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<title>04 May, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Social activity promotes resilience against loneliness in depressed individuals: A study over 14-days of physical isolation during the COVID-19 pandemic in Australia</strong> -
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Loneliness is a subjectively perceived state of social isolation that is associated with negative emotional, cognitive, and physical health outcomes. Physical distancing and shelter-in-place public health responses designed to curb COVID-19 transmission has led to concerns over elevated risk of loneliness. Given that physical isolation does not necessitate social isolation in the age of digital communication, this study investigated the relationship between the frequency of social interaction and loneliness over a two-week period in people engaging in physical distancing, and examined whether this relationship was moderated by physical isolation level, age, or depression. A self-selected sample of N = 469 individuals across Australia who were engaged in physically distanced living completed daily surveys for 14-days during April to June of 2020. Multilevel modelling showed that more frequent social interaction with close, but not intermediate or distant contacts, was uniquely associated with lower loneliness. In addition, being younger, more depressed, more anxious, or having a mental health condition diagnosis (past or present) were also independently associated with higher loneliness. Critically, depression was the only significant moderator of the relationship between social interaction and loneliness over time, where more frequent social interaction with close contacts buffered against loneliness over time in high depression individuals only. The findings suggest that encouraging social activity with close contacts may promote resilience against loneliness in individuals with elevated depression symptoms.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/ejdmp/" target="_blank">Social activity promotes resilience against loneliness in depressed individuals: A study over 14-days of physical isolation during the COVID-19 pandemic in Australia</a>
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<li><strong>Spatiotemporal landscape of SARS-CoV-2 pulmonary infection reveals Slamf9+Spp1+ macrophages promoting viral clearance and inflammation resolution</strong> -
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While SARS-CoV-2 pathogenesis has been intensively investigated, the host mechanisms of viral clearance and inflammation resolution are still elusive because of the ethical limitation of human studies based on COVID-19 convalescents. Here we infected Syrian hamsters by authentic SARS-CoV-2 and built an ideal model to simulate the natural recovery process of SARS-CoV-2 infection from severe pneumonia. We developed and applied a spatial transcriptomic sequencing technique with subcellular resolution and tissue-scale extensibility, i.e., Stereo-seq, together with single- cell RNA sequencing (scRNA-seq), to the entire lung lobes of 45 hamsters and obtained an elaborate map of the pulmonary spatiotemporal changes from acute infection, severe pneumonia to the late viral clearance and inflammation resolution. While SARS-CoV-2 infection caused massive damages to the hamster lungs, including naive T cell infection and deaths related to lymphopenia, we identified a group of monocyte-derived proliferating Slamf9+Spp1+ macrophages, which were SARS-CoV-2 infection-inducible and cell death-resistant, recruiting neutrophils to clear viruses together. After viral clearance, the Slamf9+Spp1+ macrophages differentiated into Trem2+ and Fbp1+ macrophages, both responsible for inflammation resolution and replenishment of alveolar macrophages. The existence of this specific macrophage subpopulation and its descendants were validated by RNAscope in hamsters, immunofluorescence in hACE2 mice, and public human autopsy scRNA-seq data of COVID-19 patients. The spatiotemporal landscape of SARS-CoV-2 infection in hamster lungs and the identification of Slamf9+Spp1+ macrophages that is pivotal to viral clearance and inflammation resolution are important to better understand the critical molecular and cellular players of COVID-19 host defense and also develop potential interventions of COVID-19 immunopathology.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.03.490381v1" target="_blank">Spatiotemporal landscape of SARS-CoV-2 pulmonary infection reveals Slamf9+Spp1+ macrophages promoting viral clearance and inflammation resolution</a>
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</div></li>
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<li><strong>Protection from Omicron and other VOCs by Bivalent S-Trimer COVID-19 Vaccine</strong> -
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The Omicron variant of SARS-COV-2 (GISAID GRA clade [B.1.1.529, BA.1 and BA.2]) is now the single dominant Variant of Concern (VOC). The high number of mutations in the Omicron Spike (S) protein promotes humoral immunological escape. Although a third homologous boost with S, derived from the ancestral strain, was able to increase neutralizing antibody titers and breadth including to Omicron, the magnitude of virus neutralization could benefit from further optimization. Moreover, combining SARS-COV-2 strains as additional valences may address the current antigenicity range occupied by VOCs. Using Trimer-TagTM platform we have previously demonstrated phase 3 efficacy and safety of a prototypic vaccine SCB-2019 in the SPECTRA trial and have submitted applications for licensure. Here, we successfully generated a bivalent vaccine candidate including both Ancestor and Omicron variant S-proteins. Preclinical studies demonstrate this SARS- CoV-2 bivalent S-Trimer subunit vaccine elicits high titers of neutralizing antibodies against all VOCs, with markedly enhanced Omicron specific neutralizing antibody responses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.03.490428v1" target="_blank">Protection from Omicron and other VOCs by Bivalent S-Trimer COVID-19 Vaccine</a>
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<li><strong>Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta</strong> -
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The SARS-CoV-2 Omicron variant is increasing in prevalence around the world. Accurate estimation of disease severity associated with Omicron is critical for pandemic planning. We found lower risk of accident and emergency (AE) attendance following SARS-CoV-2 infection with Omicron compared to Delta (HR: 0.39 (95% CI: 0.30 to 0.51; P<.0001). For AE attendances that lead to hospital admission, Omicron was associated with an 85% lower hazard compared with Delta (HR: 0.14 (95% CI: 0.09 to 0.24; P<.0001)).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274602v1" target="_blank">Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta</a>
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<li><strong>Population-based Oral Cancer Service Screening Disrupted by COVID-19 Pandemic: Observational and Simulation Study</strong> -
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<b><i>Background</i>:</b> It is important for understanding the impact of COVID-19 pandemic on the missing opportunity for the early detection of oral cancer. This study aimed to assess the impact of COVID-19 pandemic on the existing population-based oral cancer (OC) service screening program in Taiwan. <b><i>Methods</i>:</b> Before and after COVID-19 pandemic design was used to assess the impact of COVID-19 on the reduction of screening rate, referral rate, and the effectiveness of this OC service screening. Data and analysis after pandemic covered non-VOC period in 2020 and VOC period in 2021 compared to the historical control before pandemic in 2019. <b><i>Results</i>:</b> The screening rate decreased substantially from 26.6% before COVID-19 in 2019 to 16.7% in 2020 and 15.3% in 2021 after pandemic. The reduction of screening rate varied with months, being the most remarkable decline in March (RR=0.61, 95% CI (0.60-0.62)) and June (RR=0.09, 95% CI (0.09-0.10)) in 2021 compared with January. The referral rate was stable at 81.5% in 2020 but it was reduced to 73.1% in 2021. The reduction of screening and referral rate led to the attenuation of effectiveness of advance cancer and mortality attenuated by 4% and 5%, respectively. <b><i>Conclusion</i>:</b> COVID-19 pandemic disrupted the screening and the referral rate and further led to statistically significant reduction in effectiveness for preventing advanced cancer and death. Appropriate prioritized strategies must be adopted to ameliorate malignant transformation and tumor upstaging due to deference from participation in the screening. <b><i>Funding</i>:</b> This study was financially supported by Health Promotion Administration of the Ministry of Health and Welfare of Taiwan (A1091116).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274618v1" target="_blank">Population-based Oral Cancer Service Screening Disrupted by COVID-19 Pandemic: Observational and Simulation Study</a>
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<li><strong>Immunogenicity of BNT162b2 Vaccine Booster Dose in Patients with Inflammatory Bowel Disease Receiving Infliximab Combination Therapy: A Prospective Observational Study</strong> -
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Introduction: Few data exist regarding the immunogenicity of third dose of BNT162b2 relative to second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy. Methods: This is prospective single center observational study conducted between January 1st, 2022 until February 28th, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine and have received two or three-dose of BNT162b2 vaccine. Patients were excluded if they were infected or had symptoms of SARS-CoV-2 previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS- CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40-45 weeks from the first dose of BNT162b2 in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated. Results: 162 patients with IBD and receiving infliximab combination therapy were recruited and the number of patients in each group was 81. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/mL (43, 192)] compared to patients who received the third booster dose [207 BAU/mL (181, 234)] (p = 0.003). Neutralizing antibody levels were also lower after the second dose [80 BAU/mL (21, 95)] compared to patients who received the third booster dose [96 BAU/mL (93, 99)] (p = <0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was higher (96.3%) than those in second dose group (90%)(p = 0.026). Percentage of patients who received third (booster) dose and achieved positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was lower (88.9%) in patients who received second dose only (p=0.009). Conclusion: Most patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40-45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received 2 doses only compared to patients who received a third dose.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274608v1" target="_blank">Immunogenicity of BNT162b2 Vaccine Booster Dose in Patients with Inflammatory Bowel Disease Receiving Infliximab Combination Therapy: A Prospective Observational Study</a>
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<li><strong>Rapid Antigen Tests (RATs) and COVID-19 prevalence</strong> -
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The article contains a Bayesian analysis to model expected rate of positive and negative COVID-19 cases, based on Rapid Antigen Test performance and COVID-19 prevalence in New Zealand. The results suggest that the majority of approved tests were excellent in identifying negative cases but might turn out too many false positives. Recommendations for a protocol for RAT-based testing concludes the article.
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🖺 Full Text HTML: <a href="https://osf.io/ud4tp/" target="_blank">Rapid Antigen Tests (RATs) and COVID-19 prevalence</a>
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<li><strong>An Early Return-to-Work Program for COVID-19 Close Contacts in Healthcare During the Omicron Wave in Japan</strong> -
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During the coronavirus disease 2019 (COVID-19) pandemic, maintaining adequate staffing in healthcare facilities is important to provide a safe work environment for healthcare workers (HCWs). Japanese early return-to-work (RTW) program may be a rational strategy at a time when there is an increased demand for the services of HCWs. We assessed whether the early RTW program for HCWs who have been in close contact with a COVID-19 case in our hospital was justified. Close contacts were identified according to the guidance of the World Health Organization. Between January and March 2022, 256 HCWs were identified as close contacts (median age, 35 years; 192 female). Thirty-seven (14%) secondary attack cases of COVID-19 were detected. Among 141 HCWs who applied to the early RTW program, nurses and doctors comprised about three-quarters of participants, with a higher participation rate by doctors (78%) than nurses (59%). Eighteen HCWs tested positive for COVID-19 by the sixth day after starting the early RTW program. No COVID-19 infection clusters were reported during the observation period. These findings suggest that the early RTW program for COVID-19 close contacts was a reasonable strategy for HCWs during the Omicron wave.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.02.22274478v1" target="_blank">An Early Return-to-Work Program for COVID-19 Close Contacts in Healthcare During the Omicron Wave in Japan</a>
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<li><strong>Kidney Transplant Recipients and Omicron: Outcomes, effect of vaccines and the efficacy and safety of novel treatments</strong> -
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We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir. From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community; 47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis; 2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy. Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, (p=0.016). In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes; its clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.03.22274524v1" target="_blank">Kidney Transplant Recipients and Omicron: Outcomes, effect of vaccines and the efficacy and safety of novel treatments</a>
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<li><strong>Validity Testing of the Conspiratorial Thinking and Anti-Expert Sentiment Scales during the COVID-19 Pandemic Across 24 Languages from a Large-Scale Global Dataset</strong> -
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In this study, we tested the validity across two scales addressing conspiratorial beliefs that may influence behaviors related to public health and the COVID-19 pandemic. Using the COVIDiSTRESSII Global Survey data from 12,261 participants, we validated the 4-item Conspiratorial Thinking Scale and 3-item Anti-Expert Sentiment Scale across 24 languages and dialects that were used by at least 100 participants per language. We employed confirmatory factor analysis, measurement invariance test, and measurement alignment for internal consistency testing. To test convergent validity of the two scales, we assessed correlations with trust in seven agents related to government, science, and public health. Although scalar invariance was not achieved when measurement invariance test was conducted initially, we found that both scales can be employed in further international studies with measurement alignment. Moreover, both conspiratorial and anti-expert beliefs were significantly and negatively correlated with trust in all agents. Findings from this study provide supporting evidence for the validity of both scales across 24 languages for future large-scale international research.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/q3rkj/" target="_blank">Validity Testing of the Conspiratorial Thinking and Anti-Expert Sentiment Scales during the COVID-19 Pandemic Across 24 Languages from a Large-Scale Global Dataset</a>
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<li><strong>Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination</strong> -
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Importance. Omicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification. Objective. To estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine. Design. Test-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022. Setting. Population-based, province of Quebec, Canada Participants. Community-dwelling ≥12-year- olds tested for SARS-CoV-2. Exposures. Prior laboratory-confirmed infection with/without mRNA vaccination. Outcomes. Laboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test- negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing- indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results. Without vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses. Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively). Conclusions and relevance. Prior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.29.22274455v2" target="_blank">Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination</a>
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<li><strong>Whole Genome DNA and RNA Sequencing of Whole Blood Elucidates the Genetic Architecture of Gene Expression Underlying a Wide Range of Diseases</strong> -
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To create a scientific resource of expression quantitative trail loci (eQTL), we conducted a genome-wide association study (GWAS) using genotypes obtained from whole genome sequencing (WGS) of DNA and gene expression levels from RNA sequencing (RNA-seq) of whole blood in 2622 participants in Framingham Heart Study. We identified 6,778,286 cis-eQTL variant-gene transcript (eGene) pairs at p<5x10-8 (2,855,111 unique cis-eQTL variants and 15,982 unique eGenes) and 1,469,754 trans-eQTL variant-eGene pairs at p<1e-12 (526,056 unique trans-eQTL variants and 7,233 unique eGenes). In addition, 442,379 cis-eQTL variants were associated with expression of 1518 long non-protein coding RNAs (lncRNAs). Gene Ontology (GO) analyses revealed that the top GO terms for cis-eGenes are enriched for immune functions (FDR <0.05). The cis-eQTL variants are enriched for SNPs reported to be associated with 815 traits in prior GWAS, including cardiovascular disease risk factors. As proof of concept, we used this eQTL resource in conjunction with genetic variants from public GWAS databases in causal inference testing (e.g., COVID-19 severity). After Bonferroni correction, Mendelian randomization analyses identified putative causal associations of 60 eGenes with systolic blood pressure, 13 genes with coronary artery disease, and seven genes with COVID-19 severity. This study created a comprehensive eQTL resource via the NCBI Molecular QTL Browser (https://www.ncbi.nlm.nih.gov/) that can be used to advance understanding of the genetic architecture of gene expression underlying a wide range of diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.13.22273841v2" target="_blank">Whole Genome DNA and RNA Sequencing of Whole Blood Elucidates the Genetic Architecture of Gene Expression Underlying a Wide Range of Diseases</a>
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<li><strong>Outbreak.info Research Library: A standardized, searchable platform to discover and explore COVID-19 resources</strong> -
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To combat the ongoing COVID-19 pandemic, scientists have been conducting research at breakneck speeds, producing over 52,000 peer reviewed articles within the first 12 months. In contrast, a little over 1,000 peer reviewed articles were published within the first 12 months of the SARS-CoV-1 pandemic starting in 2002. In addition to publications, there has also been an upsurge in clinical trials to develop vaccines and treatments, scientific protocols to study SARS-CoV-2, methodology for epidemiological modeling, and datasets spanning molecular studies to social science research. One of the largest challenges has been keeping track of the vast amounts of newly generated disparate data and research that exist in independent repositories. To address this issue, we developed outbreak.info, which provides a standardized, searchable interface of heterogeneous data resources on COVID-19 and SARS-CoV-2. Unifying metadata from 14 data repositories, we have assembled a collection of over 200,000 publications, clinical trials, datasets, protocols, and other resources as of October 2021. We used a rigorous schema to enforce a consistent format across different data sources and resource types, and linked related resources where possible. This enables users to quickly retrieve information across data repositories, regardless of resource type or repository location. Outbreak.info also combines the combined research library with spatiotemporal genomics data on SARS-CoV-2 variants and epidemiological data on COVID-19 cases and deaths. The web interface provides interactive visualizations and reports to explore the unified data and generate hypotheses. In addition to providing a web interface, we also publish the data we have assembled and standardized in a high performance public API and an R package. Finally, we discuss the challenges inherent in combining metadata from scattered and heterogeneous resources and provide recommendations to streamline this process to aid scientific research.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.01.20.477133v3" target="_blank">Outbreak.info Research Library: A standardized, searchable platform to discover and explore COVID-19 resources</a>
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</div></li>
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<li><strong>Immunogenicity and reactogenicity of a third dose of BNT162b2 vaccine for COVID-19 after a primary regimen with BBIBP-CorV or BNT162b2 vaccines in Lima, Peru.</strong> -
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Background: The administration of a third (booster) dose of COVID-19 vaccines in Peru initially employed the BNT162b2 (Pfizer) mRNA vaccine. The national vaccination program started with healthcare workers who received BBIBP-CorV (Sinopharm) vaccine as primary regimen and elderly people previously immunized with BNT162b2. This study evaluated the reactogenicity and immunogenicity of the “booster” dose in these two groups in Lima, Peru. Methods: We conducted a prospective cohort study, recruiting participants from November to December of 2021 in Lima, Peru. We evaluated immunogenicity and reactogenicity in HCW and elderly patients previously vaccinated with either two doses of BBIBP-CorV (heterologous regimen) or BTN162b2 (homologous regimen). Immunogenicity was measured by anti-SARS-CoV-2 IgG antibody levels immediately before boosting dose and 14 days later. IgG geometric means (GM) and medians were obtained, and modeled using ANCOVA and quantile regressions. Results: The GM of IgG levels increased significantly after boosting: from 28.5±5.0 AU/mL up to 486.6±1.2 AU/mL (p<0.001) which corresponds to a 17-fold increase. The heterologous vaccine regimen produced higher GM of post-booster anti-SARS-CoV-2 IgG levels, eliciting a 13% fold increase in the geometric mean ratio (95%CI: 1.02-1.27) and a median difference of 92.3 AU/ml (95%CI: 24.9-159.7). Both were safe and well tolerated. Previous COVID-19 infection was also associated with higher pre and post-booster IgG GM levels. Conclusion: Although both boosting regimens were highly immunogenic, two doses of BBIBP-CorV boosted with BTN162b2 produced a stronger IgG antibody response than the homologous BNT162b2 regimen in the Peruvian population. Additionally, both regimens were mildly reactogenic and well-tolerated.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.01.22274548v1" target="_blank">Immunogenicity and reactogenicity of a third dose of BNT162b2 vaccine for COVID-19 after a primary regimen with BBIBP-CorV or BNT162b2 vaccines in Lima, Peru.</a>
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<li><strong>SARS-CoV-2 infection dynamics revealed by wastewater sequencing analysis and deconvolution</strong> -
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The use of RNA sequencing from wastewater samples is a valuable way for estimating infection dynamics and circulating lineages of SARS-CoV-2. This approach is independent from testing individuals and can therefore become the key tool to monitor this and potentially other viruses. However, it is equally important to develop easily accessible and scalable tools which can highlight critical changes in infection rates and dynamics over time across different locations given sequencing data from wastewater. Here, we provide an analysis of lineage dynamics in Berlin and New York City using wastewater sequencing and present PiGx SARS-CoV-2, a highly reproducible computational analysis pipeline with comprehensive reports. This end-to-end pipeline includes all steps from raw data to shareable reports, additional taxonomic analysis, deconvolution and geospatial time series analyses. Using simulated datasets (in silico generated and spiked-in samples) we could demonstrate the accuracy of our pipeline calculating proportions of Variants of Concern (VOC) from environmental as well as pre-mixed samples (spiked-in). By applying our pipeline on a dataset of wastewater samples from Berlin between February 2021 and January 2022, we could reconstruct the emergence of B.1.1.7(alpha) in February/March 2021 and the replacement dynamics from B.1.617.2 (delta) to BA.1 and BA.2 (omicron) during the winter of 2021/2022. Using data from very-short-reads generated in an industrial scale setting, we could see even higher accuracy in our deconvolution. Lastly, using a targeted sequencing dataset from New York City (receptor-binding-domain (RBD) only), we could reproduce the results recovering the proportions of the so-called cryptic lineages shown in the original study. Overall our study provides an in-depth analysis reconstructing virus lineage dynamics from wastewater, and that our tool can be used to identify new mutations and to detect any emerging new lineages with different amplification and sequencing methods. Our approach can support efforts to establish continuous monitoring and early-warning projects for detecting SARS-CoV-2 or any other pathogen.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.30.21266952v3" target="_blank">SARS-CoV-2 infection dynamics revealed by wastewater sequencing analysis and deconvolution</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2<br/><b>Sponsors</b>: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E; Biological: mRNA-1273<br/><b>Sponsor</b>: Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AmnioPul-02<br/><b>Sponsor</b>: Amniotics AB<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Chinese herbal medicine<br/><b>Sponsor</b>: <br/>
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Hong Kong Baptist University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-based Exercise Program in Patients With the Post-COVID-19 Condition</strong> - <b>Conditions</b>: Long COVID; Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: Home- based physical training<br/><b>Sponsor</b>: University of Sao Paulo<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo<br/><b>Sponsor</b>: Shaperon<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics)</strong> - <b>Conditions</b>: COVID-19; Post Intensive Care Syndrome<br/><b>Interventions</b>: <br/>
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Other: Aerobic Exercise Training; Other: Home Plan<br/><b>Sponsor</b>: Riphah International University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Drug: EXOFLO<br/><b>Sponsor</b>: Direct Biologics, LLC<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High Frequency Percussive Ventilation in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Acute Respiratory Failure<br/><b>Intervention</b>: <br/>
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Device: High frequency Percussive ventilation<br/><b>Sponsor</b>: University Magna Graecia<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of JT001 (VV116) Compared With Paxlovid</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Paxlovid<br/><b>Sponsor</b>: <br/>
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Vigonvita Life Sciences<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Knowledge Mobilization Activities to Support Decision-Making by Youth, Parents and Adults: Study Protocol</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Plain Language Recommendation (PLR); Other: Standard Language Version (SLV)<br/><b>Sponsors</b>: McMaster University; Western University; The Hospital for Sick Children; University of Alberta<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sample Collection for Evaluation of the Panbio™ COVID-19/ Flu A&B Rapid Panel.</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B<br/><b>Intervention</b>: Diagnostic Test: Nasal and Nasopharyngeal Sampling of the Panbio™ COVID-19/ Flu A&B Rapid Panel<br/><b>Sponsor</b>: Abbott Rapid Dx<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of an At-home Metal Corrosion Laboratory Experiment for STEM Outreach in Biomaterials During the Covid-19 Pandemic</strong> - Due to the coronavirus disease 2019 (COVID-19) pandemic, many universities and outreach programs have switched to online learning platforms, which inhibits students from completing formative hands-on experiments. To address this, we developed a series of at-home experiments for undergraduate engineering students and adapted one of these experiments for outreach purposes. This experiment was well received by middle school students in the Young Eisner Scholars (YES) Program and resulted in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Building integrated, adaptive and responsive healthcare systems - lessons from paramedicine in Ontario, Canada</strong> - CONCLUSIONS: The findings of this study add to the discourse on governing health systems towards being more integrated, adaptive and responsive to population needs. Governance strategies include: supporting networks of local organizational relationships; considering the role of a functionally flexible health workforce; promoting a shared vision and framework for collaboration; and enabling distributed, local control and experimentation.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants</strong> - As global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computational study on the affinity of potential drugs to SARS-CoV-2 main protease</strong> - Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using Molecular and Quantum Mechanics as well as Molecular Docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the Docking…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pirfenidone ameliorates early pulmonary fibrosis in LPS-induced acute respiratory distress syndrome by inhibiting endothelial-to-mesenchymal transition via the Hedgehog signaling pathway</strong> - Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>2’- and 3’-Ribose Modifications of Nucleotide Analogues Establish the Structural Basis to Inhibit the Viral Replication of SARS-CoV-2</strong> - Inhibition of RNA-dependent RNA polymerase (RdRp) by nucleotide analogues with ribose modification provides a promising antiviral strategy for the treatment of SARS-CoV-2. Previous works have shown that remdesivir carrying 1’-substitution can act as a “delayed chain terminator”, while nucleotide analogues with 2’-methyl group substitution could immediately terminate the chain extension. However, how the inhibition can be established by the 3’-ribose modification as well as other 2’-ribose…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era</strong> - Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identifying SARS-CoV-2 main protease inhibitors by applying the computer screening of a large database of molecules</strong> - The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 affected global health. Its infection agent was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Wearing a mask, maintaining social distance, and vaccination are effective ways to prevent infection of SARS-CoV-2, but none of them help infected people. Targeting the enzymes of SARS-CoV-2 is an effective way to stop the replication of the virus in infected people and treat COVID-19 patients. SARS-CoV-2 main…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthetic lethality-based prediction of anti-SARS-CoV-2 targets</strong> - Novel strategies are needed to identify drug targets and treatments for the COVID-19 pandemic. The altered gene expression of virus-infected host cells provides an opportunity to specifically inhibit viral propagation via targeting the synthetic lethal and synthetic dosage lethal (SL/SDL) partners of such altered host genes. Pursuing this disparate antiviral strategy, here we comprehensively analyzed multiple in vitro and in vivo bulk and single-cell RNA-sequencing datasets of SARS-CoV-2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prediction of COVID-19 manipulation by selective ACE inhibitory compounds of <em>Potentilla reptant</em> root: <em>In silico</em> study and ADMET profile</strong> - In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico evidence of antiviral activity against SARS-CoV-2 main protease of oligosaccharides from Porphyridium sp</strong> - The coronavirus pandemic (COVID-19) has created an urgent need to develop effective strategies for prevention and treatment. In this context, therapies against protease M^(pro), a conserved viral target, would be essential to contain the spread of the virus and reduce mortality. Using combined techniques of structure modelling, in silico docking and pharmacokinetics prediction, many compounds from algae were tested for their ability to inhibit the SARS-CoV-2 main protease and compared to the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>TARDBP Inhibits Porcine Epidemic Diarrhea Virus Replication through Degrading Viral Nucleocapsid Protein and Activating Type I Interferon Signaling</strong> - In global infection and serious morbidity and mortality, porcine epidemic diarrhea virus (PEDV) has been regarded as a dreadful porcine pathogen, but the existing commercial vaccines are not enough to fully protect against the epidemic strains. Therefore, it is of great necessity to feature the PEDV-host interaction and develop efficient countermeasures against viral infection. As an RNA/DNA protein, the trans-active response DNA binding protein (TARDBP) plays a variety of functions in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Journey of remdesivir from the inhibition of hepatitis C virus to the treatment of COVID-19</strong> - If a planned path reaches a dead-end, one can simply stop. Or one can turn around, walk back to the last intersection and take another path, or one can consider taking few paths in parallel. The last scenario is reflective of the journey of remdesivir, the first antiviral for the treatment of COVID-19, that was approved by FDA less than 10 months after the isolation of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. As of January 2022, 10 million COVID-19 patients have been treated…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Oral hymecromone decreases hyaluronan in human study participants</strong> - BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bis-indolylation of aldehydes and ketones using silica-supported FeCl<sub>3</sub>: molecular docking studies of bisindoles by targeting SARS-CoV-2 main protease binding sites</strong> - We report herein an operationally simple, efficient and versatile procedure for the synthesis of bis-indolylmethanes via the reaction of indoles with aldehydes or ketones in the presence of silica-supported ferric chloride under grindstone conditions. The prepared supported catalyst was characterized by SEM and EDX spectroscopy. The present protocol has several advantages such as shorter reaction time, high yield, avoidance of using harmful organic solvents during the reaction and tolerance of a…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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