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<title>06 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>Impact of the COVID-19 Pandemic on International Business Travel and Associated Health Issues: A Survey of Japanese Public Companies</strong> -
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Objectives: Compared to long-term expatriates, the health issues of short-term international business travellers are less clear. Particularly, there are no reports on the impact of the COVID-19 pandemic. We explored the changes in health challenges faced by Japanese international business travellers owing to the COVID-19 pandemic. Design: Cross-sectional survey research using questionnaires Setting: We surveyed 3,845 listed public companies in Japan in September 2021. Participants: A total of 251 companies responded (response rate: 6.5%), of which 131 (52%) had foreign travel requirements for their business. Primary and secondary outcome measures: The survey included questions regarding company size, business type, necessity for foreign travel, destination and number of trips, common health issues that arise, and the importance of business travel before and after the COVID-19 pandemic. Results: Among the companies, 44% replied that they could not predict the number of foreign business trips after the pandemic. However, 64% of companies responded that business travel would continue to be important in the future. Before the COVID-19 pandemic, the most important health concerns faced by business travellers were illness during travel (42%), followed by the prevention of infectious diseases and lifestyle disease management. Post-pandemic, 48% of the responses were for infectious diseases, including COVID-19, followed by 40% for travel-related diseases, and 25% for lifestyle-related diseases. Conclusions: Owing to global economic and social activities, business travel will continue to be necessary in the post-COVID-19 era. Comprehensive health management including prevention of infectious diseases is desirable for business travel.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293302v1" target="_blank">Impact of the COVID-19 Pandemic on International Business Travel and Associated Health Issues: A Survey of Japanese Public Companies</a>
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<li><strong>Racial/Ethnic Differences in COVID-19-Traumatic Symptoms, Sleep, Coping Outcomes in a Group of New-Yorkers</strong> -
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Background: Little research has examined within/between group predictors and mediators of race/ethnic differences or disparities in mental and sleep health outcomes arising from the experience of the COVID-19 pandemic. Objectives: This study sought to evaluate the effect of COVID-19 experiences on trauma-related symptoms and sleep quality among a multiracial/ethnic sample in New York. Method: This is a cross-sectional study conducted online among multiethnic adults (n=541) who experienced the pandemic in New York from September to November 2020. Comparisons of characteristics and mean scores by race/ethnicity status were conducted using one-way ANOVA and independent samples t-tests for continuous variables and chi-square tests for categorical variables. Multilinear regression was used for associations between social determinants of health and/or SES, trauma-related symptoms, coping, and sleep. Results: Compared to Whites [Mean (SD)= (24.1(7.6)] and other group [Mean (SD)=24.9(8.2), Blacks [Mean (SD)=(26.3(6.4)] and Hispanics [Mean(SD)=(27.2(8.2)] reported higher level of peritraumatic distress [ df= 3; F=4273; p=0.005). The prevalence of clinically significant PTSD symptoms was 21.4%(n=113): [Whites=31(16.3%); Blacks=28(25.7%); Hispanics=24(25%); and other groups=30(22.4%); x2 =4.93; p=0.177]. This rate doubled [48.3%(257)] when it comes to the overall clinically significant depression level. Compared to all subcategories, [Blacks=52(47.7%); Hispanics =62(64.6%); other group=66(49.3%)], depression symptoms were lower among Whites [77(39.9%; x2 =15.71; p=0.001]. We found a prevalence of insufficient sleep <6 hours of 41%(198): [Whites=69(39.4%); Blacks=43(41.7%); Hispanics=46(52.3%); other groups=40(34.2%); x2=12.21; p=0.057]. Several unique demographic predictors of PTSD emerged for distinct racial/ethnic groups. Among Blacks, sex [β = −0.22; p < .01] and employment [β = −0.159; p < .05] emerged as significant predictors for PTSD, but for no other racial/ethnic group. Interestingly, among Hispanics [β = −0.144; p = .064] and Blacks [β = −0.174; p = .0.076], coping strategies did not mitigate PTSD or depressive symptoms. Conclusion: As New York and the rest of the world are trying to bounce back from the COVID-19 consequences, mental health outcomes are devastating, particularly among historically marginalized communities. This study provides insight into the emergency for policymakers to invest in racial justice programs and provide free access to culturally responsive mental health care for the most vulnerable groups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293452v1" target="_blank">Racial/Ethnic Differences in COVID-19-Traumatic Symptoms, Sleep, Coping Outcomes in a Group of New-Yorkers</a>
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<li><strong>Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection</strong> -
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Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293337v1" target="_blank">Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection</a>
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<li><strong>Healthcare resource utilization and costs associated with COVID-19 among pediatrics managed in the community or hospital setting in England: a population-based cohort study</strong> -
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Background Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial healthcare resource burden. This study aimed to describe healthcare resource utilization (HCRU) and costs associated with COVID-19 in pediatrics aged 1-17 years in England. Methods A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care (HES APC) secondary care data. HCRU and associated costs to the National Health Service (NHS) were stratified by age, risk of severe COVID-19, and immunocompromized status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022). Results This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those aged 1-4 years (face-to-face: 4.3%; telephone: 6.0%) compared to those aged 5-11 (2.0%; 2.1%) and 12-17 years (2.2%; 2.5%). In the hospitalized cohort, mean [SD] length of stay was longer (5.0 [5.8] days) among those aged 12-17 years (n=24) than those aged 1-4 (n=15; 1.8 [0.9] days) and 5-11 years (n=21; 2.8 [2.1] days). Conclusions Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those aged 12-17 years. Our results may help optimize the management and resource allocation of COVID-19 in this population.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293335v1" target="_blank">Healthcare resource utilization and costs associated with COVID-19 among pediatrics managed in the community or hospital setting in England: a population-based cohort study</a>
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<li><strong>Systematic Review and Meta-Analysis Protocol of the Efficacy and Safety of COVID-19 Drug Candidates Targeting Host Enzymes Involved in Immune Response</strong> -
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COVID-19 is a rapidly spreading infectious disease caused by the SARS-CoV-2 virus. Although several therapeutic interventions have been developed, the mortality rate of the disease remains high, and effective treatment options are urgently needed. Host-directed therapies targeting enzymes involved in the immune response represent a promising strategy for the development of novel therapeutics against COVID-19. This study aims to conduct a systematic review and meta-analysis of the literature to evaluate the potential of drug candidates targeting host enzymes involved in the immune response for the treatment of COVID-19. We will conduct a systematic search of electronic databases including PubMed, Embase, and Cochrane Library, as well as preprint servers and clinical trial registries for relevant studies. We will include randomized controlled trials, observational studies, and preclinical studies evaluating the efficacy of drug candidates targeting host enzymes involved in the immune response in COVID-19. Two reviewers will independently screen articles, extract data, and assess study quality. The primary outcome will be the effect of drug candidates on mortality, while secondary outcomes will include time to recovery, adverse events, and changes in immune markers. A meta-analysis will be performed to estimate pooled effect sizes of the interventions, and a narrative synthesis will be conducted for studies that are not amenable to quantitative analysis. This study will provide a comprehensive evaluation of the potential of host-directed therapies targeting enzymes involved in the immune response for the treatment of COVID-19. The results of this study may guide the development of novel therapeutics against COVID-19 and inform clinical practice.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293338v1" target="_blank">Systematic Review and Meta-Analysis Protocol of the Efficacy and Safety of COVID-19 Drug Candidates Targeting Host Enzymes Involved in Immune Response</a>
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<li><strong>Vaccine effectiveness against hospitalisation and comparative odds of hospital admission and severe outcomes with BQ.1, CH.1.1. and XBB.1.5 in England.</strong> -
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Background Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity. Methods A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant. Findings There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5 to 56.0%), 29.7% (95% C.I.; 7.5 to 46.6%) and 52.7% (95% C.I.; 24.6 to 70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5 to 9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77 to 0.99) and 0.88 (95% C.I.; 0.75 to 1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71 to 1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44 to 1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant. Interpretation Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1. Funding None.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293333v1" target="_blank">Vaccine effectiveness against hospitalisation and comparative odds of hospital admission and severe outcomes with BQ.1, CH.1.1. and XBB.1.5 in England.</a>
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<li><strong>Phylogenies increase power to detect highly transmissible viral genome variants</strong> -
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As demonstrated by the SARS-CoV-2 pandemic, the emergence of novel viral strains with increased transmission rates poses a significant threat to global health. Viral genome sequences, combined with statistical models of sequence evolution, may provide a critical tool for early detection of these strains. Using a novel statistical model that links transmission rates to the entire viral genome sequence, we study the power of phylogenetic methods—using a phylogenetic tree relating viral samples—and count-based methods—using case-counts of variants over time—to detect increased transmission rates, and to identify causative mutations. We find that phylogenies in particular can detect novel variants very soon after their origin, and may facilitate the development of early detection systems for outbreak surveillance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293332v1" target="_blank">Phylogenies increase power to detect highly transmissible viral genome variants</a>
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<li><strong>SARS-CoV-2 live virus culture and sample freeze-thaw stability</strong> -
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The COVID-19 pandemic has presented unique diagnostic challenges including the need to store and test large number of samples for clinical and research studies. While SARS CoV-2 diagnosis relies on RT-qPCR and antigen testing, live virus culture remains an important surrogate for viral 9infectiousness9, as we previously described in 9SARS-CoV-2 Antigen Tests Predict Infectivity Based on Viral Culture: Comparison of Antigen, PCR Viral Load and Viral Culture Testing on a Large Sample Cohort9 (Clin Microbiol Infect, 2022, PMC9293398). Live virus isolation and characterization has also been important to the SARS CoV-2 research community, to assess viral fitness, cellular tropism, and live virus neutralization, particularly with the emergence of new variants. Many clinical and research studies make use of samples that are frozen in transport media and investigated at later dates. The effect of freezing on RT-qPCR results is well established. However, the effect of freeze-thaw on viral viability has not been. Here, we therefore examined the effect of freeze-thaw on viral culture isolation from a large number of clinical samples that were split, and then cultured either fresh or after being frozen for 7 or 17-18 days. Samples represented the range of viral loads (genome copies/mL) observed in our patient population. We found that freeze-thaw did not significantly affect viral culture isolation. Therefore, the ability to assess infectiousness of samples previously frozen in transport medium appears to be maintained.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.29.23293373v1" target="_blank">SARS-CoV-2 live virus culture and sample freeze-thaw stability</a>
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<li><strong>CLINICAL AND SEROLOGICAL PREDICTORS OF POST COVID-19 CONDITION: FINDINGS FROM A CANADIAN PROSPECTIVE COHORT STUDY</strong> -
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Introduction: More than three years into the pandemic, there is persisting uncertainty as to the etiology, biomarkers, and risk factors of Post COVID-19 Condition (PCC). Serological research data remain a largely untapped resource. Few studies have investigated the potential relationships between post-acute serology and PCC, while accounting for clinical covariates. Methods: We compared clinical and serological predictors among COVID-19 survivors with (n=102 cases) and without (n=122 controls) persistent symptoms ≥ 12 weeks post-infection. We selected four primary serological predictors (anti-nucleocapsid (N), anti-Spike, and anti-receptor binding domain (RBD) IgG titres, and neutralization efficiency), and specified clinical covariates a priori. Results: Similar proportions of PCC-cases (66.7%, n=68) and infected-controls (71.3%, n=87) tested positive for anti-N IgG. More cases tested positive for anti-Spike (94.1%, n=96) and anti-RBD (95.1%, n=97) IgG, as compared with controls (anti-Spike: 89.3%, n=109; anti-RBD: 84.4%, n=103). Similar trends were observed among unvaccinated participants. Effects of IgG titres on PCC status were non-significant in univariate and multivariate analyses. Adjusting for age and sex, PCC-cases were more likely to be efficient neutralizers (OR 2.2, 95% CI 1.11 - 4.49), and odds was further increased among cases to report deterioration in quality of life (OR 3.4, 95% CI 1.64 - 7.31). Clinical covariates found to be significantly related to PCC included obesity (OR 2.3, p=0.02), number of months post COVID-19 (OR 1.1, p<0.01), allergies (OR 1.8, p=0.04), and need for medical support (OR 4.1, p<0.01). Conclusion: Despite past COVID-19 infection, approximately one third of PCC-cases and infected-controls were seronegative for anti-N IgG. Findings suggest higher neutralization efficiency among cases as compared with controls, and that this relationship is stronger among cases with more severe PCC. Cases also required more medical support for COVID-19 symptoms, and described complex, ongoing health sequelae. More data from larger cohorts are needed to substantiate results, permit subgroup analyses of IgG titres, and explore for differences between clusters of PCC symptoms. Future assessment of IgG subtypes may also elucidate new findings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.29.23293334v1" target="_blank">CLINICAL AND SEROLOGICAL PREDICTORS OF POST COVID-19 CONDITION: FINDINGS FROM A CANADIAN PROSPECTIVE COHORT STUDY</a>
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<li><strong>Advances and pitfalls in measuring transportation equity</strong> -
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Transportation systems play a pivotal role in facilitating access to out-of-home activities, enabling participation in various aspects of social life. But because of budgetary and physical limitations, they cannot provide equal access to all locations; inevitably, some places will be better served than others. This realization gives rise to two fundamental concerns in transportation equity: 1) accessibility inequality and 2) accessibility poverty. Accessibility inequalities may rise to the level of injustice when some socioeconomic groups systematically have lower access to opportunities than others. Accessibility poverty occurs when people are unable to meet their daily needs and live a dignified, fulfilling life because of a lack of access to essential services and opportunities. In this paper, we review two of the most widely used approaches for evaluating transport justice concerns with accessibility inequality and accessibility poverty: Gini coefficients/Lorenz curves and needs-gap/transit desert approaches, respectively. We discuss how their theoretical underpinnings are inconsistent with egalitarian and sufficientarian concerns in transport justice, and show how the underlying assumptions of these methods and their applications found in the transportation equity literature embody many previously unacknowledged limitations that severely limit their utility. We substantiate these concerns by analysing the equity impacts of Covid-19-related service cuts undertaken in Washington, D.C. during 2020. The paper also discusses how alternative methods for measuring transportation equity both better comport with the known impacts of such changes and are consistent with underlying moral concerns.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/y246u/" target="_blank">Advances and pitfalls in measuring transportation equity</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/10.1101/2023.07.28.23293269v1" 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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<li><strong>Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner</strong> -
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Post-acute Sequelae of COVID-19 (PASC), also known as Long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19 infection. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited. Using a sample of 55,257 participants from the National COVID Cohort Collaborative, as part of the NIH Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. We predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal, AUC-maximizing combination of gradient boosting and random forest algorithms. We were able to predict individual PASC diagnoses accurately (AUC 0.947). Temporally, we found that baseline characteristics were most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after COVID-19 infection. This finding supports the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients prior to acute COVID diagnosis, which could improve early interventions and preventive care. We found that medical utilization, demographics and anthropometry, and respiratory factors were most predictive of PASC diagnosis. This highlights the importance of respiratory characteristics in PASC risk assessment. The methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.27.23293272v1" target="_blank">Predicting Long COVID in the National COVID Cohort Collaborative Using Super Learner</a>
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<li><strong>Exploring Disparities and Novel Insights into Metabo-Nutritional Comorbidities among COVID-19 Patients in Mexico</strong> -
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During the previous years, particularly at the beginning of the COVID- 19 pandemic, the potential role of metabo-nutritional comorbidities in the severity and lethality of SARS-CoV2 infection has been widely dis- cussed, often describing ambiguous outcomes. Here we investigate the prevalence of metabo-nutritional comorbidities among COVID-19 patients in Mexico. Using a retrospective observational study design, data was collected from official databases of COVID-19 patients admitted to pub- lic and private hospitals in Mexico City. Our study found a discordant prevalence of metabo-nutritional comorbidities among COVID-19 patients, particularly obesity, hypertension, and diabetes. Discordance consists in geographic location-dependent over and under-representation phenomena, that is the prevalence of such comorbidities in COVID-19 patients was significantly over or under the reported value for the general population in each location. These findings highlight the importance of screening for metabo-nutritional comorbidities in COVID-19 patients and suggest the need for tailored interventions for this population. The study also provides insights into the complex relationships between COVID-19 and metabo-nutritional comorbidities, which may inform future research and clinical practice.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.31.23293471v1" target="_blank">Exploring Disparities and Novel Insights into Metabo-Nutritional Comorbidities among COVID-19 Patients in Mexico</a>
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<li><strong>Text mining biomedical literature to identify extremely unbalanced data for digital epidemiology and systematic reviews: dataset and methods for a SARS-CoV-2 genomic epidemiology study</strong> -
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There are many studies that require researchers to extract specific information from the published literature, such as details about sequence records or about a randomized control trial. While manual extraction is cost efficient for small studies, larger studies such as systematic reviews are much more costly and time-consuming. To avoid exhaustive manual searches and extraction, and their related cost and effort, natural language processing (NLP) methods can be tailored for the more subtle extraction and decision tasks that typically only humans have performed. The need for such studies that use the published literature as a data source became even more evident as the COVID-19 pandemic raged through the world and millions of sequenced samples were deposited in public repositories such as GISAID and GenBank, promising large genomic epidemiology studies, but more often than not lacked many important details that prevented large-scale studies. Thus, granular geographic location or the most basic patient-relevant data such as demographic information, or clinical outcomes were not noted in the sequence record. However, some of these data was indeed published, but in the text, tables, or supplementary material of a corresponding published article. We present here methods to identify relevant journal articles that report having produced and made available in GenBank or GISAID, new SARS-CoV-2 sequences, as those that initially produced and made available the sequences are the most likely articles to include the high-level details about the patients from whom the sequences were obtained. Human annotators validated the approach, creating a gold standard set for training and validation of a machine learning classifier. Identifying these articles is a crucial step to enable future automated informatics pipelines that will apply Machine Learning and Natural Language Processing to identify patient characteristics such as co-morbidities, outcomes, age, gender, and race, enriching SARS-CoV-2 sequence databases with actionable information for defining large genomic epidemiology studies. Thus, enriched patient metadata can enable secondary data analysis, at scale, to uncover associations between the viral genome (including variants of concern and their sublineages), transmission risk, and health outcomes. However, for such enrichment to happen, the right papers need to be found and very detailed data needs to be extracted from them. Further, finding the very specific articles needed for inclusion is a task that also facilitates scoping and systematic reviews, greatly reducing the time needed for full-text analysis and extraction.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.29.23293370v1" target="_blank">Text mining biomedical literature to identify extremely unbalanced data for digital epidemiology and systematic reviews: dataset and methods for a SARS-CoV-2 genomic epidemiology study</a>
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<li><strong>Bi-directional associations between mask usage and the associated reasons before and after the downgrading of the legal status of COVID-19 in Japan: A longitudinal study</strong> -
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Objectives: From a public health perspective, it is important to clarify the associations between mask usage and the associated reasons in situations when mask usage is promoted or mitigated. Therefore, I clarified the changes in mask usage and the associated reasons before and after the downgrading of the legal status of COVID-19 in Japan, and analyzed the bi-directional associations between the two. Design: Longitudinal study. Methods: Online surveys were conducted in two waves, between April 18-19, 2023 and June 6-15, 2023, among people aged 20-69 years living in Japan. A total of 291 participants completed both the surveys. The associations between mask usage and beliefs about the reasons for mask usage were analyzed using a cross-lagged panel model. Results: Mask usage decreased slightly, but significantly, from the first to the second wave (P < 0.001, Cohen9s d = -0.23). Of the eight beliefs regarding mask usage, slight but significant decreases were observed in terms of relief and information effects (P = 0.046, Cohen9s d = -0.12; P = 0.018, Cohen9s d = -0.14). There was a significant association between socio-psychological reasons other than infection risk avoidance (such as norm and relief) during the first wave and mask usage during the second wave [standard estimates:0.25 (95% confidence interval (CI):0.06-0.44)]. Contrarily, mask usage during the first wave was significantly associated with the reasons for infection risk avoidance during the second wave [standard estimates:0.13 (0.03-0.24)]. Conclusions: The impact of downgrading the legal status of COVID-19 in Japan on mask usage and the associated reasons were found to be limited. In terms of promoting or mitigating mask usage, the significance of risk communication based on socio-psychological reasons other than infection risk avoidance, such as norms and relief, was highlighted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.28.23293298v1" target="_blank">Bi-directional associations between mask usage and the associated reasons before and after the downgrading of the legal status of COVID-19 in Japan: A longitudinal study</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>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Freeze-dried Mare Milk (Saumal)<br/><b>Sponsor</b>: Asfendiyarov Kazakh National Medical 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>Effects of Exercise Training on Patients With Long COVID-19</strong> - <b>Condition</b>: Long COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training<br/><b>Sponsor</b>: Guangdong Provincial People’s 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>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>A Phase 2/3 Open-Label Study to Evaluate the Safety and Immunogenicity of an XBB.1.5 (Omicron Subvariant) SARS CoV-2 rS Vaccine.</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>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>A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 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>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>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>Non-ventilated Prone Positioning in the COVID-19 Population</strong> - <b>Conditions</b>: COVID-19; Proning; Oxygenation; Length of Stay<br/><b>Interventions</b>: Other: Proning group; Other: Control group<br/><b>Sponsor</b>: Baylor St. Luke’s Medical Center<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>HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19</strong> - <b>Conditions</b>: COVID-19; Delirium; Critical Illness<br/><b>Interventions</b>: Combination Product: Active HD-tDCS; Combination Product: Sham HD-tDCS<br/><b>Sponsors</b>: Suellen Andrade; City University of New York<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>RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms</strong> - <b>Conditions</b>: Long COVID-19; Long COVID<br/><b>Interventions</b>: Drug: Paxlovid 25 day dosing; Drug: Paxlovid 15 day dosing; Drug: Control<br/><b>Sponsor</b>: Kanecia Obie Zimmerman<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: CV0701 Bivalent High dose; Biological: CV0701 Bivalent Medium dose; Biological: CV0701 Bivalent Low dose; Biological: CV0601 Monovalent High dose; Biological: Control vaccine<br/><b>Sponsors</b>: GlaxoSmithKline; CureVac<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>RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19<br/><b>Interventions</b>: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham<br/><b>Sponsor</b>: Duke 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>Directed Topical Drug Delivery for Treatment for PASC Hyposmia</strong> - <b>Condition</b>: Post Acute Sequelae Covid-19 Hyposmia<br/><b>Interventions</b>: Drug: Beclomethasone; Other: Placebo; Device: Microsponge<br/><b>Sponsor</b>: Duke 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>RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19<br/><b>Interventions</b>: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham<br/><b>Sponsor</b>: Duke University<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Self-Assembly Properties of an Amphiphilic Phosphate Ester Prodrug Designed for the Treatment of COVID-19</strong> - PF-07304814 is a water-soluble phosphate ester prodrug of a small molecule inhibitor for the SARS CoV-2 3CL protease designed for the treatment of COVID-19. The amphiphilicity and self-assembly behavior of the prodrug was investigated computationally and experimentally via multiple orthogonal techniques to better design formulations for intravenous infusion. The self-assembly of PF-07304814 into micellar structures enabled an increase in the solubility of lipophilic impurities by up to 1900x in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters</strong> - ABSTRACTPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing 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>Novel computational and drug design strategies for inhibition of monkeypox virus and <em>Babesia microti</em>: molecular docking, molecular dynamic simulation and drug design approach by natural compounds</strong> - CONCLUSION: These advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and 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>Reflections on access to care for heavy menstrual bleeding: Past, present, and in times of the COVID-19 pandemic</strong> - The symptom of heavy menstrual bleeding (HMB) affects at least a quarter of reproductive-age menstruators. However, given the variance in diagnosing the underlying causes, barriers, and inequity in access to care for HMB, and therefore reporting of HMB, this figure is likely to be a gross underestimate. HMB can have a detrimental impact on quality of life. From the limited reports available it is estimated that around 50%-80% of people with HMB do not seek care for this debilitating symptom, 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>Inhibition by components of <em>Glycyrrhiza uralensis</em> of 3CLpro and HCoV-OC43 proliferation</strong> - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 3CLpro is a key enzyme in coronavirus proliferation and a treatment target for COVID-19. In vitro and in silico, compounds 1-3 from Glycyrrhiza uralensis had inhibitory activity and binding affinity for 3CLpro. These compounds decreased HCoV-OC43 cytotoxicity in RD cells. Moreover, they inhibited viral growth by reducing the amounts of the necessary proteins (M, N,…</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>An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen</strong> - The threat to global health caused by three highly pathogenic human coronaviruses (HCoV), SARS-CoV-2, MERS-CoV and SARS-CoV, calls for the development of pan-HCoV therapeutics and vaccines. This study reports the design and engineering of a recombinant protein designated HR1LS. It contains 3 linked molecules, each consisting of three structural domains, including a heptad repeat 1 (HR1), a central helix (CH), and a stem helix (SH) region, in the S2 subunit of SARS-CoV-2 spike (S) protein. It was…</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>Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation</strong> - NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM…</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>Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease</strong> - Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate 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>Crystal structures of main protease (M<sup>pro</sup>) mutants of SARS-CoV-2 variants bound to PF-07304814</strong> - There is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (M^(pro)) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 M^(pro) with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment…</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>Direct blue 53, a biological dye, inhibits SARS-CoV-2 infection by blocking ACE2 and spike interaction in vitro and in vivo</strong> - COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles’ ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five…</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>Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model</strong> - Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells 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>Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury</strong> - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…</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>Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis</strong> - CONCLUSIONS: Potentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions.</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 main protease targeting potent fluorescent inhibitors: Repurposing thioxanthones</strong> - The coronavirus disease, COVID-19, is the major focus of the whole world due to insufficient treatment options. It has spread all around the world and is responsible for the death of numerous human beings. The future consequences for the disease survivors are still unknown. Hence, all contributions to understand the disease and effectively inhibit the effects of the disease have great importance. In this study, different thioxanthone based molecules, which are known to be fluorescent compounds,…</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 a small chemical as a lysosomal calcium mobilizer and characterization of its ability to inhibit autophagy and viral infection</strong> - We previously identified GAPDH as one of the cyclic adenosine diphosphoribose (cADPR)’s binding proteins and found that GAPDH participates in cADPR-mediated Ca^(2+) release from ER via ryanodine receptors (RyRs). Here we aimed to chemically synthesize and pharmacologically characterize novel cADPR analogues. Based on the simulated cADPR-GAPDH complex structure, we performed the structure-based drug screening, identified several small chemicals with high docking scores to cADPR’s binding pocket…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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