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<title>20 January, 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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<ul>
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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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The Gendered Effects of COVID-19 on Well-being: A Household Perspective</strong> -
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<div>
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We investigate the causal effect of COVID-19 incidence rates on changes in subjective well-being. Specifically, we employ a household-level perspective and expect that household composition (i.e., single and multi-person households and caregiving duties for children or older adults) and affluence (i.e., housing quality and financial resources) moderate the effect of COVID-19 incidence rates, with a special focus on gender differences. Employing longitudinal household data from the Panel Labour Market and Social Security (PASS) and a difference-in-difference (DiD) approach, we find an overall negative effect. This effect is stronger for individuals with caregiving responsibilities. In contrast to our theoretical expectations, our results indicate stronger negative effects on individuals from households with high living standards and high financial resources. Strikingly, our findings indicate that the relevant negative subjective well-being changes are concentrated among women with caregiving obligations. Overall, our study underscores the need for further sociological research based on strong methodological designs.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/h2fa7/" target="_blank">The Gendered Effects of COVID-19 on Well-being: A Household Perspective</a>
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<li><strong>IL6 and IL1RN is differentially expressed and transcriptionally induced in models of SARS coronavirus infection.</strong> -
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<div>
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The coronavirus COVID19 pandemic is an emerging biosafety threat to the nation and the world (1). There are no treatments approved for coronavirus infection in humans (2) and there is a lack of information available regarding the basic transcriptional behavior of human cells and mammalian tissues following coronavirus infection. We mined independent published (3-5) and public (6) datasets, containing transcriptome data from infection models of the human coronavirus 229E and of severe acute respiratory syndrome (SARS) coronavirus to discover genes that are differentially expressed in coronaviruses and identify potential therapeutic targets and host cell vulnerabilities. We identified IL6 and IL1RN as conserved differentially expressed genes following coronavirus infection. IL6 and IL1RN may be involved in the cellular response to COVID19 infection.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/h9bmt/" target="_blank">IL6 and IL1RN is differentially expressed and transcriptionally induced in models of SARS coronavirus infection.</a>
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</div></li>
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<li><strong>Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential</strong> -
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<div>
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While the COVID-19 pandemic, caused by SARS-CoV-2, has renewed genomic surveillance efforts in wildlife, there has been limited characterisation of bat-borne coronaviruses in Europe. We collected 48 faecal samples from all but one of the 17 bat species breeding in the UK, through an extensive network of bat rehabilitators and conservationists, and screened them for coronaviruses using deep RNA sequencing. We assembled nine novel, high-quality coronaviral genomes, comprising four alphacoronaviruses from Myotis daubentonii and Pipistrellus pipistrellus, a Middle East respiratory syndrome (MERS)-related coronavirus from Plecotus auritus, and four closely-related sarbecoviruses isolated from both horseshoe bat species Rhinolophus hipposideros and R. ferrumequinum. We further used in vitro assays to demonstrate that at least one of these sarbecoviruses can bind ACE2, the receptor used by SARS-CoV-2 to infect human cells, which was also supported using in silico structural and sequence analyses. Although this sarbecovirus can enter human cells in vitro when ACE2 is over-expressed, our analyses indicate that it is unlikely to infect humans and would require adaptations to do so. Our findings highlight the importance of working collaboratively with conservation networks to enable larger, coordinated viral surveillance efforts and prevent the emergence of zoonoses from wildlife.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.17.524183v1" target="_blank">Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential</a>
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</div></li>
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<li><strong>SARS-CoV-2 Omicron XBB.1.5 may be a cautionary variant by in silico study</strong> -
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<div>
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In this research, we aimed to predict the relative risk of the recent new variants of SARS-CoV-2 as based on our previous research. First, we performed the molecular docking simulation analyses of the spike proteins with human angiotensin-converting enzyme 2 (ACE2) to understand the binding affinities to human cells of three new variants of SARS-CoV-2, Omicron BQ.1, XBB.1 and XBB.1.5 Then, three variants were subjected to determine the evolutionary distance of the spike protein gene (S gene) from the Wuhan, Omicron BA.1 and Omicron BA.4/5 variants, to appreciate the changes in the S gene. The result indicated that the XBB.1.5 had the highest binding affinity level of the spike protein with ACE2 and the longest evolutionary distance of the S gene. It suggested that the XBB.1.5 may be infected farther and faster than can infections of preexisting variants.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.18.524660v1" target="_blank">SARS-CoV-2 Omicron XBB.1.5 may be a cautionary variant by in silico study</a>
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</div></li>
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<li><strong>Trajectories of COVID-19: a longitudinal analysis of many nations and subnational regions</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The COVID-19 pandemic is the first to be rapidly and sequentially measured by nation-wide PCR community testing for the presence of the viral RNA at a global scale. We take advantage of the novel “natural experiment” where diverse nations and major subnational regions implemented various policies including social distancing and vaccination at different times with different levels of stringency and adherence. Initially, case numbers expanding exponentially with doubling times of ~1-2 weeks. In the nations where lockdowns were not implemented or ineffectual, case numbers increased exponentially but then stabilized around 102-to-103 new infections (per km2 built-up area per day). Dynamics under strict lockdowns were perturbed and infections decayed to low levels. They rebounded following the lifting of the policies but converged on an equilibrium setpoint. Here we deploy a mathematical model which captures this behavior, incorporates a direct measure of lockdown efficacies, and allows derivation of a maximal estimate for the basic reproductive number Ro (mean 1.6-1.8). We were able to test this approach by comparing the approximated “herd immunity” to the vaccination coverage observed that corresponded to rapid declines in community infections during 2021. The estimates reported here agree with the observed phenomena. Moreover, the decay rates d (0.4-0.5) and rebound rates r0 (0.2-0.3) were similar throughout the pandemic and among all the nations and regions studied. Finally, a longitudinal analysis comparing multiple national and regional results provides insights on the underlying epidemiology of SARS-CoV-2 and lockdown and vaccine efficacy, as well as evidence for the existence of an endemic steady state of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.19.23284768v1" target="_blank">Trajectories of COVID-19: a longitudinal analysis of many nations and subnational regions</a>
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</div></li>
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<li><strong>The fourth dose of mRNA COVID-19 vaccine following 12 different three-dose regimens: Safety and immunogenicity to Omicron BA.4/BA.5</strong> -
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<b>Objective:</b> To investigate the reactogenicity and immunogenicity of the fourth dose using mRNA vaccines after different three-dose regimens and to compare the 30 μg BNT162b2 and 50 μg mRNA-1273 vaccines. <b>Methods:</b> This prospective cohort study was conducted between June and October 2022. The self-recorded reactogenicity was evaluated on the subsequent 7 days after a fourth dose. Binding and neutralizing activity of antibodies against the Omicron BA.4/5 variants were determined. <b>Results:</b> Overall, 292 healthy adults were enrolled and received BNT162b2 or mRNA-1273. Reactogenicity was mild to moderate and well-tolerated after a few days. Sixty-five individuals were excluded. Thus, 227 eligible individuals received a fourth booster dose of BNT162b2 (n=109) and mRNA-1273 (n=118). Most participants, regardless the type of previous three dose regimens, elicited a significantly high level of binding antibodies and neutralizing activity against the Omicron BA.4/5 28 days after a fourth dose. The neutralizing activity against the Omicron BA.4/5 between the BNT162b2 (82.8%) and mRNA-1273 (84.2%) groups was comparable with a median ratio of 1.02. <b>Conclusion:</b> This study found that the BNT162b2 and mRNA-1273 vaccines can be used as a fourth booster dose for individuals who were previously immunized with any prior mix and match three dose COVID-19 vaccine.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.19.23284761v1" target="_blank">The fourth dose of mRNA COVID-19 vaccine following 12 different three-dose regimens: Safety and immunogenicity to Omicron BA.4/BA.5</a>
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<li><strong>A computable phenotype for patients with SARS-CoV2 testing that occurred outside the hospital</strong> -
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Objective: To identify a cohort of COVID-19 cases, including when evidence of virus positivity was only mentioned in the clinical text, not in structured laboratory data in the electronic health record (EHR). Materials and Methods: Statistical classifiers were trained on feature representations derived from unstructured text in patient electronic health records (EHRs). We used a proxy dataset of patients with COVID-19 polymerase chain reaction (PCR) tests for training. We selected a model based on performance on our proxy dataset and applied it to instances without COVID-19 PCR tests. A physician reviewed a sample of these instances to validate the classifier. Results: On the test split of the proxy dataset, our best classifier obtained 0.56 F1, 0.6 precision, and 0.52 recall scores for SARS-CoV2 positive cases. In an expert validation, the classifier correctly identified 90.8% (79/87) as COVID-19 positive and 97.8% (91/93) as not SARS-CoV2 positive. The classifier identified an additional 960 positive cases that did not have SARS-CoV2 lab tests in hospital, and only 177 of those cases had the ICD-10 code for COVID-19. Discussion: Proxy dataset performance may be worse because these instances sometimes include discussion of pending lab tests. The most predictive features are meaningful and interpretable. The type of external test that was performed is rarely mentioned. Conclusion: COVID-19 cases that had testing done outside of the hospital can be reliably detected from the text in EHRs. Training on a proxy dataset was a suitable method for developing a highly performant classifier without labor intensive labeling efforts.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.19.23284738v1" target="_blank">A computable phenotype for patients with SARS-CoV2 testing that occurred outside the hospital</a>
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<li><strong>Raman spectroscopy, used trans-cutaneously and non-invasively from a finger, to predict COVID-19: A feasibility, proof-of-concept study.</strong> -
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Abstract BACKGROUND A definitive COVID-19 infection typically is diagnosed by laboratory tests, including real-time, reverse-transcriptase Polymerase Chain Reaction (PCR)-based testing. These currently available COVID-19 tests require the patient to provide an extra-corporeal specimen and the results may not be immediate. Consequently, a variety of rapid antigen tests for COVID-19, all with a wide range of accuracy in terms of sensitivity and specificity, has proliferated (1,2). These rapid tests now represent a significantly larger proportion of all testing done for COVID-19, yet suffer from requiring a physical specimen from the nose or mouth and waiting 15 minutes for most. As a solution, we propose a non-invasive, trans-cutaneous, real-time viral detection device, based on the principles of Raman spectroscopy and machine learning. It does not require any extra-corporeal specimens and can be configured for self-administration. It can be easily used by non-experts and does not require medical training. Our approach suggests that our non-invasive, transcutaneous method may be broadly useful not only in COVID-19 diagnosis, but also in other diagnoses. METHODS 160 COVID positive (+) patients and 316 COVID negative (-) patients prospectively underwent nasal PCR testing concurrently with testing using our non-invasive, transcutaneous, immediate viral detector. Both the PCR and our experimental viral detector tests were performed side-by-side on outpatients (N=389) as well as inpatients (N= 87) at Holy Name Medical Center in Teaneck, NJ between June 2021 and August, 2022. The spectroscopic data were generated using an 830nm Raman System with SpectraSoft (W2 Innovations)and then, using machine learning, processed to provide an immediate prediction. A unique patient- interface for finger insertion enabled the application of Raman spectroscopy to viral detection in humans. RESULTS The data analysis algorithm demonstrates that there is an informative Raman spectrum output from the device, and that individual Raman peaks vary between cases and controls. Our proof-of-concept study yields encouraging results, with a specificity for COVID-19 of 0.75, and a sensitivity (including asymptomatic patients) of 0.80. CONCLUSIONS The combination of Raman spectroscopy, artificial intelligence, and our unique patient-interface admitting only a patient finger achieved test results of 0.75 specificity and 0.80 sensitivity for COVID-19 testing in this first in human proof-of-concept study. More significantly, the predictability improved with increasing data.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.19.23284747v1" target="_blank">Raman spectroscopy, used trans-cutaneously and non-invasively from a finger, to predict COVID-19: A feasibility, proof-of-concept study.</a>
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<li><strong>Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection</strong> -
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The incidence of long COVID is substantial, even in people who did not require hospitalization for acute COVID–19. The pathobiological mechanisms of long COVID and the role of early viral kinetics in its development are largely unknown. Seventy–three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS–CoV–2 RT–PCR test, and mid–turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS–CoV–2 using RT–PCR and additional test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1, 3, 6, 12, and 18 months post–COVID–19 diagnosis. Time from acute COVID–19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90 or more days from acute COVID–19 symptom onset. Brain fog and muscle pain at 90 or more days after acute COVID–19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID–19 onset with adjustment for age, sex, BMI over 25, and COVID vaccination status prior to COVID–19 (brain fog: aRR 0.46, 95% CI 0.22 – 0.95; muscle pain: aRR 0.28, 95% CI 0.08 – 0.94). This work indicates that at least two long COVID symptoms, brain fog and muscle pain, at 90 or more days from acute COVID–19 onset are specifically associated with longer time to clearance of SARS–CoV–2 RNA from the upper respiratory tract.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.18.23284742v1" target="_blank">Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection</a>
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<li><strong>Early risk-assessment of pathogen genomic variants emergence</strong> -
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Accurate, reliable, and timely estimates of pathogen variant risk are essential for informing effective public health responses to infectious diseases. Despite decades of use for influenza vaccine strain selection and PCR-based molecular diagnostics, data on pathogen variant prevalence and growth advantage has only risen to its current prominence during the SARS-CoV-2 pandemic. However, such data are still often sparse: novel variants are initially rare or a region has limited sequencing. To ensure real-time estimates of risk are available in these types of data-sparse conditions, we develop a hierarchical modeling approach that estimates variant fitness advantage and prevalence by pooling data across geographic regions. We apply this method to estimate SARS-CoV-2 variant dynamics at the country-level and assess its stability with retrospective validation. Our results show that more stable and robust estimates can be obtained even when sequencing data are sparse, as compared to established, single-country estimation approaches. We discuss how this method can inform risk assessment of novel emerging variants and provide situational awareness on currently circulating variants, for a range of pathogens and use-cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.02.23284123v2" target="_blank">Early risk-assessment of pathogen genomic variants emergence</a>
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<li><strong>A Phase 2/3 observer-blind, randomized, controlled study to determine the safety and immunogenicity of SARS-CoV-2 recombinant spike protein vaccine in Indian children and adolescents aged 2 to 17 years</strong> -
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Background: A recombinant, adjuvanted COVID-19 vaccine, SII-NVX-CoV2373 was manufactured in India and evaluated in Indian children and adolescents to assess safety and immunogenicity. Methods: This was a Phase 2/3 observer-blind, randomized, controlled immuno-bridging study in children and adolescents aged 2 to 17 years. Participants were randomly assigned in 3:1 ratio to receive two doses of SII-NVX-CoV2373 or placebo on day 1 and day 22. Solicited adverse events (AEs) were collected for 7 days after each vaccination. Unsolicited AEs were collected for 35 days following first dose and serious AEs (SAEs) and adverse events of special interest (AESI) were collected throughout the study. Anti S IgG and neutralizing antibodies against the SARS-CoV-2 were measured at baseline, day 22, day 36 and day 180. Variant immune responses were assessed in a subset of participants at baseline, day 36 and day 180. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 in each pediatric age group (12 to 17 years and 2 to 11 years, separately) to that in adults in terms of ratio of titers of both anti-S IgG and neutralizing antibodies 14 days after the second dose (day 36). Non-inferiority was to be concluded if the lower bound of 95% CI of the ratio was >0.67. Results: A total of 920 children and adolescents (460 in each age cohort; 12 to 17 years and 2 to 11 years) were randomized and vaccinated. The demographic and baseline characteristics between the two groups were comparable in both age groups. After the second dose, there were more than 100-fold rise in anti-S IgG GMEUs and more than 84-fold rise in neutralizing antibodies GMTs from baseline in the participants who received SII-NVX-CoV2373. The lower bound of 95% CI of GMT ratios for anti-S IgG GMEUs and neutralizing antibodies in both age groups to those observed in Indian adults were >0.67, thus non-inferiority was met [Anti-S IgG GMT ratios 1.52 (1.38, 1.67), 1.20 (1.08, 1.34) and neutralizing antibodies GMT ratios 1.93 (1.70, 2.18), 1.33 (1.17, 1.50) for 2 to 11 years and 12 to 17 years groups, respectively]. The seroconversion rate was ≥ 98% (anti-S IgG) and ≥ 97.9 % (neutralizing antibodies) in both age groups, respectively. Similar findings were seen in the baseline seronegative participants. SII-NVX-CoV2373 also showed robust responses against various variants of concern. Injection site pain, tenderness, swelling, erythema and fever, headache, malaise, fatigue, were the common (≥5%) solicited adverse events which were transient and resolved without any sequelae. Throughout the study, only two causally unrelated SAEs and no AESI were reported. Conclusion: SII-NVX-CoV2373 has been found safe and well tolerated in children and adolescents of 2 to 17 years. The vaccine was highly immunogenic and the immune response was non-inferior to that in adults.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.23284130v2" target="_blank">A Phase 2/3 observer-blind, randomized, controlled study to determine the safety and immunogenicity of SARS-CoV-2 recombinant spike protein vaccine in Indian children and adolescents aged 2 to 17 years</a>
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<li><strong>Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis</strong> -
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The omicron variant is thought to cause less olfactory dysfunction than previous variants of SARS-CoV-2, but the reported prevalence differs greatly between populations and studies. Our systematic review and meta-analysis provide information about regional differences in prevalence as well as an estimate of the global prevalence of olfactory dysfunction based on 62 studies reporting on nearly 626,035 patients infected with the omicron variant. Our estimate of the omicron-induced prevalence of olfactory dysfunction in populations of European ancestry is 11.7%, while it is significantly lower in all other populations, ranging between 1.9% and 4.9%. When ethnic differences and population sizes are taken into account, the global prevalence of omicron-induced olfactory dysfunction in adults is estimated at 3.7%. The effect of omicron on olfaction is twofold to tenfold lower than that of the alpha or delta variant, according to previous meta-analyses and our analysis of studies that directly compared prevalence of olfactory dysfunction between omicron and previous variants. The profile of prevalence differences between ethnicities mirrors the results of a recent genome-wide association study that implicated a gene locus encoding an odorant-metabolizing enzyme, UDP glycosyltransferase, to be linked to the extent of COVID-related loss of smell. Our analysis is consistent with the hypothesis that this enzyme contributes to the observed population differences.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.16.22283582v2" target="_blank">Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis</a>
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<li><strong>Ensemble of deep learning language models to support the creation of living systematic reviews for the COVID-19 literature: a retrospective study</strong> -
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Background: The COVID-19 pandemic has led to an unprecedented amount of scientific publications, growing at a pace never seen before. Multiple living systematic reviews have been developed to assist professionals with up-to-date and trustworthy health information, but it is increasingly challenging for systematic reviewers to keep up with the evidence in electronic databases. We aimed to investigate deep learning-based machine learning algorithms to classify COVID-19 related publications to help scale-up the epidemiological curation process. Methods: In this retrospective study, five different pre-trained deep learning-based language models were fine-tuned on a dataset of 6,365 publications manually classified into two classes, three subclasses and 22 sub-subclasses relevant for epidemiological triage purposes. In a k-fold cross-validation setting, each standalone model was assessed on a classification task and compared against an ensemble, which takes the standalone model predictions as input and uses different strategies to infer the optimal article class. A ranking task was also considered, in which the model outputs a ranked list of sub-subclasses associated with the article. Results: The ensemble model significantly outperformed the standalone classifiers, achieving a F1-score of 89.2 at the class level of the classification task. The difference between the standalone and ensemble models increases at the sub-subclass level, where the ensemble reaches a micro F1-score of 70% against 67% for the best performing standalone model. For the ranking task, the ensemble obtained the highest recall@3, with a performance of 89%. Using an unanimity voting rule, the ensemble can provide predictions with higher confidence on a subset of the data, achieving detection of original papers with a F1-score up to 97% on a subset of 80% of the collection instead of 93% on the whole dataset. Conclusion: This study shows the potential of using deep learning language models to perform triage of COVID-19 references efficiently and support epidemiological curation and review. The ensemble consistently and significantly outperforms any standalone model. Fine-tuning the voting strategy thresholds is an interesting alternative to annotate a subset with higher predictive confidence.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.18.524571v1" target="_blank">Ensemble of deep learning language models to support the creation of living systematic reviews for the COVID-19 literature: a retrospective study</a>
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<li><strong>Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study</strong> -
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As the number of confirmed COVID-19 cases now exceeds 100 million cases in the United States and continues to climb, concerns have been increasingly raised over the future public health and economic burden of long COVID including disability and concomitant declines in labor force participation. Only a handful of US population-based studies have explored sociodemographic and socioeconomic characteristics that put people at risk of long COVID or have investigated its mental health and socioeconomic sequelae. Herein, I report findings from the largest multivariable analysis to date using US nationally-representative data on 153,543 adults including 19,985 adults with long COVID to explore key predictors and sequelae of long COVID. An estimated 14.0% of adults aged 18-84 y (35.11 million adults) and 15.5% of working-aged adults aged 18-64 y (30.65 million adults) had developed long COVID by November 2022. Several sociodemographic and socioeconomic factors predicted long COVID including lower household income, being aged 30-49 y, Hispanic, female, gay/lesbian or bisexual, and divorced/separated. Even after accounting for such factors, having long COVID was linked to higher risks of recent unemployment, financial hardship, and anxiety and depressive symptomatology, with evidence of dose-response relationships. Overall, an estimated 27.7 million US adults aged 18-84 y and 24.2 million working-aged adults with long COVID who had been or may still be at risk of adverse socioeconomic and mental health outcomes. Lost work was further calculated to be the equivalent of 3 million workers annually, and the estimated annual lost earnings due to long COVID among working-aged adults totaled $175 billion. These preliminary findings highlight the substantial public health and economic implications of long COVID among Americans and should prompt further inquiry and intervention.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.06.23284199v2" target="_blank">Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study</a>
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<li><strong>Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection</strong> -
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There is limited data directly comparing the effectiveness of COVID-19 vaccines. We compared rates of SARS-CoV-2 Omicron BA.1/2 infection in Australian adults during March to May 2022 who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose. As a primary course, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For booster dose, respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60). Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines, but further studies are required due to small numbers of recipients of ChAdOx-1 nCov-19 and NVX-CoV2373.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.22.22283869v2" target="_blank">Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection</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>Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Digital based contact tracing<br/><b>Sponsors</b>: Elizabeth Glaser Pediatric AIDS Foundation; Find<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>Evaluation of the Outcome of COVID-19 Patients Discharged Home on Oxygen Therapy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Phone satisfaction questionnaire<br/><b>Sponsor</b>: Centre Hospitalier René Dubos<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>Postural Changes and Severe COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Postural interventions based on pulmonary imaging<br/><b>Sponsor</b>: Wuhan Union Hospital, China<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Chatbot to Enhance COVID-19 Knowledge</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: chatbot; Other: Printed educational booklet<br/><b>Sponsor</b>: Sun Yat-sen 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>Awaken Prone Positioning Ventinlation in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Awaken prone positioning ventilation<br/><b>Sponsor</b>: Southeast University, China<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>Study of SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 dose 1; Drug: SHEN26 dose 2; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bright Light Therapy for Post-COVID-19 Fatigue</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Device: Bright light therapy; Device: Dim red light therapy<br/><b>Sponsor</b>: Chinese University of Hong Kong<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>Study on the Safety and Efficacy of Meplazumab for Injection Patients COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab foe injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio 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>Study on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio 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>A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally 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>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>Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).<br/><b>Sponsor</b>: Hospital General Nuestra Señora del Prado<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 Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: DNA vaccine OC-007; Other: Placebo<br/><b>Sponsor</b>: Matti Sällberg<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>Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies 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>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Interventions</b>: Biological: umbilical cord mesenchymal stem cells; Drug: paxlovid<br/><b>Sponsor</b>: Shanghai East Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Positive Emotions With Long COVID-19</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Microdosing of mindfulness<br/><b>Sponsor</b>: University of California, Davis<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>SURFing SARS-CoV-2 inhibition</strong> - No abstract</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>Com probe implemented STexS II greatly enhances specificity in SARS-CoV-2 variant detection</strong> - The initial introduction of utilizing double helix structural oligonucleotides known as SNP typing with excellent specificity (STexS) in a standard PCR greatly improved the detection of single nucleotide polymorphisms (SNP) by enhancing amplification rates of primer-matching strands and interrupting mismatched strands by constant instability of kinetics regarding alignment attaching and detaching. The model was beneficial overall in detecting SNP variants consisting of large amounts of wildtype…</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>Characterization of RNA G-quadruplexes in porcine epidemic diarrhea virus genome and the antiviral activity of G-quadruplex ligands</strong> - Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there are still no anti-PEDV drugs with accurate targets. G-quadruplexes (G4s) are non-canonical secondary structures formed within guanine-rich regions of DNA or RNA, and have attracted great attention as potential targets for antiviral strategy. In this study, we reported two putative G4-forming sequences (PQS) in S and Nsp5 genes of PEDV genome based on…</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>Thorectidiol A Isolated from the Marine Sponge <em>Dactylospongia elegans</em> Disrupts Interactions of the SARS-CoV-2 Spike Receptor Binding Domain with the Host ACE2 Receptor</strong> - Thorectidiols isolated from the marine sponge Dactylospongia elegans (family Thorectidae, order Dictyoceratida) collected in Papua New Guinea are a family of symmetrical and unsymmetrical dimeric biphenyl meroterpenoid stereoisomers presumed to be products of oxidative phenol coupling of a co-occurring racemic monomer, thorectidol (3). One member of the family, thorectidiol A (1), has been isolated in its natural form, and its structure has been elucidated by analysis of NMR, MS, and ECD 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>Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17</strong> - Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, 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>Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration</strong> - Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible…</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>Antiviral Potential of Melissa officinalis L.: A Literature Review</strong> - The use of synthetic drugs has increased in recent years; however, herbal medicine is yet more trusted among a huge population worldwide; This could be due to minimal side effects, affordable prices, and traditional beliefs. Lemongrass (Melissa officinalis) has been widely used for reducing stress and anxiety, increasing appetite and sleep, reducing pain, healing wounds, and treating poisonous insect bites and bee stings for a long time. Today, research has shown that this plant can also fight…</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>Broad-Spectrum Cyclopropane-Based Inhibitors of Coronavirus 3C-like Proteases: Biochemical, Structural, and Virological Studies</strong> - The advent of SARS-CoV-2, the causative agent of COVID-19, and its worldwide impact on global health, have provided the impetus for the development of effective countermeasures that can be deployed against the virus, including vaccines, monoclonal antibodies, and direct-acting antivirals (DAAs). Despite these efforts, the current paucity of DAAs has created an urgent need for the creation of an enhanced and diversified portfolio of broadly acting agents with different mechanisms of action that…</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>Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19</strong> - This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is…</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>PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection</strong> - CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).</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 Natural Products Inhibiting SARS-CoV-2 by Targeting Viral Proteases: A Combined in Silico and in Vitro Approach</strong> - In this study, an integrated in silico-in vitro approach was employed to discover natural products (NPs) active against SARS-CoV-2. The two SARS-CoV-2 viral proteases, i.e., main protease (M^(pro)) and papain-like protease (PL^(pro)), were selected as targets for the in silico study. Virtual hits were obtained by docking more than 140,000 NPs and NP derivatives available in-house and from commercial sources, and 38 virtual hits were experimentally validated in vitro using two enzyme-based…</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>Potential of plant extracts in targeting SARS-CoV-2 main protease: an <em>in vitro</em> and <em>in silico</em> study</strong> - The deaths caused by the covid-19 pandemic have recently decreased due to a worldwide effort in vaccination campaigns. However, even vaccinated people can develop a severe form of the disease that requires ICU admission. As a result, the search for antiviral drugs to treat these severe cases has become a necessity. In this context, natural products are an interesting alternative to synthetic medicines used in drug repositioning, as they have been consumed for a long time through traditional…</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>Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants</strong> - As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C(60) fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit…</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>Detailed Insights into the Inhibitory Mechanism of New Ebselen Derivatives against Main Protease (M<sup>pro</sup>) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)</strong> - SARS-CoV-2 main protease (M<sup>(pro)/3CL</sup>(pro)) is a crucial target for therapeutics, which is responsible for viral polyprotein cleavage and plays a vital role in virus replication and survival. Recent studies suggest that 2-phenylbenzisoselenazol-3(2H)-one (ebselen) is a potent covalent inhibitor of M^(pro), which affects its enzymatic activity and virus survival. Herein, we synthesized various ebselen derivatives to understand the mechanism of M^(pro) inhibition by ebselen. Using ebselen…</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 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses</strong> - SARS-CoV-2 infection can trigger strong inflammatory responses and cause severe lung damage in COVID-19 patients with critical illness. However, the molecular mechanisms by which the infection induces excessive inflammatory responses are not fully understood. Here, we report that SARS-CoV-2 infection results in the formation of viral Z-RNA in the cytoplasm of infected cells and thereby activates the ZBP1-RIPK3 pathway. Pharmacological inhibition of RIPK3 by GSK872 or genetic deletion of MLKL…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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