Covid-19 Sentry

Contents

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

From Preprints

• Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools -
  Quantifying SARS-like coronavirus (SL-CoV) evolution is critical to understanding the origins of SARS-CoV-2 and the molecular processes that could underlie future epidemic viruses. While genomic evidence implicates recombination as a factor in the emergence of SARS-CoV-2, few studies have quantified recombination rates among SL-CoVs. Here, we infer recombination rates of SL-CoVs from correlated substitutions in sequencing data using a coalescent model with recombination. Our computationally-efficient, non-phylogenetic method infers recombination parameters of both sampled sequences and the unsampled gene pools with which they recombine. We apply this approach to infer recombination parameters for a range of positive-sense RNA viruses. We then analyze a set of 191 SL-CoV sequences (including SARS-CoV-2) and find that ORF1ab and S genes frequently undergo recombination. We identify which SL-CoV sequence clusters have recombined with shared gene pools, and show that these pools have distinct structures and high recombination rates, with multiple recombination events occurring per synonymous substitution. We find that individual genes have recombined with different viral reservoirs. By decoupling contributions from mutation and recombination, we recover the phylogeny of non-recombined portions for many of these SL-CoVs, including the position of SARS-CoV-2 in this clonal phylogeny. Lastly, by analyzing 444,145 SARS-CoV-2 whole genome sequences, we show current diversity levels are insufficient to infer the within-population recombination rate of the virus since the pandemic began. Our work offers new methods for inferring recombination rates in RNA viruses with implications for understanding recombination in SARS-CoV-2 evolution and the structure of clonal relationships and gene pools shaping its origins.
  🖺 Full Text HTML: Correlated substitutions reveal SARS-like coronaviruses recombine frequently with a diverse set of structured gene pools
• SARS-CoV-2 Omicron BA.2.75 variant may be much more infective than preexisting variants -
  ABSTRACT Objectives: In our previous research, we have reported mathematical model with molecular simulation analysis to predict the infectivity of seven SARS-CoV-2 variants. In this report, we aimed to predict the relative risk of the recent new variants of SARS-CoV-2 based on our previous research. Methods: We subjected Omicron BA.4/5 or BA.2.75 variant of SARS-CoV-2 to the analysis for the evolutionary distance of the spike protein gene (S gene) to appreciate the changes of the spike protein. We performed the molecular docking simulation analyses of the spike protein with human angiotensin-converting enzyme 2 (ACE2) to understand the docking affinity in these variants. We then compared the evolutionary distance and the docking affinity of these variants with that of the seven variants which were analyzed in our previous research. Results: The evolutionary distance of the S gene in BA.4/5 or BA.2.75 from the Wuhan variant were longer than the other variants. The highest docking affinity of the spike protein with ACE2 (ratio per Wuhan variant) was observed in BA.2.75. Conclusion: It is important to note that BA.2.75 has both the highest docking affinity and the longest evolutionary distance of the S gene. These results suggest that the infection of BA.2.75 can be spread further than preexisting variants.
  🖺 Full Text HTML: SARS-CoV-2 Omicron BA.2.75 variant may be much more infective than preexisting variants
• Enhancer deregulation in TET2 Mutant Clonal Hematopoiesis is associated with increased COVID-19 related inflammation severity and mortality -
  Coronavirus disease 2019 (COVID-19) is associated with significant morbidity and mortality, albeit with considerable heterogeneity among affected individuals. It remains unclear which factors determine severity of illness and long-term outcomes. Emerging evidence points towards an important role of preexisting host factors, such as a deregulated inflammatory response at the time of infection. Here, we demonstrate the negative impact of clonal hematopoiesis, a prevalent clonal disorder of ageing individuals, on COVID-19-related cytokine release severity and mortality. We show that mutations in the gene coding for the methylcytosine dioxygenase TET2 promotes amplification of classical and intermediate monocyte subsets. Using single cell multiomic sequencing approaches, we identify cell-specific gene expression changes associated with the loss of TET2 and significant epigenomic deregulation affecting enhancer accessibility of a subset of transcription factors involved in monocyte differentiation. We further identify EGR1 down-regulation secondary to TET2-mediated hypermethylation, resulting in overexpression of MALAT1, a lncRNA that plays a role in hematopoietic stem cell differentiation and monocyte lineage commitment. Together, these data provide a mechanistic insight to the poor prognostic value of clonal hematopoiesis in patients infected with Sars-COV2.
  🖺 Full Text HTML: Enhancer deregulation in TET2 Mutant Clonal Hematopoiesis is associated with increased COVID-19 related inflammation severity and mortality
• Predicting the efficacy of variant-modified COVID-19 vaccine boosters -

  As a result of the emergence and circulation of antigenically distinct SARS-CoV-2 variants, a number of variant-modified COVID-19 vaccines have been developed. Here we perform a meta-analysis of the available data on neutralisation titres from clinical studies comparing booster vaccination with either the current ancestral-based vaccines or variant-modified vaccines. We then use this to predict the relative efficacies of these booster vaccines under different scenarios.

  🖺 Full Text HTML: Predicting the efficacy of variant-modified COVID-19 vaccine boosters
• Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps -

  The disinfection of air using Germicidal Ultraviolet light (GUV) is a long-standing technique, which has received intense attention during the COVID-19 pandemic. GUV generally uses UVC lamps as its light source, which are known to initiate photochemistry in air. However, the impact of GUV on indoor air quality and chemistry has not been investigated in detail, to our knowledge. In this study, we model the chemistry initiated by GUV at 254 or 222 nm (“GUV254” or “GUV222”) in a typical room with typical indoor pollutant levels, and for different ventilation levels. GUV254 is irritating for skin and eyes, has an occupational exposure limit, and thus these fixtures typically irradiate a smaller volume near the ceiling, or inside ventilation ducts. In contrast, GUV222 is described by some as harmless to skin or eyes due to rapid absorption in a very thin external layer. Our analysis showed that GUV254 is able to significantly photolyze O3, generating OH radicals, which initiates the oxidation of all indoor volatile organic compounds (VOCs). While secondary organic aerosol (SOA) can be formed as a product of VOC oxidation, most of SOA in our case studies is produced through GUV-independent terpene ozonolysis. GUV254-induced SOA formation is of the order of 0.1-1 μg m-3. GUV222 with the same effective virus removal rate makes a smaller impact on indoor air quality, mainly because of the significantly lower UV irradiance needed and substantially less efficient O3 photolysis (for primary OH generation) than at 254 nm.

  🖺 Full Text HTML: Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps
• International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship -

  Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality.

  🖺 Full Text HTML: International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship
• Mortality Improvements in Adult Patients Hospitalised with Community Acquired COVID-19 in Wales From March 2020 to Decemeber 2021 -

  Background A COVID-19 hospital guideline was implemented across all acute hospitals in Wales in March 2020, and data was collected across the first 3 Waves of the pandemic. We aimed to observe trends in mortality with a focus on ward-based outcomes. Methods Retrospective case-note review of data for adults admitted to hospital with community acquired COVID-19 between March 2020 and December 2021 Results 5887 cases were analysed. Overall mortality from COVID-19 fell from 31.5% in Wave 1 to 22.6% in Wave 2 to 18.8% in Wave 3 (p<0.01). Ward mortality for patients on oxygen fell from 34.6% in Wave 1 to 19.5% in Wave 2 (p<0.01) to 14.3% in Wave 3 (p=0.03). For those managed with CPAP/HFNO on wards, the mortality reduced from 58.9% in Wave 1 to 45.6% in Wave 2 (p=0.05) and further to 42.6% in Wave 3 (p=0.03). The mortality for patients managed with CPAP/HFNO on ICU reduced from 43.8% in Wave 1 to 24.7% in Wave 2 (p=0.12) and further to 20.4% in Wave 3 (p=0.03). Patients receiving CPAP/HFNO on the wards were on average 11 years older and more co-morbid than those on ICU. In Wave 3, 77% of hospital admissions with COVID-19 were unvaccinated with mortality rates of 20.5% compared to 4.8% mortality in those who had received three vaccines (p<0.01). Conclusions There were successive reductions in mortality in inpatients over the 3 Waves reflecting new treatments and better management of complications. The impact of vaccines on outcomes of hospitalised patients was notable in Wave 3.

  🖺 Full Text HTML: Mortality Improvements in Adult Patients Hospitalised with Community Acquired COVID-19 in Wales From March 2020 to Decemeber 2021
• Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study) -

  Background: There are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. Methods: We conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. Results: We enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac (“CC-C”, n=101) or BNT162b2 (“CC-B”, n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac (“BB-C”, n=118) or BNT162b2 (“BB-B”, n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Third doses significantly increased neutralising PRNT50 antibody titers against ancestral virus and Omicron BA.1 variant in all four study arms, and against Omicron BA.2 in all arms except CC-C, with statistically significant improvements for recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. Boosting of CD4+ T cells only occurred in CoronaVac-primed arms, but we did not identify overall differences between vaccine groups in CD4+ and CD8+ T cell responses. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). Conclusions: Similar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

  🖺 Full Text HTML: Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)
• Use of whole genome sequencing to estimate the contribution of immune evasion and waning immunity to decreasing COVID-19 vaccine effectiveness during alpha and delta variant waves -

  Background: The decline in COVID-19 mRNA vaccine effectiveness (VE) is well established, however the impact of variant-specific immune evasion and waning protection remains unclear. Here, we use whole-genome-sequencing (WGS) to tease apart the contribution of these factors on the decline observed following the introduction of the Delta variant. Further, we evaluate the utility of calendar-period-based variant classification as an alternative to WGS. Methods: We conducted a test-negative-case-control study among people who received SARS-CoV-2 RT-PCR testing in the Yale New Haven Health System between April 1 and August 24, 2021. Variant classification was performed using WGS and secondarily by calendar-period. We estimated VE as one minus the ratio comparing the odds of infection among vaccinated and unvaccinated people. Results: Overall, 2,029 cases (RT-PCR positive, sequenced samples) and 343,985 controls (negative RT-PCRs) were included. VE 14-89 days after 2nd dose was significantly higher against WGS-classified Alpha infection (84.4%, 95% confidence interval: 75.6-90.0%) than Delta infection (68.9%, CI: 58.0-77.1%, p-value: 0.013). The odds of WGS-classified Delta infection were significantly higher 90-149 than 14-89 days after 2nd dose (Odds ratio: 1.6, CI: 1.2-2.3). While estimates of VE against calendar-period-classified infections approximated estimates against WGS-classified infections, calendar-period-based classification was subject to outcome misclassification (35% during Alpha period, 4% during Delta period). Conclusions: These findings suggest that both waning protection and variant-specific immune evasion contributed to the lower effectiveness. While estimates of VE against calendar-period-classified infections mirrored that against WGS-classified infections, our analysis highlights the need for WGS when variants are co-circulating and misclassification is likely.

  🖺 Full Text HTML: Use of whole genome sequencing to estimate the contribution of immune evasion and waning immunity to decreasing COVID-19 vaccine effectiveness during alpha and delta variant waves
• Susceptibility and infectiousness of SARS-CoV-2 in children versus adults, by variant (wild-type, Alpha, Delta): a systematic review and meta-analysis of household contact studies -

  Importance: Understanding the susceptibility and infectiousness of children and adolescents in comparison to adults is important to appreciate their role in the COVID-19 pandemic. Objective: To determine SARS-CoV-2 susceptibility and infectiousness of children and adolescents with adults as comparator for three variants (wild-type, Alpha, Delta) in the household setting. We aimed to identify the effects independent of vaccination. Data Sources: We searched EMBASE, PubMed and medRxiv up to January 2022. Additional studies were identified through contacting subject experts. Study Selection: Two reviewers independently identified studies providing secondary attack rates (SAR) for SARS-CoV-2 infection in children (0-9 years), adolescents (10-19 years) or both compared with adults (20 years and older) derived from household data. Data Extraction and Synthesis: Two reviewers independently performed data extraction. We assessed risk of bias of included studies using a critical appraisal checklist and a random-effects meta-analysis model to pool association estimates. Main Outcomes and Measures: Odds ratio (OR) for SARS-CoV-2 infection comparing children and adolescents with adults stratified by wild-type, Alpha, and Delta variant, respectively. Susceptibility was defined as the secondary attack rate (SAR) among susceptible household contacts irrespective of the age of the index case. Infectiousness was defined as the SAR irrespective of the age of household contacts when children/adolescents/adults were the index case. Results: Twenty-eight studies (308,857 contacts) were included in the susceptibility analysis, for Delta only one (large) study was available. Compared to adults children and adolescents were less susceptible to the wild-type and Delta variant, but equally susceptible to the Alpha variant. In the infectiousness analysis, 21 studies (201,199 index cases) were included. Compared to adults, children and adolescents were less infectious when infected with the wild-type and Delta variant. Alpha variant-related infectiousness remained unclear, 0-9 year old children were at least as infectious as adults. SAR among household contacts was highest during circulation of the Alpha variant, lowest during wild-type circulation and intermediate during Delta circulation. Conclusions and Relevance: When considering the potential role of children and adolescents, for each variant susceptibility, infectiousness, age group and overall transmissibility need to be assessed to guide public health policy.

  🖺 Full Text HTML: Susceptibility and infectiousness of SARS-CoV-2 in children versus adults, by variant (wild-type, Alpha, Delta): a systematic review and meta-analysis of household contact studies
• Two mathematical models for the waning of anti-RBD IgG SARS-CoV-2 antibody titers after a two-dose BNT162b2 mRNA vaccination. -

  Objective. Serum antibody levels have been linked to immune protection in SARS-CoV-2 infection. After exposure to the virus and/or vaccination there is an increase in serum antibody titers followed by progressive non-linear waning of antibody levels. Our aim was to find out if this waning of antibody titers would adjust to a mathematical model. Methods. We studied serum anti-RBD (receptor binding domain) IgG antibody titers over a ten month period in a cohort of 54 health-care workers who were either never infected with SARS-CoV-2 (naive, nHCWs group, n = 27) or previously infected (experienced, eHCWs group, n = 27) with the virus after the second dose of the BNT162b2 mRNA vaccine. We have selected a risk threshold of 1000 UA/ml anti-RBD Ab titer for symptomatic infection based on the upper titer threshold for those volunteers who suffered infection prior to the omicron outbreak. Two mathematical models, exponential and potential, were used to quantify antibody waning kinetics and the relative quality of the goodness of fit to the data between both models was compared using the Akaike Information Criterion. Results. We found that the waning of anti-RBD IgG antibody levels adjusted significantly to both exponential and potential models in all participants from both the naive and experienced groups. Moreover, the waning slopes were significantly more pronounced for the naive when compared to the experienced health-care workers. In the nHCWs group, titers would descend below this 1000-units threshold at a median of 210.6 days (IQ range: 74,2). However, for the eHCWs group, the risk threshold would be reached at 440.0 days (IQ range: 135,2) post-vaccination. Conclusions. The goodness of the fit of the anti-RBD IgG antibody waning would allow us to predict when the antibody titers would fall below an established threshold in both naive and previously infected subjects.

  🖺 Full Text HTML: Two mathematical models for the waning of anti-RBD IgG SARS-CoV-2 antibody titers after a two-dose BNT162b2 mRNA vaccination.
• 1,000 ancient genomes uncover 10,000 years of natural selection in Europe -
  Ancient DNA has revolutionized our understanding of human population history. However, its potential to examine how rapid cultural evolution to new lifestyles may have driven biological adaptation has not been met, largely due to limited sample sizes. We assembled genome-wide data from 1,291 individuals from Europe over 10,000 years, providing a dataset that is large enough to resolve the timing of selection into the Neolithic, Bronze Age, and Historical periods. We identified 25 genetic loci with rapid changes in frequency during these periods, a majority of which were previously undetected. Signals specific to the Neolithic transition are associated with body weight, diet, and lipid metabolism-related phenotypes. They also include immune phenotypes, most notably a locus that confers immunity to Salmonella infection at a time when ancient Salmonella genomes have been shown to adapt to human hosts, thus providing a possible example of human-pathogen co-evolution. In the Bronze Age, selection signals are enriched near genes involved in pigmentation and immune-related traits, including at a key human protein interactor of SARS-CoV-2. Only in the Historical period do the selection candidates we detect largely mirror previously-reported signals, highlighting how the statistical power of previous studies was limited to the last few millennia. The Historical period also has multiple signals associated with vitamin D binding, providing evidence that lactase persistence may have been part of an oligogenic adaptation for efficient calcium uptake and challenging the theory that its adaptive value lies only in facilitating caloric supplementation during times of scarcity. Finally, we detect selection on complex traits in all three periods, including selection favoring variants that reduce body weight in the Neolithic. In the Historical period, we detect selection favoring variants that increase risk for cardiovascular disease plausibly reflecting selection for a more active inflammatory response that would have been adaptive in the face of increased infectious disease exposure. Our results provide an evolutionary rationale for the high prevalence of these deadly diseases in modern societies today and highlight the unique power of ancient DNA in elucidating biological change that accompanied the profound cultural transformations of recent human history.
  🖺 Full Text HTML: 1,000 ancient genomes uncover 10,000 years of natural selection in Europe
• Applications of GIS and Geospatial analyses in COVID-19 research: A systematic review -
  Geographic Information Science (GIS) had established itself as a distinct domain and incredibly useful whenever the research is related to geography, space, and other spatio-temporal dimensions. However, the scientific landscape on the integration of GIS in the COVID related studies is largely unknown. In this systematic review, we assessed the current evidence on the implementation of GIS and other geospatial tools and technologies in COVID-19 pandemic. We systematically retrieved and reviewed 79 research articles that either directly used GIS or other Geospatial tools as part of their analysis. We grouped the identified papers under six broader thematic groups based on the objectives and research questions of the study- environmental, socio-economic, and cultural, public health, spatial transmission, computer-aided modeling, and data mining. The interdisciplinary nature of how geographic and spatial analysis was used in COVID-19 research was noticeable among the reviewed papers. Although GIS has substantial potential in planning to slow down the spread, surveillance, contact tracing, and identify the trends and hotspots of breakdowns, it was not employed as much as it could have been. This review not only provided an overarching view on how GIS has been used in COVID-19 research so far but also concluded that this geospatial analysis and technologies could be used in future public health emergencies along with statistical and other socio-economic modeling techniques. Our systematic review also provides how both scientific communities and policymakers could leverage GIS to extract useful information to make an informed decision in the coming days.
  🖺 Full Text HTML: Applications of GIS and Geospatial analyses in COVID-19 research: A systematic review
• Social capital and mental health during the COVID-19 pandemic -
  COVID-19 pandemic is affecting mental health and wellbeing across populations. The continued burden of psychosocial stressors in different contexts necessitates multipronged interventions that address mental health problems and associated disparities. Global evidence suggests that social capital plays a critical role in determining mental health outcomes in communities, which can be leveraged for improving mental health in COVID-19. As communities with better social capital is likely to have a lower burden of mental disorders, it is necessary to assess potential measures to use social capital for mental health promotion in vulnerable populations. The existing forms of social capital may provide social support within and between communities that are critically affected by COVID-19. Alongside faster recovery from socioeconomic challenges, social capital interventions may strengthen the social determinants of mental health and empower communities to alleviate the psychosocial consequences of this pandemic.
  🖺 Full Text HTML: Social capital and mental health during the COVID-19 pandemic
• COVID-19 vaccination hesitancy, misinformation and conspiracy theories on social media: A content analysis of Twitter data -
  Background: The coronavirus disease (COVID-19) pandemic has caused a significant burden of mortality and morbidity. A vaccine will be the most effective global preventive strategy to end the pandemic. Studies have maintained that exposure to negative sentiments related to vaccination on social media increase vaccine hesitancy and refusal. Despite the influence social media has on vaccination behavior, there is a lack of studies exploring the public’s exposure to misinformation, conspiracy theories, and concerns on Twitter regarding a potential COVID-19 vaccination. Objective: The study aims to identify the major thematic areas about a potential COVID-19 vaccination based on the contents of Twitter data. Method: We retrieved 1,286,659 publicly available tweets posted within the timeline of July 19, 2020, to August 19, 2020, leveraging the Twint package. Following the extraction, we used Latent Dirichlet Allocation for topic modelling and identified 20 topics discussed in the tweets. We selected 4,868 tweets with the highest probability of belonging in the specific cluster and manually labeled as positive, negative, neutral, or irrelevant. The negative tweets were further assigned to a theme and subtheme based on the content Result: The negative tweets were further categorized into 7 major themes: “safety and effectiveness,” “misinformation,” “conspiracy theories,” “mistrust of scientists and governments,” “lack of intent to get a COVID-19 vaccine,” “freedom of choice,” and "religious beliefs. Negative tweets predominantly consisted of misleading statements (n=424) that immunization against coronavirus is unnecessary as the survival rate is high. The second most prevalent theme to emerge was tweets constituting safety and effectiveness related concerns (n=276) regarding the side effects of a potential vaccine developed at an unprecedented speed. Conclusion: Our findings suggest a need to formulate a large-scale vaccine communication plan that will address the safety concerns and debunk the misinformation and conspiracy theories spreading across social media platforms, increasing the public’s acceptance of a COVID-19 vaccination.
  🖺 Full Text HTML: COVID-19 vaccination hesitancy, misinformation and conspiracy theories on social media: A content analysis of Twitter data

From Clinical Trials

• A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SIM0417;   Drug: Placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology - Condition:   COVID-19
  Intervention:   Other: Self-management of post COVID-19 respiratory outcomes
  Sponsor:   University of Manitoba
  Not yet recruiting

• Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Casirivimab and Imdevimab Drug Combination;   Drug: Remdesivir;   Drug: Favipiravir
  Sponsor:   Mansoura University Hospital
  Completed

• The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines - Condition:   COVID-19
  Interventions:   Biological: BCG (Bacillus Calmette-Guérin) vaccine;   Other: Placebo
  Sponsors:   Oswaldo Cruz Foundation;   University of Sao Paulo;   Federal University of Juiz de Fora
  Recruiting

• Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2) - Condition:   COVID-19
  Interventions:   Diagnostic Test: Nasal Swab;   Diagnostic Test: Nasopharyngeal swab
  Sponsor:   LumiraDx UK Limited
  Recruiting

• Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities - Condition:   COVID-19
  Interventions:   Other: Education;   Other: Motivational
  Sponsor:   University of Chicago
  Not yet recruiting

• Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults. - Condition:   COVID-19
  Intervention:   Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)
  Sponsors:   The Aurum Institute NPC;   Coalition for Epidemic Preparedness Innovations
  Recruiting

• Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19 - Condition:   COVID-19 Infection
  Interventions:   Biological: Allogeneic umbilical cord mesenchymal stem cells;   Biological: Controlled normal saline
  Sponsor:   Ever Supreme Bio Technology Co., Ltd.
  Active, not recruiting

• The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients - Conditions:   COVID-19;   Vitamin D Deficiency
  Intervention:   Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion
  Sponsor:   Pauls Stradins Clinical University Hospital
  Completed

• UNAIR Inactivated COVID-19 Vaccine Phase 3 - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccines
  Interventions:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-19 Vaccine
  Sponsors:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia
  Recruiting

• Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19 - Conditions:   COVID-19;   AMS-H-03;   Hydrogen-oxygen Gas
  Interventions:   Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03;   Other: basic treatment
  Sponsor:   Shanghai Zhongshan Hospital
  Recruiting

• COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study - Conditions:   COVID-19;   Kidney Transplant
  Intervention:   Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   PPD;   Johns Hopkins University;   Sanofi Pasteur, a Sanofi Company
  Not yet recruiting

• Huashi Baidu Granule in the Treatment of Pediatric Patients With Mild Coronavirus Disease 2019 - Condition:   Coronavirus Disease 2019
  Interventions:   Drug: Huashi Baidu granule;   Drug: compound pholcodine oral solution
  Sponsor:   Shanghai Children’s Medical Center
  Completed

• Canadian Adaptive Platform Trial for Long COVID - Condition:   Long COVID, Post COVID Condition, Post Acute Sequelae of COVID-19
  Interventions:   Drug: Ibudilast;   Dietary Supplement: Whey Protein Isolate;   Drug: Pentoxifylline;   Other: Placebo
  Sponsor:   University Health Network, Toronto
  Not yet recruiting

• Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection - Conditions:   COVID-19;   Child, Only
  Intervention:   Drug: Jinzhen oral liquid or Jinhuaqinggan granules
  Sponsor:   The Affiliated Hospital of Qingdao University
  Recruiting

From PubMed

• Are herbal-peptides effective as adjunctive therapy in Coronavirus disease COVID-19? - CONCLUSION: Herbal medicines with AVP, especially those with a long history of antiviral effects, might be a good choice in complement therapy against the COVID-19 virus.

• The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms - The proceeding pandemic of coronavirus disease 2019 is the latest global challenge. Like most other infectious diseases, inflammation, oxidative stress, and immune system dysfunctions play a pivotal role in the pathogenesis of COVID-19. Furthermore, the quest of finding a potential pharmaceutical therapy for preventing and treating COVID-19 is still ongoing. Silymarin, a mixture of flavonolignans extracted from the milk thistle, has exhibited numerous therapeutic benefits. We reviewed the…

• IMMUNE DYSREGULATION INDUCED BY SPIKE PROTEIN 1 OF SARS-COV-2 INCREASES ENDOTHELIAL CELL DYSFUNCTION VIA TYPE I AND TYPE III INTERFERON ACTIVATION PATHWAYS - CONCLUSIONS: In ECs, S1P, IFNα and IFNL3 increased ISG15 and IL-6, processes that involve ADAM17. Inflammation induced by S1P was amplified by IFNs. IFNs induce vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This is especially important in the presence of cardiovascular risk factors, including hypertension.

• PREVENTIVE EFFECT OF STATINS AGAINST RESPIRATORY TRACT INFECTION: A SYSTEMATIC REVIEW AND META-ANALYSIS - CONCLUSIONS: The findings of our systematic review and meta-analysis do not support the hypothesis that statins reduce the risk of including RTIs.

• Establishment of Neutralizing Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 by the Screening with Exosomes Expressing the Viral Spike Protein - Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, are the important tools both for the diagnosis and therapeutics of this infectious disease. The high-performance antibody against spike protein of SARS-CoV-2 is expected to inhibit the binding of viruses to their receptors on the surface of their target cells. In this study, we propose the novel screening method for mAbs against the pathogenic infectious virus using exosome….

• IMPAIRED BETA-2ADRENERGIC ENDOTHELIUM-DEPENDENT VASODILATION IS REVERSED BY PHOSPHODIESTERASE INHIBITION IN PATIENTS PREVIOUSLY HOSPITALIZED WITH COVID-19 - CONCLUSIONS: In subjects previously hospitalized with severe COVID-19, endothelial function is impaired for many months after hospital discharge and the impaired NO-cGMP mediated vasodilation may be reversed by sildenafil.

• Advances in cell death mechanisms involved in viral myocarditis - Viral myocarditis is an acute inflammatory disease of the myocardium. Although many etiopathogenic factors exist, coxsackievirus B3 is a the leading cause of viral myocarditis. Abnormal cardiomyocyte death is the underlying problem for most cardiovascular diseases and fatalities. Various types of cell death occur and are regulated to varying degrees. In this review, we discuss the different cell death mechanisms in viral myocarditis and the potential interactions between them. We also explore…

• Dynamicity and persistence of severe acute respiratory syndrome coronavirus-2 antibody response after double dose and the third dose with BBV-152 and AZD1222 vaccines: A prospective, longitudinal cohort study - CONCLUSION: This year-long follow-up study found a 7- and 5-fold antibody waning in Covaxin and Covishield recipients, respectively, without any breakthrough infection history. However, individuals with booster breakthrough had mild symptoms and did not require hospital admission. The data also indicate the possible escape of omicron variants despite the presence of vaccine-induced neutralizing antibodies.

• Exploring the Impact of ACE Inhibition in Immunity and Disease - Angiotensin-converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and is crucial in the renin-angiotensin-aldosterone system (RAAS) but also implicated in immune regulation. Intrinsic ACE has been detected in several immune cell populations, including macrophages and neutrophils, where its overexpression results in enhanced bactericidal and antitumour responses, independent of angiotensin II. With roles in antigen presentation and inflammation, the impact of ACE inhibitors must…

• Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development - COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit the…

• Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection - Porcine deltacoronavirus (PDCoV) is a recently discovered enteropathogenic coronavirus and has caused significant economic impacts on the pork industry. Although studies have partly uncovered the molecular mechanism of PDCoV-host interaction, it requires further research. In this study, we explored the roles of Stromal Antigen 2 (STAG2) in PDCoV infection. We found that STAG2-deficient cells inhibited infection with vesicular stomatitis virus (VSV) and PDCoV, whereas restoration of STAG2…

• Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-γH2AX Signaling Pathways to Foster Its Replication - DNA damage response (DDR) is an evolutionarily conserved mechanism by which eukaryotic cells sense DNA lesions caused by intrinsic and extrinsic stimuli, including virus infection. Although interactions between DNA viruses and DDR have been extensively studied, how RNA viruses, especially coronaviruses, regulate DDR remains unknown. A previous study showed that the porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the Coronaviridae family, induces DDR in infected…

• Ionophore Antibiotics Inhibit Type II Feline Coronavirus Proliferation In Vitro - Feline coronaviruses (FCoVs) infect cats worldwide and cause severe systemic diseases, such as feline infectious peritonitis (FIP). FIP has a high mortality rate, and drugs approved by the Food and Drug Administration have been ineffective for the treatment of FIP. Investigating host factors and the functions required for FCoV replication is necessary to develop effective drugs for the treatment of FIP. FCoV utilizes an endosomal trafficking system for cellular entry after binding between the…

• Evaluation of Novel Guanidino-Containing Isonipecotamide Inhibitors of Blood Coagulation Factors against SARS-CoV-2 Virus Infection - Coagulation factor Xa (fXa) and thrombin (thr) are widely expressed in pulmonary tissues, where they may catalyze, together with the transmembrane serine protease 2 (TMPRSS2), the coronaviruses spike protein (SP) cleavage and activation, thus enhancing the SP binding to ACE2 and cell infection. In this study, we evaluate in vitro the ability of approved (i.e., dabigatran and rivaroxaban) and newly synthesized isonipecotamide-based reversible inhibitors of fXa/thr (cmpds 1-3) to hinder the…

• Anti-Spike and Neutralizing Antibodies after Two Doses of COVID-19 Sinopharm/BIBP Vaccine - Host response to COVID-19 vaccines is partially evaluated through the estimation of antibody response, specifically the binding anti-spike (anti-S) and the neutralizing antibodies (nAbs) against SARS-CoV-2. Vaccine-induced humoral response affects decisions on the choice of vaccine type, vaccine acceptance, and the need for boosting. Identification of risk factors for poor antibody response helps to stratify individuals who might potentially require booster doses. The primary objective of this…

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