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<title>16 August, 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>Digital Mental Health Service engagement changes during Covid-19 in children and young people across the UK: presenting concerns, service activity, and access by gender, ethnicity, and deprivation</strong> -
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The adoption of digital health technologies accelerated during Covid-19, with concerns over the equity of access due to digital exclusion. Using data from a text-based online mental health service for children and young people we explore the impact of the pandemic on service access and presenting concerns and whether differences were observed by sociodemographic characteristics in terms of access (gender, ethnicity and deprivation). We used interrupted time-series models to assess whether there was a change in the level and rate of service use during the Covid-19 pandemic (April 2020-April 2021) compared to pre-pandemic trends (June 2019-March 2020). Routinely collected data from 61221 service users were extracted for observation, those represented half of the service population as only those with consent to share their data were used. The majority of users identified as female (74%) and White (80%), with an age range between 13 and 20 years of age,. There was evidence of a sudden increase (13%) in service access at the start of the pandemic (RR 1.13 95% CI 1.02, 1.25), followed by a reduced rate (from 25% to 21%) of engagement during the pandemic compared to pre-pandemic trends (RR 0.97 95% CI 0.95,0.98). There was a sudden increase in almost all presenting issues apart from physical complaints. There was evidence of a step increase in the number of contacts for Black/African/Caribbean/Black British (38% increase; 95% CI: 1%-90%) and White ethnic groups (14% increase; 95% CI: 2%-27%) ), sudden increase in service use at the start of the pandemic for the most (58% increase; 95% CI: 1%-247%) and least (47% increase; 95% CI: 6%-204%) deprived areas. During the pandemic, contact rates decreased, and referral sources change at the start. Findings on access and service activity align with other studies observing reduced service utilization. The lack of differences in deprivation levels and ethnicity at lockdown suggests exploring equity of access to the anonymous service. The study provides unique insights into changes in digital mental health use during Covid-19 in the UK.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.11.23293977v1" target="_blank">Digital Mental Health Service engagement changes during Covid-19 in children and young people across the UK: presenting concerns, service activity, and access by gender, ethnicity, and deprivation</a>
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<li><strong>Stellate Ganglion Block to Treat Long COVID-19 Syndrome, A 41 Patient Retrospective Cohort Study</strong> -
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Post Covid-19 condition (PCC), long COVID-19 syndrome and post-acute sequelae of SARS-CoV-2 (PASC) all refer to a constellation of symptoms that are unresolved long after the acute phase of the viral infection. The severity of symptoms varies from mild and tolerable to severe and debilitating 1, 2. Due to the evolving nature of the SARS-CoV-2 pandemic, treatment protocols for the acute illness are also in a constant state of evolution. Due to the infancy of long COVID-19 syndrome, there is a lack of evidence-based treatment protocols to treat or at the very least attenuate the symptoms of long COVID-19. Current treatment regimens include homeopathic medicine, system focused treatments by specialists, infusion therapies, hyperbaric oxygenation, and polypharmacy. Most of these treatments have partial efficacy at best and place a substantial financial burden on the patients. The physiological, psychological, and societal impact of long COVID-19 cannot be approached casually and must govern the intensity with which the healthcare community approaches treatment of long COVID-19 syndrome. In this 41-patient cohort study from a chronic pain management practice in Colorado, the use of either unilateral or bilateral stellate ganglion block (SGB) was explored to manage symptoms associated with long COVID-19 syndrome. Results indicated that a substantial proportion of patients (86%) experienced a significant reduction of their symptoms following SGB treatment, while 61% achieved a reduction in all their symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.10.23290338v1" target="_blank">Stellate Ganglion Block to Treat Long COVID-19 Syndrome, A 41 Patient Retrospective Cohort Study</a>
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<li><strong>Immune Changes in Pregnancy: Associations with Pre-existing Conditions and Obstetrical Complications at the 20th Gestational Week - A Prospective Cohort Study</strong> -
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Background Pregnancy is a complex biological process and serious complications can arise when the delicate balance between the maternal immune system and the semi-allogeneic fetal immune system is disrupted or challenged. Gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth, and low birth weight, pose serious threats to maternal and fetal health. Identification of early biomarkers through an in-depth understanding of molecular mechanisms is critical for early intervention. Methods We analyzed the associations between 47 proteins involved in inflammation, chemotaxis, angiogenesis, and immune system regulation, maternal and neonatal health outcomes, and the baseline characteristics and pre-existing conditions (diseases and obstetric history) of the mother in a prospective cohort of 1,049 pregnant women around the 20th gestational week. Bayesian linear regression models were used to examine the impact of risk factors on biomarker levels and Bayesian cause-specific parametric proportional hazards models were used to analyze the effect of biomarkers on maternal and neonatal health outcomes. Finally, we evaluated the predictive value of baseline characteristics and the 47 proteins using machine-learning models. Shapley additive explanation (SHAP) scores were used to dissect the machine learning models to identify biomarkers most important for predictions. Results Associations were identified between specific inflammatory markers and existing conditions, including maternal age and pre-pregnancy BMI, chronic diseases, complications from prior pregnancies, and COVID-19 exposure. Smoking during pregnancy significantly affected GM-CSF and 9 other biomarkers. Distinct biomarker patterns were observed for different ethnicities. In obstetric complications, IL-6 inversely correlated with pre-eclampsia risk, while acute cesarean section and birth weight to gestational age ratio were linked to markers such as VEGF or PlGF. GDM was associated with IL-1RA, IL-17D, and Eotaxin-3. Severe PPH correlated with CRP and proteins of the IL-17 family. Predictive modeling using MSD biomarkers yielded ROC-AUC values of 0.708 and 0.672 for GDM and pre-eclampsia, respectively. Significant predictive biomarkers for GDM included IL-1RA and Eotaxin-3, while pre-eclampsia prediction yielded highest predictions when including MIP-1β, IL-1RA, and IL-12p70. Conclusion Our study provides novel insights into the interplay between preexisting conditions and immune dysregulation in pregnancy. These findings contribute to our understanding of the pathophysiology of obstetric complications and the identification of novel biomarkers for early intervention(s) to improve maternal and fetal health.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.10.23293934v1" target="_blank">Immune Changes in Pregnancy: Associations with Pre-existing Conditions and Obstetrical Complications at the 20th Gestational Week - A Prospective Cohort Study</a>
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<li><strong>Effect of vaccination certification with mass vaccination and non-pharmaceutical interventions on mitigating COVID-19</strong> -
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As COVID-19 vaccines became abundantly available around the world since the second half of 2021, many countries carried out a vaccination certificate (green pass) policy to encourage vaccination and help reopen their economies. This policy granted certified people more freedom of gathering and movement than unvaccinated individuals. Accordingly, pre-existing non-pharmaceutical interventions (NPIs) were adjusted under the vaccination certificate policy. The vaccination certificate also induced heterogeneous behaviors between unvaccinated and vaccinated groups, which complicates the modeling of COVID-19 transmission. Still, limited work is available in evaluating the impact of the green pass policy on COVID-19 transmission using quantitative methods. To characterize the major changes caused by the green pass policy, a modified susceptible-exposed-infected-removed (SEIR) epidemiological model SEIQRD2 is proposed in this paper. By integrating different behavior patterns of unvaccinated and vaccinated groups under the green pass policy, SEIQRD2 adopts the inherent variability and complexity of human behaviors in the context of vaccination and NPIs and their effect on COVID-19 transmissions. Three countries: Greece, Austria, and Israel are selected as case studies to demonstrate the validity of SEIQRD2. The simulation results illustrate that the combination of NPIs and vaccination still plays a pivotal role in containing the resurgence of COVID-19 by enforcing vaccination certification.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.10.23293925v1" target="_blank">Effect of vaccination certification with mass vaccination and non-pharmaceutical interventions on mitigating COVID-19</a>
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<li><strong>RSV Neutralizing Antibodies in Dried Blood</strong> -
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The key correlate of protection of respiratory syncytial virus (RSV) vaccines and monoclonal antibodies (mAb) is virus neutralization, measured using sera obtained through venipuncture. Dried blood obtained with a finger prick can simplify acquisition, processing, storage, and transport in trials, and thereby reduce costs. In this study we aim to validate a low-tech assay to measure RSV neutralization in dried capillary blood. Recovery of mAb from dried blood (volumetric absorptive microsampling) was used to validate the elution method using indirect ELISA. Functional antibodies measured by a neutralization assay were compared between matched serum and dried blood samples from a phase I trial with RSM01, a novel investigational anti-RSV Prefusion F mAb. Hep-2 cells were infected with a serial dilution of sample-virus mixture using RSV-A2-mKate to determine half-maximal inhibitory concentration. Stability of dried blood was evaluated over time and during temperature stress. Functional antibodies in dried blood were highly correlated with serum (R2 = 0.98, p < 0.0001). The intra-assay, inter-assay, and inter-operator precision of the assay for dried blood was similar to serum. The function of mAb remained stable for 9 months at room temperature and frozen dried blood samples but lower concentrations showed instability after 6 months. Dried blood samples resisted 48 hours of temperature stress. We demonstrated the feasibility of measuring RSV neutralization using dried blood as an alternative to serum. Measuring antibody function using dried blood is a patient-centered solution that may replace serology testing in trials against RSV or other viruses, such as influenza and SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.10.23293875v1" target="_blank">RSV Neutralizing Antibodies in Dried Blood</a>
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<li><strong>Novel risk loci for COVID-19 hospitalization among admixed American populations</strong> -
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The genetic basis of severe COVID-19 has been thoroughly studied and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we have conducted the largest GWAS meta-analysis for COVID-19 hospitalization in admixed Americans, comprising a total of 4,702 hospitalized cases recruited by SCOURGE and other seven participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and first discovered in Latin-American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.11.23293871v1" target="_blank">Novel risk loci for COVID-19 hospitalization among admixed American populations</a>
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<li><strong>A Single-Tube Colorimetric Loop-Mediated Isothermal Amplification for Rapid Detection of SARS-CoV-2 RNA</strong> -
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Since SARS-CoV-2 is a highly transmissible virus, a rapid and accurate diagnostic method is necessary to prevent virus spread. We aimed to develop and evaluate a new rapid colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for SARS-CoV-2 detection in a single closed-tube. Nasopharyngeal and throat swabs collected from at-risk individuals testing for SARS-CoV-2 were used to assess the sensitivity and specificity of a new RT-LAMP assay against a commercial qRT-PCR assay. Total RNA extracts were submitted to the RT-LAMP reaction under optimal conditions and amplified at 65℃ for 30 minutes using three sets of specific primers targeting the nucleocapsid gene. The reaction was detected using two different indicator dyes, hydroxynaphthol blue (HNB) and cresol red. A total of 82 samples were used for detection with HNB and 94 samples with cresol red, and results were compared with the qRT-PCR assay. The sensitivity of the RT-LAMP-based HNB assay was 92.1% and the specificity was 93.2%. The sensitivity of the RT-LAMP-based cresol red assay was 80.3%, and the specificity was 97%. This colorimetric feature makes this assay highly accessible, low-cost, and user-friendly, which can be deployed for massive scale-up and rapid diagnosis of SARS-CoV-2 infection, particularly in low-resource settings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.10.23293869v1" target="_blank">A Single-Tube Colorimetric Loop-Mediated Isothermal Amplification for Rapid Detection of SARS-CoV-2 RNA</a>
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<li><strong>Individual level analysis of digital proximity tracing for COVID-19 in Belgium highlights major bottlenecks</strong> -
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To complement labour-intensive conventional contact tracing, digital proximity tracing was implemented widely during the COVID-19 pandemic. However, the privacy-centred design of the dominant Google-Apple exposure notification framework has hindered assessment of its effectiveness. Between October 2021 and January 2022, we systematically collected app use and notification receipt data within a test and trace programme for university students in Leuven, Belgium. Due to low success rates in each studied step of the digital notification cascade, only 4.3% of exposed contacts (CI: 2.8-6.1%) received such notifications, resulting in 10 times more cases detected through conventional contact tracing. Moreover, the infection risk of digitally traced contacts (5.0%; CI: 3.0-7.7%) was lower than that of conventionally traced non-app users (9.8%; CI: 8.8-10.7%; p=0.002). Contrary to common perception as near instantaneous, there was a 1.2-day delay (CI: 0.6-2.2) between case PCR result and digital contact notifications. These results highlight major limitations of the dominant digital proximity tracing framework.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.11.23293971v1" target="_blank">Individual level analysis of digital proximity tracing for COVID-19 in Belgium highlights major bottlenecks</a>
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<li><strong>Published benefits of ivermectin use in Itajaí, Brazil for COVID-19 infection, hospitalisation, and mortality are entirely explained by statistical artefacts</strong> -
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<b>Background</b> Two recent publications by Kerr et al. (Cureus 14(1):e21272; Cureus 14(8): e28624) reported dramatic effects of prophylactic ivermectin use for both prevention of COVID-19 and reduction of COVID-19-related hospitalisation and mortality, including a dose-dependent effect of ivermectin prophylaxis. These papers have gained an unusually large public influence: they were incorporated into debates around COVID-19 policies and may have contributed to decreased trust in vaccine efficacy and public health authorities more broadly. Both studies were based on retrospective observational analysis of city-wide registry data from the city of Itajaí, Brazil from July-December 2020. <b>Methods</b> Starting with initially identified sources of error, we conducted a revised statistical analysis of available data, including data made available with the original papers and public data from the Brazil Ministry of Health. We identified additional uncorrected sources of bias and errors from the original analysis, including incorrect subject exclusion and missing subjects, an enrolment time bias, and multiple sources of immortal time bias. In models assuming no actual effect from ivermectin use, we conducted Monte Carlo simulations to estimate the contribution of these biases to any observed effect. <b>Results</b> Untreated statistical artefacts and methodological errors alone lead to dramatic apparent risk reduction associated with ivermectin use in both studies. The magnitude of apparent risk reduction from these artefacts is comparable to the results reported by the studies themselves, including apparent protection from infection, hospitalisation, and death, and including the reported apparent dose-response relationship. <b>Conclusions</b> The inference of ivermectin efficacy reported in both papers is unsupported, as the observed effects are entirely explained by untreated statistical artefacts and methodological errors. Our re-analysis calls for caution in interpreting highly publicised observational studies and highlights the importance of common sources of bias in clinical research.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.10.23293924v1" target="_blank">Published benefits of ivermectin use in Itajaí, Brazil for COVID-19 infection, hospitalisation, and mortality are entirely explained by statistical artefacts</a>
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<li><strong>A Susceptible Vaccinated Exposed Infected Hospitalised and Removed/Recovered (SVEIHR) Model Framework for COVID-19</strong> -
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In reaction to the severe socio-economic effects and upheavals that the Covid-19 sickness had on the world within the first few weeks of its introduction, everyone involved had to act quickly to look for possible solutions for preventing the ensuing epidemics. A prompt response is more critical given Nigeria9s subpar social, economic, and healthcare infrastructure. Investigated was the efficacy of various pharmacological, non-pharmaceutical, or a combination of both therapies in flattening the Covid-19 incidence curve. In order to investigate the impact of these interventions, a deterministic SVEIHR model was created and applied. The Nigerian Center for Disease Control (NCDC) portal9s Covid-19 data were used to parametrize the model. For simulations using a system dynamic simulation, estimated parameters were employed. The fundamental reproduction number, R0, was used to evaluate the success of our suggested intervention in effectively managing COVID-19 transmission. The simulation results demonstrated that the use of only non-pharmaceutical interventions, such as the use of face masks, a light lockdown, and hand washing at baseline or high levels, is insufficient, with the R0 varying from vaccination at the vaccination rate of 0.5% with non-pharmaceutical interventions at any level of compliance, and a combination of vaccination at 0.05% and high hygiene level were effective in flattening the Covid-19 disease incidence curve in Nigeria, returning a R0 less than 0. Furthermore, maintaining a high level of cleanliness, which includes hand washing and the use of a face mask, would be sufficient to stop the spread of Covid-19 disease and eventually flatten Covid-19 disease incidence curve in Nigeria, given a low turnout of 0.05% for vaccination and the easing of lockdown.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.10.23293942v1" target="_blank">A Susceptible Vaccinated Exposed Infected Hospitalised and Removed/Recovered (SVEIHR) Model Framework for COVID-19</a>
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<li><strong>“Getting pregnant during the COVID 19 was a big risk because getting the help from the clinic was not easy”: COVID-19 experiences of women and healthcare providers in Harare, Zimbabwe.</strong> -
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Background The COVID-19 pandemic and associated measures may have disrupted delivery of maternal and neonatal healthcare services and reversed the progress made towards dual elimination of mother-to-child transmission of HIV and syphilis in Zimbabwe. This qualitative study explores the impact of the pandemic on the provision and uptake of prevention of mother-to-child transmission (PMTCT) services from the perspectives of women and maternal healthcare providers. Methods Longitudinal in-depth interviews were conducted with 20 pregnant and breastfeeding women aged 20-39 years living with HIV and 20 healthcare workers in two maternity polyclinics in low-income suburbs of Harare, Zimbabwe. Semi-structured interviews were held after the second and third waves of COVID-19 in March and November 2021 respectively. Data were analysed using the modified grounded theory approach. Results While eight antenatal care contacts are recommended by Zimbabwe’s Ministry of Health and Child Care, women reported only being able to access two contacts. At antenatal booking, women were told to return at onset of labour; subsequent visits were suspended. Healthcare workers reported this reduction in antenatal attendance was a result of limited availability of personal protective equipment and fear that patients and services providers would contract SARS-CoV-2. Although HIV testing, antiretroviral therapy (ART) refills and syphilis screening services were accessible at first contact, other services such as HIV-viral load monitoring and enhanced adherence counselling were not available for those on ART. Closure of clinics and shortened operating hours during the second COVID-19 wave resulted in more antenatal bookings occurring later during pregnancy and more home deliveries. Six of the 20 interviewed women reported giving birth at home assisted by untrained traditional midwives as clinics were closed. Babies delivered at home missed ART) prophylaxis and HIV testing at birth despite being HIV-exposed. Although women were faced with multiple challenges, they continued to attempt to access services after delivery. Conclusions The COVID-19 pandemic disrupted provision and uptake of PMTCT services; antenatal care contacts were significantly reduced, home deliveries increased and babies born at home missed out on the necessary ARV prophylaxis. These findings underline the importance of investing in robust health systems that are able to respond to emergency situations to ensure continuity of essential HIV prevention, treatment and care services.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.11.23293472v1" target="_blank">“Getting pregnant during the COVID 19 was a big risk because getting the help from the clinic was not easy”: COVID-19 experiences of women and healthcare providers in Harare, Zimbabwe.</a>
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<li><strong>Multiple Mediation of the Meaning of the Law</strong> -
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Dominant narratives about the early COVID-19 pandemic suggest that state-enacted policies, particularly “lockdowns,” played a significant role in the widespread transition to remote work that was observed in April 2020. In this paper, I develop Edelman’s theory on the organizational role in interpreting laws, arguing that lockdowns were highly ambiguous policies that gave incredible latitude to private employers to determine appropriate measures of compliance. Using two novel datasets of state regulations and individual-level patterns of work, I show that lockdowns had a modest effect on remote work, furlough, and unemployment. Employers instead relied on cultural cues to determine their response.
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🖺 Full Text HTML: <a href="https://osf.io/6fgy9/" target="_blank">Multiple Mediation of the Meaning of the Law</a>
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<li><strong>Employment outcomes of people with Long Covid symptoms: community-based cohort study</strong> -
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Background: Evidence on the long-term employment consequences of SARS-CoV-2 infection is lacking. We used data from a large, community-based sample in the UK to estimate associations between Long Covid and subsequent employment outcomes. Methods: This was an observational, longitudinal study using a pre-post design. We included UK COVID-19 Infection Survey participants who completed questionnaires on Long Covid from 3 February 2021 to 30 September 2022 when they were aged 16 to 64 years and not in full-time education. We used conditional logit modelling to explore the time-varying relationship between Long Covid status ≥12 weeks after a first test-confirmed SARS-CoV-2 infection (reference: pre-infection) and labour market inactivity (neither working nor looking for work) or workplace absence lasting ≥4 weeks. Results: Of 206,299 included participants (mean age 45 years, 54% female, 92% white), 15% were ever inactive in the labour market and 10% were ever long-term absent during follow-up. Compared with pre-infection, inactivity was higher in participants reporting Long Covid 30 to <40 weeks (adjusted odds ratio (aOR): 1.45; 95% CI: 1.17 to 1.81) or 40 to <52 weeks (1.34; 1.05 to 1.72) post-infection. Compared with pre-infection, reporting Long Covid was also associated with increased odds of long-term absence 18 to <24 weeks (1.40; 1.04 to 1.90) and 24 to <30 weeks (1.45; 1.03 to 2.04) post-infection, but not beyond 30 weeks. Combining with official statistics on Long Covid prevalence, our estimates translate to 27,000 (95% CI: 6,000 to 47,000) working-age adults in the UK being inactive because of their Long Covid symptoms in July 2022. Conclusions: Long Covid is likely to have contributed to reduced levels of participation in the UK labour market, though it is unlikely to be the sole driver. Further research is required to quantify the contribution of other factors, such as indirect health effects of the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.21.23287524v2" target="_blank">Employment outcomes of people with Long Covid symptoms: community-based cohort study</a>
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<li><strong>KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution</strong> -
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Testing was paramount in the management of the COVID-19 pandemic. Rapid deployment of new laboratories became widespread worldwide. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva at 20 to 50% the price of commercial kits. We performed 158,277 PCRs in saliva for staff, students and their household contacts of Kings College London, free of charge and with an average turnaround time of 8 hours. Our pipeline is mainly made of open-source automation and non-commercial reagents and has been recently recommended for ISO15189 accreditation. Here we provide our blueprint and results to enable the rapid launch of diagnostic laboratories where and when needed. Our data span over 18 months and parallels that of the UK Office for National Statistics, with a lower positive rate and virtually no delta wave. Our observations strongly support regular asymptomatic community testing to decrease outbreaks and provide safe working spaces. KCL TEST demonstrates that universities can provide agile, resilient and accurate testing that reflects the infection rate and trend of the general population. We call for the integration of academic institutions in pandemic preparedness, with capabilities to rapidly deploy highly skilled staff, as well as develop, test and accommodate efficient low-cost pipelines.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.25.23293154v2" target="_blank">KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution</a>
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<li><strong>Fit notes associated with COVID-19 in 24 million patients’ primary care records: A cohort study in OpenSAFELY-TPP</strong> -
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Background: Fit notes (“sick notes”) are issued by general practitioners (GPs) when a person can9t work for health reasons and is an indication of the public health and economic burden for people recovering from COVID-19. Methods: With NHS England approval, we used routine clinical data from >24 million patients to compare fit note incidence in people 18-64 years with and without evidence of COVID-19 in 2020, 2021 and 2022. We fit Cox regression models to estimate adjusted hazard ratios, overall and by time post-diagnosis and within demographic subgroups. Results: We identified 365,421, 1,206,555 and 1,321,313 people with evidence of COVID-19 in 2020, 2021 and 2022. The fit note rate was 4.88 per 100 person-months (95%CI 4.83-4.93) in 2020, 2.66 (95%CI 2.64-2.67) in 2021, and 1.73 (95%CI 1.72-1.73) in 2022. Compared with the age, sex and region matched general population, the hazard ratio (HR) adjusted for demographics and clinical characteristics over the follow-up period was 4.07 (95%CI 4.02-4.12) in 2020 decreasing to 1.57 (95%CI 1.56-1.58) in 2022. The HR was highest in the first 30 days in all years. Conclusions: Despite likely underestimation of the fit note rate, we identified a considerable increase among people with COVID-19, even in an era when most people are vaccinated. Most fit notes are associated with the acute phase of the disease, but the increased risk several months post-diagnosis provides further evidence of the long-term impact.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293269v2" target="_blank">Fit notes associated with COVID-19 in 24 million patients’ primary care records: A cohort study in OpenSAFELY-TPP</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>A Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose in Previously Vaccinated Participants and Unvaccinated Participants.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: XBB.1.5 Vaccine (Booster); Biological: XBB.1.5 Vaccine (single dose)<br/><b>Sponsor</b>: Novavax<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 COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: rehacom<br/><b>Sponsor</b>: Cairo University<br/><b>Enrolling by invitation</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>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</strong> - <b>Conditions</b>: Vaccination; Infection; COVID-19<br/><b>Intervention</b>: Biological: Comirnaty<br/><b>Sponsor</b>: Radboud University Medical Center<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>Immunogenicity and Safety of AdCLD-CoV19-1 OMI as a Booster: A SARS-CoV-2 (COVID-19) Preventive Vaccine in Healthy Volunteers</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Biological: AdCLD-CoV19-1 OMI; Biological: Comirnaty Bivalent 0.1mg/mL (tozinameran and riltozinameran)<br/><b>Sponsor</b>: Cellid 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>Using Text Messages to Boost COVID-19 Vaccine Booking Rate</strong> - <b>Conditions</b>: Vaccination Hesitancy; COVID-19<br/><b>Interventions</b>: Behavioral: Behavioural science-informed text messages; Behavioral: Control<br/><b>Sponsors</b>: The Behavioural Insights Team; Public Health England; Department of Health and Social Care; NHS England and NHS Improvement<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>Ivermectin to Prevent SARS-CoV-2 (COVID-19) Hospitalisation in Subjects Over 50</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Drug: Ivermectin; Drug: Placebo<br/><b>Sponsor</b>: Insud Pharma<br/><b>Terminated</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 Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-CR-04 vaccine 10μg; Biological: mRNA-CR-04 vaccine 30μg; Biological: mRNA-CR-04 vaccine 100μg; Drug: Placebo<br/><b>Sponsor</b>: GlaxoSmithKline<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>Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS)</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Methylprednisolone<br/><b>Sponsor</b>: Charite University, Berlin, Germany<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine; Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br/><b>Sponsor</b>: Novavax<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>Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Fatigue<br/><b>Interventions</b>: Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome; Other: Attention Control<br/><b>Sponsor</b>: University of Maryland, Baltimore<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>Hyperbaric on Pulmonary Functions in Post Covid -19 Patients.</strong> - <b>Condition</b>: Post COVID-19 Patients<br/><b>Interventions</b>: Device: hyperbaric oxygen therapy; Device: breathing exercise; Drug: medical treatment<br/><b>Sponsor</b>: Cairo University<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 Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19</strong> - <b>Conditions</b>: SARS CoV 2 Infection; Influenza, Human<br/><b>Interventions</b>: Biological: BIMERVAX; Biological: SIIV<br/><b>Sponsor</b>: Hipra Scientific, S.L.U<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>Pulmonary Artery Pressure in COVID-19 Survivors</strong> - <b>Condition</b>: Pulmonary Hypertension Secondary<br/><b>Intervention</b>: Diagnostic Test: right heart catheterization (RHC).<br/><b>Sponsor</b>: Mansoura University Hospital<br/><b>Enrolling by invitation</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>Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic</strong> - <b>Conditions</b>: Cardiovascular Health; Physical Function<br/><b>Intervention</b>: Behavioral: Golden Circle<br/><b>Sponsor</b>: University of Illinois at Urbana-Champaign<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>Supported Employment COVID-19 Rapid Testing for PWID</strong> - <b>Condition</b>: Health Behavior<br/><b>Intervention</b>: Behavioral: Supported Employment<br/><b>Sponsor</b>: University of Oregon<br/><b>Not yet recruiting</b></p></li>
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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>Forodesine and Riboprine Exhibit Strong Anti-SARS-CoV-2 Repurposing Potential: <em>In Silico</em> and <em>In Vitro</em> Studies</strong> - Lately, nucleos(t)ide antivirals topped the scene as top options for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Targeting the two broadly conserved SARS-CoV-2 enzymes, RNA-dependent RNA polymerase (RdRp) and 3’-to-5’ exoribonuclease (ExoN), together using only one shot is a very successful new tactic to stop SARS-CoV-2 multiplication irrespective of the SARS-CoV-2 variant type. Herein, the current…</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>Anticancer pan-ErbB inhibitors reduce inflammation and tissue injury and exert broad-spectrum antiviral effects</strong> - Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib…</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>Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses</strong> - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to be one of the largest dangers to human health around the world. The need for effective antiviral and anti-inflammatory treatments is still extremely high as newly emerging variants threaten the efficacy of currently used treatment options. Many compounds are effective at inhibiting SARS-CoV-2 infection in vitro but fail to recapitulate that efficacy in vivo….</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>Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CL<sup>pro</sup> through Structure-Based Virtual Screening and Experimental Approaches</strong> - 3CL^(pro) is a viable target for developing antiviral therapies against the coronavirus. With the urgent need to find new possible inhibitors, a structure-based virtual screening approach was developed. This study recognized 75 pharmacologically bioactive compounds from our in-house library of 1052 natural product-based compounds that satisfied drug-likeness criteria and exhibited good bioavailability and membrane permeability. Among these compounds, three promising sulfonamide chalcones were…</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>TGF-β1 inhibition of ACE2 mediated by miRNA uncovers novel mechanism of SARS-CoV-2 pathogenesis</strong> - SARS-CoV-2 utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin-converting enzyme 2 (ACE2). Decreased cell surface density of ACE2 contributes to mortality during COVID-19. Studies published early during the pandemic reported that people with cystic fibrosis (PwCF) treated with the high efficiency CFTR modulators ETI (elexacaftor-tezacaftor-ivacaftor) had higher ACE2 levels and milder COVID-19 symptoms, compared to people without CF. Subsequent studies did…</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>WASF3 disrupts mitochondrial respiration and may mediate exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome</strong> - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by various disabling symptoms including exercise intolerance and is diagnosed in the absence of a specific cause, making its clinical management challenging. A better understanding of the molecular mechanism underlying this apparent bioenergetic deficiency state may reveal insights for developing targeted treatment strategies. We report that overexpression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3),…</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>Endogenous and Therapeutic 25-hydroxycholesterols May Worsen Early SARS-CoV-2 Pathogenesis in Mice</strong> - Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro studies and two…</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>Design of a bifunctional pan-sarbecovirus entry inhibitor targeting the cell receptor and viral fusion protein</strong> - Development of highly effective antivirals that are robust to viral evolution is a practical strategy for combating the continuously evolved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inspired by viral multistep entry process, we here focus on developing a bispecific SARS-CoV-2 entry inhibitor, which acts on the cell receptor angiotensin converting enzyme 2 (ACE2) and viral S2 fusion protein. First, we identified a panel of diverse spike (S) receptor-binding domains (RBDs) 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>A novel robust inhibitor of papain-like protease (PLpro) as a COVID-19 drug</strong> - Regarding the significance of SARS-CoV-2, scientists have shown considerable interest in developing effective drugs. Inhibitors for PLpro are the primary strategies for locating suitable COVID-19 drugs. Natural compounds comprise the majority of COVID-19 drugs. Due to limitations on the safety of clinical trials in cases of COVID, computational methods are typically utilized for inhibition studies. Whereas papain is highly similar to PLpro and is entirely safe, the current study aimed to examine…</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>Growth media affects susceptibility of air-lifted human nasal epithelial cell cultures to SARS-CoV2, but not Influenza A, virus infection</strong> - Primary differentiated human epithelial cell cultures have been widely used by researchers to study viral fitness and virus-host interactions, especially during the COVID19 pandemic. These cultures recapitulate important characteristics of the respiratory epithelium such as diverse cell type composition, polarization, and innate immune responses. However, standardization and validation of these cultures remains an open issue. In this study, two different expansion medias were evaluated and 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>Protegrin-2, a potential inhibitor for targeting SARS-CoV-2 main protease M<sup>pro</sup></strong> - CONCLUSIONS: Our in silico and experimental studies identified Protegrin-2 as a potent inhibitor of M^(pro) that could be pursued further towards drug development against COVID-19 infection.</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>Real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the Delta and Omicron variants: Systematic review</strong> - CONCLUSION: Because of the natural diminishing effectiveness of the vaccine, the need for booster dose to restore its efficacy is vital. From a research perspective, the use of highly heterogeneous outcome measures inhibits the comparison, contrast, and integration of the results which makes data pooling across different studies problematic. While pharmaceutical intervention like vaccination is important to fight an epidemic, utilizing common outcome measurements or carrying out studies with…</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 pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery</strong> - Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent need for new antivirals with pan-SARS-CoV-2 inhibitory activity. We previously reported that a peptide fusion inhibitor, P3, targeting heptad repeated-1 (HR1) of SARS-CoV-2 spike (S) protein, could…</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>Age differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - effects of vitamin D</strong> - Young age and high vitamin D plasma levels have been associated with lower SARS-CoV-2 infection risk and favourable disease outcomes. This study investigated mechanisms associated with differential responses to SARS-CoV-2 across age groups and effects of vitamin D. Nasal epithelia were collected from healthy children and adults and cultured for four weeks at air-liquid interface with and without vitamin D. Gene expression (NanoString) and DNA methylation (Illumina EPIC850K) were investigated….</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>Spike protein mutations and structural insights of pangolin lineage B.1.1.25 with implications for viral pathogenicity and ACE2 binding affinity</strong> - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID -19, is constantly evolving, requiring continuous genomic surveillance. In this study, we used whole-genome sequencing to investigate the genetic epidemiology of SARS-CoV-2 in Bangladesh, with particular emphasis on identifying dominant variants and associated mutations. We used high-throughput next-generation sequencing (NGS) to obtain DNA sequences from COVID-19 patient samples and compared these…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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