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<title>18 May, 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>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Promoting Urban Farming for Creating Sustainable Cities in Nepal</strong> -
<div>
This paper responds to the research question, “can urban farming in Nepal help create sustainable cities?” Especially after the COVID-19 pandemic, urban residents have begun to realize that food transported from long distances is not always reliable. Urban farming can help produce fresh food locally and help urban residents become self-reliant by engaging in healthy eating habits and practicing sustainable agricultural techniques in food-desert areas, while creating a positive impact on the environment through regenerative agricultural methods. In doing so, urban farms can help the growers save on food expenditures and even earn some additional income, while also improving air quality and minimizing the effects of urban heat islands. This practice also helps reduce greenhouse gases through plant carbon use efficiency (CUE), as vegetation carbon dynamics (VCD) can be adjusted while supporting the circular economy. As urban lands command higher prices than agricultural land, urban farming usually happens on residential yards, roofs, balconies, community gardens, and dedicated areas in public parks. Rainwater harvesting and redirecting can help irrigate urban farms, which can be part of rain gardens. The national census of 2021 identified that 66% of Nepal’s population lives in urban areas. However, the World Bank (2018) showed that only 21 of Nepal’s population was projected to live in urban areas in 2021. It is not debatable that the urbanization process in Nepal is on the rise. Thus, urban agriculture can play an important role in supplementing residents’ food needs. Many cities in Nepal have already successfully adapted to urban farming wherein residents grow food on their building sites, balconies, and rooftop, often growing plants in pots, vases, and other types of containers. The UN-Habitat, with the support of the European Union and local agencies, published a rooftop farming training manual (2014), showing the feasibility of urban farming in Nepal. This paper discusses how public-private partnership (PPP) can promote urban agriculture and make the process more effective and attractive to urban-farming households. It also analyzes how a PPP approach also facilitates the use of better technology, advisory support, and use of research extension activities. This paper draws on a literature review, uses remote-sensing imagery data and data from National Census Nepal 2021, and the authors’ professional experiences related to best practices in the areas to analyze the benefits and challenges related to urban farming both in Nepal and Arizona, USA. The paper provides recommendations for Nepali cities to maximize the benefit provided by urban farming.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/xz4t7/" target="_blank">Promoting Urban Farming for Creating Sustainable Cities in Nepal</a>
</div></li>
<li><strong>Minority Communities United Against COVID-19: It Takes a Village</strong> -
<div>
COVID-19 has illuminated how racial inequities across multiple institutions in the United States have converged and resulted in profound and lasting negative impacts on people and communities of color. Disparities in the treatment of Native (Indigenous) Americans, African (Black) Americans, and Latinx individuals in the United States concomitant with health disparities more prevalent in these populations have resulted in COVID-19 death rates that have been consistently higher than that of white counterparts and at rates that are significantly higher than their percentage of the population. While reports have focused have necessarily focused on the despair in these communities and the disparities in case and death rates, we report on the historical resilience of these communities and how this has been used to mobilize interventions in these communities that have served to mitigate the negative impact of COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/3zm7w/" target="_blank">Minority Communities United Against COVID-19: It Takes a Village</a>
</div></li>
<li><strong>Longitudinal analysis of memory T follicular helper cells and antibody response following CoronaVac vaccination</strong> -
<div>
The inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared to other vaccine platforms. Here, we recruited 88 healthy individuals that received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4+ T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the 2nd and 3rd dose of vaccination induced robust spike-specific neutralizing antibodies, with a 3rd vaccine further increased the overall magnitude of antibody response, and neutralization against Omicron sub-lineages B.1.1.529, BA.2, BA.4/BA.5 and BA.2.75.2. Spike-specific CD4+ T cell and circulating T follicular helper (cTFH) cells were markedly increased by the 2nd and 3rd dose of CoronaVac vaccine, accompanied with altered composition of functional cTFH cell subsets with distinct effector and memory potential. Additionally, cTFH cells are positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine-induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.541033v1" target="_blank">Longitudinal analysis of memory T follicular helper cells and antibody response following CoronaVac vaccination</a>
</div></li>
<li><strong>SARS-CoV-2 infection leads to Tau pathological signature in neurons</strong> -
<div>
Background: The coronavirus disease 19 (COVID-19) has represented an issue for global health since its outbreak in March 2020. It is now evident that the SARS-CoV-2 infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer's disease. Little is known about the molecular basis of these manifestations. Methods: Several SARS-CoV-2 strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated using immunoblot and immunofluorescence on cellular extracts, subcellular fractions, and brain tissue. The viral proteins Spike, Nucleocapsid, and Membrane were overexpressed in SH-SY5Y cells and the direct effect on Tau phosphorylation was checked using immunoblot experiments. Results: Upon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer's disease and other tauopathies. Moreover, this event increases Tau's propensity to form insoluble aggregates and alters its subcellular localization. Conclusions: Our data support the evidence that SARS-CoV-2 infection in the Central Nervous System triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541098v1" target="_blank">SARS-CoV-2 infection leads to Tau pathological signature in neurons</a>
</div></li>
<li><strong>Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The origin of divergent SARS-CoV-2 spike sequences found in wastewater, but not in clinical surveillance, remains unclear. These cryptic wastewater sequences have harbored many of the same mutations that later emerged in Omicron lineages. We first detected a cryptic lineage in municipal wastewater in Wisconsin in January 2022. Named the Wisconsin Lineage, we sought to determine the geographic origin of this virus and characterize its persistence and evolution over time. Methods: We systematically sampled maintenance holes to trace the origin of the Wisconsin Lineage. We sequenced spike RBD domains, and where possible, whole viral genomes, to characterize the evolution of this lineage over the 13 consecutive months that it was detectable. Findings: The persistence of the Wisconsin Lineage signal allowed us to trace it from a central wastewater plant to a single facility, with a high concentration of viral RNA. The viral sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in Wisconsin at low levels from October 2020 to February 2021, while mutations in the spike gene resembled those subsequently found in Omicron variants. Interpretation: We propose that prolonged detection of the Wisconsin Lineage in wastewater represents persistent shedding of SARS-CoV-2 from an infected individual, with ongoing within-host viral evolution leading to an ancestral B.1.234 virus accumulating Omicron-like mutations. Funding: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention (CDC), National Institute on Drug Abuse (NIDA), and the Center for Research on Influenza Pathogenesis and Transmission.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.28.22281553v2" target="_blank">Tracing the origin of SARS-CoV-2 Omicron-like Spike sequences detected in wastewater</a>
</div></li>
<li><strong>Detection of SARS-CoV-2 B.1.1.529 (Omicron) variant by SYBR Green‑based RT‑qPCR</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The COVID-19 pandemic is unceasingly spreading across the globe, and recently a highly transmissible Omicron SARS-CoV-2 variant (B.1.1.529) has been discovered in South Africa and Botswana. Rapid identification of this variant is essential for pandemic assessment and containment. However, variant identification is mainly being performed using expensive and time-consuming genomic sequencing. Methods and results: In this study we propose an alternative RT-qPCR approach for the detection of the Omicron BA.1 variant using a low-cost and rapid SYBR Green method. We have designed specific primers to confirm the deletion mutations in the spike (S ∆143-145) and the nucleocapsid (N ∆31-33) which are characteristics of this variant. For the evaluation, we used 120 clinical samples from patients with PCR-confirmed SARS-CoV-2 infections, and displaying an S-gene target failure (SGTF) when using TaqPath COVID-19 kit (Thermo Fisher Scientific, Waltham, USA) that included the ORF1ab, S, and N gene targets. Our results showed that all the 120 samples harbored S ∆143-145 and N ∆31-33, which was further confirmed by Whole genome sequencing (WGS) of 4 samples thereby validating our SYBR Green-based protocol. Conclusions: This protocol can be easily implemented to rapidly confirm the diagnosis of the Omicron BA.1 variant in COVID-19 patients and prevent its spread among populations, especially in countries with high prevalence of SGTF profile.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.16.23289717v1" target="_blank">Detection of SARS-CoV-2 B.1.1.529 (Omicron) variant by SYBR Green‑based RT‑qPCR</a>
</div></li>
<li><strong>Examining outpatients’ hand hygiene behaviour and its relation to other infection prevention measures.</strong> -
<div>
Background: The increasing demand for outpatient care is associated with a higher risk of infection transmission in these settings. However, there is limited research on infection prevention and control practices in ambulatory clinics, and none focuses on patients. Aim: Consequently, this study aims to examine outpatients’ hand hygiene behaviours, their determinants, and their associations with other infection prevention measures during the COVID-19 pandemic. Methods: We observed the hand hygiene behaviour of patients in one outpatient clinic and surveyed outpatients in five clinics about their hand hygiene practice in outpatient facilities. A questionnaire based on the Theoretical Domains Framework (TDF) was used to examine predictors of the behaviour. Moreover, patients indicated their compliance with COVID-19 infection prevention measures, vaccination status, disease risk perception, and vaccine hesitancy. Findings: Observed hand hygiene rates among 618 patients were low (12.8%), while 67.3% of the 300 surveyed patients indicated sanitising their hands upon entering the clinic. The TDF domains memory, attention, and decision processes, and emotions significantly predicted both current (today’s) and general hand hygiene behaviour in outpatient clinics. Hand hygiene behaviour and compliance with COVID-19 infection prevention showed a positive association; however, no significant connection was found with patients’ vaccination status, suggesting different behavioural motivators. Conclusion: Hand hygiene among outpatients should be improved through interventions focusing on helping patients remember to clean their hands. More research on infection prevention in outpatient facilities is needed to ensure patient safety.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/wrzfa/" target="_blank">Examining outpatients’ hand hygiene behaviour and its relation to other infection prevention measures.</a>
</div></li>
<li><strong>Single-cycle SARS-CoV-2 vaccine elicits high protection and sterilizing immunity in hamsters</strong> -
<div>
Vaccines have been central in ending the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants increasingly escape first-generation vaccine protection. To fill this gap, live particle-based vaccines mimicking natural infection aim at protecting against a broader spectrum of virus variants. We designed "single-cycle SARS-CoV-2 viruses" (SCVs) that lack essential viral genes, possess superior immune-modulatory features and provide an excellent safety profile in the Syrian hamster model. Full protection of all intranasally vaccinated animals was achieved against an autologous challenge with SARS-CoV-2 virus using an Envelope-gene-deleted vaccine candidate. By deleting key immune-downregulating genes, sterilizing immunity was achieved with an advanced candidate without virus spread to contact animals. Hence, SCVs have the potential to induce a broad and durable protection against COVID-19 superior to a natural infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.17.541127v1" target="_blank">Single-cycle SARS-CoV-2 vaccine elicits high protection and sterilizing immunity in hamsters</a>
</div></li>
<li><strong>Discovery of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro)</strong> -
<div>
Papain-like protease (PLpro) is a viral protease found in some coronaviruses, including SARS-CoV-2, the virus that causes COVID -19, and is a target for antiviral drug development. Inhibition of PLpro activity could potentially limit viral replication, making it an attractive target for antiviral drug development. This work describes the discovery of novel allosteric residues of SARS-CoV-2 PLpro that can be targeted with antiviral drugs. First, a computational analysis was performed to identify potential druggable pockets on the surface of SARS-CoV-2 PLpro. The computational analysis predicted three druggable pockets that span the surface of PLpro and are located at the interface of its four domains. Pocket 1 is located at the interface between the Ub1 and thumb domains, pocket 2 is at the interface between the thumb, finger, and palm domains, and pocket 3 is at the interface between the finger and palm domains. Targeted alanine mutagenesis of selected residues with important structural interactions revealed that 12 of 23 allosteric residues (D12, Y71, Y83, Q122, Q133, R140, T277, S278, S212, Y213, K254, and Y305) are essential for maintaining a catalytically active and thermodynamically stable PLpro. This work provides experimental confirmation of essential contacts in the allosteric sites of PLpro that could be targeted with non-competitive inhibitors as novel therapeutics against COVID -19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.16.540953v1" target="_blank">Discovery of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro)</a>
</div></li>
<li><strong>Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</strong> -
<div>
Host RNA binding proteins recognize viral RNA and play key roles in virus replication and antiviral defense mechanisms. SARS-CoV-2 generates a series of tiered subgenomic RNAs (sgRNAs), each encoding distinct viral protein(s) that regulate different aspects of viral replication. Here, for the first time, we demonstrate the successful isolation of SARS-CoV-2 genomic RNA and three distinct sgRNAs (N, S, and ORF8) from a single population of infected cells and characterize their protein interactomes. Over 500 protein interactors (including 260 previously unknown) were identified as associated with one or more target RNA at either of two time points. These included protein interactors unique to a single RNA pool and others present in multiple pools, highlighting our ability to discriminate between distinct viral RNA interactomes despite high sequence similarity. The interactomes indicated viral associations with cell response pathways including regulation of cytoplasmic ribonucleoprotein granules and posttranscriptional gene silencing. We validated the significance of five protein interactors predicted to exhibit antiviral activity (APOBEC3F, TRIM71, PPP1CC, LIN28B, and MSI2) using siRNA knockdowns, with each knockdown yielding increases in viral production. This study describes new technology for studying SARS-CoV-2 and reveals a wealth of new viral RNA-associated host factors of potential functional significance to infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.15.540806v1" target="_blank">Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</a>
</div></li>
<li><strong>Disparities in COVID-19-related trauma and internalizing symptoms across sexual orientation, race/ethnicity, and their intersection during the pandemic</strong> -
<div>
Sexual minority individuals face elevated risk for internalizing problems due to minority stress, and internalizing problems may have been exacerbated with the onset of the COVID-19 pandemic. This study examined sexual orientation- and race/ethnicity-related mental health disparities during the first four months of COVID-19 stay-at-home orders. We investigated disparities in COVID-19-related trauma (CRT) and internalizing symptoms (depression, anxiety) in a university community sample via surveys in March-April (Wave 1) and May-June 2020 (Wave 2) cross-sectionally using t-tests and longitudinally using residualized change score regressions. The analytic sample (N = 646; M age = 25.70, SD age = 10.16 at Wave 1) comprised 350 (54.2%) non-Hispanic White and 296 (45.8%) racial/ethnic minority participants; and 514 (79.6%) heterosexual and 132 (20.4%) sexual minority participants. Except for Wave 1 CRT, sexual minority individuals reported greater symptomatology than heterosexual individuals across all outcomes at each wave and racial/ethnic minority individuals reported no differences in outcomes compared to non-Hispanic White individuals. Longitudinally, sexual minority individuals reported less recovery from CRT compared to heterosexual individuals. No similar longitudinal disparities were identified across race/ethnicity. These findings build upon a growing body of literature of mental health disparities during the COVID-19 pandemic. Results highlight the importance of examining CRT to understand the effects of the pandemic on minoritized populations, particularly sexual minority individuals. Further work is needed to elucidate the potential exacerbating effects of minority stress on these disparities.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/5jsz9/" target="_blank">Disparities in COVID-19-related trauma and internalizing symptoms across sexual orientation, race/ethnicity, and their intersection during the pandemic</a>
</div></li>
<li><strong>Quantifying and Realizing the Benefits of Targeting for Pandemic Response</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
To respond to pandemics such as COVID-19, policy makers have relied on interventions that target specific population groups or activities. Because targeting is operationally challenging and contentious, rigorously quantifying its benefits and designing practically implementable policies that achieve some of these benefits is critical for effective and equitable pandemic control. We propose a flexible framework that leverages publicly available data and a novel optimization algorithm based on model predictive control and trust region methods to compute optimized interventions that can target two dimensions of heterogeneity: age groups and the specific activities that individuals normally engage in. We showcase a complete implementation focused on the Ile-de-France region of France and use this case study to quantify the benefits of dual targeting and to propose practically implementable policies. We find that dual targeting can lead to Pareto improvements, reducing the number of deaths and the economic losses. Additionally, dual targeting allows maintaining higher activity levels for most age groups and, importantly, for those groups that are most confined, thus leading to confinements that are arguably more equitable. We then fit decision trees to explain the decisions and gains of dual-targeted policies and find that they prioritize confinements intuitively, by allowing increased activity levels for group-activity pairs with high marginal economic value prorated by social contacts, which generates important complementarities. Because dual targeting can face significant implementation challenges, we introduce two practical proposals inspired by real-world interventions - based on curfews and recommendations - that achieve a significant portion of the benefits without explicitly discriminating based on age.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.23.21254155v6" target="_blank">Quantifying and Realizing the Benefits of Targeting for Pandemic Response</a>
</div></li>
<li><strong>Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment. Methods With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk individuals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models. Results Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81;1.22) [BA.1] and 1.22 (0.96;1.56) [BA.2]; corresponding HRs for sotrovimab versus untreated were 0.76 (0.66;0.89) [BA.1] and 0.92 (0.79;1.06) [BA.2]. Interpretation Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289914v1" target="_blank">Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform</a>
</div></li>
<li><strong>Predictors of Mortality in Hospitalized Patients with COVID-19: A One-Year Case-Control Study</strong> -
<div>
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Objective: To determine the associated factors with mortality, in addition to age and sex, in a high-complexity hospital in Bogota, Colombia, during the first year of the pandemic. Design: A case-control study. Setting: High-complexity center above 2,640 meters above sea level (masl) in Colombia. Methods: A case-control study was conducted on 564 patients admitted to the hospital with confirmed COVID-19. Deceased patients (n: 282) and a control group (n: 282), matched by age, sex, and month of admission, were included. Clinical and paraclinical variables were retrospectively obtained by systematic revision of clinical records. Multiple imputations by chained equation (MICE) were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalization. Results: Most of the patients included were males in the seventh decade of life. Most of the admissions occurred between July and August 2021. Surprisingly, recovered patients reported heterogeneous symptomatology, whereas deceased patients were most likely to present respiratory distress, dyspnea, and seizures on admission. In addition, the latter group exhibited a higher burden of comorbidities and alterations in laboratory parameters. After the imputation of datasets, CART analysis estimated 14 clinical profiles based on respiratory distress, LDH, dyspnea, hemoglobin, D-dimer, ferritin, blood urea nitrogen, C-reactive protein, PaO2/FiO2, dysgeusia, total bilirubin, platelets, and gastroesophageal reflux disease. The accuracy model for prediction was 85.6% (P &lt; 0.0001). Conclusion: Multivariate analysis yielded a reliable model to predict mortality in COVID-19. This analysis revealed new interactions between clinical and paraclinical features in addition to age and sex. Furthermore, this predictive model could offer new clues for the personalized management of this condition in clinical settings. Keywords: SARS-CoV-2, COVID-19, Mortality, Predictors, Risk Factors
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289918v1" target="_blank">Predictors of Mortality in Hospitalized Patients with COVID-19: A One-Year Case-Control Study</a>
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<li><strong>Immunoglobulin A as a key immunological molecular signature of post-COVID-19 conditions</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account gender, vaccination, hospitalization and age. Fatigue and myalgia were the most common symptoms and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant for the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.11.23289866v1" target="_blank">Immunoglobulin A as a key immunological molecular signature of post-COVID-19 conditions</a>
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</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Glucocorticoid<br/><b>Sponsor</b>:   Huashan Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19</strong> - <b>Condition</b>:   Patients With COVID-19<br/><b>Interventions</b>:   Drug: The drug “Rutan 0.1”.;   Other: Basic treatment<br/><b>Sponsor</b>:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Arginine Replacement Therapy in COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Arginine Hydrochloride<br/><b>Sponsor</b>:   Emory University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Intramuscularly administered Ad5-nCoV vaccine;   Biological: Aerosolized Ad5-nCoV;   Biological: DelNS1-2019-nCoV-RBD-OPT1;   Biological: SYS6006<br/><b>Sponsor</b>:   Jiangsu Province Centers for Disease Control and Prevention<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI</strong> - <b>Condition</b>:   COVID-19 Respiratory Infection<br/><b>Interventions</b>:   Drug: Rutan 25 mg;   Other: Control group<br/><b>Sponsor</b>:   Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment</strong> - <b>Condition</b>:   Post COVID-19 Cognitive Impairment<br/><b>Interventions</b>:   Device: Vielight Neuro RX Gamma active device;   Device: Vielight Neuro RX Gamma sham device<br/><b>Sponsor</b>:   Vielight Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway</strong> - <b>Conditions</b>:   Post COVID-19 Condition, Unspecified;   SARS-CoV2 Infection;   COVID-19<br/><b>Interventions</b>:   Drug: Nirmatrelvir/ritonavir;   Drug: Placebo<br/><b>Sponsors</b>:   Haukeland University Hospital;   University of Bergen<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study .</strong> - <b>Condition</b>:   SARS CoV 2 Infection<br/><b>Interventions</b>:   Other: Spray with Hypochlorous Acid Group;   Other: Spray with Placebo Group<br/><b>Sponsor</b>:   University of Monastir<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response</strong> - <b>Condition</b>:   COVID-19 Respiratory Infection<br/><b>Intervention</b>:   Combination Product: Vitamin-D<br/><b>Sponsor</b>:   Sulaimany Polytechnic university<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>REVERSE-Long COVID-19 With Baricitinib Pilot Study</strong> - <b>Condition</b>:   Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>:   Drug: Baricitinib 4 MG<br/><b>Sponsors</b>:   Vanderbilt University Medical Center;   Emory University;   University of California, San Francisco;   University of Minnesota;   Vanderbilt University;   Yale University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention</strong> - <b>Condition</b>:   Sars-CoV-2 Infection<br/><b>Interventions</b>:   Drug: Alveavax-v1.2;   Drug: Janssen Ad26.COV2.S<br/><b>Sponsor</b>:   Alvea Holdings, LLC<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial</strong> - <b>Conditions</b>:   Post-Acute COVID-19 Syndrome;   Dysautonomia<br/><b>Interventions</b>:   Procedure: Rehabilitation;   Procedure: Standard of Care<br/><b>Sponsors</b>:   Evangelismos Hospital;   National and Kapodistrian University of Athens;   LONG COVID GREECE;   414 Military Hospital of Special Diseases<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exercise for Health in Patients With Post-acute Sequelae of COVID-19</strong> - <b>Condition</b>:   Long COVID<br/><b>Intervention</b>:   Other: Rehabilitation program<br/><b>Sponsors</b>:   Campus docent Sant Joan de Déu-Universitat de Barcelona;   Hospital de Mataró;   University of Barcelona<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome.</strong> - <b>Condition</b>:   Post-COVID Syndrome<br/><b>Interventions</b>:   Behavioral: RehabCovid_Telematic;   Behavioral: RehabCovid_ImmersiveVR;   Behavioral: Control_Condition<br/><b>Sponsors</b>:   Consorci Sanitari de Terrassa;   University of Barcelona;   Universitat de Girona;   Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment;   Politecnic University of Catalonia;   Corporación Fisiogestión<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RADx-UP- Impact of Community Health Worker Deployment</strong> - <b>Conditions</b>:   Diabetes;   COVID-19;   Community Health Workers;   Health Behavior;   Health Knowledge, Attitudes, Practice<br/><b>Intervention</b>:   Behavioral: Impact of Community Health Worker Home Deployment on COVID-19 Vaccine Confidence and Uptake<br/><b>Sponsor</b>:   Morehouse School of Medicine<br/><b>Active, not recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein</strong> - Omicron is a novel variant of SARS-CoV-2 that is currently spreading globally as the dominant strain. The virus first enters the host cell through the receptor binding domain (RBD) of the spike protein by interacting with the angiotensin-converting enzyme 2 (ACE2). Thus, the RBD protein is an ideal target for the design of drugs against the Omicron variant. Here, we designed several miniprotein inhibitors in silico to combat the SARS-CoV-2 Omicron variant using single- and double-point mutation…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Conformal Hydrogel-Skin Coating on a Microfluidic Channel through Microstamping Transfer of the Masking Layer</strong> - Poly(dimethylsiloxane) (PDMS) is used in microfluidics owing to its biocompatibility and simple fabrication. However, its intrinsic hydrophobicity and biofouling inhibit its microfluidic applications. Conformal hydrogel-skin coating for PDMS microchannels, involving the microstamping transfer of the masking layer, is reported herein. A selective uniform hydrogel layer with a thickness of ∼1 μm was coated in diverse PDMS microchannels with a resolution of ∼3 μm, maintaining its structure and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The C-terminal 32-mer fragment of hemoglobin alpha is an amyloidogenic peptide with antimicrobial properties</strong> - Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Challenges and Progress in Designing Broad-Spectrum Vaccines Against Rapidly Mutating Viruses</strong> - Viruses evolve to evade prior immunity, causing significant disease burden. Vaccine effectiveness deteriorates as pathogens mutate, requiring redesign. This is a problem that has grown worse due to population increase, global travel, and farming practices. Thus, there is significant interest in developing broad-spectrum vaccines that mitigate disease severity and ideally inhibit disease transmission without requiring frequent updates. Even in cases where vaccines against rapidly mutating…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies</strong> - CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of dual S-RBD/NRP1-targeting peptides: structure-based virtual screening, synthesis, biological evaluation, and molecular dynamics simulation studies</strong> - Both receptor-binding domain in spike protein (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human neuropilin-1 (NRP1) are important in the virus entry, and their concomitant inhibition may become a potential strategy against the SARS-CoV-2 infection. Herein, five novel dual S-RBD/NRP1-targeting peptides with nanomolar binding affinities were identified by structure-based virtual screening. Particularly, RN-4 was found to be the most promising peptide targeting S-RBD…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Compounds from myrtle flowers as antibacterial agents and SARS-CoV-2 inhibitors: <em>In-vitro</em> and molecular docking studies</strong> - Plants and their related phytochemicals play a key role in the treatment of bacterial and viral infections, which inspire scientists to design and develop more efficient drugs starting from the phytochemical active scaffold. This work aims to characterize the chemical compounds of Myrtus communis essential oil (EO) from Algeria and to evaluate its in vitro antibacterial effect, as well as the in silico anti-SARS-CoV-2 activity. The chemical profile of hydrodistilled EO from myrtle flowers was…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines</strong> - CONCLUSION: KTRs’ humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of &gt;10 years.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang</strong> - BACKGROUND: Jing Guan Fang (JGF) is an anti-COVID-19 Chinese Medicine decoction comprised of five medicinal herbs to possess anti-inflammatory and antiviral properties for treatment. This study aims to electrochemically decipher the anti-coronavirus activity of JGF and show that microbial fuel cells may serve as a platform for screening efficacious herbal medicines and providing scientific bases for the mechanism of action (MOA) of TCMs.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Physicochemical characterization of reusable facemasks and theoretical adhesion by a challenged bacterium</strong> - CONCLUSION: Such information is valuable to understand attachment of biological particles and to contribute in the inhibition of this attachment.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Screening of SARS-CoV-2 antivirals through a cell-based RNA-dependent RNA polymerase (RdRp) reporter assay</strong> - COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2) continues to pose an international public health threat and thus far, has resulted in greater than 6.4 million deaths worldwide. Vaccines are critical tools to limit COVID-19 spread, but antiviral drug development is an ongoing global priority due to fast-spreading COVID-19 variants that may elude vaccine efficacies. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is an essential…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Omicron sub-lineages differentially modulate interferon response in human lung epithelial cells</strong> - Although most of the attention was focused on the characterization of changes in the Spike protein among variants of SARS-CoV-2 virus, mutations outside the Spike region are likely to contribute to virus pathogenesis, virus adaptation and escape to the immune system. Phylogenetic analysis of SARS-CoV-2 Omicron strains reveals that several virus sub-lineages could be distinguished, from BA.1 up to BA.5. Regarding BA.1, BA.2 and BA.5, several mutations concern viral proteins with antagonistic…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Purification and characterisation of heparin-like sulfated polysaccharides with potent anti-SARS-CoV-2 activity from snail mucus of Achatina fulica</strong> - Heparin-like sulfated polysaccharide, acharan sulfate, was purified from the mucus of an African giant snail with unique sulfated glycosaminoglycans (GAGs). This study reported on finding novel and safe heparin resources from Achatina fulica for further use as well as easy isolation and purification of the active fraction from the initial raw material. Its structure was characterised by a strong-anion exchange combined with high-performance liquid chromatography (HPLC) and nuclear magnetic…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-guided optimization of adenosine mimetics as selective and potent inhibitors of coronavirus nsp14 N7-methyltransferases</strong> - The COVID-19 pandemic reveals the urgent need to develop new therapeutics targeting the SARS-CoV-2 replication machinery. The first antiviral drugs were nucleoside analogues targeting RdRp and protease inhibitors active on nsp5 Mpro. In addition to these common antiviral targets, SARS-CoV-2 codes for the highly conserved protein nsp14 harbouring N7-methyltransferase (MTase) activity. Nsp14 is involved in cap N7-methylation of viral RNA and its inhibition impairs viral RNA translation and immune…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunization with Recombinant Accessory Protein-Deficient SARS-CoV-2 Protects against Lethal Challenge and Viral Transmission</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide coronavirus disease 2019 (COVID-19) pandemic. Despite the high efficacy of the authorized vaccines, there may be uncertain and unknown side effects or disadvantages associated with current vaccination approaches. Live-attenuated vaccines (LAVs) have been shown to elicit robust and long-term protection by the induction of host innate and adaptive immune responses. In this study, we sought to verify an attenuation…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Don’t Believe Donald Trump: A Failure to Raise the Debt Ceiling Would Be Disastrous</strong> - The ex-President’s intervention has made a fraught situation even more complicated. - <a href="https://www.newyorker.com/news/our-columnists/dont-believe-donald-trump-a-failure-to-raise-the-debt-ceiling-would-be-disastrous">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Vanishing Acts of Vladimir Putin</strong> - One of the seeming paradoxes of the Russian President is the degree to which he is at once a unitary micromanager and an absent, aloof, and often indecisive leader. - <a href="https://www.newyorker.com/news/daily-comment/the-vanishing-acts-of-vladimir-putin">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Salmon in the Sky</strong> - A painted plane that flew the Alaskan coast. - <a href="https://www.newyorker.com/news/afterword/the-salmon-in-the-sky">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Fight for the Soul of a School Board</strong> - In a small Missouri town, a campaign to remove literature from the high-school library forced members of the community to reckon with the meaning of “parents’ rights.” - <a href="https://www.newyorker.com/news/dispatch/the-fight-for-the-soul-of-a-school-board">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Black Families Seeking Reparations in California’s Gold Country</strong> - Descendants of enslaved people want land seized by the state returned and recognition of the gold rush’s rich, and largely ignored, Black history. - <a href="https://www.newyorker.com/news/dispatch/the-black-families-seeking-reparations-in-californias-gold-country">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Your company can screw you over even after you leave</strong> -
<figure>
<img alt="A woman running away from a giant hand trying to grab her." src="https://cdn.vox-cdn.com/thumbor/hSwNiU0hZSRdvRTtwMgd_Nd6Vp0=/0x0:1996x1497/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72291242/GettyImages_646812428.0.jpg"/>
<figcaption>
Relieved you finally escaped that job you hate? Think again. | Erhui1979 via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
From non-competes to non-disparagement agreements, your employer has plenty of ways to lock you down even after you leave.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0a9x1D">
You’d think that when a job is over, it’s over. You quit or you’re fired or laid off and then that’s that. Except that’s not always what happens. A lot of the time, even after you’ve cut ties, your former employer maintains some control over what you can say or do. It’s like a toxic ex you can’t warn anyone about because they might sue you, and who gets a say in who you go out with next.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3l7ogN">
It’s true that at the current moment, swaths of workers are <a href="https://www.vox.com/recode/22841490/work-remote-wages-labor-force-participation-great-resignation-unions-quits">more in the driver’s seat</a> <a href="https://www.vox.com/technology/23649895/worker-power-bosses-recession-layoffs-quits">than they have been in years</a>, thanks to a hot labor market that’s driven wages up, provided some people mobility, and given workers more leverage against their employers. But work <a href="https://www.vox.com/the-highlight/22977654/future-of-work-restaurants-retail-hospitality">hasn’t changed as much</a> as some more optimistic headlines might suggest, and many of the fundamental power dynamics remain.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZOnfDK">
When you take on a new job, it’s often still a my-way-or-the-highway situation with your employer, and not just while you’re working your 9 to 5. Once you leave, companies have mechanisms such as non-compete clauses and non-disparagement agreements that make your post-work life a little bit harder. Much of the time, they don’t enforce those mechanisms, but the threat that they might gives them power.
</p>
<aside id="BJ0liG">
<div>
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</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="79XZTo">
I recently spoke with Peter Shamshiri, a former employment lawyer, about all the ways your boss keeps control of you even if they’re no longer your boss. Shamshiri is a host of two podcasts, <a href="https://podcasts.apple.com/us/podcast/if-books-could-kill/id1651876897"><em>If Books Could Kill</em></a>, about airport bestsellers, and <a href="https://www.fivefourpod.com/"><em>5-4</em></a>, about the <a href="https://www.vox.com/scotus">Supreme Court</a>. The latter podcast, <em>5-4</em>, <a href="https://www.vulture.com/2022/10/supreme-court-podcast-fired-interview.html">lost him his job last year</a> when the higher-ups found out he was on it (he’d previously been anonymous). Our conversation, edited for length and clarity, is below.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oZTU7D">
<strong>It feels like when your company fires you or you quit, they should really not be able to have any more control over what you do. But that’s not the case, right?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="a4taqr">
There are a couple of ways that companies can maintain contractual control over you after your employment ends. One is that you sign something during your employment that applies to your post-employment period. So you will sign a document that delineates all these obligations you have as an employee, and some of them implicitly or explicitly stretch beyond the termination of your employment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cb6Qrc">
The other one is you agree when you part with the company to certain terms that include restrictive covenants — so non-competes, trade secret agreements, non-solicitation, things like that. In exchange for severance, for example, you’d be agreeing to that stuff. It’s still the company leveraging their position to get you to agree to restrictive covenants after you’re done with them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xc1CvS">
<strong>So if Vox axes me tomorrow, which I hope they don’t, there are probably definitely rules somewhere about what I can say about them or whatever?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Sl7fh4">
Most likely, you have at some point signed something saying that you will agree to certain levels of confidentiality with respect to their proprietary information, their trade secrets. It’s quite possible that that agreement also extends to you going to a competitor within a set period of time or you soliciting Vox employees once you are at a competitor, for example.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eZow8m">
A lot of large companies will, essentially, when someone is onboarded, hand them a piece of paper and say, “Hey, to come work here, you need to sign this.” And it has all of these terms, and some of them will stretch beyond their employment, which could literally be years, decades in the future at the time of signing. People sign because it’s a prerequisite for maintaining the job.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UKp4TD">
<strong>Whenever I start a new job, I think, “Oh, I should look through this,” and then it’s like, “What am I going to do? Say no?” Is it possible to negotiate?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QxwwOg">
You may be able to negotiate yourself out of certain restrictive covenants if you are of particular import or the company is a little bit smaller. But if you’re at a large enough company, they’re not going to set the precedent of individually negotiating with people on this stuff. They’re just going to say, “Sign it or turn down the job.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q8cMJm">
<strong>To get into specifics, let’s talk noncompetes a little. Those are the clauses that say an employee can’t work for a competitor. I feel like a lot of people have come across them when looking for a job, or you hear the horror stories of, like, </strong><a href="https://www.nytimes.com/2021/09/29/opinion/noncompete-agreement-workers.html"><strong>restaurants using them</strong></a><strong>. How are they even allowed?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uLp4Cf">
Well, they’re not allowed everywhere, and I’ll get to that in a second.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o3XR9u">
The purpose of them generally is to try to protect company secrets. When you’re an employee, the company is trusting you with their proprietary and confidential information, and if you go over to a competitor, all of a sudden, the competitor has access to this stuff. Now, what’s odd about that is most companies will have you already agree to maintain confidentiality, to maintain the secrecy of their trade secrets. So the noncompete is substantively duplicative of that. The reason companies use that is because if someone goes to a competitor, it’s hard to figure out if they’ve spilled the beans on company secrets. So the easy solution is just to prevent them from going to the competitor altogether.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GO0wLl">
Almost all jurisdictions have restrictions on these. They need to be limited in duration, meaning maybe six or 12 months after you leave, but not beyond that. They need to be limited in their geographic scope. A lot of companies limit them by industry or even specifically name competitors that you can’t go to. Under California labor laws, you cannot use noncompetes. The FTC <a href="https://www.ftc.gov/news-events/news/press-releases/2023/01/ftc-proposes-rule-ban-noncompete-clauses-which-hurt-workers-harm-competition">has proposed a rule to ban them</a>. They say that the cost to employees is something like $300 billion a year.
</p>
<div class="c-float-right">
<aside id="qnpbm3">
<q>“They’re just being used as intimidation”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="X6Ewac">
The restaurant industry is a great example of how and where these can be abused, because it’s just the Wild West out there. I don’t think that any judge in most jurisdictions would hold up a noncompete in the restaurant industry, but no one’s going to lawyer up over a restaurant job and try to figure that out. So, they’re just being used as intimidation, essentially.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="n1zaNi">
<strong>Years ago I had a friend who basically didn’t take a job because of a noncompete. The fear was like, well what happens if it doesn’t work out? You can never work in your area for the next year?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fyGwWr">
That’s what’s so bizarre about it. Say you have a career in selling life insurance, and they tell you in your contract you can’t go over to a competitor. What exactly are you supposed to do? You’re being blocked out of the only industry where you have expertise. They’ll often say it’s only within a 100-mile radius. But what does that tell you? You can’t work at a company in the industry that you’re familiar with, in the city that you live in, or anywhere nearby. If you want to move across the country, then you can do it, or if you totally want to switch careers, you’re good.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wfVoLe">
It doesn’t make sense, and that’s why there’s been a push to limit these, to outlaw them altogether. The legitimate uses of this are like 5 percent of the reason that companies use them. They are used to intimidate employees, to keep employees in their roles and make them nervous about where they go next. Frankly, they prevent other companies from coming over and hiring too many folks so that you have legal leverage when companies try to do that.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uunwHO">
<strong>In </strong><a href="https://www.vox.com/business-and-finance"><strong>finance</strong></a><strong>, isn’t it the case that sometimes employers will pay you to not do anything for six months or something? You get “garden leave.”</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pDxjB1">
Garden leaves are relatively rare. In certain industries where the pay is high, employees have a little more leverage in general, so they can say, fine, I’m at JPMorgan, I won’t go over to Goldman, but I want my six months of pay right then. If you’re serving tables, then you’re on your own. Essentially, noncompetes are more effective the more financially unstable someone is.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wM6OJM">
<strong>Are noncompetes even enforced though?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IgHZln">
Almost never. It’s a conversation that will occasionally happen when higher-level folks may come from one company to another between legal departments, but these things go to court once in a blue moon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="i1wGOy">
It’s a bluff that employees can often call, but a) you need to know that, and b) you’re still running a risk. If a company feels like dragging you into court over this, at the very least, it’s going to make you miserable.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gza5Nc">
<strong>What about nondisclosure agreements, the contracts that say what people can’t say about their employers or former employers?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MbOtO7">
I would say that NDAs are a little bit distinct. I wouldn’t put them in the same bucket as most of these post-employment restrictive covenants — trade secret protections; noncompetes; non-solicitations, meaning you can’t solicit colleagues to come join you at a new company; non-disparagement agreements, meaning you can’t say anything disparaging about the company; and non-interference provisions, which means you can’t go try to intercept your old company’s clients.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MozPp9">
NDAs tend to be limited to specific circumstances. So if you’re a lawyer or a finance person, you’ll often sign NDAs when you’re on a confidential deal. The controversial use of NDAs is: Okay, hey, you were harassed during your time at our company, we will compensate you in some way and in exchange you sign this NDA so we don’t have a PR problem here. We’ve seen more restrictions around that recently, especially in the <a href="https://www.vox.com/sexual-harassment">sexual harassment</a> context. That’s not something that would generally be part of your post-employment suite of obligations by default. It’s usually circumstantial.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4eGMGv">
<strong>What about non-disparagement agreements? Like, people have to promise not to say anything bad, even though they’ve got plenty of bad things to say?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MSHPdY">
Non-disparagement has got to be the most bizarre of the post-employment restrictive covenants, and they’ll often apply during employment too.
</p>
<div class="c-float-right">
<aside id="qZ4y3X">
<q>“I don’t know anyone who has never said something a little bit disparaging about their employer”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aQBXwT">
“I won’t say anything mean at the company,” at a certain high level, if you’re an employee, might make some sense. If you’re a Vox employee and you go on <a href="https://www.vox.com/twitter">Twitter</a> and say, “You know, I think Vox sucks, just like, substantively, I think the coverage is awful.” I think what the company would say was, well, do we really have to allow our employees to say that the product is awful, for example? On the other side of that, is there literally anyone who doesn’t violate this? Maybe I’m hanging out with a cynical crowd, but I don’t know anyone who has never said something a little bit disparaging about their employer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="z8IFP0">
The way that these operate is that because their scope is so broad, if you get laid off, for example, and vent about it on social media, which is a relatively human experience and human reaction, all of a sudden, your company can claim that you violated non-disparagement. If part of your severance package is non-disparagement, what they’re saying is, “We don’t want to hear about this on social media.” And your ability to criticize your employer, even in ways that are substantively true, is limited.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cPmbcx">
What’s different about defamation is that what you say has to be false for it to be defamation. If you say something true, that’s not defamation. People can accurately relay what happened to them at a company, and if the company says that that’s disparaging, that that would hurt their reputation, you still violated the non-disparagement clause, even though you didn’t tell a lie.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GPS2Zz">
<strong>So if I lose my job tomorrow and go to Twitter and say “this person doesn’t do their job” or something, and that’s true, would the repercussions be that the company takes away my severance? Can they sue me? </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lFsRDi">
If we’re talking about a severance agreement you violated, the agreement itself would tell you what the damages are. At the very least, they would try to seek an injunction telling you to stop, that’s pretty minimal. Most of them have outlined monetary damages — say either you’re going to pay back the severance or you’re going to pay back some set amount of damages.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8a123l">
It depends on the contract, but companies have a lot of options available to them. Generally speaking, and I’m being very general here because there are different cultures, it’s rare, even with a violation, to see someone go after an already-paid severance just because the PR can be so brutal. But they maintain that right, and that’s the whole point — all the risk is in the employee’s court. They are chilling the ability of the employee to speak confidently and freely about their experience.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="B8eqw8">
<strong>Can I sue my employer? What is a forced arbitration clause?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BUuQpQ">
That’s basically saying that if there’s a dispute about your employment, we’re going to arbitrate it, we’re not going to go to court. Arbitration is much more favorable to employers — they win more frequently, the costs are lower, it just sucks for employees. But that’s another thing that’s frequently buried in your employment contract — you’re signing away your ability to sue in court. Though I think “<a href="https://www.vox.com/culture/21437879/stay-woke-wokeness-history-origin-evolution-controversy">woke</a>” employers have moved away from this in the last couple of years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vZmzw1">
<strong>What if someone’s employer, say, committed a crime? With Theranos, some employees knew there was a problem and were afraid to speak out because of NDAs and non-disparagement agreements, right?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o1Ketr">
Technically, there are carve-outs — most agreements say you have the right to report things to certain government agencies, etc. But Theranos is a good example of how an aggressive legal team can make that irrelevant. You had employees being like, “Hey, this seems like maybe it’s fraud,” and you had some of the best lawyers in the country coming down on them with threats of litigation. Even if you’re technically, legally in the right, the whole point of these is for the company to maintain leverage to squeeze you if they want to.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9pIHLl">
In most situations, if the company is violating the law, you are legally allowed to talk about that and to escalate that to regulators. But is being legally in the right going to save you when you have David Boies knocking on your door and pointing to your NDA and threatening litigation?
</p>
<div class="c-float-right">
<aside id="7BcBwd">
<q>“We are a country and a society that worships contracts as a method of doing business”</q>
</aside>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lpYUu9">
<strong>So I guess the big overarching question here is, why are we like this? Or rather, why are companies allowed to behave like this? You quit or you’re laid off or fired, and they still have all this control even though you basically have no relationship anymore?</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="miFb7E">
We are a country and a society that worships contracts as a method of doing business. This is something that, a century ago, the Supreme Court was holding up as a foundational element of our society, during the <a href="https://en.wikipedia.org/wiki/Lochner_era">Lochner era</a>, where they were upholding all these brutal labor practices and saying we should allow people to contract to whatever they want. That era is over to some degree — labor regulations kicked in in the ’20s and ’30s and exist to some degree to this day, but I think the worship of contract is what brings us here. The idea that someone can’t agree to something on their own terms, even if the leverage and the power dynamics are completely out of whack, Americans have a hard time with that. That’s why stuff like this is so prolific.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k2AUGv">
There’s also a real argument that much of this is anti-competitive. These restrictions are preventing market forces from maximizing their efficiency to some degree, right? You can’t go over to another employer, you can’t hire away your former colleague, you can’t try to convince our clients that they should come follow you to the new company. All of these things are anti-competitive, they’re not in the spirit of market capitalism, and yet they are extremely common.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Grps5r">
<strong>Like if I want to steal all of your clients and I’m better than you, maybe I should be able to. </strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wD6Cj6">
Right. If you have a pitch to the client to come join you, why exactly shouldn’t that be allowed? It’s hard to make the argument from the broader economic perspective.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5G5qzT">
<em>We live in a world that’s constantly trying to sucker us and trick us, where we’re always surrounded by scams big and small. It can feel impossible to navigate. Every two weeks, join Emily Stewart to look at all the little ways our economic systems control and manipulate the average person. Welcome to </em><a href="https://www.vox.com/the-big-squeeze"><em><strong>The Big Squeeze</strong></em></a><em>.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NF25sR">
<a href="http://vox.com/big-squeeze-newsletter"><em><strong>Sign up to get this column in your inbox</strong></em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fEmYHz">
<em>Have ideas for a future column or thoughts on this one? Email </em><a href="mailto:emily.stewart@vox.com"><em><strong>emily.stewart@vox.com</strong></em></a>.
</p></li>
<li><strong>Half the world is at risk of dengue. Why is there no universal way to prevent it?</strong> -
<figure>
<img alt="A close-up photo of a mosquito on skin." src="https://cdn.vox-cdn.com/thumbor/FVTalCLcZ7U-kV0mfjYJdqJXLyo=/951x555:1899x1266/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72291157/1251781184.0.jpg"/>
<figcaption>
Soumyabrata Roy/NurPhoto via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This painful, mosquito-borne virus could spread even more if new innovations can’t scale.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nKr61L">
<a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue">Break-bone fever</a>. <a href="https://www.hsph.harvard.edu/magazine/magazine_article/breaking-breakbone-fever/">Break heart fever</a>. <a href="https://www.ncbi.nlm.nih.gov/books/NBK430732/">Seven-day fever</a>. They are all names for the painful — often <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651993/">debilitating</a> and sometimes deadly — mosquito-borne disease called dengue fever.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="etskh7">
Dengue can <a href="https://www.cdc.gov/dengue/symptoms/index.html">cause</a> high fever, nausea, rash, body aches, and stiff movements, and can leave patients suffering from <a href="https://www.hsph.harvard.edu/magazine/magazine_article/breaking-breakbone-fever/">depression and fatigue</a> in its wake.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vnO7jM">
Dengue has been around since at least the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516305/">17th century</a>, but cases of the infection <a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue">skyrocketed</a> in the last two decades — from only a little over 505,000 cases in 2000, to 5.2 million cases in 2019<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516305/"></a><a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/dengue-vaccine"></a>. Today, <a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue">half the world’s population</a> — who live in areas where Dengue-carrying mosquitoes are prevalent — is at risk of the illness. While dengue is already endemic in 100 countries, new regions are reporting cases of the virus every year, <a href="https://news.mongabay.com/2022/10/in-temperate-nepal-climate-change-paves-way-for-tropical-dengue-fever/"></a><a href="http://%E2%80%8B%E2%80%8Bhttps://www.who.int/emergencies/disease-outbreak-news/item/2019-DON218"></a><a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue#:~:text=Local%20transmission%20was%20reported%20for,reported%20globally%20was%20in%202019"></a>thanks to travel, trade, urbanization, and <a href="https://www.vox.com/climate">climate change</a> <a href="https://www.nature.com/articles/s41564-019-0376-y">expanding the range</a> of the mosquitoes<em> </em>that transmit dengue.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="50xgGw">
In March, Sudan, a country <a href="https://www.vox.com/world-politics/23712710/sudan-war-khartoum-burhan-hemedt-rsf">currently embroiled in a civil war</a>, experienced its widest outbreak of the disease and<a href="https://www.reuters.com/business/healthcare-pharmaceuticals/dengue-fever-spreads-across-sudan-with-health-response-weakened-2023-03-30/"> detected</a> dengue fever for the first time on record in its capital city of Khartoum. At the same time, Argentina <a href="https://crisis24.garda.com/alerts/2023/04/argentina-elevated-dengue-fever-activity-reported-nationwide-through-march-update-1">reported “elevated” dengue fever</a> activity across the country.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aBGNei">
While dengue fever isn’t as <a href="https://www3.paho.org/data/index.php/en/mnu-topics/indicadores-dengue-en/dengue-nacional-en/255-dengue-letalidad-en.html">deadly</a> as other mosquito-borne viruses — such as <a href="https://www.who.int/news-room/fact-sheets/detail/japanese-encephalitis#:~:text=The%20case%2Dfatality%20rate%20can,or%20the%20inability%20to%20speak.">Japanese Encephalitis</a>, a dengue-related virus found in southern and eastern Asia — large outbreaks can quickly overwhelm <a href="https://www.vox.com/health-care">health care</a> systems, worsening the toll of other illnesses and medical problems. <a href="https://otter.ai/u/eD3bSsrEDqO9_eOU4t_sC7YrvEU?utm_source=copy_url"></a>“It’s one of those rare diseases that impact families, impacts communities, and impacts the country-level health systems,” said Derek Wallace, a physician who is the dengue vaccine program lead for the pharmaceutical company Takeda.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oC9FAc">
But even as the threat of dengue grows, new developments over the past decade — including a <a href="https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-for-use-in-european-union">recently approved vaccine</a> and an <a href="https://www.worldmosquitoprogram.org/en/work/wolbachia-method">initiative to infect mosquitos with a virus-resistant bacteria</a> — could mean that dengue eradication is on the horizon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p4Tysc">
“I think one of the terrible things about dengue, if you live in an endemic transmission area, is you can’t really protect against it,” said Scott O’Neill, founder and CEO of the <a href="https://www.worldmosquitoprogram.org/">World Mosquito Program</a>, a nonprofit aiming to eliminate mosquito-borne illnesses. “When you live in a situation where you can’t control your exposure, that can be quite a frightening thing, and many people live with a lot of fear around diseases like dengue and Zika, and what it could do to their children or to their family.” <a href="https://otter.ai/u/5VasWt6743FCYvLbkCjSBYvUaK4?utm_source=copy_url"></a>
</p>
<h3 id="Qbinot">
What is dengue?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="D4NjcR">
Dengue fever and many other vector-borne viruses — including chikungunya, Zika fever, and yellow fever — are usually transmitted via the bite of the <a href="https://www.cdc.gov/mosquitoes/mosquito-control/professionals/range.html">tropical</a> Aedes mosquito. This mosquito <a href="https://www.cdc.gov/mosquitoes/mosquito-control/professionals/range.html">prefers to live near and feed on humans</a>, and can easily pass these viruses from an infected individual to others in the population. In the case of dengue fever, mosquitos are the vector — the living organisms that can spread infectious pathogens between humans — but other <a href="https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases">common disease-spreading vectors</a> are ticks, flies, and fleas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5XPKQs">
And since dengue fever <a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue#:~:text=Dengue%20(break%2Dbone%20fever),body%20aches%2C%20nausea%20and%20rash.">symptoms</a> normally do not appear until four to 10 days after infection, people often go about their normal life, going outside, and exposing themselves to mosquitos. When a mosquito bites an infected individual, it will then carry that virus and pass it on to other people via its bite.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o8I9Mj">
“Sometimes people actually have asymptomatic disease. They don’t even know that they had dengue,” said Ashley St. John, an associate professor at Duke-NUS Medical School who researches vector-borne pathogens like dengue. “That’s a major way it spreads is through people who don’t realize that they’re infected still going about their daily routine, and being in an environment where mosquitoes can continue to transmit the virus.” <a href="https://otter.ai/u/22S_r41QFqoYPaQmi3xtJa9UyEw?utm_source=copy_url"></a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZWUsL9">
Unlike other vectors, the Aedes mosquito thrives in urban environments since it can breed in very small quantities of water, such as the water pooled in a leaf, said St. John. As more people <a href="https://ourworldindata.org/urbanization#:~:text=Urbanization%20is%20a%20trend%20unique,areas%20as%20they%20become%20richer.">live in urban areas</a>, the risk the Aedes mosquitos pose — given their ability to thrive in populous communities— grows.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dOrBSk">
“Another aspect that goes hand-in-hand with it is really human mobility,” said St. John. “Overall, we’re traveling a lot more than we used to. Travelers are a major group who are at risk for exposure to dengue when they arrive in some of these dengue-endemic regions.” When a traveler is exposed to dengue in an endemic region, they risk bringing the disease back to their community.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zaWfic">
Dengue fever causes a range of mild to severe symptoms, but one of the most concerning is <a href="https://www.cdc.gov/dengue/training/cme/ccm/Plasma%20Leakage%20Audio%20Narration_final.pdf">plasma leakage</a>, or when fluid leaves the blood vessels and enters the lungs or abdomen. This deadly condition occurs in only a small portion of the annual <a href="https://aho.org/fact-sheets/dengue-and-severe-dengue-fact-sheet/">half a million</a> dengue-related hospitalizations, but treatment for the problem — IV fluids — is not foolproof, said Wallace. If too much IV fluid is given to a patient, it can drown the lungs and send them into respiratory distress. This life-or-death balancing act often plays out over an approximately seven-hour period following an <a href="https://www.nature.com/scitable/topicpage/what-is-dengue-fever-22399100/">infected individual’s fever breaking</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hIBJ2Q">
The primary reason scientists and researchers struggled to make progress on dengue prevention and treatment methods is because there are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199925/#:~:text=Dengue%20is%20caused%20by%20four,immunity%20to%20that%20particular%20serotype.">four different serotypes</a> — or variations — of the virus that cause dengue fever. That essentially means that dengue fever behaves like four different viruses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="84NX3V">
When someone is infected with one of the four dengue serotypes, they develop antibodies that help them beat the infection and protect them against future infections of the same serotype. But, unlike many illnesses, dengue’s serotypes are so different that the antibodies that protect against one serotype of the virus <a href="https://pubmed.ncbi.nlm.nih.gov/33027653/">may not protect</a> against the other three, said St. John.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VJ0o87">
Sounds a little bit like another virus circulating around: Covid. Between <a href="https://www.vox.com/22846444/omicron-variant-tranmission-risk-covid-pandemic">omicron</a>, <a href="https://www.vox.com/22547537/delta-coronavirus-variant-covid-19-vaccines-masks-lockdown">delta</a>, and beta, Covid had <a href="https://www.cdc.gov/coronavirus/2019-ncov/variants/index.html">many different variants</a>, and genetic diversity, said David Martinez, a co-author of a <a href="https://pubmed.ncbi.nlm.nih.gov/33027653/">2020 study</a> on the diversity within dengue serotype genomes and an assistant professor of immunobiology at the Yale School of Medicine. <a href="https://otter.ai/u/Z9a0vCUiw8RSxhxVQTeToUhQgQ8?utm_source=copy_url"></a>“Vast genetic diversity is certainly out there for many different viral families. So this is not unique to dengue,” he said. “But within the flaviviruses [<a href="https://www.nature.com/articles/s41564-020-0714-0">vector-borne RNA viruses</a>] that can infect humans and are actually a major problem in human populations, then dengue does seem to be a bit more unique in that regard.”
</p>
<h3 id="kEO0sL">
The challenge with a dengue vaccine
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VoksGB">
There is still no treatment to counter the dengue virus itself, and there is <a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue#:~:text=Dengue%20(break%2Dbone%20fever),body%20aches%2C%20nausea%20and%20rash.">no universally available prevention method</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PPqj8d">
Instead, the <a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue#:~:text=Dengue%20(break%2Dbone%20fever),body%20aches%2C%20nausea%20and%20rash.">World Health Organization (WHO) recommends</a> that infected individuals rest, hydrate, and take over-the-counter pain relievers — treatments that can address symptoms. To prevent infection, WHO suggests avoiding mosquito bites by wearing full-coverage clothing, sleeping with <a href="https://www.vox.com/future-perfect/2018/10/18/17984040/bednets-tools-fight-mosquitoes-malaria-myths-fishing">insect-repellent-treated nets</a>, and installing window screens.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hIZtvF">
But no one can stay indoors or under a mosquito net forever — which is why researchers have for decades been working on an effective dengue vaccine.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7EDla9">
In 2015, <a href="https://www.nytimes.com/2015/12/10/business/first-dengue-fever-vaccine-approved-by-mexico.html">Mexico approved</a> the first dengue vaccine, <a href="https://www.sanofi.com/en/your-health/vaccines/dengue">Sanofi Pasteur’s Dengvaxia</a>. At first, health experts welcomed the shot, given it was the only available medical prevention measure, but, two years later, after <a href="https://www.reuters.com/article/us-sanofi-vacccine/sanofis-dengue-vaccine-approved-in-11-countries-idUSKCN1240C5">at least 11 countries</a> approved it, concerns <a href="https://www.nytimes.com/2017/12/17/health/sanofi-dengue-vaccine-philippines.html">began to arise</a> around its safety for those who had never been infected with dengue before.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GxBCey">
In most types of viral infections, antibodies protect someone from developing severe disease. But dengue can act differently, essentially “hitching a ride” on antibodies and using them to enter and infect healthy cells, said Martinez. That’s why a strong immune response — where antibodies are produced — is not always beneficial, and instead can increase the risk of severe disease.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y0MwKc">
<a href="https://pubmed.ncbi.nlm.nih.gov/27898668/">An analysis</a> by Sanofi, WHO, and partnered researchers of long-term data showed that individuals who were never infected — seronegative people — were more likely to develop a severe reaction to a first-time infection if they received the Dengvaxia vaccine. The shot contains a <a href="https://www.hhs.gov/immunization/basics/types/index.html#:~:text=Rabies-,Live%2Dattenuated%20vaccines,and%20long%2Dlasting%20immune%20response.">live, weakened virus</a> that teaches a recipient’s body to produce antibodies, which is also similar to how the <a href="https://www.hhs.gov/immunization/basics/types/index.html">chickenpox and measles</a> vaccines work. (Dengvaxia uses a genetically engineered yellow fever virus to create this response.) But some researchers <a href="https://www.cidrap.umn.edu/dengue/sanofi-restricts-dengue-vaccine-downplays-antibody-enhancement">believe</a> that because antibodies can help dengue infect cells instead of fight the virus, first-time dengue infections after the vaccines become more similar to reinfections, which are more likely to be severe.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nlBxr9">
In response, <a href="https://www.sanofi.com/en/media-room/press-releases/2017/2017-11-29-16-36-30-1210526">Sanofi updated its guidance</a> for the shot in 2017, recommending the vaccine only be given to those with a confirmed prior dengue infection, or seropositive people. But the damage was already done — in the Philippines, where the vaccine was rolled out as part of a national campaign, <a href="https://www.tandfonline.com/doi/full/10.1080/21645515.2018.1522468?journalCode=khvi20">parental confidence in vaccines plummeted</a>, from 82 percent in 2015 to 21 percent in 2018.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kWIs8y">
Aside from the Dengvaxia vaccine (which is still approved in over a dozen countries, including the <a href="https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-dengue-disease-endemic-regions">US</a>, for those with a laboratory-confirmed prior dengue infection), there are <a href="https://www.who.int/news-room/questions-and-answers/item/dengue-vaccines">approximately five other dengue vaccines</a> in development as of 2018. The Japanese pharma company Takeda’s vaccine, TAK-003, is showing promising results. It’s a <a href="https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-for-use-in-european-union">live-attenuated vaccine</a> like Dengvaxia’s shot, but rather than using the yellow fever virus as its backbone, it uses the dengue serotype 2 virus. Takeda’s series of shots have been approved in <a href="https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-in-indonesia-for-use-regardless-of-prior-dengue-exposure">Indonesia</a>, <a href="https://buenosairesherald.com/society/health/regulator-approves-dengue-vaccine-in-argentina">Argentina</a>, and <a href="https://www.takeda.com/newsroom/newsreleases/2023/takedas-qdenga-approved-in-brazil">Brazil</a> for both seropositive and seronegative people, and the <a href="https://www.takeda.com/newsroom/newsreleases/2022/takedas-biologics-license-application-bla-for-dengue-vaccine-candidate-tak-003-granted-priority-review-by-us-food-and-drug-administration">US Food and Drug Administration</a> has granted the shot priority review.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="m9MBof">
One reason for the vaccine’s seeming success is that the Takeda team distinguished between seropositive and seronegative individuals in its trials (to ensure the vaccine was effective and safe for both populations), said Wallace, who is leading Takeda’s dengue vaccine development. “From a vaccine perspective, what we don’t want to do is be priming somebody for a worse infection later,” said Wallace. “We don’t want the vaccine to be acting like a primary infection, meaning the first real natural exposure to dengue is worse than it would otherwise have been.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fbNoJH">
To ensure this safety, the trial took baseline blood samples from 20,000 children across eight countries, Wallace said. Additionally, the team collected data over four and a half years on the efficacy of the vaccine. This <a href="https://www.takeda.com/newsroom/newsreleases/2022/takedas-dengue-vaccine-candidate-provides-continued-protection-against-dengue-fever-through-4.5-years-in-pivotal-clinical-trial">data showed</a> that the vaccine prevented 84 percent of hospitalized dengue cases and 61 percent of symptomatic dengue cases.
</p>
<h3 id="i1VB9O">
Outside-the-box prevention methods
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nH28A6">
In the last two decades researchers have made tremendous progress in dengue-vaccine development, but the nature of the virus means it’s likely a single immunization alone will not stop the disease.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KdFNE3">
A vaccine that uses only one serotype to protect against dengue fever may not create a balanced immune response, said St. John. Over time, immunity to the four different serotypes diminishes at different rates, making an individual more susceptible to certain serotypes of dengue but not others.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hH3EyH">
“When we’re thinking about whether a vaccine is good, we think not only on the immediate protection that comes out on the first clinical trials, but also the longevity of this protection and how those immune responses are shaped over time as you get further and further away from that exposure,” said St. John.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vEVazJ">
One non-vaccine approach that has seen success is the World Mosquito Program’s initiative to <a href="https://www.worldmosquitoprogram.org/en/work/wolbachia-method/how-it-works">breed virus-resistant mosquitoes</a>. The bacterium <a href="https://www.who.int/groups/vector-control-advisory-group/summary-of-new-interventions-for-vector-control/reduced-pathogen-transmission-by-a-microorganism">Wolbachia</a> prevents the Aedes mosquito from passing on dengue, yellow fever, chikungunya, and Zika virus. The World Mosquito Program breeds mosquitos that carry this naturally occurring bacteria and then release them into the natural environment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1roC4i">
“It’s exactly the same rationale for how vaccination works for humans. So you don’t need to vaccinate 100 percent of the people in the population to give protection to the whole population,” said O’Neill. “It’s effectively the same for our intervention … the bacteria that causes this effect has its own mechanism to transmit itself into the mosquito population.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UOtXsB">
This initiative <a href="https://www.worldmosquitoprogram.org/en/global-progress/australia">launched in Australia in 2011</a>, and since then the country has reported no dengue transmission and the Wolbachia-positive mosquito population has become self-sustaining, said O’Neill. Additionally, this <a href="https://www.vox.com/public-health">public health</a> approach is cost-effective and <a href="https://www.worldmosquitoprogram.org/sites/default/files/scott_oneill_082018.pdf">socially acceptable</a>. The initiative addresses multiple viruses at once, is self-sustaining, and does not create the same fear among those living in endemic areas as practices such as genetic engineering do, he added.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mrp31C">
As the world turns its attention away from Covid, it’s important that scientists and policymakers continue to make progress — through vaccines and other more experimental methods — on long-existing diseases that continue to incapacitate and kill many people, especially the poor. And when it comes to dengue fever, vaccine manufacturers and public health leaders need to learn from past mistakes to ensure faith in these interventions does not wane.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kqMWCK">
“We should be using evidence to guide policy in the area of dengue control,” said O’Neill. “Any new intervention has to be able to show with the highest epidemiological evidence that their treatment or their innovation actually reduces disease before it can be heavily recommended.”
</p></li>
<li><strong>Everything old is new again</strong> -
<figure>
<img alt="A figure holds their finger in the air. Their head is a lightbulb with the recycling symbol inside. Flowers and a bird surround the figure." src="https://cdn.vox-cdn.com/thumbor/ZGePaQXu4Da3tjIrA3floMXBs4s=/226x0:1666x1080/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/72280675/CristinaSpano_NoNewIdeas_Cover.0.jpg"/>
<figcaption>
Cristina Spanò for Vox
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Is it possible to be truly original anymore — in your own life, in commerce, in art?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1NaybJ">
We’re in a cultural moment where it feels like so much is being rehashed, repackaged, and resold to a captive audience. This is certainly the case in entertainment, where the Hollywood reboot machine is the driving force behind what makes it to our screens; even “original” programming is frequently built from familiar storytelling tropes and formats. The same kind of recycling — sorry, <em>remixing</em> — holds true in pop music.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ettJdm">
This carries over into matters of business and politics with just as much resonance. And when it comes to lifestyle topics like dieting, parenting, and even sex, we wind up circling the drain and repackaging old trends and ideas as hot new fads, too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OCRHX8">
What makes newness, or novelty, or originality, so important in the first place, particularly in a society that heavily prioritizes individual comfort and choices? Are we in a uniquely not-new moment, or has it actually always felt this way?
</p>
<hr class="p-entry-hr" id="ychhL0"/>
<figure class="e-image">
<img alt="A cluster of mermaids drawn in various styles to show different iterations throughout history." src="https://cdn.vox-cdn.com/thumbor/MHrW4PyZ8LFGsHgIFhjotq6aKcg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24630032/2Spot.jpg"/> <cite>Cristina Spanò for Vox</cite>
</figure>
<h3 id="QOLupP">
<a href="https://www.vox.com/the-highlight/23668199/fallacy-new-ideas-original-story-little-mermaid"><strong>The fallacy of new ideas, and why we want them anyway</strong></a>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tIQp0o">
Could we ever really tell a new story about a very old mermaid?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="N6EYPi">
<em>By Alissa Wilkinson</em>
</p>
<hr class="p-entry-hr" id="Z62zJB"/>
<figure class="e-image">
<img alt="A cartoon drawing of two figures riding in battle tanks, facing each other, yelling at one another through bullhorns. A laptop sits in the background between them. The laptop screen reads “XXX.”" src="https://cdn.vox-cdn.com/thumbor/IOl-G4ji6RrceNwlQv2C1po--fU=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24630262/3Spot.jpg"/> <cite>Cristina Spanò for Vox</cite>
</figure>
<h3 id="lp2WLg">
<a href="https://www.vox.com/the-highlight/23699724/pornography-wars-feminism-pornhub-andrea-dworkin-catharine-mackinnon-amia-srinivasan-kelsy-burke"><strong>The return of the porn wars</strong></a>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="V3vI5m">
How today’s fight over pornography is rooted in a 40-year-old feminist schism.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nP0SQK">
<em>By Constance Grady</em>
</p>
<hr class="p-entry-hr" id="ygZkQj"/>
<figure class="e-image">
<img alt="Row of parents holding babies with speech bubbles above their heads. They are all offering the same advice to new parents." src="https://cdn.vox-cdn.com/thumbor/Vo9pWaxb3xxLIovbzvaAT3lSXvM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24630385/5Spot.jpg"/> <cite>Cristina Spanò for Vox</cite>
</figure>
<h3 id="iDER1r">
<a href="https://www.vox.com/the-highlight/23700540/parenting-advice-endless-recycling-dr-spock-gentle-parenting"><strong>From banning hugs to gentle parenting, how are you supposed to raise kids, anyway?</strong></a>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="piM15a">
The endless cycling — and recycling — of parenting advice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cqNjat">
<em>By Anna North</em>
</p>
<hr class="p-entry-hr" id="ieuIG7"/>
<figure class="e-image">
<img alt="A cartoon drawing of a large figure sitting proudly on top of several people, who are struggling to hold the weight. The scene looks like a king on a throne with two bitcoins in place of arm rests." src="https://cdn.vox-cdn.com/thumbor/KZSpLxZnJF6wsRAoUkjBijDfw5E=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24630061/4Spot.jpg"/> <cite>Cristina Spanò for Vox</cite>
</figure>
<h3 id="LwS7GY">
<a href="https://www.vox.com/the-highlight/23678646/crypto-ftx-bitcoin-fraud-scams-capitalism-ethereum-sbf"><strong>Crypto: New. Fraud: Old.</strong></a>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5i1yyS">
When you democratize finance, you get the good and the bad.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lc4tkl">
<em>By Emily Stewart</em>
</p>
<hr class="p-entry-hr" id="JipfNj"/>
<figure class="e-image">
<img alt="A figure stands on a stage, which looks like a $100 bill, surrounded by showy rays of light. Audience members below reach their hands toward the stage to show their fandom." src="https://cdn.vox-cdn.com/thumbor/AjAdHvTIPEuOnFUfNs-Hs5k1UkE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24635258/1Spot.jpg"/> <cite>Cristina Spanò for Vox</cite>
</figure>
<h3 id="nhVVwa">
<strong>The billionaire’s guide to self-help </strong><em><strong>(Coming Friday)</strong></em>
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NlkYoC">
Self-improvement is old. What’s new is the bootstrapping mythos and toxic positivity of the very rich.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fve35E">
<em>By Whizy Kim</em>
</p>
<hr class="p-entry-hr" id="2Dd4j4"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jW6hDf">
<strong>CREDITS</strong>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="otp9Bk">
<strong>Editors: </strong>Meredith Haggerty, Alanna Okun, Lavanya Ramanathan, Julia Rubin<br/><strong>Copy editors/fact-checkers:</strong> Elizabeth Crane, Kim Eggleston, Tanya Pai, Caitlin PenzeyMoog<br/><strong>Additional fact-checking: </strong>Anouck Dussaud, Matt Giles<br/><strong>Art direction: </strong>Dion Lee, Paige Vickers<br/><strong>Audience:</strong> Gabriela Fernandez, Shira Tarlo, Agnes Mazur<br/><strong>Production/project editors:</strong> Lauren Katz, Nathan Hall
</p>
<div id="hq8rvd">
</div>
<div id="8eFsli">
<div id="money_pixel_page_level_exception">
</div></div></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hockey | Indian women lose 2-4 to Australia in first Test</strong> - India’s goal scorers were Sangita Kumari (29th) and Sharmila Devi (40th)</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Archery World Cup: India crash out of recurve team events</strong> - The women’s trio put up a sloppy show to make a first-round exit</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2023, RR vs PBKS | Fate out of their own hands, Rajasthan Royals and Punjab Kings face desperate situation</strong> - Royals are better placed than Punjab Kings ahead of their final league game but both will have to rely on other results after an up and down season</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Djokovic says new generation has arrived after Rome quarterfinal exit</strong> - Novak Djokovic, who lost to 20-year-old Dane Holger Rune in the Italian Open quarterfinals, said the next generation of players led by world number two Carlos Alcaraz is like a breath of fresh air for the sport.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Three out of four sexual assault charges against SL cricket Gunathilaka dropped</strong> - Gunathilaka was charged with four counts of sexual intercourse without consent for which the 32-year-old had been arrested by the Sydney police from the team hotel last November</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Political parties in Tamil Nadu hail Supreme Court’s verdict upholding the law allowing jallikattu</strong> - The upshot of the ruling is that the State Assemblies can pass legislation on subjects placed on the Concurrent List, says Anbumani Ramadoss; Supreme Court has accepted the law passed by the State Cabinet, says K.S. Alagiri</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>BJP tried to manipulate civic polls in U.P. but didn’t succeed: Mayawati</strong> - Accusing the ruling party of misusing official machinery, the Bahujan Samaj Party leader said people did not allow the BJP’s plans to succeed</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why can’t Old City become New City?</strong> - Muslims should realise they are being used only as vote banks, says BJP Telangana president Bandi Sanjay Kumar</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>BJP makes a ‘BC Declaration’, to mobilise BCs to come to power in TS</strong> - Congress and Bharat Rashtra Samithi governments have only betrayed the interests of the BCs, says BJP BC Morcha national president K. Lakshman</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Review of regulatory framework needed to create a vibrant real estate sector: study</strong> - Report by Gulati Institute of Finance and Taxation recommends reduction of stamp duty to 5%</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Russia launches ninth wave of missile attacks on Kyiv this month</strong> - All missiles over the capital were shot down, but falling debris caused some damage, Ukraine says.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Italy floods leave nine dead and force 13,000 from their homes</strong> - Almost every river flooded between the coast and the city of Bologna, leaving nine people dead.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine: The Mariupol steel workers longing for home</strong> - Mariupol’s former Azovstal workers yearn for their old lives in the now Russian-held city.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Italy floods: F1 Imola race cancelled as deadly deluge sparks evacuations in Emilia-Romagna</strong> - About 10,000 people flee their homes in Emilia-Romagna, with nine confirmed deaths across the region.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine conflict: Black Sea grain deal extended for two months</strong> - Russia allows exports of grain from Black Sea ports to continue, but criticises Western sanctions.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>We’re effectively alone in the Universe, and that’s OK</strong> - Solitude is not a curse—it urges us to explore the mysteries of our galaxy and beyond. - <a href="https://arstechnica.com/?p=1939849">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What to expect from Sony’s May 24 not-E3 livestream</strong> - <em>Spider-Man 2</em> and <em>Final Fantasy XVI</em> seem like givens—but what else will we see? - <a href="https://arstechnica.com/?p=1939994">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Elizabeth Holmes’ no good, very bad day: Bail denied and a bill for $452 million</strong> - Holmes will use the next 13 days to get her affairs in order, she told the court. - <a href="https://arstechnica.com/?p=1939999">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>3D “digital twin” showcases wreck of Titanic in unprecedented detail</strong> - “This is a new phase for underwater forensic investigation and examination.” - <a href="https://arstechnica.com/?p=1939778">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Google’s new “inactive account” policy won’t delete years of YouTube videos</strong> - Google is going to wipe out old accounts, but not ones with YouTube videos? - <a href="https://arstechnica.com/?p=1939941">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Russian wife turned to her husband and asked…</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What’s this special military operation our glorious leader keeps talking about?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Her husband replied, “It’s a proxy war between Russia and NATO.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Oh, right. How’s it going?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well,” he replied, “so far we’ve lost 200,000 soldiers, 4,000 tanks, 500 aircraft, numerous helicopters, loads of armoured vehicles and artillery pieces along with our ‘flag ship’.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Wow! What about NATO?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“They haven’t turned up yet.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Alpha-Studios"> /u/Alpha-Studios </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13kq7sv/a_russian_wife_turned_to_her_husband_and_asked/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13kq7sv/a_russian_wife_turned_to_her_husband_and_asked/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>My girlfriend decided to surprise me, she dressed up as a policewoman and told me I was under arrest on suspicion of being good in bed.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After 2 minutes all charges were dropped due to a lack of evidence.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HelpingHandsUs"> /u/HelpingHandsUs </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13kuxhx/my_girlfriend_decided_to_surprise_me_she_dressed/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13kuxhx/my_girlfriend_decided_to_surprise_me_she_dressed/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What has 4 letters, sometimes 9 letters, always 6 letters, but never has 5 letters.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Hint: Not a question
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HelpingHandsUs"> /u/HelpingHandsUs </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13kk2k1/what_has_4_letters_sometimes_9_letters_always_6/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13kk2k1/what_has_4_letters_sometimes_9_letters_always_6/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I dig, you dig, he dig, she dig, we dig, they dig.</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It’s not a long poem,but it’s very deep.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/iushdulal"> /u/iushdulal </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13kk7x3/i_dig_you_dig_he_dig_she_dig_we_dig_they_dig/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13kk7x3/i_dig_you_dig_he_dig_she_dig_we_dig_they_dig/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What’s the difference between alzheimers and dementia?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
What’s the difference between alzheimers and dementia?
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/whatwhatinthewhonow"> /u/whatwhatinthewhonow </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/13khr3r/whats_the_difference_between_alzheimers_and/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/13khr3r/whats_the_difference_between_alzheimers_and/">[comments]</a></span></p></li>
</ul>
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