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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>A social media-based framework for quantifying temporal changes to wildlife viewing intensity: Case study of sea turtles before and during COVID-19</strong> -
<div>
Documenting how human pressure on wildlife changes over time is important to minimise potential adverse effects through implementing appropriate management and policy actions; however, obtaining objective measures of these changes and their potential impacts is often logistically challenging, particularly in the natural environment. Here, we developed a modular stochastic model that infers the ratio of actual viewing pressure on wildlife in consecutive time periods (years) using social media, as this medium is widespread and easily accessible. Pressure was calculated from the number of times individual animals appeared in social media in pre-defined time windows, accounting for time-dependent variables that influence them (e.g. number of people with access to social media). Formulas for the confidence intervals of viewing pressure ratios were rigorously developed and validated, and corresponding uncertainty was quantified. We applied the developed framework to calculate changes to wildlife viewing pressure on loggerhead sea turtles (Caretta caretta) at Zakynthos island (Greece) before and during the COVID-19 pandemic (2019-2021) based on 2646 social media entries. Our model ensured temporal comparability across years of social media data grouped in time window sizes, by correcting for the interannual increase of social media use. Optimal sizes for these windows were delineated, reducing uncertainty while maintaining high time-scale resolution. The optimal time window was around 7-days during the peak tourist season when more data were available in all three years, and &gt;15 days during the low season. In contrast, raw social media data exhibited clear bias when quantifying changes to viewing pressure, with unknown uncertainty. The framework developed here allows widely-available social media data to be used objectively when quantifying temporal changes to wildlife viewing pressure. Its modularity allowed viewing pressure to be quantified for all data combined, or subsets of data (different groups, situations or locations), and could be applied to any site supporting wildlife exposed to tourism.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.19.492636v1" target="_blank">A social media-based framework for quantifying temporal changes to wildlife viewing intensity: Case study of sea turtles before and during COVID-19</a>
</div></li>
<li><strong>mRNA-based vaccines against SARS-CoV-2 do not stimulate interferon stimulatory gene expression in individuals affected by Aicardi Goutieres Syndrome.</strong> -
<div>
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses threats to individuals with rare disease, in part because so little is known about the impact of COVID-19 infection and vaccination safety in rare disease populations. Of particular concern, given the overlap in disease manifestations and interferon dysregulation, are a group of heritable autoinflammatory conditions called type I interferonopathies. The most common of these, Aicardi Goutieres Syndrome (AGS), is caused by altered nucleic acid metabolism and sensing, resulting in additional concerns surrounding the use of mRNA vaccination approaches. To determine whether mRNA vaccines induce an interferon response in AGS, we applied mRNA SARS-CoV-2 vaccines to whole blood samples and assessed internalization and interferon signaling gene expression responses to the mRNA. In all cases (11 AGS and 11 control samples), interferon signatures did not significantly increase from baseline, regardless of baricitinib treatment status in the AGS subjects, and were even decreased, when using codon optimized SARS-CoV-2 di-proline modified spike sequence (S2P). Internalization of S2P in human dendritic cells was verified by Western Blot, and in control and AGS blood cells was verified by Luciferase activity. Although numbers of tested samples in this rare disease are small, based on these findings, we suggest that COVID vaccination is unlikely to directly stimulate the interferon signaling gene expression in AGS patients via response to mRNA internalization. The in vitro nature of this study cannot exclude an exaggerated interferon response to spike protein production at a systemic level in individuals with a primary heritable interferonopathy. In the context of continued SARS-CoV-2 spread in the community, we do not recommend withholding vaccination in this rare disease group. However, we recommend that vaccinations for AGS patients are provided in a controlled setting with appropriate observation and used with caution in individuals with prior vaccine associated adverse events.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.18.492546v1" target="_blank">mRNA-based vaccines against SARS- CoV-2 do not stimulate interferon stimulatory gene expression in individuals affected by Aicardi Goutieres Syndrome.</a>
</div></li>
<li><strong>Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates</strong> -
<div>
Despite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
</div>
<div class="article-link article- html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.19.492649v1" target="_blank">Programming the lymph node immune response with Amphiphile-CpG induces potent cellular and humoral immunity following COVID-19 subunit vaccination in mice and non-human primates</a>
</div></li>
<li><strong>Parameter Estimation for a Modified SEIR Model of the COVID-19 Dynamics in the Philippines using Genetic Algorithm</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Philippines has been under a series of different levels of community quarantine and this affected the dynamics of the COVID-19 spread in the country. Predicting the trajectory has been an interest of various research groups. To provide a more efficient method to estimate the parameters of the Age-Stratified, Quarantine-modified SEIR model with Nonlinear Incidence Rates (ASQ-SEIR-NLIR) other than the shooting method, a genetic algorithm approach is explored. By defining constraints for each parameter, the algorithm arrived at an acceptable optimal value for each parameter. The experiment is done on two regions of interest: the Philippines (country-level) and Quezon City, Metro Manila (city-level). The ASQ-SEIR-NLIR model, using the parameters generated by the genetic algorithm, is able to produce an average trajectory compared to the actual data, which may be deemed noisy. The dynamics of the COVID-19 spread between Quezon City and average country level is compared, showing that the city population is being exposed to the virus at a much faster rate than the country average and may have more asymptomatics not getting tested than the country average. Given the average trajectory, the peak daily infection projection is way lower at 0.0823% of the country population for the country projection and 0.1494% of the Quezon City population for the city projection, which is below than previous literature estimates of 3-10%.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.17.22275187v1" target="_blank">Parameter Estimation for a Modified SEIR Model of the COVID-19 Dynamics in the Philippines using Genetic Algorithm</a>
</div></li>
<li><strong>COMPARISON OF SARS-COV-2 WUHAN AND ALPHA VARIANTS: CLINICAL AND LABORATORY HIGHLIGHTS</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Since December 2019, after the declaration of new cases regarding novel coronavirus disease, many variants have emerged as a consequence of the viral evolution. Though the SARS-CoV-2 variants have been studied for molecular basis, the clinical and pathologic disparities of them have been understood inadequately. The aim of this research was to figure out the differences between the SARS-CoV-2 Alpha (B1.1.7) variant and the classical Wuhan groups on the clinical basis and laboratory results of the COVID-19 patients who had positive PCR test. The study was done retrospectively inclusive of epidemiological, laboratory data and clinical symptoms of patients who were admitted to the emergency service between February 15 and March 15, 2021 and had positive COVID-19 PCR test results. Though there was no statistically significant difference in symptoms between SARS-CoV-2 Alpha variant and classical variant (Wuhan type) groups; C-reactive protein (CRP), lymphocyte and leukocyte counts were statistically significantly higher in the Wuhan type group; prothrombin time (PT), International Normalized Ratio (INR) and serum creatinine values were statistically significantly higher in the Alpha group. Studies such as ours that investigate both the clinical features and laboratory data of SARS-CoV-2 variants will close the knowledge gaps, so better decisions may be made by health policy makers. Additional studies in this area will increase the understanding of the topic.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.17.22275188v1" target="_blank">COMPARISON OF SARS-COV-2 WUHAN AND ALPHA VARIANTS: CLINICAL AND LABORATORY HIGHLIGHTS</a>
</div></li>
<li><strong>Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.
</p>
</div>
<div class="article-link article- html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.15.22275051v1" target="_blank">Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study</a>
</div></li>
<li><strong>Comprehensive analysis of pathways in Coronavirus 2019 (COVID-19) using an unsupervised machine learning method</strong> -
<div>
The World Health Organization (WHO) introduced “Coronavirus disease 19” or “COVID19” as a novel coronavirus in March 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the fast discovery of effective treatments to fight this worldwide crisis. Artificial intelligence and bioinformatics analysis pipelines can assist with finding biomarkers, explanations, and cures. Artificial intelligence and machine learning methods provide powerful infrastructures for interpreting and understanding the available data. On the other hand, pathway enrichment analysis, as a dominant tool, could help researchers discover potential key targets present in biological pathways of host cells that are targeted by SARS-CoV-2. In this work, we propose a two-stage machine learning approach for pathway analysis. During the first stage, four informative gene sets that can represent important COVID-19 related pathways are selected. These “representative genes” are associated with the COVID-19 pathology. Then, two distinctive networks were constructed for COVID-19 related signaling and disease pathways. In the second stage, the pathways of each network are ranked with respect to some unsupervised scorning method based on our defined informative features. Finally, we present a comprehensive analysis of the top important pathways in both networks.
</div>
<div class="article-link article-html- link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.18.492441v1" target="_blank">Comprehensive analysis of pathways in Coronavirus 2019 (COVID-19) using an unsupervised machine learning method</a>
</div></li>
<li><strong>COVID-19 lockdown reveals fish density may be much higher in marine reserves</strong> -
<div>
Marine reserves generally allow ecotourism to offer an alternative income to fishing. However, we need to assess its impact on wildlife to make this activity sustainable. The COVID-19 lockdown provided a unique opportunity to evaluate wildlife diversity in the absence of human activity. In a Mexican reserve, we monitored fish assemblages before, during, and just after the lockdown. We show that ecotourism activities alter the behavior of fishes by finding a 2.5-fold density rise during the lockdown. We suggest that the noise pollution generated by the numerous recreational vessels is a significant factor of perturbation. In the absence of noise pollution, some fishes may be bolder (less hidden) and others can come back to the reserve from usually quieter areas (e.g., deeper waters). Our results represent a great worldwide incentive to improve the health of marine reserves by establishing concrete measures in managing plans to mitigate noise pollution.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.17.492376v1" target="_blank">COVID-19 lockdown reveals fish density may be much higher in marine reserves</a>
</div></li>
<li><strong>Impact of the COVID-19 pandemic on Infant Feeding Practices in the U.S.: Food Insecurity, Supply Shortages, and Deleterious Feeding Practices</strong> -
<div>
The COVID-19 pandemic drastically increased food insecurity among U.S. households, however, little is known about how infants, who rely primarily on human milk and/or infant formula, were impacted. We conducted an online survey with U.S. caregivers of infants (&lt;2 years) (N=319) to assess how the COVID-19 pandemic impacted breastfeeding, formula-feeding, and household ability to obtain infant-feeding supplies and lactation support (68% mothers; 66% white; 8% living in poverty). Results suggest that the COVID-19 pandemic had a greater negative impact on formula-feeding families, largely due to formula shortages and financial strain. We found 31% of formula-feeding families indicated they experienced various challenges to obtaining formula, citing the following top three reasons: formula was sold out (20%), had to travel to multiple stores (21%), or too expensive (8%). In response, 33% of formula-feeding families reported resorting to potentially harmful feeding practices such as diluting formula with extra water (12%) or cereal (10%), preparing smaller bottles (8%), or feeding left-over/expired formula (11%). Only 15% of breastfeeding families reported feeding difficulties directly as a result of the pandemic—15% were reluctant to obtain lactation support and 9% weaned early. In fact, 51% of breastfeeding families reported increased provision of human milk to infants due to perceived benefits for the infant’s immune system (37%), ability to work remotely/stay home (31%), or concerns about money (8%) or formula shortages (8%). To protect infants from malnutrition in future crises, our results underscore the need for policies to support breastfeeding families and ensure equitable access to infant formula.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/gx5qr/" target="_blank">Impact of the COVID-19 pandemic on Infant Feeding Practices in the U.S.: Food Insecurity, Supply Shortages, and Deleterious Feeding Practices</a>
</div></li>
<li><strong>How Should COVID-19 Vaccines be Distributed between the Global North and South? A Discrete Choice Experiment in Six European Countries</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The global distribution of COVID-19 vaccinations remains highly unequal. We examine public preferences in six European countries regarding the allocation of COVID-19 vaccines between the Global South and Global North. Methods: We conducted online discrete choice experiments with adult participants in France (n=766), Germany (n=1964), Italy (n=767), Poland (n=670), Spain (n=925), and Sweden (n=938). Respondents were asked to decide which one of two candidates, who varied along four attributes: age, mortality risk, employment, and living in a low- or high-income country, should receive the vaccine first. We analysed the relevance of each attribute in allocation decisions using a conditional logit regression. Results: Across countries, respondents selected candidates with a high mortality and infection risk, irrespective of whether the candidate lived in their own country. All else equal, respondents in Italy, France, Spain, and Sweden gave priority to a candidate from a low-income country, whereas German respondents were significantly more likely to choose the candidate from their own country. Female, younger, and more educated respondents were more favourable of an equitable vaccine distribution. Conclusions: Given these preferences for global solidarity, European governments should promote vaccine transfers to poorer world regions.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.19.22275055v1" target="_blank">How Should COVID-19 Vaccines be Distributed between the Global North and South? A Discrete Choice Experiment in Six European Countries</a>
</div></li>
<li><strong>Epitope Mapping of SARS-CoV-2 Spike Protein Reveals Distinguishable Antibody Binding Activity of Vaccinated and Infected Individuals.</strong> -
<div>
A multitude of studies have attempted to characterize the antibody response of individuals to the SARS-CoV-2 virus on a linear peptide level by utilizing peptide microarrays. These studies have helped to identify epitopes that have potential to be used for diagnostic tests to identify infected individuals, however the immunological responses of individuals who have received the currently available mRNA vaccines have not been characterized. We aimed to identify linear peptides of the SARS-CoV-2 spike protein that elicited high IgA or IgG binding activity and compare the immunoreactivity of infected individuals to those who received recommended doses of either the Moderna mRNA-1273 or Pfizer BNT162b2 vaccines by utilizing peptide microarrays. Our results revealed peptide epitopes of significant IgG binding among recently infected individuals, many of which are located near functional domains implicated in the high infectivity of SARS-CoV-2. Vaccinated individuals were found to have less intense antibody binding activity than those acutely infected, yet novel markers of IgG binding were identified in the vaccinated group.
</div>
<div class="article- link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.13.487697v3" target="_blank">Epitope Mapping of SARS-CoV-2 Spike Protein Reveals Distinguishable Antibody Binding Activity of Vaccinated and Infected Individuals.</a>
</div></li>
<li><strong>Evaluation of anti-spike glycoprotein antibody and neutralizing antibody response of different vaccine platforms. A protocol of systematic review and meta-analysis of COVID-19 vaccine clinical trial studies</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. SARS-CoV-2 transmit among the people fast and infected thousands of people daily around the world. Because of rapid transmission of SARS-CoV-2 among the people, there is an urgent need to prevent people from infection or hospitalization and control the disease. Methods: We will search electronic databases such as PubMed, Web of Science, Cochrane (CENTRAL), Scopus, Google scholar, the key journals (vaccine and vaccines). Moreover, trial registry including clinicalTrials.gov, WHO ICTRP, and ISRCTN will be searched. We will only select all clinical trial studies in any phases of evaluation (i.e. phase I, II, II, IV). For anti-spike glycoprotein antibody (IgG) response and neutralizing antibody response, we will report Ratio of Geometric Mean (RoGM), Ratio of Mean (RoM) or standardized mean difference (SMD) depends on type of articles. Discussion: Various vaccine platforms have been developed to increase the resistance to the SARS-CoV2 virus and reduce hospitalization and mortality rates. The comprehensive data gathering and analysis of results will guide scientists about the best available evidence. Moreover, the current study results may indicate which of the vaccine platforms are more effective and safe for COVID-19.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.18.22275247v1" target="_blank">Evaluation of anti-spike glycoprotein antibody and neutralizing antibody response of different vaccine platforms. A protocol of systematic review and meta-analysis of COVID-19 vaccine clinical trial studies</a>
</div></li>
<li><strong>Sequence Proven Reinfections with SARS-CoV-2 at a Large Academic Center</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Increased reinfection rates with SARS-CoV-2 have recently been reported, with some locations basing reinfection on a second positive PCR test at least 90 days after initial infection. We investigated sequencing and clinical data on the 750 patients (920 samples) we identified with these criteria. The median time between tests was 377 days, and 724 (79%) of the post 90-day positives were collected after the emergence of the Omicron variant in November 2021. Successful sequencing occurred in 127 of 231 attempted samples, spiked during the Omicron surge and showed higher median days from initial infection compared to failed sequences (median 398 days compared to 276 days, p&lt;0.0005). A total of 122 (98%) patients showed evidence of reinfection, 45 of which had sequence proven reinfection and 77 had inferred reinfections (later sequence showed a clade that was not circulating when the patient was initially infected). Children accounted for only 4% of reinfections. 43 (96%) of 45 infections with sequence proven reinfection were caused by the Omicron variant, 41 (91%) were symptomatic, 32 (71%), were vaccinated prior to the second infection, and 6 (13%) were Immunosuppressed. Only 2 (4%) were hospitalized, and both had underlying conditions.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.17.22275210v1" target="_blank">Sequence Proven Reinfections with SARS-CoV-2 at a Large Academic Center</a>
</div></li>
<li><strong>Reduced Exercise Capacity, Chronotropic Incompetence, Inflammation and Symptoms in Post-Acute COVID-19</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
BACKGROUND Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring. METHODS In the Long-Term Impact of Infection with Novel Coronavirus (LIINC) Cohort, we performed CMR, CPET, and ambulatory rhythm monitoring among adults &gt; 1 year after PCR-confirmed SARS-CoV-2 infection. We used logistic and linear regression to compare those with and without cardiopulmonary symptoms (dyspnea, chest pain, palpitations) adjusting for confounders. RESULTS One hundred twenty individuals were studied, among whom 46 participants (unselected for symptom status) had at least one advanced test performed at median 17 months (IQR 15-18). Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), smaller RV volume and stroke volume and higher extracellular volume were present among those with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/15 (87%) participants with reduced exercise capacity (&lt;85% predicted) reported cardiopulmonary symptoms or fatigue (p=0.008). Adjusted peak VO2 was 2.7 ml/kg/min lower among those with cardiopulmonary symptoms (95%CI -6.9 to 1.5; p=0.20) or -11% predicted (95%CI -27 to 5, p=0.17). Including fatigue along with cardiopulmonary symptoms, the adjusted difference in peak VO2 was -5.9 ml/kg/min (-9.6 to -2.3; p=0.002) or -21% predicted (-35 to -7; p=0.006). Chronotropic incompetence was the primary abnormality among 9/15 with reduced peak VO2. Adjusted heart rate reserve &lt;80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Those with chronotropic incompetence had higher hsCRP, lower heart rate recovery, and lower heart rate variability suggestive of autonomic dysfunction. CONCLUSIONS Reduced exercise capacity and reduced heart rate response to exercise, and hsCRP are associated with persistent cardiopulmonary symptoms more than 1 year following COVID-19. Chronic inflammation and autonomic dysfunction may underlie cardiopulmonary PASC.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.17.22275235v1" target="_blank">Reduced Exercise Capacity, Chronotropic Incompetence, Inflammation and Symptoms in Post-Acute COVID-19</a>
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<li><strong>Assessment of the humoral response to the homologous Gam-COVID-Vac (Sputnik V) or heterologous Sputnik V/mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in dialysis patients.</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Introduction: The humoral response to vaccines is the most used tool to evaluate the protection against SARS- CoV-2 infection. Dialysis patients are a high-risk population and have a reduced immune response to vaccination. Objective: To assess the humoral response to homologous Gam-COVID-Vac (Sputnik V) and heterologous Sputnik V/mRNA-1273 (Moderna) vaccination in dialysis patients. Methods: SARS-CoV-2 anti-spike IgG (RBD) concentration was estimated 3-16 weeks after complete vaccination. Reactogenicity was evaluated until day 7 by patients self-reported side events. Results: 107 participants were enrolled [n=84 homologous (SpV/SpV), n=23 heterologous (SpV/Mod)]. Median (IQR) age was 64 (50-75) years old and 79 (73.8%) were male. Additionally, 19 (22.6%) of the SpV/SpV and 4 (17.4%) of the SpV/Mod group had a prior confirmed SARS-CoV-2 infection (p=0.589). In the overall population, 103 patients reached seroconversion (96.3%). Anti-S-RBD IgG median titers (IQR) were higher in the heterologous [1222 (288-5680) BAU/mL] than in the homologous scheme [447 (100-1551) BAU/mL], p=0.022. In a linear model adjusted for age and gender, previous SARS-COV-2 infection (B: 1944.3; CI95: 1136.2-2753.4; p&lt;0.001), and SpV/Mod vaccination scheme (B: 1241.5; CI95: 420.39-2062.6; p=0.003) were independently associated with anti-S-RBD levels. Finally, a higher frequency of adverse effects was associated with the heterologous scheme, although they were well tolerated by all individuals. Conclusion: The present study provides evidence that the homologous SpV/SpV and heterologous SpV/Mod schemes showed good efficacy and safety under dialysis conditions. These results could be useful for future vaccination strategies, especially aimed at this risk group.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.13.22275049v1" target="_blank">Assessment of the humoral response to the homologous Gam-COVID-Vac (Sputnik V) or heterologous Sputnik V/mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in dialysis patients.</a>
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<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 Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)<br/><b>Sponsors</b>:   University of California, Irvine;   Hudson Valley Healing Arts Center<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>Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: STI-9199;   Drug: Placebo<br/><b>Sponsor</b>:  <br/>
Sorrento Therapeutics, 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>A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Shulan (Hangzhou) Hospital<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>Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>:  <br/>
China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Hunan Provincial Center for Disease Control and Prevention<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>Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Radiation: [18F]DPA-714 positron emission tomography (PET) scan<br/><b>Sponsors</b>:   Amsterdam UMC, location VUmc;   ZonMw: The Netherlands Organisation for Health Research and Development<br/><b>Enrolling by invitation</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>Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Palbociclib<br/><b>Sponsor</b>:   biotx.ai GmbH<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>Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo<br/><b>Sponsor</b>:   CanSino Biologics 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>Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVID-19 mRNA vaccine;   Biological: Placebo<br/><b>Sponsor</b>:   CanSino Biologics 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>THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AAHI-SC2 Vaccine;   Biological: AAHI- SC3 Vaccine;   Biological: EUA or approved vaccine<br/><b>Sponsor</b>:   ImmunityBio, Inc.<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>To Evaluate SSD8432/Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SSD8432 dose;   Drug: SSD8432 placebo<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<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>A Study to Evaluate the Efficacy and Safety of DXP604 in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: DXP604<br/><b>Sponsor</b>:  <br/>
Wuhan Institute of Biological Products Co., Ltd<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>Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SSD8432 dose1;   Drug: SSD8432 dose2;   Drug: SSD8432Placebo<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<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>Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell);   Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.;   Wuhan Institute of Biological Products Co., Ltd;   The University of Hong Kong<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>Immunogenicity and Safety of Booster Immunization of COVID-19 Vaccine (Vero Cell), Inactivated (Omicron Variant) in Healthy People Aged 18 Years and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVID-19 Vaccine (Vero cell), Inactivated (Omicron variant);   Biological: COVID-19 Vaccine (Vero cell), Inactivated (CZ strain)<br/><b>Sponsor</b>:  <br/>
Sinovac Research and Development Co., Ltd.<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>To Evaluate SSD8432/ Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>:   COVID-19 Patients<br/><b>Interventions</b>:   Drug: SSD8432 dose 1/Ritonavir;   Drug: SSD8432 dose 2/Ritonavir<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>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>HDAC Inhibition as Potential Therapeutic Strategy to Restore the Deregulated Immune Response in Severe COVID-19</strong> - The COVID-19 pandemic has had a devastating impact worldwide and has been a great challenge for the scientific community. Vaccines against SARS-CoV-2 are now efficiently lessening COVID-19 mortality, although finding a cure for this infection is still a priority. An unbalanced immune response and the uncontrolled release of proinflammatory cytokines are features of COVID-19 pathophysiology and contribute to disease progression and worsening. Histone deacetylases (HDACs) have gained interest in…</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>Intranasal Delivery of Thermostable Subunit Vaccine for Cross-Reactive Mucosal and Systemic Antibody Responses Against SARS-CoV-2</strong> - Despite the remarkable efficacy of currently approved COVID-19 vaccines, there are several opportunities for continued vaccine development against SARS-CoV-2 and future lethal respiratory viruses. In particular, restricted vaccine access and hesitancy have limited immunization rates. In addition, current vaccines are unable to prevent breakthrough infections, leading to prolonged virus circulation. To improve access, a subunit vaccine with enhanced thermostability was designed to eliminate the…</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>Importance of Influenza Anti-Hemagglutinin Antibodies During the SARS-CoV-2 Pandemic in the 2019/2020 Epidemic Season in Poland</strong> - BACKGROUND The aim of this study was to determine the level of anti-hemagglutinin antibodies in the serum of recovered patients during the SARS-CoV-2 pandemic in the 2019/2020 epidemic season in Poland, and the course of COVID-19. MATERIAL AND METHODS The material for the study consisted of the sera of COVID-19 convalescents obtained from the following 9 Regional Blood Donation and Blood Supply Centers located in 8 voivodeships. The hemagglutination inhibition reaction assay (HAI) using 8 viral…</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>Nanocomposites of Graphene Oxide-Silver Nanoparticles for Enhanced Antibacterial Activity: Mechanism of Action and Medical Textiles Coating</strong> - The resistance of microorganisms to antibiotics is a crucial problem for which the application of nanomaterials is among a growing number of solutions. The aim of the study was to create a nanocomposite (composed of graphene oxide and silver nanoparticles) with a precise mode of antibacterial action: what enables textiles to be coated in order to exhibit antibacterial properties. A characterization of nanomaterials (silver nanoparticles and graphene oxide) by size distribution, zeta potential…</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>Ginkgolic acid and anacardic acid are reversible inhibitors of SARS-CoV-2 3-chymotrypsin-like protease</strong> - Because of the emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different regions of the world, the battle with infectious coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been seesawing. Therefore, the identification of antiviral drugs is of particular importance. In order to rapidly identify inhibitors for SARS-CoV-2 3-chymotrypsin-like protease (3CL^(pro)), an enzyme essential for viral replication, we combined the fluorescence polarization (FP)…</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>Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro</strong> - A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with &gt;99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic…</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 sublineages show comparable cell entry but differential neutralization by therapeutic antibodies</strong> - The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified-BA.1, BA.2, and BA.3-and BA.2 exhibits increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-mediated inhibition. Here, we show that BA.1, BA.2, and BA.3 enter and fuse target cells with similar efficiency and in an ACE2-dependent manner. However,…</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>Inhibition of IRAK4 dysregulates SARS-CoV-2 spike protein-induced macrophage inflammatory and glycolytic reprogramming</strong> - Escalated innate immunity plays a critical role in SARS-CoV-2 pathology; however, the molecular mechanism is incompletely understood. Thus, we aim to characterize the molecular mechanism by which SARS-CoV-2 Spike protein advances human macrophage (Mϴ) inflammatory and glycolytic phenotypes and uncover novel therapeutic strategies. We found that human Mϴs exposed to Spike protein activate IRAK4 phosphorylation. Blockade of IRAK4 in Spike protein-stimulated Mϴs nullifies signaling of IRAK4, AKT,…</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>ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), continues to cause significant morbidity and mortality in the ongoing global pandemic. Understanding the fundamental mechanisms that govern innate immune and inflammatory responses during SARS-CoV-2 infection is critical for developing effective therapeutic strategies. While IFN-based therapies are generally expected to be beneficial during viral infection, clinical trials…</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>Clofoctol inhibits SARS-CoV-2 replication and reduces lung pathology in mice</strong> - Drug repurposing has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, 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>Circulatory Exosomes from COVID-19 Patients Trigger NLRP3 Inflammasome in Endothelial Cells</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces inflammatory response, cytokine storm, venous thromboembolism, coagulopathy, and multiple organ damage. Resting endothelial cells prevent coagulation, control blood flow, and inhibit inflammation. However, it remains unknown how SARS-CoV-2 induces strong molecular signals in distant cells for immunopathogenesis. In this study, we examined the consequence of human endothelial cells, microvascular endothelial cells…</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>Antiviral Activity of Selected Lamiaceae Essential Oils and Their Monoterpenes Against SARS-Cov-2</strong> - This study presents the very first report on the in vitro antiviral activity of selected essential oils of Lamiaceae plant species and their monoterpenes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nineteen essential oils were obtained by hydrodistillation of dried plant material, and their monoterpene profiles were determined. In addition, the exact concentrations of each monoterpene that were found at a significant level were defined. Both essential oils and their…</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>Ivermectin as a possible treatment for COVID-19: a review of the 2022 protocols</strong> - Ivermectin is a safe and effective drug in humans and has been approved for use in numerous parasitic infections for over 50 years. In addition, many studies have already shown its antiviral activity. Ivermectin is generally well tolerated, with no indication of central nervous system-associated toxicity at doses up to 10 times the highest FDA- approved dose of 200 µg/kg. The in vitro results of ivermectin for reducing SARS-CoV-2 viral load are promising and show that Ivermectin kills SARS-CoV-2…</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>Feasibility analysis and mechanism exploration of <em>Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus</em> (RS) against COVID-19</strong> - Introduction. As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for…</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>Mutations in Porcine Epidemic Diarrhea Virus nsp1 Cause Increased Viral Sensitivity to Host Interferon Responses and Attenuation <em>In Vivo</em></strong> - Coronavirus (CoV) nonstructural protein 1 (nsp1) inhibits cellular gene expression and antagonizes interferon (IFN) response. Porcine epidemic diarrhea virus (PEDV) infects pigs and causes high mortality in neonatal piglets. We hypothesized that a recombinant PEDV carrying mutations at the conserved residues N93 and N95 of nsp1 induces higher IFN responses and is more sensitive to IFN responses, leading to virus attenuation. We mutated PEDV nsp1 N93 and N95 to A93 and A95 to generate the…</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>Trump Brings His Big Lie Playbook to the G.O.P. Primaries</strong> - Tuesday was a mixed bag for candidates endorsed by the former President, who is making fresh suggestions of election fraud. - <a href="https://www.newyorker.com/news/our-columnists/trump-brings-his-big-lie-playbook-to-the-gop-primaries">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inside Putin’s Propaganda Machine</strong> - Current and former employees describe Russian state television as an army, one with a few generals and many foot soldiers who never question their orders. - <a href="https://www.newyorker.com/news/annals-of-communications/inside-putins-propaganda-machine">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Problem with Blaming Robots for Taking Our Jobs</strong> - For decades, the effects of automation have been fiercely debated. Are we missing the bigger picture? - <a href="https://www.newyorker.com/books/under-review/the-problem-with-blaming-robots-for-taking-our-jobs">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How Putin’s War Remade Washington</strong> - From a revitalization of NATO to the return of superpower nuclear anxiety, it’s been a breathtaking three months. - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/how-putins-war-remade-washington">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Other Kind of Racism in Buffalo</strong> - Keeanga-Yamahtta Taylor on the policies that excluded and impoverished the city’s Black population—long before last week’s shooting. - <a href="https://www.newyorker.com/podcast/politics-and-more/the-other-kind-of-racism-in-buffalo">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One Good Thing: The Jane Campion film that captures spring euphoria</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/TTIoD64b5aW5cSJ-
oRw2ZhOPTn8=/89x0:1540x1088/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70891279/Screen_Shot_2022_05_17_at_3.47.30_PM.0.png"/>
<figcaption>
Abbie Cornish, Kerry Fox, Ben Whishaw, Thomas Brodie-Sangster, and Edie Martin star in the film. | IMDB
</figcaption></figure></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Bright Star” manages to bottle the fleeting feeling of spring bliss.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kRecxv">
Spring is glorious and terrible, especially in the Northeast United States. The first signs of flowers and greenery are so gorgeous and well-deserved after winter that a simple walk outside can feel positively giddy. There’s that vertiginous falling-in-love feeling that happens when the first actual not-cold breeze hits your skin. Then, just as you’ve taken a selfie with your spectacular neighborhood cherry blossoms, the petals flutter to the ground, and it’s over. Here in New York, the sidewalks heat up and reanimate the winter’s dormant dog pee, the city smells like garbage, and we have to wait a whole year to feel the ecstasy again.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9XdCAf">
If you wish there were a way to bottle the fleeting feeling of spring bliss like I do, I urge you to watch <em>Bright Star</em>, the Jane Campion film from 2009 about John Keats and his love, Fanny Brawne, played by Ben Whishaw and Abbie Cornish.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RDRdLC">
<a href="https://www.poetryfoundation.org/poets/john-keats">John Keats was an early 19th-century poe</a>t, now famed for being one of the greatest lyric poets in the English language. He was deeply inspired by William Shakespeare and <a href="https://www.poetryfoundation.org/poems/45192/the-faerie-queene-book-i-canto-i">Edmund Spenser</a>, and he wrote odes and ballads like “<a href="https://www.poetryfoundation.org/poems/44479/ode-to-a-nightingale">Ode to a Nightingale</a>” and “<a href="https://www.poetryfoundation.org/poems/44475/la-belle-dame-sans-merci-a-ballad">La Belle Dame sans Merci: A Ballad</a>.” He died young and penniless of tuberculosis at age 25, and his work didn’t become famous until after his death. He fell in love with Fanny Brawne, an accomplished seamstress and nearby neighbor, but because of his financial situation, fragile health, and the general social mores of the Regency era, they couldn’t marry. He secretly gave her an engagement ring that she wore until her death, long after Keats had passed away and she married and had a family of her own (swoon!). It was during their love affair that Keats had his most prolific and inspired writing period, and it’s this three-year stretch — from meeting Brawne until his death — that is captured in the film.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WSuJ84">
Jane Campion’s hallmark is edgy, groundbreaking direction — she made the erotic thriller <em>In the Cut</em> before <em>Bright Star —</em> so a bonneted, empire-waisted costume drama doesn’t seem to promise the exciting filmmaking she is known for. But this is not a Jane Austen story where somehow everyone manages to get married at the end. Keats and Brawne’s love isn’t almost doomed; it’s <em>actually</em> doomed. All that makes its flame burn all the brighter, especially against the insanely gorgeous natural backdrop of this movie. Natural beauty was one of Keats’ strongest inspirations, and it’s clear that Campion took this to heart. The spring love sequences are some of the closest scenes I’ve seen on film to accurately capturing the sensation of being totally blissed out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uK213D">
There’s Keats, gangly and tousled, scrambling barefoot up the rough trunk of a blooming apple tree to find a nightingale nest, the prickly bark and branches swaying under his weight until he finds a perch to close his eyes and dream (and get inspiration for one of his <a href="https://www.poetryfoundation.org/poems/44479/ode-to-a-
nightingale">masterpieces</a>).
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9TbdgZ">
There’s Brawne, reading a missive from Keats in an endless field of bluebells, so overwhelmed by joy that she grabs her little sister, Toots, and plants ferocious kisses all over her forehead.
</p>
<div id="QeWrP6">
<div style="width: 100%; height: 0; padding-bottom: 56.25%;">
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MximZ6">
There’s Brawne again, making her siblings go out and capture butterflies because Keats had written: “I almost wish we were butterflies and liv’d but three summer days — three such days with you I could fill with more delight than 50 common years could ever contain.” She lays in her sunny bedroom dizzily re-reading his letters as the insects flutter on her fingers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ydmP7R">
And then there’s the first kiss between the lovers, on a moist forest floor, filled with so much sweetness, sensuality, and anticipation that my heart rate goes up every time. The soundtrack is nothing but birdsong, and you can hear the shifting of their bodies on the earth and the touch of their lips.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gvQIot">
I can’t remember when I saw this film for the first time, but it quickly became a repeat watch. There’s a quality to this film that I haven’t seen anywhere else and that I have come to crave when seeking a certain feeling. Keats coined a term, “negative capability,” that he used often in his letters. He defined it as “when man is capable of being in uncertainties, mysteries, doubts, without any irritable reaching after fact and reason.” <a href="https://www.youtube.com/watch?v=LYB2pi8mrnU&amp;t=577s">In an interview</a> about the making of the film, Campion says that “negative capability” became a guide to the creative process. You can see how that approach extends from the actors’ performances to the story itself. It’s as if Keats and Brawne are whispering to us from the past: We don’t know how long we have on this Earth, but it’s worth it to express and enjoy as much love and beauty as we possibly can.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="q0QIEh">
Spring doesn’t last forever, not even in the film. There’s grief, longing, and dead butterflies swept into a dustbin. It’s an exquisite, brief time that fades much too soon, but the film reminds us that it’s worth succumbing to the beauty completely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hZB2tZ">
I don’t know how many people have seen this movie, but by my scientific estimation, it’s not enough. I just went back and read a bunch of reviews and learned that a <a href="https://www.theguardian.com/culture/charlottehigginsblog/2009/may/18/cannes-bright-star-scorsese">few critics at the screening in Cannes</a> were huffy because some of the plants depicted were in the wrong season for the story, and some butterflies were species that can’t be found in England. Ignore them. They’re just irritably reaching for fact and reason. Watch this film. Then take off your shoes and go climb a tree.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HvgfAM">
Bright Star <em>is available to </em><a href="https://www.amazon.com/Bright-Star-Abbie-
Cornish/dp/B002WY65VA/ref=sr_1_2?crid=3KAXTGTFTN3HM&amp;keywords=bright+star+movie&amp;qid=1652817754&amp;sprefix=bright+star%2Caps%2C225&amp;sr=8-2"><em>purchase on DVD</em></a><em>. For more recommendations from the world of culture, check out the </em><a href="https://www.vox.com/one-good-thing"><em><strong>One Good Thing</strong></em></a><em> archives.</em>
</p>
<ul>
<li><strong>Why the FDA rejected fluvoxamine as a Covid-19 drug</strong> -
<figure>
<img alt="Parents Demand FDA Issue Emergency Authorization For COVID Vaccine For Under 5’s In May" src="https://cdn.vox-cdn.com/thumbor/Os_WRtAzl_69773wVGvXeo_XvKY=/0x37:4765x3611/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70891174/1396339533.0.jpg"/>
<figcaption>
Demonstrators in Washington, DC, hold up signs urging the FDA to authorize vaccines for children under 5. The FDA’s handling of Covid has drawn criticism for poor communication and slow decision-making. | Jemal Countess/Getty Images for Protect Their Future
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The FDA made a reasonable decision — but one that still shows much of what’s wrong with our current system for emergency approvals.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gmail-7sdhsx">
Last year, researchers who were testing cheap generic drugs in the hope that one or more of them might prove to work as a Covid-19 treatment stumbled across a promising candidate: the antidepressant <a href="https://medlineplus.gov/druginfo/meds/a695004.html">fluvoxamine</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sMaWbU">
In a massive randomized controlled trial, <a href="https://www.togethertrial.com/flv">called Together</a>, researchers at McMaster University compared eight different repurposed<strong> </strong>drugs, and found<strong> </strong>most of them — including ivermectin, the antiparasitic that many embraced as a Covid-19 miracle cure — failed to do much against the disease. But fluvoxamine appeared to reduce severe disease by about 30 percent. While fluvoxamine had already shown some promise<strong> </strong>in <a href="https://jamanetwork.com/journals/jama/fullarticle/2773108">small-scale trials last year</a>, small-scale trials can sometimes turn up spurious good results, so most people didn’t take fluvoxamine seriously until the impressive data from the Together trial.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Mo5Zjo">
“This already feels different from hydroxychloroquine and company given the high quality of the research,” Paul Sax <a href="https://blogs.jwatch.org/hiv-
id-observations/index.php/could-this-be-our-first-effective-inexpensive-widely-available-outpatient-treatment-for-
covid-19/2021/08/12/">argued</a> in NEJM Journal Watch, which analyzes recent research. “We might finally be onto something.” Government regulators, though, remained more skeptical — in part because the regulatory system isn’t exactly designed for adding new indications for drugs that have already been approved by the FDA without a pharmaceutical company sponsoring them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gMLJFe">
Another researcher who was convinced of the case for fluvoxamine, David Boulware, decided to take matters into his own hands. The FDA didn’t know how to deal with submissions for a drug to be approved for a new indication without someone responsible for the submission? Fine. He’d <a href="https://www.medpagetoday.com/special-reports/exclusives/96431">submit it himself</a>. In December, he wrote and submitted an emergency use application for fluvoxamine as a treatment for Covid-19.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gjO7AT">
In a lot of ways, it was a heartwarming story about the power of citizen science. But that’s not how it turned out.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="92PkEP">
This week, the FDA <a href="https://www.healio.com/news/infectious-disease/20220516/fda-declines-request-
for-fluvoxamine-to-be-used-as-covid19-treatment">rejected the application</a> for an emergency use authorization of fluvoxamine. Regulators argued that the results from the Together trial were more ambiguous than they looked — most of the benefits came from a reduction in extended observation in the emergency room, an endpoint fairly specific to the study’s clinical setting in Brazil and not necessarily all that useful. They pointed out that since the Together trial, additional studies have attempted to find a record of fluvoxamine’s benefits, and mostly haven’t found results as large.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1O0qIf">
In an unusual step, the FDA <a href="https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/EUA%20110%20Fluvoxamine%20Decisional%20Memo_Redacted.pdf">released an explanation</a> for the rejection, and for the most part it’s very reasonable. But the whole episode still showcases what’s broken about how we review and approve drugs.
</p>
<h3 id="nKzr9z">
The drug approval game
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QrGlju">
For eight months, the National Institutes of Health, which maintains an up-to-date database of research findings on treatments for Covid-19, <a href="https://www.vox.com/future-perfect/22772612/early-treatment-for-covid-
fluvoxamine-molnupiravir-paxlovid">didn’t update the fluvoxamine page</a> with any information on the new, promising studies. (The NIH states on <a href="https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/fluvoxamine/">that page</a> today, as it has for the last year, that “There is insufficient evidence for the COVID-19 Treatment Guidelines Panel (the Panel) to recommend either for or against the use of fluvoxamine for the treatment of COVID-19.”)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="edDCJz">
That frustrated researchers, especially this past winter as omicron cases started to grow and the best treatments for Covid-19, like Paxlovid, were not widely available. Many of them told me that with results like these, the FDA would approve a drug that had a pharmaceutical company backing it, and that what was working against fluvoxamine was what they considered its biggest upside: that it was cheap and well-known.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EAxHaD">
To be clear, fluvoxamine was already approved by the FDA — for obsessive-compulsive disorder (OCD). That means doctors can prescribe it in any context they think is appropriate, and it’s frequently prescribed off-label for anxiety and depression. It could also be prescribed off-label for Covid-19, but many doctors aren’t willing to do such off-label prescriptions. For that reason, the drug’s advocates wanted the FDA to determine that fluvoxamine is additionally indicated for Covid-19, so that treatment for the disease would be officially added to its listed uses alongside OCD. But many experts were skeptical.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dfPcp5">
“I don’t think the FDA ever will approve it for Covid,” Eric Lenze, the co-author of some <a href="https://jamanetwork.com/journals/jama/fullarticle/2773108">early research</a> on fluvoxamine, told me in December. “The reason the FDA will never approve it for Covid is exactly the reason it’s so useful for Covid; namely, it’s cheap and it’s widely available. No one can make any money off it, so no one is going to spend the money to appeal to the FDA to approve it.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xlvXQR">
“The guidelines are overly conservative in that they have not yet endorsed fluvoxamine,” Ed Mills, one of the lead researchers of <a href="https://www.togethertrial.com/">the Together trial</a>, told me in November. Why was the FDA not giving fluvoxamine the same review it would give other drugs? “They don’t know how to deal with submissions where there isn’t someone to be responsible for it,” Mills said. The process of adding an indication is generally initiated by the drug developer, whose lobbyists work closely with the FDA to make sure they’re submitting the evidence the FDA wants to see for approval.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="myU7zw">
Fluvoxamine research had been largely funded through <a href="https://www.vox.com/future-perfect/2020/4/21/21228156/coronavirus-fast-grants-tyler-cowen-
patrick-collison">Fast Grants</a>, a private philanthropic effort to make Covid-19 research work happen, and as the drug is generic, no one would make money from its approval for Covid-19. “It’s very disappointing as a scientist to see that it’s actually not about clinical evidence, it’s about lobbying,” Mills told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KoHqlw">
The FDA’s rejection notice this week made their thinking clear, and it’s clearly not purely about lobbying.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TPOfXE">
It’s important to note that the crucial justification for fluvoxamine as a treatment is much weaker now than it was this winter when Boulware filed the application. At the time, there was a serious dearth of effective Covid-19 treatments that could be taken at home rather than in the hospital. Monoclonal antibodies, the first line of treatment in earlier waves of the pandemic, weren’t working well against omicron. Many other therapies were only recommended for hospitalized patients. There was no simple pill a person could take at home while their case was mild to prevent progression into severe disease.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zxUXUY">
Today, there is: antiviral drug <a href="https://www.vox.com/coronavirus-
covid19/23035464/covid-19-us-paxlovid-antiviral-vaccine-availability">Paxlovid</a>. Even fluvoxamine’s strongest advocates agree that Paxlovid works a lot better — it appears to reduce severe disease by 80 to 90 percent. And while this winter Paxlovid was scarce, today there are plenty of doses in the US — though many sick Americans <a href="https://www.wbez.org/stories/paxlovid-saves-lives-so-why-is-it-hard-to-
access/d6d04f08-27a4-45c0-8230-f2e14b5eb1fe">still have trouble accessing the drug</a> because of a lack of primary care doctors they can talk to, while too many doctors remain misinformed about when to prescribe it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4cZ9wL">
But<strong> </strong>Paxlovid isn’t a panacea, and it’d still be good to have more options in our portfolio. “There are effective therapeutics that are available. But not everyone has access to them. Not everyone can tolerate them. Some people have contraindications,” Boulware <a href="https://www.reuters.com/business/healthcare-
pharmaceuticals/fda-declines-authorize-common-antidepressant-covid-treatment-2022-05-16/">argued in response to the FDA rejection</a>. “And if you go elsewhere in the world, low- and middle-income countries, they have access to no therapeutics.” Still, that Paxlovid, which is a significantly better option, is now widely available weakens the case for fluvoxamine in the US, even though countries that don’t have Paxlovid access should likely make their own calculus.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6y0Ylk">
On the whole, then, the FDA’s decision to decline the EUA for fluvoxamine seems reasonable — even to me, a person who has been enthusiastic about the research supporting fluvoxamine. However, the decision still highlights a lot that should be improved about how the FDA makes and communicates decisions about Covid-19 treatment.
</p>
<h3 id="HB3mjx">
Our Covid-19 treatment failures
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pAyvuF">
For much of the pandemic, if you tested positive for Covid-19, the advice from public health authorities was to do nothing unless your symptoms worsened. Until recently, the official CDC page about <a href="https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/steps-when-
sick.html">what to do if sick with Covid-19</a> only advised you to wear a mask, wash your hands, and clean high-touch surfaces to avoid infecting those around you. If your breathing deteriorates or you show signs of severe illness like confusion or an inability to stay awake, the CDC advises you to go to the hospital.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xOwj0n">
Recently, the CDC added an info box highlighting that if you are at high risk of severe disease, <a href="https://www.cdc.gov/coronavirus/2019-ncov/your-health/treatments-for-severe-illness.html">treatment may be available</a>. But for people who aren’t categorized as high-risk — which includes older adults or those with <a href="https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html">medical conditions</a> — the recommendations still don’t include any treatment options.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BM2id5">
At first, the lack of treatment recommendations was likely because the evidence for any treatment option was pretty weak. Early in the pandemic, treatments like hydroxychloroquine were hyped but turned out not to work. Later, ivermectin was embraced as a miracle cure. (<a href="https://www.vox.com/future-perfect/22663127/ivermectin-covid-treatments-vaccines-evidence">It isn’t</a>.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="igvTpB">
But the lack of treatment options was also the product of a process that wasn’t very good at identifying them and communicating that information to a confused public. The fluvoxamine clinical trial — and many other clinical trials of prospective treatments — was funded by private philanthropy because government processes were too slow to rely on. NIH official recommendation pages meant to summarize the state of research for various treatments were often months out of date; I <a href="https://www.vox.com/future-perfect/22772612/early-treatment-for-covid-
fluvoxamine-molnupiravir-paxlovid">wrote in November 2021</a> that the fluvoxamine page had last seen an update in the previous April.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jIK1GJ">
And instead of the FDA proactively working with researchers to set up clinical trials the agency would be willing to rely on to recommend or disrecommend drugs, researchers had to design and conduct trials themselves, and then some doctors had to fill out the EUA application to get the FDA to look at the work they’d done.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="51IFKZ">
Right now, the need for fluvoxamine is limited, the evidence is mixed, and the FDA’s decision not to recommend the drug is pretty reasonable. But ideally, the FDA would have been actively involved in the research process as soon as fluvoxamine first showed promise, and the government would have participated in designing and funding more definitive trials instead of waiting for a submission from an interested group of citizens.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uzuFkc">
The fact that the evidence about fluvoxamine is still inconclusive at this point is a good reason not to issue an EUA — but it’s also a sign of a glaring failure in our system for investigating promising Covid-19 treatments. Covid-19 is going to be with us for a long time, and other pandemics might be on the horizon. The process for developing treatments — and communicating with the public about them — needs to get better.
</p></li>
<li><strong>Why monkeypox isn’t like Covid-19</strong> -
<figure>
<img alt="" src="https://cdn.vox-
cdn.com/thumbor/8ms64d2aKS_sgqhuLpxTKWFll8U=/265x0:2642x1783/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70889421/greyscalemonkeypox.0.jpg"/>
<figcaption>
An electron microscopic image depicting a monkeypox virion, obtained from a clinical sample associated with the 2003 prairie dog outbreak. | Cynthia S. Goldsmith and Russell Regnery/CDC; AP
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Experts are cautiously concerned, but this is a fundamentally different outbreak.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vqibuY">
On Wednesday, the CDC confirmed a case of monkeypox in a Massachusetts man who had recently traveled to Canada.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="94i3TN">
It wasn’t the first time the US has seen a case of monkeypox, a virus related to smallpox that causes flu-like symptoms and a rash, and can sometimes be deadly. Occasionally, public health authorities <a href="https://www.cdc.gov/poxvirus/monkeypox/outbreak/us-
outbreaks.html">identify single cases</a> in people recently returned from West or Central Africa, where the disease is more common.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PZ2BpA">
What’s different — and concerning — about this Massachusetts case is that it’s occurring as clusters of monkeypox infections are popping up in other countries where the virus is also rare.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7sTyIs">
Since early May, the UK Health Security Agency has detected a total of <a href="https://www.gov.uk/government/news/monkeypox-cases-confirmed-in-england-latest-updates">9 cases</a> of the infection, and Portugal and Spain have reported <a href="https://www.reuters.com/business/healthcare-
pharmaceuticals/portugal-spain-detect-new-cases-monkeypox-infection-2022-05-19/">14</a> and <a href="https://www.theguardian.com/world/2022/may/18/monkeypox-alert-spain-men-show-symptoms">23</a> suspected cases, respectively. (The numbers are changing rapidly; a University of Oxford epidemiologist <a href="https://twitter.com/MOUGK/status/1527055553876348928">tweeted</a> a link to a makeshift tracker where you can see the latest figures.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="voAjVk">
With so many monkeypox cases concurrently popping up in different countries, public health officials’ immediate questions are whether the cases are related, and whether monkeypox is spreading in other communities undetected.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jn6Bfm">
“The worldwide concern from public health authorities is trying to understand how these are related to each other and what the causes are,” said Agam Rao, an infectious disease specialist and poxvirus expert at the CDC.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9U9ZLO">
Only weeks into this outbreak, it’s too early to tell what exactly is going on, and whether this outbreak has epidemic potential. For the time being, said Rao, the general public doesn’t need to be particularly worried. “The risk is still very rare,” she said, and the strain of monkeypox currently being detected is relatively mild.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8WYK2I">
Two years into a deeply divisive global pandemic, word of another pathogen spreading unchecked might make some people want to launch themselves directly into the sun.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hm7i4b">
But with monkeypox, the world faces a very different situation than in the early days of Covid-19.<br/>
Monkeypox, unlike SARS-CoV-2, is a known quantity. We have more tools to prevent and treat it — far more than we did for Covid-19 at the outset of the pandemic — and both public health and the general public have had a lot of practice taking measures to prevent infections from spreading. Still, the trajectory of the outbreak is as yet uncertain, and public health experts remain vigilant.
</p>
<h3 id="ZCEcYD">
What is monkeypox?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BBQg1O">
Monkeypox viruses generally circulate among wild animals in Central and West Africa, and usually spread to people when they eat or have other close contact with infected animals. The virus was first identified among <a href="https://www.cdc.gov/poxvirus/monkeypox/index.html#:~:text=Monkeypox%20was%20first%20discovered%20in,intensified%20effort%20to%20eliminate%20smallpox.">research animals at the CDC</a> in the 1950s (that’s how it got its name “monkeypox”), and for a long time afterward, human infections were sporadic, even in countries where lots of animals are infected.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iAItGI">
That’s partly because monkeypox is related to the smallpox virus, and immunity to smallpox is protective against monkeypox. But <a href="https://www.cdc.gov/smallpox/index.html#:~:text=Smallpox%20Virus&amp;text=Thanks%20to%20the%20success%20of,occurring%20smallpox%20have%20happened%20since.">as of 1980</a>, smallpox has been eradicated in humans, and vaccinations against smallpox have grown rare — and human cases of monkeypox have been on the rise. It’s still rare: According to the CDC, Nigeria has reported 450 cases since<br/>
2017, when public health authorities began seeing more cases among humans.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AUo46i">
Infection with the monkeypox virus usually causes a flu-like illness with fever, headache, muscle aches, swollen lymph nodes, and a rash. Although monkeypox is not related to chickenpox, the <a href="https://www.cdc.gov/poxvirus/monkeypox/clinicians/clinical-recognition.html">characteristic monkeypox rash</a> looks a lot like it, starting as red spots on the mouth and face, then spreading to the arms and legs. Over four to five days, the spots turn into small fluid-filled blisters that are often tender to the touch, eventually become doughnut- shaped, and begin to crust over by the two-week mark.
</p>
<figure class="e-image">
<img alt="A man stands in
front of a podium with the CDC log on it. Behind him is a poster on a board showing a monkeypox virus under a
microscope." src="https://cdn.vox-cdn.com/thumbor/1SydRIJ3uFZpE62cuIqLOmcZ868=/800x0/filters:no_upscale()/cdn.vox-
cdn.com/uploads/chorus_asset/file/23575738/GettyImages_909695428t.jpg"/> <cite>Smith Collection/Gado via Getty Images</cite>
<figcaption>
Dr. David Fleming speaks to the press at a CDC briefing about the spread of the monkeypox virus and measures taken for its prevention on June 11, 2003.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HdXd78">
Studies have suggested the virus’s R0 — the number of people who will hypothetically contract a communicable disease from a person infected with that disease — is relatively low, somewhere between one and two.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BefImt">
“It’s not as highly transmissible as something like smallpox, or measles, or certainly not Covid,” said <a href="https://www.ph.ucla.edu/epi/faculty/rimoin/rimoin.html">Anne Rimoin</a>, an infectious disease epidemiologist at the University of California Los Angeles with expertise in monkeypox and other emerging diseases.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UiKnlo">
Transmission can occur through close contact with body fluids of an infected person, sores, or items that have touched fluids or sores (like bedding); the virus can also spread via <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509329/">respiratory droplets or aerosols</a> that linger in the air. But unlike Covid-19, where people who are infected can spread the disease before getting sick,<strong> </strong><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463189/#:~:text=Monkeypox%20is%20not%20considered%20contagious,respiratory%20tract%20or%20skin%20lesions.">monkeypox isn’t considered contagious before people develop symptoms</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UPEc0c">
There are two predominant strains of monkeypox: the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131633/#B6">“West African” version</a> and the “Congo Basin” version. Of the two, the Congo Basin version has historically spread more easily from person-to-person and caused more deaths. The current outbreak involves the West African version.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bDeVlD">
The infection <a href="https://pubmed.ncbi.nlm.nih.gov/35148313/">does not commonly lead to deaths in high-resource countries</a> like the United States because people living there generally have better access to the supportive care that resolves most monkeypox infections, said Rimoin. In 2003, at least 53 people in the midwestern United States <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5223a1.htm">caught the infection from pet prairie dogs</a> who’d been infected when they were housed near rodents imported from Ghana; none of the infected people died.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JWetZW">
In rural parts of Africa, where access to hospital care is lower, infection has led to death in about 4 percent of people infected with the virus.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LS2IU7">
<a href="https://www.fda.gov/news-events/press-
announcements/fda-approves-first-drug-indication-treatment-smallpox">Several</a> <a href="https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-smallpox">treatments</a> approved for smallpox treatment could potentially be used to treat monkeypox infections if necessary. However, most cases are relatively mild; it’s unclear whether any of the currently affected patients needed or received any of these medications.
</p>
<h3 id="3pVa6R">
What’s different about the latest monkeypox cases?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iMDFRO">
The latest clusters of monkeypox cases are different from previous clusters in a few ways.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vupNAV">
For starters, the current cluster involves many infections happening concurrently beyond the African countries where the disease circulates in wild animals. “We’ve never had a situation where so many cases have occurred outside of those countries concurrently,” said Rao.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fdTO7h">
What’s also unusual about the latest cases is that many of them so far have occurred among men who have sex with men (monkeypox transmission has not previously been associated with sexual preference or intimate contact). Many of the cases are presenting with <a href="https://www.ecdc.europa.eu/en/news-
events/monkeypox-cases-reported-uk-and-portugal">clusters of pimple-like spots in the genital area</a> — an uncommon area for the monkeypox rash to start.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qlNYar">
After clinicians made the first few diagnoses among men coming to sexual health clinics with unusual rashes, health officials began asking sexual health clinics to look out for monkeypox cases. This doesn’t mean monkeypox is only circulating among men who have sex with men, and some infections have been diagnosed in people who are not gay or bisexual men.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DXNSwl">
“We’re finding where we’re looking,” Maria Van Kerkhove, a World Health Organization emerging diseases and zoonoses expert, said in an interview with <a href="https://www.statnews.com/2022/05/18/spain-portugal-report-monkeypox-cases-raising-specter-of-wider-
outbreak/#:~:text=The%20symptoms%20of%20monkeypox%20are,often%20starting%20on%20the%20face.">STAT</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rHFdA0">
If this monkeypox outbreak does end up linked to sexual networks among men, that doesn’t mean it’s necessarily a sexually transmitted infection; it may simply be a question of who’s getting close enough to an infected person to get infected, themselves. Other germs spread by close — but not specifically <em>sexual</em> — contact have previously caused clusters of infections among gay and bisexual men and college-aged students, such as<strong> </strong><a href="https://www.cdc.gov/meningococcal/outbreaks/FL2022.html">meningitis</a>, a disease spread by respiratory droplets in close settings.
</p>
<h3 id="exfjbJ">
How concerned should the general public be about this outbreak?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bOwd4S">
In addition to trying to understand the cause of the current outbreak and the routes of transmission, public health authorities are working to sequence the viruses isolated from individual patients to better understand whether it has changed in any ways that might make it more or differently transmissible, said Rao.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9JyUJE">
For the moment, however, there’s no reason to think the virus has undergone any meaningful mutation, she said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qRR7am">
Currently, the general public doesn’t need to be particularly worried about the risk monkeypox viruses pose to themselves and their loved ones. “It does not spread easily from person to person, the risk to the general public is low,” said Rimoin. And with health providers now on high alert for the infection, it is more likely to be recognized quickly among people who do get infected and quickly contained, halting chains of transmission.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PPwDX3">
“We’d have to see a significant cluster of cases events and ongoing transmission” before public health authorities put any broad preventive measures in place, said Rimoin.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fo4S1k">
Even a large monkeypox outbreak would likely be much easier to handle than the Covid-19 pandemic. For one, the fact the virus isn’t considered contagious before people show symptoms could make it harder for people to unknowingly spread it. And in addition to treatments, we already have excellent <a href="https://www.fda.gov/emergency-preparedness-and-response/mcm-
issues/smallpox-preparedness-and-response-updates-fda">vaccines</a> to protect those at highest risk from infection — public health authorities in the UK are currently <a href="https://www.who.int/emergencies/disease-outbreak-
news/item/2022-DON383">vaccinating close contacts</a> of cases to prevent further spread of infection.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zyITh9">
This isn’t a novel disease — so if monkeypox does become a much larger outbreak than it already is, public health authorities are better equipped with tools to manage it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Cd5rve">
In fact, as a consequence of the Covid-19 pandemic, public health is in a relatively strong place to handle this outbreak.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LZP8fB">
“I think we’re in a good position to respond to monkeypox because most health departments have staffing, lab networks, and funding from Covid that can be used for emergency response,” said Jay Varma, a physician and epidemiologist based in New York City who recently was senior advisor to the Africa Centers for Disease Control and Prevention. “The real risk is what happens when that funding runs out over the next few years.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nF68DX">
</p></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>Borussia Dortmund sacks Marco Rose after just one season as coach</strong> - Borussia Dortmund has dismissed coach Marco Rose after what the Bundesliga club called an “unsatisfactory” maiden season that yielded no trophies</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>Sindhu reaches Thailand Open semifinals by defeating Yamaguchi</strong> - P.V. Sindhu overcame world No. 1 Akane Yamaguchi 21-15, 20-22, 21-13 in the quarterfinals of the Thailand Open to set up a clash with Olympic champion Chen Yu Fei in the semifinals</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 year on, Naomi Osaka's French Open exit blazes path for mental health discussion</strong> - Naomi Osaka had stunned the tennis world when she withdrew from the 2021 French Open after boycotting post-match media duties. A year, the sport is addressing the mental toll on athletes</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>Wild Emperor, Ballerina, Aracana, Multifaceted, Ravishing Form, and All Attractive excel</strong> -</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 2022 | Disappointed Mumbai Indians coach Jayawardene concedes team didn’t win crucial moments</strong> - Mumbai Indians are likely to end up last on the points table even if they manage to win their last game against Delhi Capitals</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>Expo to raise funds for ailing artist</strong> -</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>Kerala Tourism holds roadshows in Muscat, Manama</strong> - State presented as a ‘Paradise, Four Hours Away’</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>Congress targets PM over reports of China building second bridge over Pangong Tso</strong> - ‘… A timid and docile response won’t do. PM must defend the nation’, tweets Rahul Gandhi</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>DGCA grants Jet Airways air operator certificate, can resume commercial flight ops</strong> - The airline intends to restart commercial flight operations in the July-September quarter..</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>Over 4,000 black spots in Kerala’s road network, says NATPAC’s draft report</strong> - Multiple black spots on corridors to be treated as cluster</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: US fully backs Sweden and Finland Nato bids, Biden says</strong> - Both countries submitted their applications to be part of the Western defence alliance this week.</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>Ukrainian widow confronts Russian soldier accused of killing her husband</strong> - The 21-year-old serviceman has pled guilty to killing her husband in a village in Ukraine’s north-east.</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>Russian McDonald’s buyer to rebrand restaurants</strong> - The fast food giant says the new owner of its 850 Russian restaurants will operate them under a new brand.</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>Monkeypox cases investigated in Europe, US, Canada and Australia</strong> - Cases of the rare disease are now confirmed in eight European countries, health authorities say.</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>Vangelis: Chariots of Fire and Blade Runner composer dies at 79</strong> - The Greek star’s Oscar-winning film scores and electronic works created “a new musical landscape”.</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>Rocket Report: Starliner soars into orbit, About those Raptor RUDs in Texas</strong> - “From the outside, it might look like an ordinary rocket.” - <a href="https://arstechnica.com/?p=1854907">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hyundai and Kia recall nearly 20,000 Ioniq 5s, EV6s</strong> - A voltage fluctuation could cause the cars to roll away when parked. - <a href="https://arstechnica.com/?p=1855408">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Texas looks to a Clarence Thomas opinion to defend its social media law</strong> - Thomas argued that social networks are like common carriers. - <a href="https://arstechnica.com/?p=1855325">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A time paradox births a “freaking Kugelblitz” in Umbrella Academy S3 trailer</strong> - Too many siblings and not enough timeline spells trouble in this Netflix series. - <a href="https://arstechnica.com/?p=1855211">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multiversus hands-on: Finally, a compelling Smash Bros. clone</strong> - Yes, the Warner Bros. pastiche is weird. But its co-op arena battling is refined. - <a href="https://arstechnica.com/?p=1855218">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>So a philosopher, a mathematician, and a physicist were at starbucks.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
So a philosopher, a mathematician, and a physicist were at starbucks.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The mathematician turns to the physicist sitting next to him and says “You know, physics is just applied mathematics!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They all have a good laugh, at which point the philosopher interjects from across the table. “And mathematics is just applied philosophy!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The laughter roars even louder, and then the physicist turns to the philosopher.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Shut the fuck up and make my coffee.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/pradeep23"> /u/pradeep23 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/utj58c/so_a_philosopher_a_mathematician_and_a_physicist/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/utj58c/so_a_philosopher_a_mathematician_and_a_physicist/">[comments]</a></span></p></li>
<li><strong>An atheist dies and goes to hell</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The devil welcomes him and says:“Let me show you around a little bit.” They walk through a nice park with green trees and the devil shows him a huge palace. “This is your house now, here are your keys.” The man is happy and thanks the devil. The devil says:“No need to say thank you, everyone gets a nice place to live in when they come down here!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
​
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They continue walking through the nice park, flowers everywhere, and the devil shows the atheist a garage full of beautiful cars. “These are your cars now!” and hands the man all the car keys. Again, the atheist tries to thank the devil, but he only says “Everyone down here gets some cool cars! How would you drive around without having cars?”.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
​
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They walk on and the area gets even nicer. There are birds chirping, squirrels running around, kittens everywhere. They arrive at a fountain, where the most beautiful woman the atheist has ever seen sits on a bench. She looks at him and they instantly fall in love with each other. The man couldn´t be any happier. The devil says “Everyone gets to have their soulmate down here, we don´t want anyone to be lonely!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
​
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
As they walk on, the atheist notices a high fence. He peeks to the other side and is totally shocked. There are people in pools of lava, screaming in pain, while little devils run around and stab them with their tridents. Other devils are skinning people alive, heads are spiked, and many more terrible things are happening. A stench of sulfur is in the air.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
​
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Terrified, the man stumbles backwards, and asks the devil “What is going on there?” The devil just shrugs and says: “Those are the christians, I don´t know why, but they prefer it that way”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/fhqwhgadsz"> /u/fhqwhgadsz </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/ut8c0s/an_atheist_dies_and_goes_to_hell/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/ut8c0s/an_atheist_dies_and_goes_to_hell/">[comments]</a></span></p></li>
<li><strong>A dog and a cat were having an argument on who is the favorite of humans</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The dog says, “Humans like us more. They even named a tooth (canine) after us. Naming such an important body part after us shows that they like us more.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The cat smiles and says, “You’re not really going to win this one you know.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Majorpain2006"> /u/Majorpain2006 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/utlx93/a_dog_and_a_cat_were_having_an_argument_on_who_is/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/utlx93/a_dog_and_a_cat_were_having_an_argument_on_who_is/">[comments]</a></span></p></li>
<li><strong>My colleagues call me “The Computer”.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Nothing to do with my intelligence. I just go to sleep if left unattended for 15 minutes.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/thisisa_fake_account"> /u/thisisa_fake_account </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/utm30e/my_colleagues_call_me_the_computer/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/utm30e/my_colleagues_call_me_the_computer/">[comments]</a></span></p></li>
<li><strong>What did our parents do to kill boredom before the internet?</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I asked my 10 brothers and sisters, but they don’t know either.
</p>
</div>
<!-- SC_ON
-->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MEforgotUSERNAME"> /u/MEforgotUSERNAME </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/ut69gm/what_did_our_parents_do_to_kill_boredom_before/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/ut69gm/what_did_our_parents_do_to_kill_boredom_before/">[comments]</a></span></p></li>
</ul>
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