Vaccine Against SARS-CoV-2 in Seropositive Adult Participants - Condition:   SARS-CoV-2
  Interventions:   Biological: CV2CoV (2 µg);   Biological: CV2CoV (4 µg);   Biological: CV2CoV (8 µg);   Biological: CV2CoV (12 µg);   Biological: CV2CoV (16 µg);   Biological: CV2CoV (20 µg)
  Sponsors:   GlaxoSmithKline;   CureVac AG
  Not yet recruiting

From PubMed

• Novel antiviral activity of PAD inhibitors against human beta-coronaviruses HCoV-OC43 and SARS-CoV-2 - The current SARS-CoV-2 pandemic, along with the likelihood that new coronavirus strains will appear in the nearby future, highlights the urgent need to develop new effective antiviral agents. In this scenario, emerging host-targeting antivirals (HTAs), which act on host-cell factors essential for viral replication, are a promising class of antiviral compounds. Here we show that a new class of HTAs targeting peptidylarginine deiminases (PADs), a family of calcium- dependent enzymes catalyzing…

• Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen - Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs,…

• ACE2 overexpressing mesenchymal stem cells alleviates COVID-19 lung injury by inhibiting pyroptosis - Mesenchymal stem cells (MSCs) have shown some efficacy in the COVID-19 treatment. We proposed that exogenous supplementation of ACE2 via MSCs (ACE2-MSCs) might have better therapeutic effects. We constructed SARS-CoV-2 spike glycoprotein stably transfected AT-II and Beas-2B cells, and used SARS-CoV-2 spike pseudovirus to infect hACE2 transgenic mice. The results showed that spike glycoprotein transfection triggers apoptotic bodies’s release and membrane pores’s formation in pyroptosis….

• Prediction of putative potential siRNAs for inhibiting SARS-CoV-2 strains, including variants of concern and interest - Aim: To predict siRNAs as a therapeutic intervention for highly infectious new variants of SARS-CoV-2. Methods: Conserved coding sequence regions of 11 SARS-CoV-2 proteins were used to construct siRNAs through sampling of metadata comprising 214,256 sequences. Results: Predicted siRNAs S1: 5’-UCAUUGAGAAAUGUUUACGCA-3’ and S2: 5’-AAAGACAUCAGCAUACUCCUG-3’ against RdRp of SARS-CoV-2 satisfied all the stringent filtering processes and showed good binding characteristics. The designed siRNAs are…

• Evaluation of a new bead-based assay to measure levels of human tissue factor antigen in extracellular vesicles in plasma - CONCLUSION: Our data suggest that the MACSPlex Exosome Kit gives a nonspecific signal for TF and does not have the sensitivity to detect TF+ EVs in plasma.

• Functional food: complementary to fight against COVID-19 - BACKGROUND: The novel coronavirus has embarked on a global pandemic and severe mortality with limited access for its treatments and medications. For the lack of time, research, and enough efficacy, most vaccines are underdeveloped or unreachable to society. However, many recent studies suggest various alternative, complementary remedies for COVID-19, which are functional foods. This review provides an overview of how functional foods can play a great role through modulating the host immune…

• Stability of Risk Perception Across Pandemic and Non-pandemic Situations Among Young Adults: Evaluating the Impact of Individual Differences - Previous research suggests a higher perceived risk associated with a risky behavior predicts a lower likelihood of involvement in that behavior; however, this relationship can vary based on personality characteristics such as impulsivity and behavioral activation. During the COVID-19 pandemic, individuals began to re-evaluate the level of risk associated with everyday behaviors. But what about risks associated with “typical” risk-taking behaviors? In the present study, 248 undergraduate student…

• Crystallization of Feline Coronavirus M(pro) With GC376 Reveals Mechanism of Inhibition - Coronaviruses infect a variety of hosts in the animal kingdom, and while each virus is taxonomically different, they all infect their host via the same mechanism. The coronavirus main protease (M^(pro), also called 3CL^(pro)), is an attractive target for drug development due to its essential role in mediating viral replication and transcription. An M^(pro) inhibitor, GC376, has been shown to treat feline infectious peritonitis (FIP), a fatal infection in cats caused by internal mutations in the…

• Potential Inhibitors Targeting Papain-Like Protease of SARS-CoV-2: Two Birds With One Stone - Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the pathogen of the Coronavirus disease-19 (COVID-19), is still devastating the world causing significant chaos to the international community and posing a significant threat to global health. Since the first outbreak in late 2019, several lines of intervention have been developed to prevent the spread of this virus. Nowadays, some vaccines have been approved and extensively administered. However, the fact that SARS-CoV-2 rapidly…

• Clofazimine derivatives as potent broad-spectrum antiviral agents with dual-target mechanism - Thirty-two clofazimine derivatives, of which twenty-two were new, were synthesized and evaluated for their antiviral effects against both rabies virus and pseudo-typed SARS-CoV-2, taking clofazimine (1) as the lead. Among them, compound 15f bearing 4-methoxy-2-pyridyl at the N5-position showed superior or comparable antiviral activities to lead 1, with the EC(50) values of 1.45 μM and 14.6 μM and the SI values of 223 and 6.1, respectively. Compound 15f inhibited rabies and SARS-CoV-2 by…

• Potential inhibitor for blocking binding between ACE2 and SARS-CoV-2 spike protein with mutations - At the time of writing, more than 440 million confirmed coronavirus disease 2019 (COVID-19) cases and more than 5.97 million COVID-19 deaths worldwide have been reported by the World Health Organization since the start of the outbreak of the pandemic in Wuhan, China. During the COVID-19 pandemic, many variants of SARS-CoV-2 have arisen because of high mutation rates. N501Y, E484K, K417N, K417T, L452R and T478K in the receptor binding domain (RBD) region may increase the infectivity in several…

• A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors - Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high- throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based…

• New AKT-dependent mechanisms of anti-COVID-19 action of high-CBD Cannabis sativa extracts - COVID-19 is caused by the SARS-CoV-2 virus, which enters target cells via interactions with ACE2 and TMPRSS2. Here, we show AKT serine/threonine kinase-dependent epigenetic control of ACE2 and TMPRSS2 expression by high-cannabidiol (CBD) cannabis extracts and their individual components. CBD alone and extracts #1, #5, #7, and #129 downregulated ACE2 and TMPRSS2 in lung fibroblast WI-38 cells through AKT-mediated inhibition. miR-200c-3p and let-7a-5p were two contributing miRNAs in CBD-mediated…

• A Natural Plant Source-Tea Polyphenols, a Potential Drug for Improving Immunity and Combating Virus - The coronavirus disease 2019 (COVID-19) is still in a global epidemic, which has profoundly affected people’s lives. Tea polyphenols (TP) has been reported to enhance the immunity of the body to COVID-19 and other viral infectious diseases. The inhibitory effect of TP on COVID-19 may be achieved through a series of mechanisms, including the inhibition of multiple viral targets, the blocking of cellular receptors, and the activation of transcription factors. Emerging evidence shows…

• Effects of Electroencephalogram Biofeedback on Emotion Regulation and Brain Homeostasis of Late Adolescents in the COVID-19 Pandemic - CONCLUSION: The results demonstrate the potential of EEG biofeedback training as an independent nursing intervention that can markedly improve anxiety, mood-repair, and self-regulation ability for emotional distress during the COVID-19 pandemic.

From Patent Search

• MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19 - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - link

• CBD Covid 19 Protection - - link

• METHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGES - ABSTRACTMETHOD AND SYSTEM FOR IMPLEMENTING IMPROVED GENERALIZED FUZZY PEER GROUP WITH MODIFIED TRILATERAL FILTER TO REMOVE MIXED IMPULSE AND ADAPTIVE WHITE GAUSSIAN NOISE FROM COLOR IMAGESThe present invention provides a new approach is proposed that includes fuzzy-based approach and similarity function for filtering the mixed noise. In a peer group, the similarity function was adaptive to edge information and local noise level, which was utilized for detecting the similarity among pixels. In addition, a new filtering method Modified Trilateral Filter (MTF) with Improved Generalized Fuzzy Peer Group (IGFPG) is proposed to remove mixed impulse and Adaptive White Gaussian Noise from Color Images. The modified trilateral filter includes Kikuchi algorithm and loopy belief propagation to solve the inference issues on the basis of passing local message. In this research work, the images were collected from KODAK dataset and a few real time multimedia images like Lena were also used for testing the effectiveness of the proposed methodology. - link

• A STUDY ON MENTAL HEALTH, STRESS AND ANXIETY AMONG COLLEGE STUDENTS DURING COVID-19 - SARS-Cov-2 virus causes an infectious disease coronavirus(COVID-19).The Students life is made harder by COVID-19.The human reaction that happens normally to everyone through physical or emotional tension is stress. Feeling of angry, nervous and frustration caused through any thought or events leads to stress. As college closures and cancelled events, students are missing out on some of the biggest moments of their young lives as well as everyday moments like chatting with friend, participating in class and cultural programme. For students facing life changes due to the outbreak are feeling anxious, isolated and disappointed which lead them to feel all alone. We like to take the help of expert adolescent psychologist to find out the techniques to practice self-care and look after their mental health. We would like to find out whether techniques used reduce the anxiety and stress among Engineering Students. - link

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

• A CENTRAL TRANSACTION AUTHENTIC SYSTEM FOR OTP VERIFICATION - The present invention relates to a central transaction authentic system (100) for OTP verification. The system (100) comprises one or more user display units (102), one or more financial units (104), an account deposit unit (106), an OTP authentication unit (108) and a service server unit (110). The central transaction authentic system (100) for OTP verification work as Anti-money laundering measure. The system (100) also helpful for minimizing rate of cybercrime. The central transaction authentic system (100) for OTP verification that can neutralize digital financial fraud. The present invention provides a central transaction authentic system (100) for OTP verification that can monitor and analyze every transaction and customer interaction across its customer base for suspicious and potentially criminal activity. - link

• FORMULATIONS AND METHOD FOR PREPARATION OF HERBAL MEDICATED TRANSPARENT SOAP - ABSTRACTFORMULATIONS AND METHOD FOR PREPARATION OF HERBAL MEDICATED TRANSPARENT SOAPThe present invention provides formulations for herbal medicated transparent soaps and method of preparation of the same. Transparent soaps are prepared by saponification of mixture of non-edible oils to get the desired consistency and cleaning action. Nonvolatile alcohols and other transparency promoters are used to get good transparency and binding properties. Herbal extracts of different herbs are added to get medicated properties. - 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 MACHINE LEARNING BASED SYSTEM FOR DETECTING OMICRON VARIANT FROM A GENOME SEQUENCE AND METHOD THEREOF - The present invention discloses a machine learning based system for detecting omicron variant from a genome sequence and method thereof. The system includes, but not limited to, a processing unit having a memory unit and a machine learning interface embedded on it for validating a variant-induced changes in the one or more condition-specific cell variables are combined to output a single numerical variant score for each of the one or more variants, the variant score computed by one of outputting the score for a fixed condition; summing the variant-induced changes across conditions; computing the maximum of the absolute variant-induced changes across conditions. - 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