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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Social Determinants of Mental Health During a Year of the COVID-19 Pandemic</strong> -
<div>
Belonging is a basic human need, with social isolation signaling a threat to biological fitness. Sensitivity to ostracism varies across individuals and the lifespan, peaking in adolescence. Government-imposed restrictions upon social interactions during COVID-19 may therefore be particularly detrimental to young people and those most sensitive to ostracism. Participants (N = 2367; 89.95% female, 11-100 years) from three countries with differing levels of government restrictions (Australia, UK, and USA) were surveyed trice at three-month intervals (May 2020 April 2021). Young people, and those living under the tightest government restrictions, reported the worst mental health, with these inequalities in mental health remaining constant throughout the study period. Further dissection of these results revealed that young people high on social rejection sensitivity reported the most mental health problems at the final assessment. These findings help account for the greater impact of enforced social isolation on young peoples mental health, and open novel avenues for intervention.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/64v7x/" target="_blank">Social Determinants of Mental Health During a Year of the COVID-19 Pandemic</a>
</div></li>
<li><strong>The preliminary safety and immunogenicity results of a randomized, double-blind, placebo-controlled Phase I trial for a recombinant two-component subunit SARS-CoV-2 vaccine ReCOV</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Summary Background The ReCOV is a recombinant trimeric two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03. We report the preliminary safety and immunogenicity results for the ReCOV. Methods This first in human, randomized, double-blind, placebo-controlled phase I study, was conducted at 2 study sites in New Zealand. Subjects were stratified into two age cohorts (18-55 years and 56-80 years old) and then randomly assigned in a 4:1 ratio to receive two 0.5 mL intramuscular doses of the ReCOV vaccine (20ug or 40ug, adjuvanted with BFA03 in each) or placebo, 21 days apart. The primary endpoints were incidence of solicited local and systemic adverse events (AEs) and unsolicited AEs after each dose; incidence of serious adverse events (SAEs) up to 30 days after the second dose; changes in clinical laboratory tests from baseline up to 7 days after each dose; and changes in vital signs from baseline up to 30 days after the second dose. The key secondary endpoints for immunogenicity were neutralizing antibody titers against SARS- CoV-2, S1 receptor binding domain (RBD) and N-terminal domain (NTD) IgG titers post-vaccination. The T cell-specific immune response elicited by ReCOV were also evaluated. The trial was registered with ClinicalTrials.gov (NCT04818801). Findings One hundred participants (50 for each age group) were randomized. The incidence of solicited local AEs in 20ug ReCOV, 40ug ReCOV, and pooled placebo group among younger adults were 60.0%, 70.0%, and 10.0%, respectively, while among older adults were 55.0%, 84.2%, and 10.0%, respectively. The incidence of solicited systemic AEs in 20ug ReCOV, 40ug ReCOV, and pooled placebo group among younger adults were 60.0%, 60.0%, and 30.0%, respectively, while among older adults were 50.0%, 52.6%, and 50.0%, respectively. All solicited AEs and unsolicited AEs were mild. No vaccination- related SAE, adverse events of special interest, and AE leading to early discontinuation were reported. ReCOV elicited SARS-CoV-2 neutralizing antibody after the first vaccination, which were increased further after the second vaccination irrespective of dose and age groups. The neutralizing antibody against wild-type SARS-CoV-2 peaked at 14 days post the second vaccination in both 20ug and 40ug ReCOV groups, with GMT of 1643.17 IU/mL and 1289.21 IU/mL among younger adults, and 1122.32 IU/mL and 680.31 IU/mL among older adults, respectively. Similarly, both anti-RBD and anti-NTD specific IgG were elicited after the first vaccination, and peaked at 14 days after the second vaccination. T helper 1 biased cellular responses were observed after ReCOV vaccinations. Interpretation Both 20 ugand 40ug ReCOV showed good safety profiles and elicited strong immune responses in the younger and the older adults. The results of this study support the accelerated development of ReCOV.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.11.22274932v1" target="_blank">The preliminary safety and immunogenicity results of a randomized, double-blind, placebo-controlled Phase I trial for a recombinant two-component subunit SARS-CoV-2 vaccine ReCOV</a>
</div></li>
<li><strong>Acceptability of a behavioural intervention to mitigate the psychological impacts of COVID-19 restrictions in older people with long-term conditions: a qualitative study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objectives The COVID-19 pandemic has heightened the need to address loneliness and social isolation (and associated incidence of depression) amongst older adults. Between June and October 2020, the Behavioural Activation in Social IsoLation (BASIL) pilot study investigated the acceptability and feasibility of a remotely delivered brief psychological intervention (Behavioural Activation, BA) to prevent and reduce loneliness and depression in older people with long term conditions (LTCs) during the COVID-19 pandemic. Design An embedded qualitative study was conducted with semi-structured interviews to generate data that was first analysed inductively using thematic analysis and then deductively using the Theoretical Framework of Acceptability (TFA). Setting National Health Service and third sector organisations in England. Participants Sixteen older adults and 9 Support Workers (BSWs) participating in the BASIL pilot trial. Results Older adults and BSWs described a positive affective attitude towards the intervention linked to altruism, however the activity planning aspect of the intervention was limited due to COVID-19 restrictions. The intervention was understood by older adults &amp; BSWs, although less understanding in older adults without low mood. A manageable burden was involved with delivering and participating in the intervention. For ethicality, older adults valued social contact and making changes, BSWs valued being able to observe those changes. Opportunity cost was low for BSWs &amp; older adults. BA was perceived to be useful in the pandemic and likely to achieve its aims, (Perceived Effectiveness) especially if tailored to people with both low mood and LTCs. Self-efficacy developed over time and with experience for both BSWs and older adults. Conclusions Overall, the BASIL pilot study processes and BA intervention were found to be acceptable. Use of the TFA provided valuable insights into how the intervention was experienced and how the acceptability of study processes and the BA intervention could be enhanced ahead of the larger definitive trial (BASIL+).
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.10.22274892v1" target="_blank">Acceptability of a behavioural intervention to mitigate the psychological impacts of COVID-19 restrictions in older people with long-term conditions: a qualitative study</a>
</div></li>
<li><strong>Radiological Imaging of Viral Pneumonia Cases Identified Before the COVID-19 Pandemic Period and COVID-19 Pneumonia Cases Comparison of Characteristics</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Thoracic CT imaging is widely used as a diagnostic method in the diagnosis of COVID-19 pneumonia. Radiological differential diagnosis and isolation of other viral agents causing pneumonia in patients gained importance, especially during the pandemic period. Aims: We aimed to investigate whether there is a difference between the CT imaging findings characteristically defined in COVID-19 pneumonia and the findings detected in pneumonia due to other viral agents, and which finding may be more effective in the diagnosis. Study Design: The study included 249 adult patients with pneumonia found in thorax CT examination and positive COVID-19 RT-PCR test and 94 patients diagnosed with non-COVID pneumonia (viral PCR positive, no bacterial/fungal agents were detected in other cultures) from the last 5 years before the pandemic. It was retrospectively analyzed using the PACS System. CT findings were evaluated by two radiologists with 5 and 20 years of experience who did not know to which group the patient belonged, and it was decided by consensus. Methods: Demographic data (age, gender, known chronic disease) and CT imaging findings (percentage of involvement, number of lesions, distribution preference, dominant pattern, ground-glass opacity distribution pattern, nodule, tree in bud sign, interstitial changes, crazy paving sign, reversed halo sign, vacuolar sign, halo sign, vascular enlargement, linear opacities, traction bronchiectasis, peribronchial wall thickness, air trapping, pleural retraction, pleural effusion, pericardial effusion, cavitation, mediastinal/hilar lymphadenopathy, dominant lesion size, consolidation, subpleural curvilinear opacities, air bronchogram, pleural thickening) of the patients were evaluated. CT findings were also evaluated with the RSNA consensus guideline and the CORADS scoring system. Data were divided into two main groups as non-COVID-19 and COVID-19 pneumonia and compared statistically with chi-square tests and multiple regression analysis of independent variables. Results: Two main groups; RSNA and CORADS classification, percentage of involvement, number of lesions, distribution preference, dominant pattern, nodule, tree in bud, interstitial changes, crazy paving, reverse halo vascular enlargement, peribronchial wall thickness, air trapping, pleural retraction, pleural/pericardial effusion, cavitation and mediastinal/hilar lymphadenopathy were compared, significant differences were found between the groups (p &lt; 0.01). Multiple linear regression analysis of independent variables found a significant effect of reverse halo sign (β = 0.097, p &lt;0.05) and pleural effusion (β = 10.631, p &lt;0.05) on COVID-19 pneumonia. Conclusion: Presence of reverse halo and absence of pleural effusion was found to be efficient in the diagnosis of COVID-19 pneumonia.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.11.22274305v1" target="_blank">Radiological Imaging of Viral Pneumonia Cases Identified Before the COVID-19 Pandemic Period and COVID-19 Pneumonia Cases Comparison of Characteristics</a>
</div></li>
<li><strong>Elevated liver enzymes and bilirubin following SARS-CoV-2 infection in children under 10</strong> -
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Recently, the Centers for Diseases and Control released a nationwide health alert about an increase in hepatitis cases of unknown origin in children, raising concern about potential sequelae of COVID-19 infection. In this study, we test whether there was increased risk of elevated serum liver enzymes and bilirubin following COVID-19 infection in children. We performed a retrospective cohort study on a nation-wide database of patient electronic health records (EHRs) in the US. The study population comprise 796,369 children between the ages of 1-10 years including 245,675 who had contracted COVID-19 during March 11, 2020 - March 11, 2022 and 550,694 who contracted non-COVID other respiratory infection (ORI) during the same timeframe. Compared to children infected with other respiratory infections, children infected with COVID- 19 infection were at significantly increased risk for elevated AST or ALT (hazard ratio or HR: 2.52, 95% confidence interval or CI: 2.03-3.12) and total bilirubin (HR: 3.35, 95% CI: 2.16- 5.18). These results suggest acute and long-term hepatic sequelae of COVID-19 in pediatric patients. Further investigation is needed to clarify if post-COVID-19 related hepatic injury described in this study is related to the current increase in pediatric hepatitis cases of unknown origin.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.10.22274866v1" target="_blank">Elevated liver enzymes and bilirubin following SARS-CoV-2 infection in children under 10</a>
</div></li>
<li><strong>Extending the German Corona Consensus Dataset (GECCO) to the immunization, pediatrics, and cardiology domains</strong> -
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<b>Background</b> The COVID-19 pandemic has spurred large-scale, inter-institutional research efforts. To enable these efforts, the German Corona Consensus (GECCO) dataset has been developed previously as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research. As GECCO has been developed as a compact core dataset across all medical fields, the focused research within particular medical domains demanded the definition of extension modules that include those data elements that are most relevant to the research performed in these individual medical specialties. <b>Main body</b> We created GECCO extension modules for the immunization, pediatrics, and cardiology domains with respect to the pandemic requests. The data elements included in each of these modules were selected in a consensus-based process by working groups of medical experts from the respective specialty to ensure that the contents are aligned with the research needs of the specialty. The selected data elements were mapped to international standardized vocabularies and data exchange specifications were created using HL7 FHIR profiles on the appropriate resources. All steps were performed in close interdisciplinary collaboration between medical domain experts, medical information scientists and FHIR developers. The profiles and vocabulary mappings were syntactically and semantically validated in a two-stage process. In that way, we defined dataset specifications for a total number of 23 (immunization), 59 (pediatrics), and 50 (cardiology) data elements that augment the GECCO core dataset. We created and published implementation guides and example implementations as well as dataset annotations for each extension module. <b>Conclusions</b> We here present extension modules for the GECCO core dataset that contain data elements most relevant to COVID-19-related patient research in immunization, pediatrics and cardiology. These extension modules were defined in an interdisciplinary, iterative, consensus-based approach that may serve as a blueprint for the development of further dataset definitions and GECCO extension modules. The here developed GECCO extension modules provide a standardized and harmonized definition of specialty-related datasets that can help to enable inter-institutional and cross-country COVID-19 research in these specialties.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.12.22274089v1" target="_blank">Extending the German Corona Consensus Dataset (GECCO) to the immunization, pediatrics, and cardiology domains</a>
</div></li>
<li><strong>VIGIL (Video In Geriatric Intervention cLinic): A randomised controlled feasibility trial protocol comparing face- to-face and video delivery of a specialist preoperative clinic for older people.</strong> -
<div>
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The Covid-19 pandemic resulted in significant challenges to the provision of face-to-face clinics in geriatric perioperative care (G-POC). There are no studies evaluating the use of telemedicine in this population. A pilot study at North Bristol NHS Trust demonstrated that delivery of GPOC clinics via video consultation was feasible, but did not record outcome measures to demonstrate effectiveness and was not compared to face to face clinic. This study aims to provide proof of concept examining the outcomes of virtual G-POC consultations, compared to a face-to-face clinic, using standardised perioperative outcomes. It will test the feasibility of the intervention with a view to developing a randomised controlled trial.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.11.22274120v1" target="_blank">VIGIL (Video In Geriatric Intervention cLinic): A randomised controlled feasibility trial protocol comparing face-to-face and video delivery of a specialist preoperative clinic for older people.</a>
</div></li>
<li><strong>Tracking changes in SARS-CoV-2 transmission with a novel outpatient sentinel surveillance system in Chicago, USA</strong> -
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Public health indicators typically used for COVID-19 surveillance can be biased or lag changing community transmission patterns. The United States city of Chicago opportunistically investigated whether sentinel surveillance of recently symptomatic individuals receiving outpatient diagnostic testing for SARS-CoV-2 could accurately assess the instantaneous reproductive number R(t) and provide early warning of changes in transmission. Patients tested at community-based diagnostic testing sites between September 2020 and June 2021, and reporting symptom onset within four days preceding their test, formed the sentinel population. R(t) calculated from sentinel cases agreed well with R(t) from other indicators. Retrospectively, trends in sentinel cases did not precede trends in COVID-19 hospital admissions by any identifiable lead time. In deployment, sentinel surveillance held an operational recency advantage of nine days over hospital admissions. The promising performance of opportunistic sentinel surveillance suggests that deliberately designed outpatient sentinel surveillance would provide robust early warning of increasing transmission.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.10.22274869v1" target="_blank">Tracking changes in SARS-CoV-2 transmission with a novel outpatient sentinel surveillance system in Chicago, USA</a>
</div></li>
<li><strong>BEHAVIOURS IN THE STOCK MARKET - AN EMPIRICAL STUDY</strong> -
<div>
This study has two main purposes. Its first purpose is to analyse the influence of sociodemographic characteristics and investment experience of individual and institutional investors on their investment behaviours in the stock market. The second purpose of the present paper is to study the impact of the investment behaviours on the investment decisions following the market selloff in March 2020 that preceded the emergence of COVID 19. Additionally, this study seeks to analyse the potential impact of the social distancing measures on the herd mentality influencing the investment decision.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/ypq8m/" target="_blank">BEHAVIOURS IN THE STOCK MARKET - AN EMPIRICAL STUDY</a>
</div></li>
<li><strong>Psychological Issues on Family Caregivers of Stroke Patients in Brunei Darussalam: In the Era of Pandemic Covid-19</strong> -
<div>
Family caregivers play an important role in providing main support for family members with a disability in order for them to function normally in their everyday life. The main goal of this research study is to promote psychological health awareness of stroke family caregivers in Brunei Darussalam, especially during the pandemic of Covid-19. This study concentrated particularly on long-term family caregivers who provide care to stroke family members who were severely affected by the disease that caused them to heavily depended on their family caretakers. This qualitative research involves interviewing 8 locals participants using snowballing sampling and a thematic analysis approach that investigate thoroughly the challenges and identifies the needs required by family caregivers in Brunei. The findings of the study discovered that all family caregivers experience psychological issues such as Depression and Stress and are in need of family support and self-care to reduce challenges they experience such as emotional exhaustion, physical problem, sleep deprivation, financial issues, and accessibility to basic needs in caregiving.
</div>
<div class="article- link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/4vce9/" target="_blank">Psychological Issues on Family Caregivers of Stroke Patients in Brunei Darussalam: In the Era of Pandemic Covid-19</a>
</div></li>
<li><strong>Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody</strong> -
<div>
The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 ug/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491770v1" target="_blank">Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody</a>
</div></li>
<li><strong>Three-doses of BNT162b2 COVID-19 mRNA vaccine establishes long-lasting CD8+ T cell immunity in CLL and MDS patients</strong> -
<div>
Patients with hematological malignancies are prioritized for COVID-19 vaccine due to their high risk for severe SARS-CoV-2 infection related disease and mortality. To understand T cell immunity, its long-term persistence, and correlation with antibody response, we evaluated the BNT162b2 COVID 19 mRNA vaccine-specific immune response in chronic lymphocytic leukemia (CLL) and myeloid dysplastic syndrome (MDS) patients. Longitudinal analysis of CD8+ T cells using DNA-barcoded peptide-MHC multimers covering the full SARS-CoV-2 Spike-protein (415 peptides) showed vaccine- specific T cell activation and persistence of memory T cells up to six months post-vaccination. Surprisingly, a higher frequency of vaccine-induced antigen-specific CD8+ T cell was observed in the patient group compared to a healthy donor group. Furthermore, and importantly, immunization with the second booster dose significantly increased the frequency of antigen-specific CD8+ T cells as well as the total number of T cell specificities. Altogether 59 BNT162b2 vaccine-derived immunogenic epitopes were identified, of which 23 established long-term CD8+ T cell memory response with a strong immunodominance for NYNYLYRLF (HLA-A24:02) and YLQPRTFLL (HLA-A02:01) epitopes. In summary, we mapped the vaccine-induced antigen-specific CD8+ T cells and showed a booster-specific activation and enrichment of memory T cells that could be important for long-term disease protection in this patient group.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491706v1" target="_blank">Three-doses of BNT162b2 COVID-19 mRNA vaccine establishes long-lasting CD8+ T cell immunity in CLL and MDS patients</a>
</div></li>
<li><strong>Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens</strong> -
<div>
The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID-19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS- CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491823v1" target="_blank">Humoral immunity to SARS- CoV-2 elicited by combination COVID-19 vaccination regimens</a>
</div></li>
<li><strong>In situ architecture and membrane fusion of SARS-CoV-2 Delta variant</strong> -
<div>
Among the current five Variants of Concern, infections caused by the SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, architecture of intact Delta virions remains veiled. Moreover, the detailed mechanism of S-mediated membrane fusion remains elusive. Here we report the molecular assembly and fusion snapshots of the authentic Delta variant. Envelope invagination and fusion events were frequently observed. Native structures of pre- and postfusion S were determined up to 4.1-A resolution. Site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S over that of the Wuhan-Hu-1 S. Based on these findings, we proposed a model for S-mediated membrane fusion and a model for the invagination formation.
</div>
<div class="article-link article-html- link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.13.491759v1" target="_blank">In situ architecture and membrane fusion of SARS-CoV-2 Delta variant</a>
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<li><strong>Optimality of Maximal-Effort Vaccination</strong> -
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It is widely acknowledged that vaccinating at maximal effort in the face of an ongoing epidemic is the best strategy to minimise infections and deaths from the disease. Despite this, no one has proved that this is guaranteed to be true if the disease follows multi-group SIR (Susceptible-Infected-Recovered) dynamics. This paper provides a novel proof of this principle for the existing SIR framework, showing that the total number of deaths or infections from an epidemic is decreasing in vaccination effort. Furthermore, it presents a novel model for vaccination which assumes that vaccines are distributed randomly to the unvaccinated population and suggests, using COVID-19 data, that this more accurately captures vaccination dynamics than the model commonly found in the literature. However, as the novel model provides a strictly larger set of possible vaccination policies, the results presented in this paper hold for both models.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.12.22275015v1" target="_blank">Optimality of Maximal-Effort Vaccination</a>
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</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)<br/><b>Sponsors</b>:   University of California, Irvine;   Hudson Valley Healing Arts Center<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: STI-9199;   Drug: Placebo<br/><b>Sponsor</b>:  <br/>
Sorrento Therapeutics, Inc.<br/><b>Not yet recruiting</b></p></li>
<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 Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Shulan (Hangzhou) Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Radiation: [18F]DPA-714 positron emission tomography (PET) scan<br/><b>Sponsors</b>:   Amsterdam UMC, location VUmc;   ZonMw: The Netherlands Organisation for Health Research and Development<br/><b>Enrolling by invitation</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Palbociclib<br/><b>Sponsor</b>:   biotx.ai GmbH<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo<br/><b>Sponsor</b>:   CanSino Biologics Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo<br/><b>Sponsor</b>:   CanSino Biologics Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate SSD8432/Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SSD8432 dose;   Drug: SSD8432 placebo<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>THEMBA II T-Cell Vaccine: A Phase 1/2 Study of Vaccination With saRNA COVID-19 Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AAHI-SC2 Vaccine;   Biological: AAHI- SC3 Vaccine;   Biological: EUA or approved vaccine<br/><b>Sponsor</b>:   ImmunityBio, Inc.<br/><b>Recruiting</b></p></li>
<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/>
Hong Kong Baptist University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SSD8432 dose1;   Drug: SSD8432 dose2;   Drug: SSD8432Placebo<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate SSD8432/ Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>:   COVID-19 Patients<br/><b>Interventions</b>:   Drug: SSD8432 dose 1/Ritonavir;   Drug: SSD8432 dose 2<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<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>:   COVID-19 Pandemic<br/><b>Interventions</b>:   Biological: A Lyophilized COVID-19 mRNA Vaccine;   Biological: Placebo<br/><b>Sponsor</b>:   Wuhan Recogen Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<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>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kesuting Syrup in the Treatment of Corona Virus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>:   COVID-19 Pneumonia;   Cough<br/><b>Interventions</b>:   Drug: Kesuting syrup;   Drug: LianHuaQingWen Granules<br/><b>Sponsor</b>:   Guizhou Bailing Group Pharmaceutical Co Ltd<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Recommendations for the management of drug-drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid<sup>®</sup> ) and comedications</strong> - The Covid-19 antiviral nirmatrelvir/ritonavir (NMV/r) (Paxlovid^(®) ) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. NMV/r will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Interactions and Inhibition of the SARS-CoV-2 Main Protease by a Thiadiazolidinone Derivative</strong> - We report molecular interactions and inhibition of the main protease (M^(Pro) ) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore conformational dynamics of M^(Pro) via docking protocols and molecular dynamics (MD) simulations in all-atom detail. We reveal local and global dynamics of M^(Pro) in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC(50) value of 1.39 ± 0.22 μM,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Conducting the RBD of SARS-CoV-2 Omicron Variant with Phytoconstituents from <em>Euphorbia dendroides</em> to Repudiate the Binding of Spike Glycoprotein Using Computational Molecular Search and Simulation Approach</strong> - (1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7),…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Flavonoids as Potential Anti-Inflammatory Molecules: A Review</strong> - Hydroxylated polyphenols, also called flavonoids, are richly present in vegetables, fruits, cereals, nuts, herbs, seeds, stems, and flowers of numerous plants. They possess numerous medicinal properties such as antioxidant, anti-cancer, anti-microbial, neuroprotective, and anti-inflammation. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect. They inhibit the secretions of enzymes such as lysozymes and β-glucuronidase and inhibit the secretion of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiinflammation Derived Suzuki-Coupled Fenbufens as COX-2 Inhibitors: Minilibrary Construction and Bioassay</strong> - A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9-17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para-amino and para-hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Semi-Synthesis of <em>N</em>-Aryl Amide Analogs of Piperine from <em>Piper nigrum</em> and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities</strong> - Piper nigrum, or black pepper, produces piperine, an alkaloid that has diverse pharmacological activities. In this study, N-aryl amide piperine analogs were prepared by semi-synthesis involving the saponification of piperine (1) to yield piperic acid (2) followed by esterification to obtain compounds 3, 4, and 5. The compounds were examined for their antitrypanosomal, antimalarial, and anti-SARS-CoV-2 main protease activities. The new 2,5-dimethoxy-substituted phenyl piperamide 5 exhibited the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel Inhibitors of 2-<em>O</em>-Methyltransferase of the SARS-CoV-2 Coronavirus</strong> - The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis and Applications of Nitrogen-Containing Heterocycles as Antiviral Agents</strong> - Viruses have been a long-term source of infectious diseases that can lead to large-scale infections and massive deaths. Especially with the recent highly contagious coronavirus (COVID-19), antiviral drugs were developed nonstop to deal with the emergence of new viruses and subject to drug resistance. Nitrogen-containing heterocycles have compatible structures and properties with exceptional biological activity for the drug design of antiviral agents. They provided a broad spectrum of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Docking Analysis of Some Bioactive Compounds from Traditional Plants against SARS-CoV-2 Target Proteins</strong> - COVID-19 is still a global pandemic that has not been stopped. Many traditional medicines have been demonstrated to be incredibly helpful for treating COVID-19 patients while fighting the disease worldwide. We introduced 10 bioactive compounds derived from traditional medicinal plants and assessed their potential for inhibiting viral spike protein (S-protein), Papain-like protease (PLpro), and RNA dependent RNA polymerase (RdRp) using molecular docking protocols where we simulate the inhibitors…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Human Whartons Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses</strong> - Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cannabinoids Alleviate the LPS-Induced Cytokine Storm via Attenuating NLRP3 Inflammasome Signaling and TYK2-Mediated STAT3 Signaling Pathways In Vitro</strong> - Cannabinoids, mainly cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients</strong> - Neutrophil Extracellular Traps (NETs) are a contributing factor of vascular thrombosis and alveolar damage in COVID-19 patients. As enoxaparin is currently used to inhibit vascular thrombosis, this study aimed to investigate whether enoxaparin also reduced inflammation and NETs in COVID-19 patients. Patients with COVID-19 infection were classified into three groups: mild, moderate, and severe (n = 10 for all groups). Plasma was collected from patients and healthy donors (n = 10). Neutrophils…</p></li>
<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 and corticosteroids: a narrative review</strong> - It has been reported that corticosteroid therapy was effective in the management of severe acute respiratory syndrome (SARS) and the Middle East Respiratory Syndrome (MERS), and recently in coronavirus disease 2019 (COVID-19). Corticosteroids are potent anti-inflammatory drugs that mitigate the risk of acute respiratory distress syndrome (ARDS) in COVID-19 and other viral pneumonia, despite a reduction of viral clearance; corticosteroids inhibit the development of cytokine storm and multi-organ…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Disrupting autorepression circuitry generates “open-loop lethality” to yield escape-resistant antiviral agents</strong> - Across biological scales, gene-regulatory networks employ autorepression (negative feedback) to maintain homeostasis and minimize failure from aberrant expression. Here, we present a proof of concept that disrupting transcriptional negative feedback dysregulates viral gene expression to therapeutically inhibit replication and confers a high evolutionary barrier to resistance. We find that nucleic-acid decoys mimicking cis-regulatory sites act as “feedback disruptors,” break homeostasis, and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Aloe-derived natural products as lead scaffolds for SARS-CoV-2 main protease (M<sup>pro</sup> ) inhibitors</strong> - In the past two years, the COVID-19 pandemic has caused over 5 million deaths and 250 million infections worldwide. Despite successful vaccination efforts and emergency approval of small molecule therapies, diverse antivirals are still needed to combat the inevitable viral resistance that will arise. The main protease of SARS-CoV-2 (M^(pro) ) is an attractive drug target due to the clinical success of protease inhibitors against other viruses, such as HIV and HCV. However, in order to combat…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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