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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>Does polyethylene glycol, used as an excipient at mRNA-based (Moderna, Pfizer) vaccines, cause an increase in the frequency of epilepsy in PWE?</strong> -
<div>
PEGs, also known as polyethylene glycol, are hydrophilic polymers of various diameters made up of repeated (-CH2-CH2-O-) units and are frequently used in commercial and medical applications like cosmetics, and pharmaceutical preparations and now increase in drug development but the concern about antibodies against PEGs is producing (1) PEGs (PEGs2000) are used as excipients in mRNA-based vaccines like Moderna and Pfizer (2) it is utilized in these vaccines to encapsulate the SLNPs, polyethylene glycol (PEG), which has been identified as the main culprit for this anaphylactic reactions4,5. PEG is used in a wide variety of additional products6, including cosmetics, meals, and pharmaceutical preparations. Its action is essential for preserving the colloidal stability of nanoparticles in biological fluids as well as for lowering the amount of uptake by filter organs, which increases the effectiveness and safety of the particles after vaccination. (3). One of the most prevalent neurological conditions, epilepsy is linked to higher morbidity and mortality rates. PWE who aspirate during seizures have a higher chance of developing pneumonia, and infections can make their PWE’s seizure symptoms worse. Patients with particular epilepsy syndromes who take immunosuppressive medications (such as those with tuberous sclerosis complex or autoimmune encephalitis) must also be regarded as “at risk.” PWE is also more likely to have comorbid conditions, which increases their chance of developing a severe SARS-CoV-2 infection. (4). In a study for colonoscopic screening using PEG as safe more than sodium, the study reported 2 cases of increased frequency of epilepsy attacks on two women who were admitted with generalized tonic-clonic seizures induced by precolonoscopic PEG preparation because of PEG effect on fluids and hyponatremia-induced epilepsy, Electrolyte solutions containing PEG have been linked to seizure activity and/or unconsciousness. Low serum osmolality and irregular electrolytes were linked to the seizure cases. Patients having a history of seizures or a tendency toward them, as well as those with known or suspected hyponatremia, should receive therapy with these drugs with caution (5) Numerous research and evaluations found no evidence linking vaccines to afebrile seizures, and they concluded that immunizations do not cause the beginning of epilepsy [6]. In patients in our cohort who grew more prone to seizures post vaccination but did not have a simultaneous fever, this finding raises doubts about the direct impact of immunization, even though these patients had more serious epilepsy with less control than our multivariate analysis did confirm that seizures frequency is only influenced by one component. The frequency pattern of pre-vaccine seizures was getting worse consequently, it is conceivable to imagine that immunization was an immediate contributing factor in altering seizure frequency, in actuality, the patients who deteriorated were affected by epilepsy that is more severe and poorly controlled. (7) According to several observational studies, individuals with epilepsy (PWE) experienced worsening seizure control during the COVID-19 pandemic. (8-13) An observational study by Isabel Martinez-Fernandez shows Seizure frequency increased after vaccination in 6.2% of people with epilepsy. 6.2% of PWE saw a meaningful increase in seizure frequency after receiving the covid-19 vaccine and in 61.5% of these cases, other probable causes were also present, the causes of worsening seizures are distinct from immunization were identifiable, and patients with a higher risk of seizures and those who had an aggravation after receiving the covid-19 immunization monthly epilepsy. (14) Understanding that PEG is immunogenic and antigenic is important. More thorough investigations are necessary to thoroughly assess the effect of anti-PEG antibodies on PEG conjugates. The chance of experiencing potential adverse effects is increased by the growing usage of PEG and PEGylated therapeutic proteins. First off, side products created during polymer production can indirectly cause hypersensitivity. Second, the pharmacokinetic behavior of the PEGylated medicines exhibits some undesirable modifications. Furthermore, there are certain unanticipated impacts of the leftovers because PEG is not biodegradable. (15) Finally, this letter to the editor gives alarming about the immune response in form of anti-PEGs antibodies as a concern in the future as PEGs are included in drug development as nanoparticles and protein bindings to decrease the clearance of these compounds. And many cases of epilepsy were reported as increasing the frequency after covid-19 vaccinations.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/p8kxj/" target="_blank">Does polyethylene glycol, used as an excipient at mRNA-based (Moderna, Pfizer) vaccines, cause an increase in the frequency of epilepsy in PWE?</a>
</div></li>
<li><strong>Can long-term post-COVID-19 fainting syndrome explain why a US artist swimmer Anita Alvarez has recurrent fainting attacks after diving during a swimming competition? Does interleukin-6 play a role?</strong> -
<div>
At the 19th FINA (Fédération Internationale De Natation.) World Aquatic Championships were held in Budapest, Hungary, American swimmer Anita Alvarez lost consciousness, experienced recurrent fainting attacks after diving during a swimming competition, and had to be pulled from the bottom of the pool by her coach. And this happens for the second time (1) Five (0.6%) of the 789 elite athletes in an observational study who tested positive for COVID-19 had CMR evidence of inflammatory cardiac disease (myocarditis or pericarditis) (2) Concern has been expressed by a number of authors on the effect of neurologic and neuromuscular problems on return to play. As they recover from COVID19 disease, athletes may experience tiredness, decreased neuromuscular function, and decreased muscle strength. Several additional COVIDrelated problems, such as general weariness, cognitive impairment, and coagulopathy, can occur in recovering athletes. (3)(4) The most common chronic cardiovascular dysautonomia in young and middle-aged people, primarily women, is postural orthostatic tachycardia syndrome (POTS). Chronic orthostatic intolerance, an abnormal increase in heart rate (HR) upon standing, and deconditioning are its defining characteristics. Post-viral autoimmune activation has been proposed as a potential cause of the condition (5) Interleukin-6 is crucial for athletes, particularly after arduous activity and after submerging in cold water. Immersion in cold water is linked to a little increase in IL-6 levels from post-exercise values. (6) Two studies described a syncopal episode in COVID-19 survivors 3 to 4 weeks after diagnosis, at the post-acute COVID-19 stage. This increases the likelihood that syncope had a role, not just during the illness’s acute stage but also as a long-term consequence. Patients in both of these cases underwent analysis for postural orthostatic tachycardia disorder, a part of the autonomic dysfunctions. As previously stated, unexplained pre/syncope accounted for 87.9% (531/604) of the detailed scenes and was the most frequent cause of the temporary loss of awareness. Reflex pre/syncope occurred 7.8% of the time overall (47/604). Orthostatic hypotension made up 2.2 percent (13/604) of the cases, and 2.2 percent (13/604) of the cases likely had cardiac pre/syncope. (7,8) Interleukin-6 (IL-6) is a localized energy sensor that is supplied to active skeletal muscle and can explain why there is an increase in plasma IL-6 during exercise. The length and intensity of the workout have an impact on the creation of IL-6, and moo muscle glycogen material supports this production. The discovery of abnormally elevated levels of IL-6 following arduous exercise has consistently been observed in several studies. After 6 minutes of vigorous exercise, a 2-fold increase in plasma IL-6 was seen. After 30 minutes of running by the treadmill, the blood level of IL-6 had significantly increased, reaching its peak after 2.5 hours. In other studies, when IL-6 levels weren’t monitored during the running workout but rather a few hours later, peak IL-6 levels were discovered right away after the workout, followed by a rapid decline. In this manner, maximal IL-6 levels (100-fold increment) were assessed immediately following the 3-3.5 h race. (9) Peak IL-6 levels are attained at the conclusion of the workout or soon after. Chronic IL-6 elevations cause hyperinsulinemia, lower body mass, and impaired insulin control of skeletal muscle glucose absorption. The level of circulating IL-6 is two to three times higher in senior patients with type 2 DM than it is in younger, healthy people. (10) As stated by NICE (National Institute for Health and Care Excellence), A significant proportion of acute COVID-19 survivors experience long-term physical and neuropsychiatric symptoms, which are categorized as “ongoing symptomatic COVID-19” (symptoms that continue for 4 to 12 weeks after the onset of the illness) and “post-COVID-19 syndrome” or “long COVID” (symptoms that continue for more than 12 weeks). We hypothesize that inflammatory cytokines like interleukin-6 may be involved in the neuro-immune cross-talk that results in these chronic COVID-19 symptoms (IL-6). This hypothesis is supported by a number of research lines, including population-based cohort and genetic Mendelian Randomization studies, which suggest that inflammation and weariness are related and that IL-6 may play a causal role in both symptoms. In particular, clinical epidemiology studies are necessary to determine whether IL-6 and/or other inflammatory cytokine levels are elevated. (11) Finally, this letter of the editor is an alarming pill for saving athletes all over the world and evaluating recurrent attacks of syncopal or cardiac arrest or other cardiovascular problems nowadays post covid-19 pandemic long-term sequelae, and more clinical studies are needed.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/4vn7e/" target="_blank">Can long-term post-COVID-19 fainting syndrome explain why a US artist swimmer Anita Alvarez has recurrent fainting attacks after diving during a swimming competition? Does interleukin-6 play a role?</a>
</div></li>
<li><strong>Intensity of sample processing methods impacts wastewater SARS-CoV-2 whole genome amplicon sequencing outcomes</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Wastewater SARS-CoV-2 surveillance has been deployed since the beginning of the COVID-19 pandemic to monitor dynamics in virus burden in local communities. Genomic surveillance of SARS-CoV-2 in wastewater, particularly the efforts for whole genome sequencing for variant tracking or identification, are comparatively challenging due to low target concentration, complex microbial and chemical background, and lack of robust nucleic acid recovery experimental procedures. The intrinsic sample limitations are inherent to wastewater. In this study, we evaluated impacts from sample types, certain sample intrinsic features, and processing and sequencing methods on sequencing outcomes with a specific focus on the breadth of genome coverage. We collected 184 composite and grab wastewater samples from the Chicago area between March to October 2021 for SARS-CoV-2 quantification and genomic surveillance. Samples were processed using a mixture of processing methods reflecting different homogenization intensities (HA+Zymo beads, HA+glass beads, and Nanotrap), and were sequenced using two sequencing library preparation kits (the Illumina COVIDseq kit and the QIAseq DIRECT kit). A synthetic SARS-CoV-2 RNA experiment was performed to validate the potential impacts of processing methods on sequencing outcomes. Our findings suggested that 1) SARS-CoV-2 whole genome sequencing outcomes were associated with sample types and processing methods 2) in less intensive method processed samples (HA+glass beads), higher genome breadth of coverage in sequencing (over 80%) was associated with N1 concentration &gt; 105 cp/L, while in intensive method (HA+Zymo beads), qPCR results were inconsistent with sequencing outcomes, and 3) sample processing methods and sequencing kits, rather than the extraction methods or intrinsic features of wastewater samples, played important roles in wastewater SARS-CoV-2 amplicon sequencing. Overall, extra attention should be paid to wastewater sample processing (e.g., concentration and homogenization) for sufficient, good quality RNA yield for downstream sequencing.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280217v1" target="_blank">Intensity of sample processing methods impacts wastewater SARS-CoV-2 whole genome amplicon sequencing outcomes</a>
</div></li>
<li><strong>Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance</strong> -
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Background: Recovery after SARS-CoV-2 infection is extremely variable, with some individuals recovering quickly, and others experiencing persistent long-term symptoms or developing new symptoms after the acute phase of infection, including fatigue, poor concentration, impaired attention, or memory deficits. Many existing studies reporting cognitive deficits associated with SARS-CoV-2 infection are limited by the exclusive use of self-reported measures or a lack of adequate comparison groups. Methods: Forty-five participants, ages 18-70, (11 Long-COVID, 14 COVID, and 20 No-COVID) underwent behavioral testing with the NIH Toolbox Neuro-Quality of Life survey and selected psychometric tests, including a flanker interference task and the d2 Test of Attention. Results: We found greater self-reported anxiety, apathy, fatigue, emotional dyscontrol, sleep disturbance and cognitive dysfunction in COVID compared No-COVID groups. After categorizing COVID patients according to self-reported concentration problems, we observed declining performance patterns in multiple attention measures across No-COVID controls, COVID and Long-COVID groups. COVID participants, compared to No-COVID controls, exhibited worse performance on NIH Toolbox assessments, including the Eriksen Flanker, Nine-Hole Pegboard and Auditory Verbal Learning tests. Conclusion: This study provides convergent evidence that previous SARS-CoV-2 infection is associated with impairments in sustained attention, processing speed, self-reported fatigue and concentration. The finding that some patients have cognitive and visuomotor dysfunction in the absence of self-reported problems suggests that SARS-CoV-2 infection can have unexpected and persistent subclinical consequences.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280222v1" target="_blank">Effects of SARS-CoV-2 Infection on Attention, Memory, and Sensorimotor Performance</a>
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<li><strong>Higher risk of SARS-CoV-2 Omicron BA.4/5 infection than of BA.2 infection after previous BA.1 infection, the Netherlands, 2 May to 24 July 2022</strong> -
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We investigate differences in protection from previous infection and/or vaccination against infection with Omicron BA.4/5 or BA.2. We observed a higher percentage of registered previous SARS-CoV-2 infections among 19836 persons infected with Omicron BA.4/5 compared to 7052 persons infected with BA.2 (31.3% vs. 20.0%) between 2 May and 24 July 2022 (adjusted odds ratio (aOR) for testing week, age group and sex: 1.4 (95%CI: 1.3-1.5)). No difference was observed in the distribution of vaccination status between BA.2 and BA.4/5 cases (aOR: 1.1 for primary and booster vaccination). Among reinfections, those newly infected with BA4/5 had a shorter interval between infections and the previous infection was more often caused by BA.1, compared to those newly infected with BA.2 (aOR: 1.9 (1.5-2.6). This suggests immunity induced by BA.1 is less effective against a BA.4/5 infection than against a BA.2 infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.21.22280189v1" target="_blank">Higher risk of SARS-CoV-2 Omicron BA.4/5 infection than of BA.2 infection after previous BA.1 infection, the Netherlands, 2 May to 24 July 2022</a>
</div></li>
<li><strong>Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue</strong> -
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Post-COVID-19 syndrome (PCS) summarizes persisting sequelae after infection with the severe-acute-respiratory-syndrome-Coronavirus-2 (SARS-CoV-2). PCS can affect patients of all covid-19 disease severities. As previous studies revealed impaired blood flow as a provoking factor for triggering PCS, it was the aim of the present study to investigate a potential association of self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT-Angiography (OCT-A) and quantified by the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic Fatigue (CF) was assessed with the variables Bell score, age and gender. The VD in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed considering the repetitions (12 times). Taking in account of such repetitions a mixed model was performed to detect possible differences in the least square means between different groups of analysis. An age effect on VD was observed between patients and controls (p&lt;0.0001). Gender analysis yielded that women with PCS showed lower VD levels in SVP compared to male patients (p=0.0015). The PCS patients showed significantly lower VD of ICP as compared to the controls (p=0.0001, [CI: 0.32; 1]). Moreover, considering PCS patients, the mixed model reveals a significant difference between chronic fatigue (CF) and without CF in VD of SVP (p=0.0033, [CI: -4.5; -0.92]). The model included age, gender and the variable Bell score, representing a subjective marker for CF. Consequently, the retinal microcirculation might be an objective biomarker in subjective-reported chronic fatigue of patients with PCS.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.23.22280264v1" target="_blank">Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue</a>
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<li><strong>Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic</strong> -
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Background: Respiratory disease is a major cause of morbidity and mortality; however, current surveillance for circulating respiratory viruses is passive and biased. Seasonal circulation of respiratory viruses changed dramatically during the COVID-19 pandemic. More active methods for understanding respiratory disease dynamics are needed to better inform public health response and to guide clinical decision making. Wastewater-based epidemiology has been used to understand COVID-19, influenza A, and RSV infection rates at a community level, but has not been used to investigate other respiratory viruses. Methods: We measured concentrations of influenza A and B, RSV A and B, human parainfluenza (1-4), rhinovirus, seasonal human coronaviruses, and human metapneumovirus RNA in wastewater solids three times per week for 17 months spanning the COVID-19 pandemic at a wastewater treatment plant in California, USA. Novel probe-based assays were developed and validated for non-influenza viral targets. We compared viral concentrations to positivity rates for viral infections from clinical specimens submitted to sentinel laboratories. Findings: We detected RNA from all target viruses in wastewater solids. Human rhinovirus and seasonal coronaviruses were found at highest concentrations. Concentrations of viruses correlated significantly and positively with positivity rates of associated viral diseases from sentinel laboratories. Measurements from wastewater indicated limited circulation of RSV A and influenza B, and human coronavirus OC43 dominated the seasonal human coronavirus infections while human parainfluenza 1 and 4A dominated among parainfluenza infections. Interpretation: Wastewater-based epidemiology can be used to obtain information on circulation of respiratory viruses at a community level without the need to test many individuals because a single sample of wastewater represents the entire contributing community. Results from wastewater can be available within 24 hours of sample collection, allowing real time information to inform public health response, clinical decision making, and individual behavior modifications.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280218v1" target="_blank">Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic</a>
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<li><strong>Commercial immunoglobulin products now contain neutralising antibodies against SARS-CoV-2 spike antibody which are detectable in patient serum</strong> -
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Antibody-deficient patients respond poorly to COVID-19 vaccination and are at risk of severe or prolonged infection. Prophylaxis with anti-SARS-CoV-2 monoclonal antibodies has been considered. We here demonstrate that many immunoglobulin preparations now contain neutralising anti-SARS-CoV-2 antibodies which are transmitted to patients in good concentrations, albeit with significant differences between products.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280216v1" target="_blank">Commercial immunoglobulin products now contain neutralising antibodies against SARS-CoV-2 spike antibody which are detectable in patient serum</a>
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<li><strong>Efficacy and safety of convalescent plasma versus standard care in hospitalized patients with COVID-19 from the Peruvian Social Security Health System: open-label, randomized, controlled clinical trial</strong> -
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OBJECTIVES: To assess the efficacy and safety of convalescent plasma plus standard of care (CP + SoC) compared with standard of care (SoC) alone in patients hospitalized for moderate to severe COVID-19 who do not yet require mechanical ventilation. METHODS: Phase 2 randomized, parallel-group, randomized, open-label, controlled, superiority, single-center clinical trial. This clinical trial has been registered in REPEC with the following ID: 013-20. Hospitalized adult patients with moderate to severe COVID-19 were enrolled. The allocation ratio was 1:1 in a variable-size permuted block randomization scheme. The primary outcome was death 28 days after the intervention. Secondary outcomes were mortality at 14 and 56 days, time to death at 56 days, time in the ICU at 28 days, time on a mechanical ventilator at 28 days, frequency of adverse events, and frequency of serious adverse events. RESULTS: A total of 64 participants were enrolled, 32 were assigned to CP + SoC, and 32 to SoC. One participant assigned to CP + SoC withdrew his informed consent before applying the treatment. At day 28, there were no statistically significant differences for the primary outcome between the CP + SoC and SoC groups (relative risk: 2.06; 95%CI 0.73 to 7.11; p = 0.190). No differences were found in the incidences of mortality at 56 days (hazard ratio: 2.21; 95%CI 0.66 to 7.33; p = 0.182), admission to the ICU at 28 days (sub-hazard ratio: 2.06; 95%CI 0.57 to 8.55; p = 0.250), admission to mechanical ventilation at 28 days (sub-hazard ratio: 2.19; 95%CI 0.57 to 8.51; p = 0.260). Estimates for days 14 were similar. No infusion-related adverse events were reported during the study. There were no statistically significant differences in the frequency of any adverse events (odds ratio: 2.74; 95%CI 0.90 to 9.10; p = 0.085) or the frequency of serious adverse events (odds ratio: 3.60; 95%CI 0.75 to 26.1; p = 0.75). CONCLUSIONS: No evidence was found that CP had a significant effect in reducing 28-day mortality. There was also no evidence that the frequency of adverse events was higher in those who received CP + SoC than those who received only SoC.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.21.22280195v1" target="_blank">Efficacy and safety of convalescent plasma versus standard care in hospitalized patients with COVID-19 from the Peruvian Social Security Health System: open-label, randomized, controlled clinical trial</a>
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<li><strong>Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19</strong> -
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Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care. Methods: We conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality. Results: A total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99-1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05-1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39-0.90). No differences in risk of serious adverse events including secondary infections. Conclusions: Infliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28-day mortality compared with standard of care. Trial registration: ClinicalTrials.gov (NCT04593940).
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.22.22280245v1" target="_blank">Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19</a>
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<li><strong>Excess death estimates from multiverse analysis in 2009-2021</strong> -
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Excess death estimates have great value in public health, but they can be sensitive to analytical choices. Here we propose a multiverse analysis approach that considers all possible different time periods for defining the reference baseline and a range of 1 to 4 years for the projected time period for which excess deaths are calculated. We used data from the Human Mortality Database on 33 countries with detailed age-stratified death information on an annual basis during the period 2009-2021. The use of different time periods for reference baseline led to large variability in the absolute magnitude of the exact excess death estimates. However, the relative ranking of different countries compared to others for specific years remained largely unaltered. Averaging across all possible analyses, distinct time patterns were discerned across different countries. Countries had declines between 2009 and 2019, but the steepness of the decline varied markedly. There were also large differences across countries on whether the COVID-19 pandemic years 2020-2021 resulted in an increase of excess deaths and by how much. Consideration of longer projected time windows resulted in substantial shrinking of the excess deaths in many, but not all countries. Multiverse analysis of excess deaths over long periods of interest can offer a more unbiased approach to understand comparative mortality trends across different countries, the range of uncertainty around estimates, and the nature of observed mortality peaks.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.21.22280219v1" target="_blank">Excess death estimates from multiverse analysis in 2009-2021</a>
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<li><strong>Fully Quantitative Measurements of Differential Antibody Binding to Spike Proteins from Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1 variants of SARS-CoV-2: Antibody Immunity Endotypes</strong> -
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A fully quantitative comparative analysis of the differential binding to spike variant proteins to SARS-CoV-2 has been performed for the variants: Wuhan (ancestral strain), Alpha, Beta, Gamma, Delta and Omicron BA.1. Evolution of immunity through five patient cohorts was studied including pre-pandemic, first infection, first vaccine, second vaccine and triple-vaccinated cohorts. A series of immunity endotypes has been observed: U(+) showing protection to all variants; single, double, triple, quadruple and quintuple dropout endotypes U(+/-;); some with no variant protection other than Wuhan vaccine spike U(-); and some unclassified, U(~). These endotypes may be imprinted. In the triple-vaccinated cohort (n = 54) there is a U(+) incidence of 65% (95% CI 51% - 76%) suggesting between half and three-quarters of the population have universal variant vaccine antibody protection; U(-) 6% (95% CI 2% - 15%) of the population have no variant antibody protection provided by the vaccine; and U(+/-;)) with at least one dropout has a incidence of 20% (95% CI 12% - 33%). Extending the cohort incidence to the population, up to 76% of the population may have an imprinted immunity endotype to an epitope that is effective against all variants; critical for both protection and binding to the ACE2 receptor: a universal immunity endotype. However, up to 33% of the population may have an immunity endotype that will never produce an effective antibody response to SARS-CoV-2 unless the immunity imprint is broken.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.23.22280271v1" target="_blank">Fully Quantitative Measurements of Differential Antibody Binding to Spike Proteins from Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1 variants of SARS-CoV-2: Antibody Immunity Endotypes</a>
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<li><strong>Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis</strong> -
<div>
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses a risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including selection of adaptive mutations and emergence of new variant lineages. Here we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate transmission of SARS-CoV-2 between human and non-human species and to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with negligible transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs, potentially due to small sample sizes. However, we identified three SNVs statistically associated with mink and 26 with deer. Of these SNVs, ~[2/3] were plausibly introduced into these animal species from local human populations, while the remaining ~[1/3] were more likely derived in animal populations and are thus top candidates for experimental studies of species-specific adaptation. Together, our results highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.02.494559v2" target="_blank">Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis</a>
</div></li>
<li><strong>Pharmacological inhibition of bromodomain and extra-terminal proteins induces NRF-2-mediated inhibition of SARS-CoV-2 replication and is subject to viral antagonism</strong> -
<div>
Inhibitors of bromodomain and extra-terminal proteins (iBETs), including JQ-1, have been suggested as potential therapeutics against SARS-CoV-2 infection. However, molecular mechanisms underlying JQ-1-induced antiviral activity and its susceptibility to viral antagonism remain incompletely understood. iBET treatment transiently inhibited infection by SARS-CoV-2 variants and SARS-CoV, but not MERS-CoV. Our functional assays confirmed JQ-1-mediated downregulation of ACE2 expression and multi-omics analysis uncovered induction of an antiviral NRF-2-mediated cytoprotective response as an additional antiviral component of JQ-1 treatment. Serial passaging of SARS-CoV-2 in the presence of JQ-1 resulted in predominance of ORF6-deficient variants. JQ-1 antiviral activity was transient in human bronchial airway epithelial cells (hBAECs) treated prior to infection and absent when administered therapeutically. We propose that JQ-1 exerts pleiotropic effects that collectively induce a transient antiviral state that is ultimately nullified by an established SARS-CoV-2 infection, raising questions on their clinical suitability in the context of COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.22.508962v1" target="_blank">Pharmacological inhibition of bromodomain and extra-terminal proteins induces NRF-2-mediated inhibition of SARS-CoV-2 replication and is subject to viral antagonism</a>
</div></li>
<li><strong>Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection</strong> -
<div>
Defective viral genomes (DVGs) have been identified in many RNA viruses as a major factor influencing antiviral immune response and viral pathogenesis. However, the generation and function of DVGs in SARS-CoV-2 infection are less known. In this study, we elucidated DVG generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from RNA-seq datasets of in vitro infections and autopsy lung tissues of COVID-19 patients. Four genomic hotspots were identified for DVG recombination and RNA secondary structures were suggested to mediate DVG formation. Functionally, bulk and single cell RNA-seq analysis indicated the IFN stimulation of SARS-CoV-2 DVGs. We further applied our criteria to the NGS dataset from a published cohort study and observed significantly higher DVG amount and frequency in symptomatic patients than that in asymptomatic patients. Finally, we observed unusually high DVG frequency in one immunosuppressive patient up to 140 days after admitted to hospital due to COVID-19, first-time suggesting an association between DVGs and persistent viral infections in SARS-CoV-2. Together, our findings strongly suggest a critical role of DVGs in modulating host IFN responses and symptom development, calling for further inquiry into the mechanisms of DVG generation and how DVGs modulate host responses and infection outcome during SARS-CoV-2 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.22.509123v1" target="_blank">Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: Olfactory training with essential oils;   Other: Olfactory training with fragrance-free oils<br/><b>Sponsor</b>:   Ditte Gertz Mogensen<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>The Efficacy and Safety of TADIOS as an Adjuvant Therapy in Patients Diagnosed With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: TADIOS;   Drug: Placebo<br/><b>Sponsor</b>:   Helixmith Co., Ltd.<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Fourth Dose Study in Australia</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Tozinameran;   Biological: Elasomeran;   Biological: Bivalent Pfizer-BioNTech;   Biological: Bivalent Moderna<br/><b>Sponsors</b>:   Murdoch Childrens Research Institute;   Coalition for Epidemic Preparedness Innovations;   The Peter Doherty Institute for Infection and Immunity<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People</strong> - <b>Conditions</b>:   SARS-CoV-2 Infection;   COVID-19<br/><b>Interventions</b>:   Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg;   Biological: BNT162b4 5 µg;   Biological: BNT162b4 10 µg;   Biological: BNT162b4 15 µg<br/><b>Sponsors</b>:   BioNTech SE;   Pfizer<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>Trial of 2nd Booster Dose of COVID-19 Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: Invitation to get a 2nd booster dose of COVID-19 vaccine<br/><b>Sponsor</b>:   Norwegian Institute of Public Health<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>PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: PBI-0451;   Drug: Placebo<br/><b>Sponsor</b>:   Pardes Biosciences, 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>Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: AD17002 + Formulation buffer;   Biological: Placebo<br/><b>Sponsors</b>:   Advagene Biopharma Co. Ltd.;   Gadjah Mada University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Community-based Health Education based on core intervention package;   Behavioral: Health Information Sharing Group<br/><b>Sponsors</b>:   The Hong Kong Polytechnic University;   Food and Health Bureau, Hong Kong<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>Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia</strong> - <b>Conditions</b>:   Olfactory Disorder;   COVID-19<br/><b>Intervention</b>:   Drug: Simvastatin<br/><b>Sponsors</b>:   Washington University School of Medicine;   Duke University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cardiopulmonary Rehabilitation in Post-acute COVID-19 Syndrome</strong> - <b>Condition</b>:   Post Acute COVID-19 Syndrome<br/><b>Interventions</b>:   Other: Cardiopulmonary rehabilitation;   Other: Health education<br/><b>Sponsor</b>:   Taipei Medical University Shuang Ho Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: Active Intervention Group<br/><b>Sponsor</b>:   Pennington Biomedical Research 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>Evaluation of the Efficacy of Mouth Rinses With Commercial Mouthwashes to Decrease Viral Load in Saliva in COVID-19 Patients</strong> - <b>Condition</b>:   covid19<br/><b>Interventions</b>:   Drug: Lacer Clorhexidina Colutorio;   Drug: Lacer Clorhexidine 0.20% Colutorio;   Drug: Gingilacer Encías Delicadas Colutorio;   Drug: Distilled water<br/><b>Sponsors</b>:   Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana;   Hospital Universitario Fundación Jiménez Díaz;   Hospital Universitario Infanta Elena<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of COVID-19 Positive Patients</strong> - <b>Conditions</b>:   Covid19;   Hydrogen-oxygen Gas;   AMS-H-03<br/><b>Interventions</b>:   Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03;   Device: the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen)<br/><b>Sponsor</b>:   Ruijin Hospital<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>Safety and Immunogenicity of COVID-19 Vaccine in Population Aged 18 Years and Above</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: low-dose LYB001;   Biological: Recombinant COVID-19 Vaccine (CHO Cell);   Biological: high-dose LYB001<br/><b>Sponsors</b>:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.<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>Long COVID-19 Syndrome in Primary Care: A Novel Protocol of Exercise Intervention “CON-VIDA Clinical Trial”</strong> - <b>Conditions</b>:   COVID-19;   Long COVID;   Post-COVID-19 Syndrome<br/><b>Intervention</b>:   Behavioral: EXERCISE<br/><b>Sponsor</b>:   Universidad San Jorge<br/><b>Active, not recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Delta and Omicron variants evade population antibody response by mutations in a single spike epitope</strong> - Population antibody response is thought to be important in selection of virus variants. We report that SARS-CoV-2 infection elicits a population immune response that is mediated by a lineage of VH1-69 germline antibodies. A representative antibody R1-32 from this lineage was isolated. By cryo-EM, we show that it targets a semi-cryptic epitope in the spike receptor-binding domain. Binding to this non-ACE2 competing epitope results in spike destruction, thereby inhibiting virus entry. On the basis…</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>Pediatric Residency Training amid the COVID-19 Pandemic: Exploring the Impact of Supervision and Clinical Practice Guidelines on Clinical and Financial Outcomes</strong> - CONCLUSION: Direct supervision inhibited the negative impact of the COVID-19 pandemic on both clinical and financial outcomes of non-COVID-19 inpatient care by pediatric residents, while CPG only inhibited the negative impact on financial outcomes. Implication of This Study. In a disaster, the availability of CPG and direct supervision makes AMC hospitals able to inhibit the negative impact of disasters on clinical and financial outcomes.</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>Jian-Ti-Kang-Yi decoction alleviates poly(I:C)-induced pneumonia by inhibiting inflammatory response, reducing oxidative stress, and modulating host metabolism</strong> - Jian-Ti-Kang-Yi decoction (JTKY) is widely used in the treatment of COVID-19. However, the protective mechanisms of JTKY against pneumonia remain unknown. In this study, polyinosinic-polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, was used to induce pneumonia in mice; the therapeutic effects of JTKY on poly(I:C)-induced pneumonia model mice were evaluated. In addition, the anti-inflammatory and anti-oxidative potentials of JTKY were also investigated. Lastly, the metabolic regulatory…</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>Structural Basis for the Inhibition of Coronaviral Main Proteases by a Benzothiazole-Based Inhibitor</strong> - The ongoing spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused hundreds of millions of cases and millions of victims worldwide with serious consequences to global health and economies. Although many vaccines protecting against SARS-CoV-2 are currently available, constantly emerging new variants necessitate the development of alternative strategies for prevention and treatment of COVID-19. Inhibitors that target the main protease (M^(pro)) of SARS-CoV-2, an…</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>Chemically Modified Bovine β-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks</strong> - Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine β-lactoglobulin (3HP-β-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Bovine Seminal Plasma Protein PDC-109 Possesses Pan-Antiviral Activity</strong> - Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines, and growth factors, with various functions during insemination and fertilization. The seminal plasma protein PDC-109 is one of the major soluble components of the bovine ejaculate and is crucially important for sperm motility, capacitation, and acrosome reaction. A hitherto underappreciated function of seminal plasma is its anti-microbial and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 RBD-Specific Antibodies Induced Early in the Pandemic by Natural Infection and Vaccination Display Cross-Variant Binding and Inhibition</strong> - The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern…</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 Small-Molecule Inhibitors of the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction from a Chemical Space of Privileged Protein Binders</strong> - Therapeutically useful small-molecule inhibitors (SMIs) of protein-protein interactions (PPIs) initiating the cell attachment and entry of viruses could provide novel alternative antivirals that act via mechanisms similar to that of neutralizing antibodies but retain the advantages of small-molecule drugs such as oral bioavailability and low likelihood of immunogenicity. From screening our library, which is focused around the chemical space of organic dyes to provide good protein binders, we…</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>Bacteriophage-Derived Double-Stranded RNA Exerts Anti-SARS-CoV-2 Activity In Vitro and in Golden Syrian Hamsters In Vivo</strong> - Bacteriophage-derived dsRNA, known as Larifan, is a nationally well-known broad-spectrum antiviral medication. This study aimed to ascertain the antiviral activity of Larifan against the novel SARS-CoV-2 virus. Larifan’s effect against SARS-CoV-2 in vitro was measured in human lung adenocarcinoma (Calu3) and primary human small airway epithelial cells (HSAEC), and in vivo in the SARS-CoV-2 infection model in golden Syrian hamsters. Larifan inhibited SARS-CoV-2 replication both in vitro and 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>Quercetin in the Prevention and Treatment of Coronavirus Infections: A Focus on SARS-CoV-2</strong> - The COVID-19 outbreak seems to be the most dangerous challenge of the third millennium due to its highly contagious nature. Amongst natural molecules for COVID-19 treatment, the flavonoid molecule quercetin (QR) is currently considered one of the most promising. QR is an active agent against SARS and MERS due to its antimicrobial, antiviral, anti-inflammatory, antioxidant, and some other beneficial effects. QR may hold therapeutic potential against SARS-CoV-2 due to its inhibitory effects on…</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>Plant Metabolites as SARS-CoV-2 Inhibitors Candidates: In Silico and In Vitro Studies</strong> - Since it acquired pandemic status, SARS-CoV-2 has been causing all kinds of damage all over the world. More than 6.3 million people have died, and many cases of sequelae are in survivors. Currently, the only products available to most of the world’s population to fight the pandemic are vaccines, which still need improvement since the number of new cases, admissions into intensive care units, and deaths are again reaching worrying rates, which makes it essential to compounds that can be used…</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>Identification of SARS-CoV-2 Main Protease Inhibitors from a Library of Minor Cannabinoids by Biochemical Inhibition Assay and Surface Plasmon Resonance Characterized Binding Affinity</strong> - The replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by its main protease (M^(pro)), which is a plausible therapeutic target for coronavirus disease 2019 (COVID-19). Although numerous in silico studies reported the potential inhibitory effects of natural products including cannabis and cannabinoids on SARS-CoV-2 M^(pro), their anti-M^(pro) activities are not well validated by biological experimental data. Herein, a library of minor cannabinoids…</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>Epigallocatechin Gallate Stabilized by Cyclodextrin Inactivates Influenza Virus and Human Coronavirus 229E</strong> - Natural products are attractive antiviral agents because they are environment-friendly and mostly harmless. Epigallocatechin gallate (EGCg), a type of catechin, is a well-known natural antiviral agent that can inhibit various viruses. However, EGCg easily oxidizes and loses its physiological activity. Although this problem can be overcome by combining EGCg with cyclodextrin (CD-EGCg), which makes it stable in water at high concentrations, the antiviral effect of this compound remains unclear….</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>1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants</strong> - SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Bases of Serotonin Reuptake Inhibitor Antidepressant-Attributed Effects in COVID-19: A New Insight on the Role of Bradykinins</strong> - Widely available effective drugs to treat coronavirus disease-2019 (COVID-19) are still limited. Various studies suggested the potential contribution of selective serotonin-reuptake inhibitor (SSRI) antidepressants to alleviate the clinical course of COVID-19. Initially, SSRI antidepressant-attributed anti-COVID-19 activity was attributed to their direct agonistic or indirect serotonin-mediated stimulation of sigma-1 receptors (Sig1-R). Thereafter, attention was drawn to the property of SSRI…</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>What Putin’s Mobilization Means for the War in Ukraine</strong> - The Kremlin announced a draft to dramatically increase its fighting force. Will the Russian public fight back? - <a href="https://www.newyorker.com/news/q-and-a/what-putins-mobilization-means-for-the-war-in-ukraine">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Breaking Down New York’s Long-Awaited Fraud Lawsuit Against Donald Trump</strong> - Letitia James, the New York attorney general, claims that the Trump Organization illegally obtained hundreds of millions of dollars by systematically exaggerating the value of its properties. - <a href="https://www.newyorker.com/news/our-columnists/breaking-down-new-yorks-long-awaited-fraud-lawsuit-against-donald-trump">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why Ron DeSantis Thinks Weaponizing Asylum Seekers Is a Winning Strategy</strong> - The Florida Governor’s political stunt rests on the cynical assumption that no one actually wants to offer refuge to people fleeing adversity. - <a href="https://www.newyorker.com/news/our-columnists/why-ron-desantis-thinks-weaponizing-asylum-seekers-is-a-winning-strategy">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>King Charles’s Vision of Britain, Writ Small</strong> - For decades, the King has overseen a planned community, Poundbury, to reflect the best of the United Kingdom’s past. What might it tell us about the future? - <a href="https://www.newyorker.com/news/letter-from-the-uk/king-charless-vision-of-britain-writ-small">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Putin’s Escalation in Ukraine Is a Losing Strategy</strong> - The push to claim new territory and mobilize more troops is unlikely to reverse Russia’s losses on the battlefield—but it could move the war into its most dangerous phase yet. - <a href="https://www.newyorker.com/news/news-desk/putins-escalation-in-ukraine-is-a-losing-strategy">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>Why Iranian women are risking everything by burning their hijabs</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/ycJgvZ-3ojAYmi1MAgzDnm5AGgg=/438x0:3941x2627/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71409581/1243371980.0.jpg"/>
<figcaption>
A picture obtained by AFP shows a demonstrator raising their arms and making the victory sign during a protest in Tehran for Mahsa Amini, on September 19, 2022.  | AFP via Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Iran is in revolt.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eSUXVo">
It was not an isolated incident of police violence in Iran. But the death of 22-year-old <a href="https://www.hrw.org/news/2022/09/16/woman-dies-custody-irans-morality-police">Mahsa Amini</a> in police custody last week has captured the country’s attention.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pedb03">
Amini was visiting the capital of Tehran, coming from the Kurdish province in the country’s northwest, and Iran’s<strong> </strong>so-called<strong> </strong><a href="https://www.bbc.com/news/world-middle-east-36101150">morality police</a> detained her, allegedly for wearing the mandatory headscarf improperly. Several hours after entering police custody, she was in a coma. She died two days later. Iranian police <a href="https://www.aljazeera.com/news/2022/9/19/irans-police-denies-women-who-died-in-custody-was-beaten">claimed</a> she died after a stroke and suffering cardiac arrest, but <a href="https://www.bbc.com/news/world-middle-east-62954648">witnesses say</a> she died after sustaining blows to the head, and shocking photos that spread online of Amini intubated in a hospital have galvanized the nation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="50la30">
Protesters have since <a href="https://www.bourseandbazaar.com/articles/2022/9/20/grief-and-grievance-in-irans-growing-protests">taken to the streets</a> in more than 50 cities across Iran. Authorities <a href="https://www.cnbc.com/2022/09/23/mass-protests-in-iran-is-the-regimes-biggest-challenge-in-years.html">reportedly</a> have killed as many as 36 people during demonstrations. The government has also <a href="https://www.reuters.com/world/middle-east/iran-restricts-access-instagram-netblocks-2022-09-21/">restricted</a> the internet, so the complete picture may not be available. But the growing arrests of human rights defenders, activists, and <a href="https://cpj.org/2022/09/iranian-security-forces-step-up-arrests-of-journalists-as-anti-state-protests-spread/">journalists</a> are particularly troubling.
</p>
<div class="c-float-right">
<div id="VIbe4w">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6CZiac">
Demonstrators have defied the repressive government regularly in the past several years, often expressing economic grievances. Women have been central to Iranian politics of resistance <a href="https://www.bookforum.com/print/2602/whisper-tapes-kate-millett-in-iran-by-negar-mottahedeh-22007">since the 1979 revolution</a>, and before. What’s different about these protests is the diversity of people out on the streets and the widespread nature of Iranian resistance, in cities big and small.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A5GNog">
The government may weather the emerging movement. Or Amini’s tragedy could prove to be Iran’s <a href="https://www.nytimes.com/2014/12/16/us/arab-spring-a-fruit-vendor-who-started-a-revolution.html">Mohamed Bouazizi</a> — the Tunisian street-seller who self-immolated in December 2010 and helped catalyze the mass protests across the Middle East and North Africa that came to be the Arab Spring.
</p>
<div id="eUFcUS">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
The protests have also provoked an outpouring of anger and sympathy from artists inside and outside of Iran.<br/><br/>These images commemorating Mahsa Amini are by artist Sahar Ghorishi<a href="https://t.co/XDh0Dt2Xt5">https://t.co/XDh0Dt2Xt5</a> <a href="https://t.co/Mcw7I3yXCF">pic.twitter.com/Mcw7I3yXCF</a>
</p>
— Alex Shams (<span class="citation" data-cites="alexshams_">@alexshams_</span>) <a href="https://twitter.com/alexshams_/status/1571984569708019712?ref_src=twsrc%5Etfw">September 19, 2022</a>
</blockquote></div></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RE06Mg">
Across the country, protesters are chanting, “<a href="https://www.nytimes.com/video/world/middleeast/100000008547381/iran-protests-video.html">Woman, Life, Freedom.</a>” Those words have resonated deeply because they’re affirmative and unifying, says University of Sussex professor Kamran Matin. “This triangular slogan is uniting different strands of discontent in Iran,” he told me. “This slogan has united every section of Iranian society which has some sort of grievance against the government.”
</p>
<h3 id="Dnw4nd">
Why Iranian women are burning headscarves
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UaeD9w">
In response to Amini’s death, Iranians are <a href="https://www.washingtonpost.com/world/2022/09/21/iran-protests-mahsa-amini-hijab/">demanding</a> an end to mandatory hijab laws and burning the scarves in powerful displays of refusal. In Tehran, they have been <a href="https://www.theguardian.com/global-development/2022/sep/23/how-iran-erupted-after-mahsa-amini-death-protests">chanting</a>, “We don’t want forced hijab.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EidHn2">
That’s connected to the police’s purported reason for detaining Amini, but the act of protest carries multiple meanings. Negar Mottahedeh, a professor of gender and feminist studies at Duke University, likened the images of Iranian women burning their headscarves to the bra-burning of the 1960s. Bra-burning meant many things at once: an expression of feminism and liberation, but also a broader rejection of the Vietnam War and of capitalism. Similarly, the images from demonstrations across Iran over the last week object to compulsory veiling and the morality police, but also against a paranoid, controlling state that has sought to police women’s bodies.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/lDlb6AlggXKtjAAzHks5gGuUnyw=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24048791/1426271324.jpg"/> <cite>Getty Images</cite>
<figcaption>
People gather in protest against the death of Mahsa Amini along the streets on September 19, 2022, in Tehran, Iran.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5XJRyZ">
The so-called morality police, an independent unit that has been around since 1979, don’t only enforce headscarves but a variety of regulations, including mixed-gender gatherings and prohibitions against drinking alcohol. During the late 1990s when Mohammad Khatami was president, Iran instituted a <a href="https://www.brookings.edu/opinions/iran-and-the-headscarf-protests/">number of reforms</a>, but his successor, Mahmoud Ahmadinejad, <a href="https://www.cbsnews.com/news/iran-cracks-down-on-womens-dress-code/">reversed</a> these. The current president, Ebrahim Raisi, a conservative, has <a href="https://studies.aljazeera.net/en/analyses/one-year-iran-president-raisi">maintained such restrictions</a> and emboldened officials to clamp down. Authorities in Iran take it upon themselves to interpret the codes, and enforcement can be arbitrary and violent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="addB3N">
Human rights researchers note that the morality police in the past few months have resorted to violence more frequently.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SCZdT3">
Even if the protests don’t immediately result in transformative change, they’ve forever changed the debate on compulsory hijab in Iran, says Tara Sepehri Far, a researcher at Human Rights Watch. “There’s no going back,” she told me. “Yes, police can pretend this never happened. But it did happen. Women took off their headscarves, walked down the street, and the debate has moved forward.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LrsaTX">
The boldness of Iranian women in the face of a police state has been one of the enduring dynamics of the country’s street politics. “From the very beginning of the revolution in 1979, women were at the forefront. They were walking shoulder to shoulder with men in front of tanks and guns, and they were seeking a different kind of government, an anti-imperialist, anti-capitalist government,” Mottahedeh told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="waG10K">
The 1979 revolution overthrew a corrupt, US-backed dictator and brought together a disparate opposition, including leftist and Islamic groups. But the political faction that took power after the revolution succeeded, which still rules today, began to implement religious-based laws that discriminated against women.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/bF6B4yAOI0-EZyprKtO2q1BNrCM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24048895/665169986.jpg"/> <cite>Christine Spengler/Sygma via Getty Images</cite>
<figcaption>
Women in the streets of Iran during the May 1, 1979, demonstration.
</figcaption>
</figure>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/G-foyU3hmFkEdWU97rS2OsEt85g=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/24048828/1243407628.jpg"/> <cite>Stephanie Keith/Getty Images</cite>
<figcaption>
People hold up a photo of Iranian woman Mahsa Amini as they participate in a protest against Iranian President Ebrahim Raisi outside of the United Nations on September 21, 2022, in New York City.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WcSHAh">
Mottahedeh emphasizes that many of the initiatives of the country’s first supreme leader, the late Ayatollah Ruhollah Khomeini, in the immediate post-1979 moment were about controlling women’s bodies, their careers (excluding them from being judges, for example), and their appearance. Back then, some of the first revolts against the revolutionary government were about the right to abortion, the right to divorce, and the right for a wife to have a say about who her husband’s second wife was going to be.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DvTb1k">
Despite severe restrictions, women have continued to push back. “It’s really important to focus on women’s resistance and resilience inside of Iran, and not see them as victims,” says Sussan Tahmasebi, executive director of the human rights organization Femena. “Iranian women — even though they deal with a lot of discriminatory laws, structural and legal discrimination — they have always taken every opportunity to advance their lives.”
</p>
<div id="1oxxwe">
<blockquote class="twitter-tweet">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" dir="ltr" lang="en">
A map showing the extent of the protests in Iran. Importantly, the 2017 and 2019 protests also took place in cities across the country.<br/><br/>What’s new about these protests is that they appear to have drawn individuals from across various classes and social groups. <a href="https://twitter.com/hashtag/MahsaAmini?src=hash&amp;ref_src=twsrc%5Etfw">#MahsaAmini</a> <a href="https://t.co/NxGY6YdHOR">pic.twitter.com/NxGY6YdHOR</a>
</p>
— Esfandyar Batmanghelidj (<span class="citation" data-cites="yarbatman">@yarbatman</span>) <a href="https://twitter.com/yarbatman/status/1572495330381365248?ref_src=twsrc%5Etfw">September 21, 2022</a>
</blockquote>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h17bmx">
Another important element of the ongoing mobilization relates to Amini’s Kurdish identity. The Iranian government has, over the years, painted Kurdish activists as separatists seeking to delegitimize the Iranian state. But now with demonstrations so dispersed across the country, the Kurdish minority’s prominence in the protests may reflect the fact that Iranians are becoming more sensitive toward the injustices inflicted upon the ethnic and sectarian minorities in the country. The national character of the protests that elevate the life of a young Kurdish woman provides crucial recognition of their plight.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PEURKA">
Matin, who studies Iranian and Kurdish politics, noted that the slogan “Woman, Life, Freedom” originates from Syrian Kurdistan. “The Kurds have always led the way in resistance against what I would describe, even in kind of scientific terms, as a semi-fascist state,” he said.
</p>
<h3 id="YzRj0o">
What’s next for an Iran in revolt
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cLAnJG">
The demonstrations come at a time when the socioeconomic conditions in Iran are extremely tenuous, with a large portion of Iranian society impoverished. This is partly because of the impact of <a href="https://prospect.org/world/iran-us-sanctions-not-an-alternative-to-war/">US sanctions over the Iran nuclear program</a>, as well as the broader global economic conditions and the <a href="https://prospect.org/coronavirus/sanctions-intensify-virus-spread-iran/">fallout from the Covid-19 pandemic</a>. The country’s economic troubles are likely to persist without a return to the <a href="https://www.vox.com/23002229/return-iran-nuclear-deal-vienna-explained">Iran nuclear deal</a>. Then-President Donald Trump unilaterally withdrew the US from the deal in 2018, and obstacles to its revival remain frozen despite diplomacy between the Biden administration, Iran, and world powers, leaving intact intensive economic sanctions on Iran. And without the money to address Iranians’ underlying grievances, the state is likely to flex its strength to deter social unrest.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rsa962">
Ali Vaez, an analyst with International Crisis Group, grew up in Iran and has been taken with the images of boys and girls fighting back against government forces. “These are scenes that were unimaginable 10 years ago, 20 years ago,” he told me. “This is a society that the Islamic Republic clearly is no longer able to control. With repression, they might be able to buy time, but they are not going to be able to address the underlying drivers of these protests.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PvwYPr">
It’s impossible to know whether the protests will carry on and grow, as they have in the 2017-18 economic protests or the massive 2009 <a href="https://www.pbs.org/wgbh/pages/frontline/tehranbureau/2010/10/iran-primer-the-green-movement.html">Green Movement</a> protests, led by a presidential candidate at the time. One thing that’s certain is that protests in Iran are becoming more frequent, says Vaez, which shows the degree of discontent. “We used to see this kind of outburst of public ire once a decade in Iran,” he told me. “Now it’s becoming every other year, basically, and it’s becoming more ferocious, more violent.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y8DV2c">
The demonstrations appear to be a spontaneous movement. But a leaderless revolt is also by extension disorganized. That may make it less likely for the movement to grow beyond a street movement into something that can transform Iranian policy and governance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WeBCUo">
Two enduring forces also stand in the way of political change: a geriatric supreme leader who is completely averse to change, heading a regime that is willing to deploy brute force against its people. (By coincidence, the protests began the same day as news broke about Supreme Leader Ayatollah Ali Khamenei’s <a href="https://www.nytimes.com/2022/09/16/world/middleeast/irans-supreme-leader-ayatollah-ali-khamenei-ill.html">ill health</a> and as the conservative President Ebrahim Raisi has left the country for the United Nations General Assembly in New York.) The discontent in the state and its crisis of legitimacy has been on display since the <a href="https://www.theguardian.com/world/2021/jun/18/iran-presidential-voting-begins-with-hardline-cleric-expected-to-win">low voter turnout</a> in the presidential election won by Raisi last year.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2ukBk3">
Now, the Iranian authorities are arresting activists, organizers, and students. “What concerns me is the escalation of the crackdown — they’re going to try to really force the protests to die down,” said Sepehri Far.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E5GfwD">
Such a brutal response to the mass protests will further expose the brittleness of the Iranian government. “It reflects the total incapacity of a political system to listen to its own population,” Vaez told me. “So there is a clear divide between state and society in the country — there is no doubt about it. But this is a system that still has the will and a fearsome capacity to repress.”
</p>
<ul>
<li><strong>The Mississippi welfare fraud involving Brett Favre, explained</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/A6NEVdbNoCHG9Tr7DkWyto2Z1RU=/501x0:4509x3006/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71409416/1402371449.0.jpg"/>
<figcaption>
Former NFL player Brett Favre at University Ridge Golf Club on June 11, 2022, in Madison, Wisconsin. | Patrick McDermott/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
How a WWE wrestler, corrupt Mississippi officials, and Brett Favre allegedly siphoned money away from poor people.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YFwty7">
We live in an age of brazen, ham-handed grift. Have you heard the one involving the retired NFL star, a WWE wrestler, corrupt Southern officials, and the millions in welfare money that they benefited from?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SIsQCe">
If you’ve heard about this scandal, it’s likely because of the involvement of former Green Bay Packer Brett Favre, specifically <a href="https://www.theguardian.com/sport/2022/sep/14/brett-favre-welfare-scandal-mississippi-governor">the $1 million in federal welfare money he received for talks he apparently did not give</a> and the $5 million he was involved in directing toward construction of a volleyball stadium at the college his daughter attended. Favre’s name is what pushed this from dry newspaper stories in 2020 announcing arrests of local bureaucrats to <a href="https://www.youtube.com/watch?v=ps_LU3tujVM">Stephen A. Smith yelling on ESPN</a> about poverty in Mississippi.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SV6WML">
But while Favre’s involvement has brought more attention to the story, it’s unfortunately narrowed the focus to a single ex-athlete, instead of taking in the extraordinarily sprawling web of corruption enveloping the state.
</p>
<div class="c-float-right">
<div id="M0Z8xu">
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AovjoH">
This scandal takes different shapes depending on the vantage from which one looks at it. Close up, it’s a sleazy, almost comically corrupt scheme by a few bureaucrats and nonprofit officials; zoom out and it looks more like an entire state government has become something closer to organized crime; pull back even further and the whole country’s welfare system is implicated, its very structure encouraging heinous misuse and waste even as poor people receive a fraction of what they need.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="e490Mv">
To understand how the fraud was perpetrated, it’s helpful to have some basic knowledge of how the United States’ alphabet soup of welfare programs works.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CEoP8L">
TANF — or Temporary Assistance to Needy Families — is the program that replaced AFDC — Aid to Families with Dependent Children — in the <a href="https://www.vox.com/2016/6/20/11789988/clintons-welfare-reform">welfare reform of 1996</a>. With the aim of “ending welfare as we know it,” TANF ended direct entitlement cash payments to poor families with children and created a block grant to states that they could use toward <a href="https://crsreports.congress.gov/product/pdf/IF/IF10036">four statutorily dictated goals</a>:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="R4NoWP">
</p><ol type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">provide assistance to needy families so that children may be cared for in their own homes or in the homes of relatives;
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xdcB7Y">
</p><ol start="2" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">end the dependence of needy parents on government benefits by promoting job preparation, work, and marriage;
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hCYWRu">
</p><ol start="3" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">prevent and reduce the incidence of out-of-wedlock pregnancies and establish annual numerical goals for preventing and reducing the incidence of these pregnancies; and
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9rlkyG">
</p><ol start="4" type="1">
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">encourage the formation and maintenance of two-parent families.
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
</li></ol></li></ol></li></ol></li></ol></blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bDEdFe">
In 2022, it’s easy to see the assumptions embedded in the law about poor people, especially poor Black women.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KomRZh">
The combined effect of relaxing rules on where money went, adding work requirements, and allowing states to define who qualified as “needy” had an effect that has only accelerated since 1996: fewer poor families receiving benefits. The Center on Budget and Policy Priorities releases a <a href="https://www.cbpp.org/research/family-income-support/cash-assistance-should-reach-millions-more-families-to-lessen#:~:text=In%202020%2C%20for%20every%20100,lowest%20in%20the%20program's%20history.">“TANF-to-poverty ratio,”</a> which tells you how many families are receiving TANF benefits for every 100 in poverty. The national number in 1996 was 68; it’s currently 21, the lowest ever. This average masks enormous interstate differences: In Texas, Mississippi, and Arkansas, just four out of 100 families in poverty receive TANF cash assistance.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qPA6wX">
As the nonpartisan <a href="https://crsreports.congress.gov/product/pdf/IF/IF10036">Congressional Research Service notes</a>, this has not been because of an overall reduction in poverty: “Most of the post-1994 decline in the cash assistance caseload resulted from a reduction in the share of eligible families receiving benefits, rather than a reduction in the number of families meeting states’ definitions of being a needy family.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aYEgoN">
The Mississippi welfare scandal has been burbling in the news for a while now, but its true import has never really sunk in beyond policy wonk circles. It’s a vivid illustration of how the welfare reform of 1996 has played out. What happened in Mississippi is less a case of criminal masterminds perpetrating a heist, and closer to walking into a vault that welfare reform left open and unguarded, all while purporting to protect the government from mooching citizens.
</p>
<h3 id="8ipHCR">
The Mississippi welfare fraud up close
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fuAnF7">
At its core, the fraud for which six people so far have <a href="https://mississippitoday.org/2021/12/23/anna-wolfe-mississippi-welfare-fraud-case/">faced criminal charges</a> was fairly simple.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="M3qhSU">
John Davis, the director of the Mississippi Department of Human Services (MDHS), funneled tens of millions of dollars in block-granted TANF money to a nonprofit, Mississippi Community Education Center, under the guise that the nonprofit was performing and subcontracting TANF-allowable activities. To be clear, the act of directing TANF funds to a nonprofit is legal so long as the nonprofit is actually performing tasks that go toward the goals outlined above.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DLIGlr">
That is not what was happening in Mississippi. Nancy New, head of the Mississippi Community Education Center, was instead kicking back money to Davis, his friends, and his family while enriching herself and her family as well. (A second nonprofit, the Family Resource Center, was also involved, but none of its personnel have been criminally charged.) On Thursday, Davis <a href="https://www.cnn.com/2022/09/22/us/mississippi-john-davis-welfare-fraud-guilty-plea">pleaded guilty</a> to federal and local charges; New herself <a href="https://www.clarionledger.com/story/news/2022/04/27/nancy-new-zach-new-plead-guilty-mississippi-welfare-misspending/9551152002/">pleaded guilty</a> in April.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xT5D5N">
The civil lawsuit the state filed to try to claw back some of the funds has <a href="https://s3.documentcloud.org/documents/21952751/msdh-civil-lawsuit-5922.pdf">38 defendants</a>, each its own lurid mess. It’s impossible to cover even a fraction of the cases here, but a few details alleged in the suit<strong> </strong>give a good sense of what was going on:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O9IZN6">
John Davis’s nephew was paid $400,000 to create “coding academies” for the two nonprofits. He had no experience as a computer programmer and produced nothing.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DFGAcR">
Davis’s brother-in-law was paid over $600,000 for a nonexistent job and a lease on a nonexistent building.
</li>
<li id="uZxcBp">
Marcus Dupree, a former college football phenom, was paid $371,000 to buy a 4,000-square-foot house, with a swimming pool, pavilion, and “adjoining acreage on which Mr. Dupree was to maintain horses.” Dupree claimed in charity filings it <a href="https://mississippitoday.org/2020/03/18/sports-legends-madison-county-horse-ranch-being-paid-for-by-nonprofit-at-center-of-welfare-embezzlement-firestorm/">would</a> be for “equestrian activities for underprivileged children.”
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MxC2ED">
To capture the full range here: “Illegal Diversions of TANF Funds To Enrich Sports Celebrities” needed its own subheading in the suit.
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ljgRBS">
Many instances of misuse didn’t even end up in the suit. For instance, <a href="https://www.clarionledger.com/story/news/politics/2020/03/27/mississippi-welfare-scandal-650-k-spent-religious-grammar-books/2907961001/">the Clarion Ledger</a> found <a href="https://mobile.twitter.com/ayewolfe/status/1553135667424755712">$43,000 spent</a> on Bible-inspired children’s books by a Christian singer named Jason Crabb. Auditors later determined this was <a href="https://www.mdhs.ms.gov/wp-content/uploads/2021/10/MDHS-Report-of-Fraud-Waste-Abuse-FINAL.pdf">“indicative of abuse and waste.”</a>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NsIsSN">
Apart from these cases, Davis, the MDHS director, became very close acquaintances with the DiBiases; sons Ted Jr. and Brett, and father Ted Sr. All are wrestlers, and Ted Sr. in particular was a prominent WWE wrestler.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="drYCTC">
According to the suit, starting in 2017, huge sums of TANF money began flowing from the two nonprofits. Ted Jr. set up dummy companies “Priceless Ventures” and “Familiae Orientem,” which were paid around<strong> </strong>$3 million. These payments were marked as “leadership training” and supporting inner city youth for purposes of TANF eligibility. Brett DiBiase’s $160,000 tab for a four-month stay at a luxury drug rehab in California called Rise in Malibu was covered, and TANF money paid for Davis’s first-class flights and accommodations to visit him — all for the ostensible purpose of examining top-notch models in drug treatment to mimic in their own state. Brett also accepted contracts and money for work he was supposedly performing during his rehab stay. Ted Sr., whose nickname as a performer was “The Million Dollar Man,” received $1.7 million in support of his wrestling ministry.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3dfqSj">
These individual cases, as ridiculous as they sound, add up to staggering sums. In all, the state auditor found at least <a href="https://www2.osa.ms.gov/news/auditor-demands-repayment-of-misspent-welfare-money/">$77 million</a> misused from 2017 to 2020. Mississippi’s yearly TANF spending has ranged anywhere from $55 million to $104 million in federal TANF funds in recent years.
</p>
<h3 id="EluKLG">
Zooming out: The Mississippi government’s role
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OxmqVX">
Reporting from Anna Wolfe — the Mississippi Today reporter whose <a href="https://mississippitoday.org/2021/12/23/anna-wolfe-mississippi-welfare-fraud-case/">years-long investigation</a> has formed the backbone of the entire story — and others has continued finding strands leading well past Davis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ytppq2">
Then-Gov. Phil Bryant (R) <a href="https://mississippitoday.org/2022/09/13/phil-bryant-brett-favre-welfare/">personally texting</a> Brett Favre reassurances is one. Another was the fact that one of those defendants under the “Sports Celebrities” subheading was a college linebacker who is current Republican Gov. Tate Reeves’s “longtime personal trainer and buddy.” He received more than $1 million in TANF money to host three fitness boot camps. Bryant personally intervened to have MDHS help his great-nephew, who allegedly ended up receiving state-funded drug rehabilitation. Nancy New, the nonprofit head, is friends with Bryant’s wife.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AkRG2C">
And the investigation itself has been less vigorous than the criminal arrests might suggest. The state auditor, Shad White, who had ties to Bryant, had in the <a href="https://mississippitoday.org/2022/05/12/shad-white-phil-bryant-welfare-investigation/">view of close observers</a><strong> </strong>waited a strangely long time to report findings to the federal government, which would have an obvious interest in federal money being stolen. An original forensic audit by MDHS in 2021 was <a href="https://mississippitoday.org/2022/08/10/mississippi-welfare-scandal-probe-limit/">clearly hamstrung by someone</a>, with the accounting firm denied access to documents and limited in scope, according to reporting by Mississippi Today. The original lawyer leading the civil suit was <a href="https://www.axios.com/2022/07/24/mississippi-lawyer-fired-subpoena-welfare">fired by the state</a> earlier this year. The depositions of the defendants in that case have been postponed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h6mtVz">
Wolfe says <a href="https://mississippitoday.org/2022/08/23/anna-wolfe-welfare-scandal-mpb/">there was</a> “a concerted effort by people in charge of this investigation at the beginning to steer the direction away from the governor, to take it as high up as John Davis and Nancy New and stop there.” She goes on to say that “the way that state government is run in Mississippi, people are totally afraid to say anything at any time for fear of losing their jobs.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MqQjV0">
But if low-level employees were in a state of fear, elites in the state were not. Text and email communications between these governors, professional athletes, and businessmen show virtually no concern that they could be documenting ongoing crimes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SWvj2R">
In addition to the volleyball and speaking money, <a href="https://mississippitoday.org/2022/04/04/phil-bryant-brett-favre-welfare-scandal-payout/">Brett Favre</a> had around <a href="https://www.osa.ms.gov/documents/single-audit/19sar.pdf">$2 million of TANF dollars routed to Prevacus</a>, a pharmaceutical company he invested in, according to Wolfe’s reporting. Prevacus’s founder and president, Jake VanLandingham, texted Bryant just days after he left office to say, “I’d like to give you a company package for all your help. … We want and need you on our team!!!” to which Bryant responded, “Sounds good. Where would be the best place to meet.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Vrz95C">
Favre <a href="https://mississippitoday.org/2022/04/04/phil-bryant-brett-favre-welfare-scandal-payout/">texted</a> VanLandingham at one point: “This all works out we need to buy her and John Davis surprise him with a vehicle I thought maybe John Davis we could get him a raptor.” [sic] Ted DiBiase Sr., on receiving a particular TANF payment for $250,000 for motivational speaking, forwarded it to his sons <a href="https://mississippitoday.org/2022/05/09/mississippi-welfare-scandal-civil-lawsuit/">saying</a>, “Look what I got today!” This feeling of impunity may be understandable: neither Favre, VanLandingham, Bryant, nor DiBiase Sr. has yet been charged with a crime.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vnTUeg">
All of this taking of funds comes alongside a deterioration in services; Mississippi saw its predominantly Black capital of <a href="https://www.vox.com/2022/8/31/23329604/jackson-mississippi-water-crisis">Jackson lose usable water</a> for a month and a half. Reeves, the current governor, joked one day after a boil-water advisory was lifted that it was <a href="https://www.wapt.com/article/a-great-day-to-not-be-in-jackson-mississippi-governor-says-during-hattiesburg-event/41252344">“as always, a great day to not be in Jackson.”</a>
</p>
<h3 id="gWd4XD">
The real welfare fraudsters
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cPRc5H">
Finally, there’s the bleak reality that while Mississippi’s TANF spending is notable for its shamelessness, it’s less of an outlier than you might think.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Yzc4Ol">
While Mississippi had a slush fund for personal gain and favors, TANF acts as a slush fund for state governments everywhere. Its structure as a block grant, its lack of oversight, and the paternalistic structures of its 1990s policy goals have allowed states to use the money on almost anything they want, whether filling budget holes or funding lawmakers’ pet projects.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZckUB7">
Some of that spending has been in theory defensible, such as money going toward college scholarships or foster care. But many states have used money that could’ve helped poor people on programs<strong> </strong>that don’t look much different from Mississippi’s.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dv8kQs">
A <a href="http://www.slate.com/articles/news_and_politics/moneybox/2016/06/_welfare_money_often_isn_t_spent_on_welfare.html">single company in Oklahoma used</a> more than $70 million in TANF money to run adult relationship classes and make pro-marriage ads. <a href="https://www.theguardian.com/world/2021/jun/04/states-divert-federal-welfare-funding-anti-abortion-clinics">Many</a> states divert welfare money to fund “crisis pregnancy centers,” or thinly veiled anti-abortion clinics. Utah cut back cash aid only to have state caseworkers repeatedly tell applicants to seek help from the LDS Church, including non-Mormons who <a href="https://www.propublica.org/article/utahs-social-safety-net-is-the-church-of-jesus-christ-of-latter-day-saints-what-does-that-mean-if-youre-not-one">would need to be baptized</a> to receive aid. Many states just don’t spend the money at all, amassing tens of billions of unspent dollars, even during the pandemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tZoWUb">
Experts I talked to were blunt about the program’s failings. Aditi Shrivastava, a senior policy analyst at CBPP, told me simply, “TANF’s focus should be cash assistance.” Heather Hahn, a senior fellow at the Urban Institute, pointed out that of “the four purposes of TANF, none of them is to reduce poverty. … The ideology of the program is not about reducing poverty.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vJjkId">
The obvious irony is that decades of welfare debates, and TANF’s structure itself, were driven by the often racist and sexist fear that mothers, especially Black mothers, were getting money they didn’t deserve and wasting it. But the kind of staggering organized theft that took place in Mississippi was only possible because of TANF’s giant-pool-of-money design. Shrivastava and Hahn both told me that such fraud would have been nigh-impossible under AFDC’s cash payment system.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mlT1D6">
One remaining question is why the program hasn’t been reformed or fixed. The answer may be found in these numbers: <a href="https://mississippitoday.org/2021/12/23/anna-wolfe-mississippi-welfare-fraud-case/">According to Wolfe</a>, in 1996, 33,000 adults were receiving assistance in Mississippi. Last year, and with at least $77 million gone elsewhere, that number was 208 adults.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bEvVKf">
In other words, it hasn’t been fixed because it’s performing the way it was designed to.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mqYHt9">
<em>Jack Meserve is the managing editor of </em><a href="https://democracyjournal.org/"><em>Democracy: A Journal of Ideas</em></a><em>.</em>
</p></li>
<li><strong>Are the walls really closing in on Trump this time?</strong> -
<figure>
<img alt=" Trump in front of a microphone." src="https://cdn.vox-cdn.com/thumbor/PeHgaDvpilSX0WJSV1--lFvOspM=/0x0:4267x3200/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71409313/GettyImages_1243417909.0.jpg"/>
<figcaption>
Former President Donald Trump spoke at the Covelli Centre in Youngstown, Ohio on September 17, 2022. | Andrew Spear for The Washington Post via Getty
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
His legal problems are worsening. But they might not take him down.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CZBgJp">
Stop me if you’ve heard this one before: New developments have put Donald Trump in even more serious legal jeopardy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RVjHYm">
A new civil fraud lawsuit from the New York attorney general’s office is <a href="https://www.vox.com/policy-and-politics/2022/9/21/23365077/trump-lawsuit-new-york-attorney-general">threatening his business</a>, while his efforts to stall the criminal investigation into whether he mishandled classified information <a href="https://www.vox.com/policy-and-politics/2022/9/22/23366712/donald-trump-special-master-aileen-cannon-11th-circuit-supreme-court-mar-a-lago-classified">seem to have failed</a>. And a separate investigation into the January 6 attack <a href="https://www.cnn.com/2022/09/13/politics/trump-world-justice-department-subpoenas-analysis">scrutinizes his associates</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nmoulD">
It all looks quite bad for him. Then again, for at least five years, much of the media has touted the seriousness of Trump’s legal peril, portraying him as on the verge of a humiliating downfall — only to see him go, in his own words, “<a href="https://www.washingtonpost.com/nation/2018/12/04/who-is-scott-free-search-meaning-after-trumps-misuse-medieval-idiom/">Scott Free</a>,” again and again.
</p>
<div class="c-float-right">
<div id="ASNTgx">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pBD9NE">
The <a href="https://www.vox.com/2019/4/18/18485602/mueller-report-findings-obstruction-russia-collusion">Mueller investigation</a>, the <a href="https://www.cnbc.com/2018/05/03/trump-and-michael-cohen-face-this-danger-in-growing-federal-probe.html">Michael Cohen investigation</a>, the <a href="https://www.vox.com/trump-impeachment-inquiry">first impeachment</a>, the <a href="https://www.vox.com/22223972/trump-impeached-house-senate-trial-former-president">second impeachment</a>, and the <a href="https://www.vox.com/2022/2/23/22947946/trump-prosecutors-new-york-bragg">Manhattan district attorney’s probe</a> were each hyped as the thing that could bring Trump down. Yet they all either fizzled out or went quiet, with Trump remaining conspicuously, well, un-brought-down.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="24CrLd">
So will this time be different? Are the walls really closing in?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="swGhv2">
It certainly seems like Trump’s threat of facing criminal charges is currently higher than it’s been since he entered politics, due to the classified documents probe, and the fact that he’s no longer an incumbent president with immunity against indictment. The New York civil lawsuit — at least on its face — <a href="https://www.theguardian.com/us-news/2022/sep/22/new-york-fraud-suit-trump-organization-letitia-james">appears to present</a> a serious threat to his business as well. The suit claims Trump and his employees “violated a host of state criminal laws” and their conduct “plausibly violates federal criminal law,” and New York Attorney General Letitia James said she’d refer her findings to federal prosecutors.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0Mvhbf">
But it’s worth remembering Trump hasn’t been criminally charged with anything yet, and that prosecutorial caution could still prevail. Even if Trump is charged, a potential trial would present further challenges, and if he is convicted, an eventual sentence might not be so harsh. And though he is facing that New York civil suit, a trial there is no sure thing either.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rhiUc1">
Trump critics hoping he will be removed from politics via indictment or prison may be hoping in vain. If he chooses to run again, it’s likely to be voters who will decide his fate.
</p>
<h3 id="mKlhJ0">
What prosecutors will consider before pursuing a Trump indictment or trial
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="vSWfhc">
Whatever you believe about the strength of the evidence against Trump in these various investigations, his status as incumbent president meant he couldn’t be indicted during his term, according to <a href="https://www.vox.com/2019/7/24/20708393/robert-mueller-report-trump-olc-justice-department-indictment-charge-sitting-president">long-standing Justice Department policy</a>. And his continued popularity among Republican voters meant that impeachment would end in acquittal (because many Senate Republicans would have been required to convict him). So, from January 2017 to January 2021, the power of his office and the power of his political base protected him.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WZQTv7">
Since Trump left office, his shield against indictment is gone. And while his political base on the right remains strong, the arena has changed — Republican politicians are no longer the key decision-makers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zwA3VE">
Instead, prosecutors have the reins. Various prosecutors — in <a href="https://www.vox.com/2022/2/23/22947946/trump-prosecutors-new-york-bragg">New York</a>, in <a href="https://www.washingtonpost.com/national-security/2022/07/26/trump-justice-investigation-january-6/">Washington, DC</a>, and in <a href="https://www.washingtonpost.com/national-security/2022/07/27/trump-georgia-investigation-explained/">Georgia</a> — have scrutinized Trump’s conduct for potential crimes in recent years, looking into his company’s business practices, his attempt to overturn the 2020 election result, and whether he improperly brought classified documents to Mar-a-Lago.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="HFikc0">
These prosecutors will have to evaluate the strength of the evidence against Trump, assessing whether he indeed did commit crimes and whether they’d likely convince a jury of that at trial. Federal prosecutors will also have to persuade higher-ups like Attorney General Merrick Garland.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uj1nGc">
Gaming out these prosecutors’ thinking is difficult because we don’t have access to the evidence they’re looking at, or their legal reasoning. For each of the Trump investigations, we don’t know whether they think they’re looking at a clear open-and-shut case of criminality, whether their legal theory is backed by ample precedent or is a bit novel, or whether similar cases tend to be brought in similar situations. (Trump’s attempt to overturn the election has little if any modern precedent in the US, so it’s difficult to even know what to compare it to.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BmjOEX">
But for many prosecutors, particularly in the US Justice Department, caution reigns supreme. Pursuing an indictment and trial in a high-profile matter takes a great deal of resources, and presents the risk of embarrassment should the trial end in acquittal. DOJ’s <a href="https://www.justice.gov/jm/jm-9-27000-principles-federal-prosecution">prosecution manual</a> says that government attorneys should not only consider whether they believe the person committed a crime, but also whether “the admissible evidence will probably be sufficient to obtain and sustain a conviction.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ufxB0k">
So prosecutors typically look for a clear-cut, open-and-shut crime. The classified documents matter might seem like one such crime: Trump had the documents, he should not have taken them, so they might reason he arguably should be charged.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nQXlQg">
Still, there are many complications that could make the government wary of a potential trial. For one, they want to keep the documents secret. Depending on whether the venue is in Florida (it’s currently unclear where they’d charge it), a jury conviction could be difficult. And while Trump’s arguments about executive privilege might seem like a stretch, this Supreme Court hasn’t weighed in on them just yet.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SgMLUy">
Note that when former CIA director David Petraeus was investigated for leaking classified material to his biographer, he <a href="https://www.washingtonpost.com/world/national-security/how-david-petraeus-avoided-felony-charges-and-possible-prison-time/2016/01/25/d77628dc-bfab-11e5-83d4-42e3bceea902_story.html">eventually struck a plea deal</a> for two years of probation and a $100,000 fine. Trump’s conduct is still murky so perhaps it was worse, and he’s unlikely to strike a plea deal like Petraeus did, but Petraeus actually did leak the information and Trump is not known to have done so. If a case were to be brought, and Trump was to be found guilty, he could face similar consequences — or even a less severe punishment.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Yg8rHL">
Now, prosecutors in Georgia and New York are elected Democrats and might be more willing to take risks to go after Trump. But even they might have reasons for caution. A Trump indictment and trial would swallow up everything else their office might do for years to come and become a grueling effort, while they’d personally become a top target of Fox News and the right. Even if that doesn’t give them pause, they could simply decide they don’t have a strong enough case.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ptrOQa">
Earlier this year, Alvin Bragg, a criminal justice reformer elected as Manhattan’s District Attorney, <a href="https://www.vox.com/2022/2/23/22947946/trump-prosecutors-new-york-bragg">reportedly expressed doubts</a> about the ongoing investigation into Trump’s business practices he had just taken over, and two prosecutors leading it soon resigned. (Bragg <a href="https://twitter.com/ManhattanDA/status/1572637408944091136?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Etweet">insisted in a statement</a> this week that his office’s Trump investigation was “active and ongoing.”)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uoaKMc">
On Wednesday, New York Attorney General Letitia James filed a civil suit in that same investigation, setting up a civil trial with potentially major consequences for the Trump organization. Even there, though, <a href="https://www.politico.com/news/2022/09/21/5-juiciest-takeaways-from-the-tish-james-lawsuit-against-donald-trump-00058171">Politico’s Josh Gerstein and Kyle Cheney argue</a> that a settlement remains a real possibility, writing, “Pursuing the case through to completion could take years and there’s no guarantee that a judge will agree to grant all the relief the AG asked for.”
</p>
<h3 id="I062m5">
Only voters can truly take Trump down
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9Qywob">
If Trump is eventually criminally charged, it would take some time before a trial. And even if he’s eventually convicted, depending on what the charges actually are, it’s not clear he’d get a particularly harsh sentence.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="I97Oay">
All of that is to say that, if Trump wants to run for president again in 2024, it seems unlikely that the cases against him could remove him from the political scene entirely. (Some liberals are excited that one penalty for mishandling government documents is disqualification from “from holding any office under the United States,” but many experts <a href="https://electionlawblog.org/?p=131265">believe</a> that is unconstitutional as applied to the presidency, since qualifications for that office are set out in the Constitution.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Cotg4S">
Instead, Trump’s political future will likely be determined at the ballot box, if he runs again — in the primary, and the general election.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xipF9m">
There is a hope among some Trump skeptics, including in the GOP, that Gov. Ron DeSantis (R-FL) will run and prove a potent challenger. Perhaps that could happen, and perhaps Trump’s legal issues will help weaken his standing if GOP voters fear he’ll be an electoral loser.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Foll1o">
Still, it’s far from clear how things will play out. As my colleague Zack Beauchamp <a href="https://www.vox.com/23287527/trump-gop-control-august-gop-primary-2022">recently wrote</a>, Trump-esque candidates have done quite well in Republican primaries this year, and Trump continues to lead <a href="https://www.realclearpolitics.com/epolls/2024/president/us/2024_republican_presidential_nomination-7548.html">all national GOP primary polls</a>, usually by large margins.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GLEnpO">
As for the general election, should Trump make it there, that’s murky too. President Biden <a href="https://www.cbsnews.com/news/president-joe-biden-2024-election-60-minutes-2022-09-18/">recently said</a> his “intention” is to run again but whether that’s a “firm decision” still “remains to be seen.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KkZS9F">
He’d be 81 years old by election day, is <a href="https://projects.fivethirtyeight.com/biden-approval-rating/">not popular</a> despite some recent improvement, and if he doesn’t run, it’s unclear which Democrat would succeed him. One might think that surely after January 6, <em>Dobbs</em>, and with criminal investigations hanging over his head, Trump is too damaged to win a general election. But as was demonstrated in 2016, the identity and political strength of the Democratic nominee will matter too.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="p4go5b">
Investigations and charges could well hurt Trump politically, though his die-hard loyalists will likely stick by him no matter what. But in either the primary and the general election, what would really be needed to beat him is a compelling alternative for voters to flock to instead. That’s the only way the Trump era in politics could really end.
</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>Turf Melody, Speed Air, Cuban Pete and Cloud Jumper impress</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>Ahead Of My Time and It’s My Time impress</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>Sucre, Salento, Raisina Star, Peyo, Prague and Angel Bliss impress</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>Cricket - Eden Gardens stand to be named after Jhulan</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>Indian team for FIFA U-17 Women's World Cup leaves for Spain to play friendly matches</strong> - The 23-member squad, along with the support staff, travelled left for Spain on Friday night</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>Migrant workers arrested on charge of sexually exploiting minor girl in Kozhikode</strong> - The Uttar Pradesh natives had met the victim during a train journey</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>‘Pakistan Zindabad’ slogan raised during PFI protest in Pune, shows video</strong> - Maharashtra CM, deputy CM vow action against those who allegedly raised slogans</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>Andhra Pradesh: TTD perform ‘Srinivasa Kalyanams’ in U.K. and other European countries</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>Adhere to A.P. High Court orders during Maha Padayatra, police advise APS members</strong> - ‘Amaravati to Arasavalli’ walkathon opposing move to set up three capitals enters Gudivada</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>Case against Maoist BK-ASR division secretary Azad for harassment of woman cadre</strong> - Based on ‘revelations’ of recently arrested Maoist</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 ‘referendums’: Soldiers go door-to-door for votes in polls</strong> - Russia is holding the self-styled referendums in parts of Ukraine it wants to claim control over.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Putin not bluffing about nuclear weapons, EU says</strong> - The EU’s warning comes after Russia’s president said he could use “all the means available to us”.</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>What Russia wants from the votes in occupied Ukraine</strong> - Russia is losing its war in Ukraine and now four regions are holding self-styled referendums.</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>Italian election campaign ends as far right bids for power</strong> - Political leaders hold rallies ahead of elections on Sunday that could bring Giorgia Meloni to power.</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>Magnus Carlsen and Hans Niemann: The cheating row that’s blowing up the chess world</strong> - Magnus Carlsen’s apparent accusation against Hans Niemann is the biggest chess scandal in years.</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>Music on the brain: Listening can influence our brain’s activity</strong> - The “Mozart effect” isn’t real—but music does affect our mental processes. - <a href="https://arstechnica.com/?p=1880612">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>GeForce GPUs are slowing down after installing the Windows 11 2022 Update</strong> - A new version of the GeForce Experience software will fix the issue. - <a href="https://arstechnica.com/?p=1884284">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NASA seems to be in full “send it” mode for the Artemis I mission</strong> - Space agency officials seem OK with leaving the rocket out in a tropical storm. - <a href="https://arstechnica.com/?p=1884140">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amazon hires unsafe trucking firms twice as often as peers, WSJ finds</strong> - Since 2015, crashes involving Amazon vehicles have killed more than 75 people. - <a href="https://arstechnica.com/?p=1884201">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>39-year-old Radio Shack laptop gets new CPU, keeps original screen</strong> - Hobbyist and IEEE editor Stephen Cass upgrades a broken laptop from 1983. - <a href="https://arstechnica.com/?p=1884104">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>I got a job in my first porno this morning.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I’m the husband leaving for work.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Po1sonator"> /u/Po1sonator </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/xmfltk/i_got_a_job_in_my_first_porno_this_morning/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/xmfltk/i_got_a_job_in_my_first_porno_this_morning/">[comments]</a></span></p></li>
<li><strong>TIL that 50% of Roger Federer’s……</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
….name is “er”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Make_the_music_stop"> /u/Make_the_music_stop </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/xmmrb9/til_that_50_of_roger_federers/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/xmmrb9/til_that_50_of_roger_federers/">[comments]</a></span></p></li>
<li><strong>what is the female version of rock out with your cock out?</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Jam out with your clam out.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/DEPMAG"> /u/DEPMAG </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/xmj2nl/what_is_the_female_version_of_rock_out_with_your/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/xmj2nl/what_is_the_female_version_of_rock_out_with_your/">[comments]</a></span></p></li>
<li><strong>What do you call a cockpit when the pilots are female?</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The box office.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/lukeallen1"> /u/lukeallen1 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/xm4j47/what_do_you_call_a_cockpit_when_the_pilots_are/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/xm4j47/what_do_you_call_a_cockpit_when_the_pilots_are/">[comments]</a></span></p></li>
<li><strong>I asked my wife why she married me.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I asked my wife why she married me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She said “Because you are funny.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I said “I thought it was because I was good in bed.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She said “See? You’re hilarious!”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Royal_Cover_9428"> /u/Royal_Cover_9428 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/xltxuc/i_asked_my_wife_why_she_married_me/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/xltxuc/i_asked_my_wife_why_she_married_me/">[comments]</a></span></p></li>
</ul>
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