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<title>19 March, 2023</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><strong>Remote work as a new dimension of polarisation: Individual and contextual determinants of the relationship between working from home and job quality</strong> -
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This chapter provides an empirical overview of the extent and distribution of working from home across EU member states and the changes due to its sharp rise following the start of the Covid-19 pandemic. The chapter describes working from a home as an increasingly important dimension in the way new digital technologies reinforce inequalities among already existing lines. Neither the possibility to move tasks remotely nor the probability of being offered the option by your employer are equally distributed. Unfortunately, they tend to be higher for those already doing better on the labour market: those in digitally advanced sectors and larger firms, those with higher skills and doing more abstract and complex tasks, and those on standard employment contracts. On top of this unevenness in access, working from home itself also carries benefits that may increase productivity and wages. Both through access and benefits a rise in working from home then risks widening the polarisation on the labour market. This chapter shows that indeed, remote work growth mainly benefited those more advantaged on the labour market, and is itself associated with better working conditions and higher wages, although also with higher working hours. Importantly, there is substantial variation in how unequally telework grows between sectors and countries. Digital intensity increases this polarisation by working from home further, while stronger worker representation through greater union density can curtail some of this inequality.
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🖺 Full Text HTML: <a href="https://osf.io/xdzhf/" target="_blank">Remote work as a new dimension of polarisation: Individual and contextual determinants of the relationship between working from home and job quality</a>
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<li><strong>Effect of Andrographis paniculata treatment for patients with early-stage COVID-19 on the prevention of pneumonia: A retrospective cohort study</strong> -
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There is a need for safe and cost-effective treatments for COVID-19. Andrographis paniculata (AP) is an herbal plant that has been used for centuries to treat upper respiratory tract infections. Andrographolide is the major active component of AP that inhibits intracellular SARS-CoV-2 replication and has anti-inflammatory action. We performed a retrospective cohort study to evaluate the therapeutic and adverse effects of oral AP-products on COVID-19 by using the risk of pneumonia diagnosed by chest radiography as an indicator. This study included patients 15 to 60 years of age with laboratory-confirmed early-stage (asymptomatic or mild) COVID-19 without comorbidities at seven hospitals in three adjacent provinces in Thailand, between December 2020 and March 2021. Patients were treated for five days with either AP-extract (60 mg andrographolide, 3 times daily) or crude-AP (48 mg andrographolide, 3 times daily), when available. Patient information was prospectively recorded in the structured medical records and retrospectively reviewed. All eligible patients who received AP-treatment were included and control patients who did not receive AP-treatment were randomly selected using a ratio of approximately 1:1. Pneumonia occurred in 1/243 AP-treatment patients and 69/285 control patients. The risks of pneumonia after adjusting for confounding effects were 0.3% (95%CI, 0%-0.9%) and 24.3% (95%CI, 19.0%-29.7%) in the AP-treatment and control groups, respectively. The number needed to treat to avoid pneumonia development in one patient was four (95% CI, 3-5). Eight patients developed mild adverse events. AP-treatment regimens are acceptably safe and associated with highly reduced rates of pneumonia for patients with early-stage COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.15.23287287v1" target="_blank">Effect of Andrographis paniculata treatment for patients with early-stage COVID-19 on the prevention of pneumonia: A retrospective cohort study</a>
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<li><strong>Protection against symptomatic SARS-CoV-2 BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original (ancestral) monovalent vaccines - a matched cohort study in France</strong> -
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This cohort study aimed to evaluate the protection against symptomatic SARS-CoV-2 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original (ancestral) monovalent vaccines. Individuals of ≥60 years old who received a booster dose between 03/10/2022 and 06/11/2022, when both the bivalent and monovalent vaccines were used in France, were included. Individuals who received a booster dose with (1) a monovalent Original mRNA vaccine (Pfizer- BioNTech or Moderna) or (2) the bivalent Pfizer-BioNTech Original/BA.4-5 vaccine were matched. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, at least seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136 852 individuals were included and followed for a median period of 77 days. The bivalent vaccine conferred an additional protection of 8% [95% CI: 0% - 16%, p=0.045] against symptomatic SARS-CoV-2 infection compared to the monovalent vaccines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.17.23287411v1" target="_blank">Protection against symptomatic SARS-CoV-2 BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original (ancestral) monovalent vaccines - a matched cohort study in France</a>
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<li><strong>Demographic and co-morbidity characteristics of patients tested for SARS-CoV-2 from March 2020 to January 2022 in a national clinical research network: results from PCORnet®</strong> -
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Background Prior studies have documented differences in the age, racial, and ethnic characteristics among patients with SARS-CoV-2 infection. However, little is known about how these characteristics changed over time during the pandemic and whether racial, ethnic, and age disparities evident early in the pandemic were persistent over time. This study reports on trends in SARS-CoV-2 infections among U.S. adults from March 1, 2020 to January, 31 2022, using data from electronic health records. Methods and Findings We captured repeated cross-sectional information from 43 large healthcare systems in 52 U.S. States and territories, participating in PCORnet®, the National Patient-Centered Clinical Research Network. Using distributed queries executed at each participating institution, we acquired information for all patients ≥ 20 years of age who were tested for SARS-CoV-2 (both positive and negative results), including care setting, age, sex, race, and ethnicity by month as well as comorbidities (assessed with diagnostic codes). During this time period, 1,325,563 patients had positive (13% inpatient) and 6,705,868 patients had negative (25% inpatient) viral tests for SARS-CoV-2. Disparities in testing positive were present across racial and ethnic groups, especially in the inpatient setting. Compared to White patients, Black or African American and other race patients had relative risks for testing positive of 1.5 or greater in the inpatient setting for 12 of the 23-month study period. Compared to nonHispanic patients, Hispanic patients had relative risks for testing positive in the inpatient setting of 1.5 or greater for 16 of 23. Ethnic and racial differences were present in emergency department and ambulatory settings but were less common across time than in inpatient settings. Trends in infections by age group demonstrated higher test positivity for older patients in the inpatient setting only for most months, except for June and July of 2020, April to August 2021, and January 2022. Comorbidities were common, with much higher rates among those hospitalized; hypertension (38% of patients SARS-CoV-2 positive vs. 29% for those negative) and type 2 diabetes mellitus (22% vs. 13%) were the most common. Conclusion and Relevance Racial and ethnic disparities changed over time among persons infected with SARS-CoV-2. These trends highlight potential underlying mechanisms, such as poor access to care and differential vaccination rates, that may have contributed to greater disparities, especially early in the pandemic. Monitoring data on characteristics of patients testing positive in real time could allow public health officials and policymakers to tailor interventions to ensure that patients and communities most in need are receiving adequate testing, mitigation strategies, and treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.17.23287396v1" target="_blank">Demographic and co-morbidity characteristics of patients tested for SARS-CoV-2 from March 2020 to January 2022 in a national clinical research network: results from PCORnet®</a>
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<li><strong>Chest CT findings and outcomes of COVID-19 in second wave: A cross-sectional study in a tertiary care centre in Northern India</strong> -
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Introduction: The COVID19 pandemic has posed a serious threat to global health, with developing nations like India being amongst the worst affected. Chest CT scans play a pivotal role in the diagnosis and evaluation of COVID19, and certain CT features may aid in predicting the prognosis of COVID19 illness. Methods: This was a single center, hospital based, cross sectional study conducted at a tertiary care center in Northern India during the second wave of the COVID19 pandemic from May June 2021. The study included 473 patients who tested positive for COVID-19. A high resolution chest CT scan was performed within five days of hospitalization, and patientrelated information was extracted retrospectively from medical records. Univariable and Multivariable analysis was done to study the predictors of poor outcome. Results: A total of 473 patients were included in the study, with 75.5% being males. The mean total CT score was 29.89 ± 9.06. Fibrosis was present in 17.1% of patients, crazy paving in 3.6%, pneumomediastinum in 8.9%, and pneumothorax in 3.6%. Males had a significantly higher total score, while the patients who survived (30.00 ± 9.55 vs 35.00 v 6.21, p value <.001), received Steroids at day 2 (28.04 ± 9.71 vs 31.66 ± 7.12, p value 0.002) or Remdesivir had lower total scores (28.04 ± 9.71 vs 31.66 ± 7.12, p value 0.002). Total CT score (aHR 1.05, 95% CI 1.02 1.08, p 0.001), pneumothorax (aHR 1.38, 95 % CI 0.67 2.87, p 0.385), pneumomediastinum (aHR 1.20, 95% CI 0.71 2.03, p 0.298) and cardiovascular accident (CVA, aHR 4.75, 95% CI 0.84 26.72, p 0.077) were associated with increased mortality, but the results were not significant after adjusting with other variables on multiple regression analysis. Conclusion: This study identifies several radiological parameters, including fibrosis, crazy paving, pneumomediastinum, and pneumothorax, that are associated with poor prognosis in COVID19. These findings highlight the role of CT thorax in COVID19 illness and the importance of timely identification and interventions in severe and critical cases of COVID19 to reduce mortality and morbidity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.17.23287423v1" target="_blank">Chest CT findings and outcomes of COVID-19 in second wave: A cross-sectional study in a tertiary care centre in Northern India</a>
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<li><strong>A general computational design strategy for stabilizing viral class I fusion proteins</strong> -
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Many pathogenic viruses, including influenza virus, Ebola virus, coronaviruses, and Pneumoviruses, rely on class I fusion proteins to fuse viral and cellular membranes. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more favorable and stable postfusion state. An increasing amount of evidence exists highlighting that antibodies targeting the prefusion conformation are the most potent. However, many mutations have to be evaluated before identifying prefusion-stabilizing substitutions. We therefore established a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. As a proof of concept, we applied this principle to the fusion protein of the RSV, hMPV, and SARS-CoV-2 viruses. For each protein, we tested less than a handful of designs to identify stable versions. Solved structures of designed proteins from the three different viruses evidenced the atomic accuracy of our approach. Furthermore, the immunological response of the RSV F design compared to a current clinical candidate in a mouse model. While the parallel design of two conformations allows identifying and selectively modifying energetically less optimized positions for one conformation, our protocol also reveals diverse molecular strategies for stabilization. We recaptured many approaches previously introduced manually for the stabilization of viral surface proteins, such as cavity-filling, optimization of polar interactions, as well as postfusion-disruptive strategies. Using our approach, it is possible to focus on the most impacting mutations and potentially preserve the immunogen as closely as possible to its native version. The latter is important as sequence re-design can cause perturbations to B and T cell epitopes. Given the clinical significance of viruses using class I fusion proteins, our algorithm can substantially contribute to vaccine development by reducing the time and resources needed to optimize these immunogens.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.16.532924v1" target="_blank">A general computational design strategy for stabilizing viral class I fusion proteins</a>
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<li><strong>Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine</strong> -
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COVID-19 continues to damage populations, communities and economies worldwide. Vaccines have reduced COVID-19-related hospitalisations and deaths, primarily in developed countries. Persisting infection rates, and highly transmissible SARS-CoV-2 Variants of Concern (VOCs) causing repeat and breakthrough infections, underscore the ongoing need for new treatments to achieve a global solution. Based on ADDomer, a self-assembling protein nanoparticle scaffold, we created ADDoCoV, a thermostable COVID-19 candidate vaccine displaying multiple copies of a SARS-CoV-2 receptor binding motif (RBM)-derived epitope. In vitro generated neutralising nanobodies combined with molecular dynamics (MD) simulations and electron cryo-microscopy (cryo-EM) established authenticity and accessibility of the epitopes displayed. A Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Antibodies generated by immunising mice cross-reacted with VOCs including Delta and Omicron. Our study elucidates nasal administration of ADDomer-based nanoparticles for active and passive immunisation against SARS-CoV-2 and provides a blueprint for designing nanoparticle reagents to combat respiratory viral infections.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.17.533092v1" target="_blank">Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine</a>
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<li><strong>How have mathematical models contributed to understanding the transmission and control of SARS-CoV-2 in healthcare settings? A systematic search and review</strong> -
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<b>Background:</b> Since the onset of the COVID-19 pandemic, mathematical models have been widely used to inform public health recommendations regarding COVID-19 control in healthcare settings. <b>Objectives:</b> To systematically review SARS-CoV-2 transmission models in healthcare settings, and summarise their contributions to understanding nosocomial COVID-19. <b>Methods:</b> Systematic search and review. <b>Data sources:</b> Published articles indexed in PubMed. <b>Study eligibility criteria:</b> Modelling studies describing dynamic inter-individual transmission of SARS-CoV-2 in healthcare settings, published by mid-February 2022. <b>Participants and interventions:</b> Any population and intervention described by included models. <b>Assessment of risk of bias:</b> Not appropriate for modelling studies. <b>Methods of data synthesis:</b> Structured narrative review. <b>Results:</b> Models have mostly focused on acute care and long-term care facilities in high-income countries. Models have quantified outbreak risk across different types of individuals and facilities, showing great variation across settings and pandemic periods. Regarding surveillance, routine testing - rather than symptom-based testing - was highlighted as essential for COVID-19 prevention due to high rates of silent transmission. Surveillance impacts were found to depend critically on testing frequency, diagnostic sensitivity, and turn-around time. Healthcare re-organization was also found to have large epidemiological impacts: beyond obvious benefits of isolating cases and limiting inter-individual contact, more complex strategies such as staggered staff scheduling and immune-based cohorting reduced infection risk. Finally, vaccination impact, while highly effective for limiting COVID-19 burden, varied substantially depending on assumed mechanistic impacts on infection acquisition, symptom onset and transmission. Studies were inconsistent regarding which individuals to prioritize for interventions, probably due to the high diversity of settings and populations investigated. <b>Conclusions:</b> Modelling results form an extensive evidence base that may inform control strategies for future waves of SARS-CoV-2 and other viral respiratory pathogens. We propose new avenues for future models of healthcare-associated outbreaks, with the aim of enhancing their efficiency and contributions to decision-making.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.17.23287403v1" target="_blank">How have mathematical models contributed to understanding the transmission and control of SARS-CoV-2 in healthcare settings? A systematic search and review</a>
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<li><strong>Relative vaccine effectiveness (rVE) of mRNA COVID-19 boosters in the UK vaccination programme, during the Spring-Summer (monovalent vaccine) and Autumn-Winter 2022 (bivalent vaccine) booster campaigns: a prospective test negative case-control study</strong> -
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Background Understanding the relative vaccine effectiveness (rVE) of new COVID-19 vaccine formulations against SARS-CoV-2 infection is an urgent public health priority. A precise comparison of the rVE of monovalent and bivalent boosters given during the 2022 Spring-Summer and Autumn-Winter campaigns, respectively, in a defined population has not been reported. We therefore assessed rVE against hospitalisation for the Spring-Summer (fourth vs third monovalent mRNA vaccine doses) and Autumn-Winter (fifth BA.1/ancestral bivalent vs fourth monovalent mRNA vaccine dose) boosters. Methods A prospective single-centre test-negative design case-control study of ≥75 year-olds hospitalised with COVID-19 or other acute respiratory disease. We conducted regression analyses controlling for age, gender, socioeconomic status, patient comorbidities, community SARS-CoV-2 prevalence, vaccine brand and time between baseline dose and hospitalisation. Results 682 controls and 182 cases were included in the Spring-Summer booster analysis; 572 controls and 152 cases for the Autumn-Winter booster analysis. A monovalent mRNA COVID-19 vaccine as fourth dose showed rVE 46∙9% (95% confidence interval [CI] 14∙4-67∙3) versus those not boosted. A bivalent mRNA COVID-19 vaccine as fifth dose had rVE 46∙4% (95%CI 17∙5-65), compared to a fourth monovalent mRNA COVID-19 vaccine dose. Interpretation Both fourth monovalent and fifth BA.1/ancestral mRNA bivalent COVID-19 vaccine doses demonstrated benefit as a booster in older adults. Bivalent mRNA boosters offer equivalent protection against hospitalisation with Omicron infection to monovalent mRNA boosters given earlier in the year. These findings support the current UK immunisation programme that advises the use of bivalent booster doses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.16.23287360v1" target="_blank">Relative vaccine effectiveness (rVE) of mRNA COVID-19 boosters in the UK vaccination programme, during the Spring-Summer (monovalent vaccine) and Autumn-Winter 2022 (bivalent vaccine) booster campaigns: a prospective test negative case-control study</a>
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<li><strong>Molecular Neuropathology and Cerebrospinal Fluid Diagnostic Biomarkers of SARS-Cov2 Infection in Central Nervous System: A Scoping Review Protocol</strong> -
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Introduction Despite the broad spectrum of neurological symptomatic manifestation in COVID19 patients, the brain tissue susceptibility and permissiveness to SARS-Cov2 infection is yet uncertain. This critical appraisal aims at bridging the gap by consolidating the body of evidence for meticulous evaluation of molecular neuropathological pathways and CSF diagnostic signatures of SARS-Cov2 infection in the central nervous system (CNS) that will underpin further strategic approach for neuroprotection and treatment of neurological COVID19 Methods and Analysis We have developed the protocol of this review according to the provisions of Joanna Briggs Institute Reviewer Manual for Evidence Synthesis ,2015 and Arksey and O Malley Methodological Framewotk ,2005.The articles for this review will be sourced from several electronic databases including EMBASE, PubMed, Scopus, Web of Science (WOS), Cochrane, Crossref Metadata and Semantic scholar. Herein we generated the search strategy using the medical subject headings [ MeSH Terms] , term in all field bibliography at all permutations in conjunctions with boolean operators Ethical Clearance and Dissemination plan Herein the review will not involve the human participants henceforth the ethical clearance approval is not applicable .We will disseminate the final findings of this review to scientific conferences at local and international level. The manuscript for final findings will be published on reputable journal of neuroscience. Keywords: Molecular, Neuropathology, CSF biomarkers, SARS-Cov2
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.17.23287405v1" target="_blank">Molecular Neuropathology and Cerebrospinal Fluid Diagnostic Biomarkers of SARS-Cov2 Infection in Central Nervous System: A Scoping Review Protocol</a>
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<li><strong>Serial SARS-CoV-2 antibody titers in vaccinated dialysis patients: prevalence of unrecognized infection and duration of seroresponse</strong> -
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Rationale & Objective: SARS-CoV-2 infections are likely underdiagnosed, but the degree of underdiagnosis among maintenance dialysis patients is unknown. Durability of the immune response after third vaccine doses in this population also remains uncertain. This study tracked antibody levels to 1) assess the rate of undiagnosed infections and 2) characterize seroresponse durability after third doses. Study Design: Retrospective observational study Setting & Participants: SARS-CoV-2 vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies (anti-spike IgG) titers were assessed monthly following vaccination. Exposure(s): Two and three doses of SARS-CoV-2 vaccine Outcome(s): Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time Analytical Approach: “Undiagnosed” SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥100 BAU/mL, not associated with receipt of vaccine or “diagnosed” SARS-CoV-2 infection (by PCR or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2660 patients without prior COVID-19 who received an initial two-dose vaccine series, 371 (76%) SARS-CoV-2 infections were diagnosed and 115 (24%) were undiagnosed. Among 1717 patients without prior COVID-19 who received a third vaccine dose, 155 (80%) SARS-CoV-2 infections were diagnosed and 39 (20%) were undiagnosed. In both cohorts, anti-spike IgG levels declined over time. Of the initial two-dose cohort, 66% had a titer ≥500 BAU/mL in the first month, with 23% maintaining a titer ≥500 BAU/mL at six months. Of the third dose cohort, 95% had a titer ≥500 BAU/mL in the first month after the third dose, with 76% maintaining a titer ≥500 BAU/mL at six months. Limitations: Assays used had upper limits. Conclusions: Among maintenance dialysis patients, 20-24% of SARS-CoV-2 infections were undiagnosed. Given this population9s vulnerability to COVID-19, ongoing infection control measures are needed. A three-dose primary mRNA vaccine series optimizes seroresponse rate and durability.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.16.23287322v1" target="_blank">Serial SARS-CoV-2 antibody titers in vaccinated dialysis patients: prevalence of unrecognized infection and duration of seroresponse</a>
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<li><strong>Pandemic telehealth flexibilities for buprenorphine treatment: A synthesis of evidence and policy implications for expanding opioid use disorder care in the U.S.</strong> -
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Buprenorphine is a highly effective treatment for opioid use disorder and a critical tool for addressing the worsening U.S. overdose crisis. However, multiple barriers to treatment, including stringent federal regulations, have historically made this medication hard to reach for many who need it. In 2020, under the COVID-19 Public Health Emergency, federal regulators substantially changed access to buprenorphine by allowing prescribers to initiate patients on buprenorphine via telehealth without first evaluating them in person. As the Public Health Emergency is set to expire in May of 2023, Congress and federal agencies can leverage extensive evidence from studies conducted during the wake of the pandemic to make evidence-based decisions on the regulation of buprenorphine going forward. To aid policy makers, this review synthesizes and interprets peer-reviewed research on the effect of buprenorphine flexibilities on uptake and implementation of telehealth, and its impact on OUD patient and prescriber experiences, access to treatment and health outcomes. Overall, our review finds that many prescribers and patients took advantage of telehealth, including the audio-only option, with a wide range of benefits and few downsides. As a result, federal regulators, including agencies and Congress, should continue non-restricted use of telehealth for buprenorphine initiation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.16.23287373v1" target="_blank">Pandemic telehealth flexibilities for buprenorphine treatment: A synthesis of evidence and policy implications for expanding opioid use disorder care in the U.S.</a>
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<li><strong>Importation of Alpha and Delta variants during the SARS-CoV-2 epidemic in Switzerland: phylogenetic analysis and intervention scenarios</strong> -
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The SARS-CoV-2 pandemic has led to the emergence of various variants of concern (VoCs) that are associated with increased transmissibility, immune evasion, or differences in disease severity. The emergence of VoCs fueled interest in understanding the potential impact of travel restrictions and surveillance strategies to prevent or delay the early spread of VoCs. We performed phylogenetic analyses and mathematical modeling to study the importation and spread of the VoCs Alpha and Delta in Switzerland in 2020 and 2021. Using a phylogenetic approach, we estimated 383-1,038 imports of Alpha and 455-1,347 imports of Delta into Switzerland. We then used the results from the phylogenetic analysis to parameterize a dynamic transmission that accurately described the subsequent spread of Alpha and Delta. We modeled different counterfactual intervention scenarios to quantify the potential impact of border closures and surveillance of travelers on the spread of Alpha and Delta. We found that implementing border closures after the announcement of VoCs would have been of limited impact to mitigate the spread of VoCs. In contrast, increased surveillance of travelers could prove to be an effective measure for delaying the spread of VoCs in situations where their severity remains unclear. Our study shows how phylogenetic analysis in combination with dynamic transmission models can be used to estimate the number of imported SARS-CoV-2 variants and the potential impact of different intervention scenarios to inform the public health response during the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.13.23287198v1" target="_blank">Importation of Alpha and Delta variants during the SARS-CoV-2 epidemic in Switzerland: phylogenetic analysis and intervention scenarios</a>
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<li><strong>Statistical Challenges when Analyzing SARS-CoV-2 RNA Measurements Below the Assay Limit of Quantification in COVID-19 Clinical Trials</strong> -
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Most clinical trials evaluating COVID-19 therapeutics include assessments of antiviral activity. In recently completed outpatient trials, changes in nasal SARS-CoV-2 RNA levels from baseline were commonly assessed using analysis of covariance (ANCOVA) or mixed models for repeated measures (MMRM) with single-imputation for results below assay lower limits of quantification (LLoQ). Analyzing changes in viral RNA levels with singly-imputed values can lead to biased estimates of treatment effects. In this paper, using an illustrative example from the ACTIV-2 trial, we highlight potential pitfalls of imputation when using ANCOVA or MMRM methods, and illustrate how these methods can be used when considering values <LLoQ as censored measurements. Best practices when analyzing quantitative viral RNA data should include details about the assay and its LLoQ, completeness summaries of viral RNA data, and outcomes among participants with baseline viral RNA ≥LLoQ, as well as those with viral RNA <LLoQ.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.13.23287208v1" target="_blank">Statistical Challenges when Analyzing SARS-CoV-2 RNA Measurements Below the Assay Limit of Quantification in COVID-19 Clinical Trials</a>
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<li><strong>Modelling the impact of hybrid immunity on future COVID-19 epidemic waves</strong> -
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Since the emergence of SARS-CoV-2 (COVID-19), there have been multiple waves of infection and multiple rounds of vaccination rollouts. Both prior infection and vaccination can prevent future infection and reduce severity of outcomes, combining to form hybrid immunity against COVID-19 at the individual and population level. Here, we explore how different combinations of hybrid immunity affect the size and severity of near-future Omicron waves. To investigate the role of hybrid immunity, we use an agent-based model of COVID-19 transmission with waning immunity to simulate outbreaks in populations with varied past attack rates and past vaccine coverages, basing the demographics and past histories on the World Health Organization (WHO) Western Pacific Region (WPR). We find that if the past infection immunity is high but vaccination levels are low, then the secondary outbreak with the same variant can occur within a few months after the first outbreak; meanwhile, high vaccination levels can suppress near-term outbreaks and delay the second wave. Additionally, hybrid immunity has limited impact on future COVID-19 waves with immune-escape variants. Enhanced understanding of the interplay between infection and vaccine exposure can aid anticipation of future epidemic activity due to current and emergent variants, including the likely impact of responsive vaccine interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.12.23287174v1" target="_blank">Modelling the impact of hybrid immunity on future COVID-19 epidemic waves</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>Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>: AccessBio, Inc.<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>Use of E-health Based Exercise Intervention After COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training using an e-health tool<br/><b>Sponsors</b>: Norwegian University of Science and Technology; University of Oslo<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>Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma 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>A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant variant COVID-19 vaccine (Sf9 cell); Biological: Recombinant COVID-19 vaccine (CHO cell); Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma 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>A Study to Compare QLS1128 With Placebo in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu Pharmaceutical 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>Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Hormone Replacement Therapy<br/><b>Interventions</b>: Drug: Climara 0.1Mg/24Hr Transdermal System; Other: Hydrogel patch<br/><b>Sponsors</b>: Istanbul University - Cerrahpasa (IUC); Turkish Menopause and Osteoporosis Society; Karakoy Rotary Club; Rebul Pharmacy<br/><b>Completed</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>Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Other: Pursed lip breathing; Other: Cognitive Behavior Therapy; Other: Diaphragmatic breathing exercise; Other: Kinesio tape<br/><b>Sponsor</b>: Cairo 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>Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Calcitriol; Other: Placebo<br/><b>Sponsor</b>: Universitas Sebelas Maret<br/><b>Completed</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>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: P1101 (Ropeginterferon alfa-2b); Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<br/><b>Active, not 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>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: Covid19; Hydrogen-oxygen Gas; AMS-H-03<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: OLO-1 Medical Molecular Sieve Oxygen Generator<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<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>Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Neoplasms Malignant<br/><b>Interventions</b>: Drug: EGCG; Drug: Placebo<br/><b>Sponsor</b>: Shandong Cancer Hospital and Institute<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>The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial.</strong> - <b>Conditions</b>: Xerostomia; COVID-19; Long COVID; Persistent COVID-19<br/><b>Interventions</b>: Combination Product: Institutional standard treatment for xerostomia and Long Covid; Radiation: Photobiomodulation Therapy; Radiation: Placebo Photobiomodulation Therapy<br/><b>Sponsor</b>: University of Nove de Julho<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>Balneotherapy for Patients With Post-acute Coronavirus Disease (COVID) Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Balneotherapy and aquatic exercises<br/><b>Sponsors</b>: Parc de Salut Mar; Caldes de Montbui’s City Council; Consorcio Centro de Investigación Biomédica en Red (CIBER); European Regional Development Fund<br/><b>Completed</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 Assess the Efficacy of HH-120 Nasal Spray for Prevention of SARS-CoV-2 Infection in Adult Close Contacts of Individuals Infected With SARS-CoV-2</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: HH-120 nasal spray 1; Drug: HH-120 nasal spray 2; Drug: Placebo Comparator 1; Drug: Placebo Comparator 2<br/><b>Sponsor</b>: Beijing Ditan Hospital<br/><b>Completed</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>Lactoferrin for COVID-19-Induced Taste or Smell Abnormality</strong> - <b>Conditions</b>: Covid19; Taste Disorder, Secondary; Taste Disorders; Dysgeusia; Smell Disorder; Ageusia; Anosmia<br/><b>Intervention</b>: Dietary Supplement: Lactoferrin<br/><b>Sponsor</b>: Wake Forest University Health Sciences<br/><b>Withdrawn</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>The relationship between serum cytokine profile and vitamin D in calves with neonatal diarrhea</strong> - It is important to know the characteristics of the immunological response in newborn calf diarrhea, which is often caused by bacterial, viral and protozoal pathogens. Cytokinesare proteins that serve as chemical messengers to regulate theinnate and adaptive arms of theimmune response. Changes in circulatory cytokine levels provide valuable information for understanding the pathophysiological process and monitoring disease progression and inflammation. Vitamin D has important immunomodulatory…</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>Xuanfei Baidu Decoction regulates NETs formation via CXCL2/CXCR2 signaling pathway that is involved in acute lung injury</strong> - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening symptoms in Coronavirus Disease 2019 (COVID-19) patients. Xuanfei Baidu Decoction (XFBD) is a recommend first-line traditional Chinese medicine (TCM) formula therapeutic strategy for COVID-19 patients. Prior studies demonstrated the pharmacological roles and mechanisms of XFBD and its derived effective components against inflammation and infections through multiple model systems, which provided 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>Digoxin and Standard-of-Care Therapy for Heart Failure Patients with COVID-19: Analysis of Data from the US Military Health System (MHS) Data Repository</strong> - CONCLUSION: The hypothesis of equivalent protection by digoxin treatment of HF patients in terms of susceptibility to COVID-19 infection appears to be supported by the data.</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>Viral target- and metabolism-based rationale for combined use of recently authorized small molecule COVID-19 medicines: molnupiravir, nirmatrelvir and remdesivir</strong> - The COVID-19 pandemic remains a major health concern worldwide, and SARS-CoV-2 is continuously evolving. There is an urgent need to identify new antiviral drugs and develop novel therapeutic strategies. Combined use of newly authorized COVID-19 medicines including molnupiravir, nirmatrelvir and remdesivir, has been actively pursued. Mechanistically, nirmatrelvir inhibits SARS-CoV-2 replication by targeting the viral main protease (M^(pro) ), a critical enzyme in the processing of the immediately…</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>SARS-CoV-2 NSP8 suppresses type I and III IFN responses by modulating the RIG-I/MDA5, TRIF, and STING signaling pathways</strong> - SARS-CoV-2 has developed a variety of approaches to counteract host innate antiviral immunity to facilitate its infection, replication and pathogenesis, but the molecular mechanisms that it employs are still not been fully understood. Here, we found that SARS-CoV-2 NSP8 inhibited the production of type I and III IFNs by acting on RIG-I/MDA5 and the signaling molecules TRIF and STING. Overexpression of NSP8 downregulated the expression of type I and III IFNs stimulated by poly (I:C) transfection…</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>Acid sphingomyelinase (ASM) and COVID-19: A review of the potential use of ASM inhibitors against SARS-CoV-2</strong> - In the last 2 years, different pharmacological agents have been indicated as potential inhibitors of SARS-CoV-2 in vitro. Specifically, drugs termed as functional inhibitors of acid sphingomyelinase (FIASMAs) have proved to inhibit the SARS-CoV-2 replication using different types of cells. Those therapeutic agents share several chemical structure characteristics and some well-known representatives are fluoxetine, escitalopram, fluvoxamine, and others. Most of the FIASMAs are primarily used as…</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>Artificial intelligence-based optimization for chitosan nanoparticles biosynthesis, characterization and in‑vitro assessment of its anti-biofilm potentiality</strong> - Chitosan nanoparticles (CNPs) are promising biopolymeric nanoparticles with excellent physicochemical, antimicrobial, and biological properties. CNPs have a wide range of applications due to their unique characteristics, including plant growth promotion and protection, drug delivery, antimicrobials, and encapsulation. The current study describes an alternative, biologically-based strategy for CNPs biosynthesis using Olea europaea leaves extract. Face centered central composite design (FCCCD),…</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>SARS-CoV-2 E protein-induced THP-1 pyroptosis is reversed by Ruscogenin</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging pathogenic coronavirus, has been reported to cause excessive inflammation and dysfunction in multiple cells and organs, but the underlying mechanisms remain largely unknown. Here we showed exogenous addition of SARS-CoV-2 envelop protein (E protein) potently induced cell death in cultured cell lines, including THP-1 monocytic leukemia cells, endothelial cells and bronchial epithelial cells, in a time- and…</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 enzymatic hydrolysate of fucoidan from Sargassum hemiphyllum triggers immunity in plants</strong> - Fucoidans are polysaccharides that consist predominantly of sulfated L-fucoses, from which, fucoidan oligosaccharides (FOSs) are prepared through different methods. Fucoidan has versatile physiological activities, like antiviral functions against SARS CoV-2 and bioactivitiy in enhancing immune responses. Although fucoidan or FOS has been widely used in mammals as functional foods and new drugs, its application in plants is still very limited. Moreover, whether fucoidan or its derived hydrolytic…</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 confirmed COVID-19 in a patient with newly diagnosed hypertension and preexisting type 2 diabetes mellitus: a case report</strong> - CONCLUSION: Poor blood glucose management in the case of COVID-19 may increase the pathogen’s susceptibility, the likelihood that patients will be admitted to the hospital, and the likelihood that mortality will be enhanced.</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>Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial</strong> - BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase (CK) values, and autoantibodies recognizing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or the signal recognition particle (SRP). There are currently no approved therapies for IMNM and many patients experience active disease despite off-label treatment with intravenous immunoglobulin, glucocorticoids, and immunosuppressants. Detection of…</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>Delivery of anti-microRNA-21 by lung-targeted liposomes for pulmonary fibrosis treatment</strong> - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder with a low survival rate. Pulmonary fibrosis is one of the complications of COVID-19 and has a high prevalence in COVID-19 patients. Currently, no effective therapies other than lung transplantation are available to cure IPF and post-COVID-19 pulmonary fibrosis. MicroRNAs are small non-coding RNAs that mediate the development and progression of pulmonary fibrosis, thus making them potent drug candidates for this serious disease….</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>Insights of different analytical approaches for estimation of budesonide as COVID-19 replication inhibitor in its novel combinations: green assessment with AGREE and GAPI approaches</strong> - Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous…</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 multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection</strong> - COVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens^(1,2). This provided insight into cellular tropism and the host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different multiplicities of…</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>Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients</strong> - CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the ‘cytokine storm’ in COVID-19.</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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