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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>A Generic Deep Learning Based Cough Analysis System from Clinically Validated Samples for Point-of-Need Covid-19 Test and Severity Levels</strong> -
<div>
We seek to evaluate the detection performance of a rapid primary screening tool of Covid-19 solely based on the cough sound from 8,380 clinically validated samples with laboratory molecular-test (2,339 Covid-19 positive and 6,041 Covid-19 negative). Samples were clinically labelled according to the results and severity based on quantitative RT-PCR (qRT-PCR) analysis, cycle threshold and lymphocytes count from the patients. Our proposed generic method is a algorithm based on Empirical Mode Decomposition (EMD) with subsequent classification based on a tensor of audio features and deep artificial neural network classifier with convolutional layers called DeepCough’. Two different versions of DeepCough based on the number of tensor dimensions, i.e. DeepCough2D and DeepCough3D, have been investigated. These methods have been deployed in a multi-platform proof-of-concept Web App CoughDetect to administer this test anonymously. Covid-19 recognition results rates achieved a promising AUC (Area Under Curve) of 98.800.83%, sensitivity of 96.431.85%, and specificity of 96.201.74%, and 81.08%5.05% AUC for the recognition of three severity levels. Our proposed web tool and underpinning algorithm for the robust, fast, point-of-need identification of Covid-19 facilitates the rapid detection of the infection. We believe that it has the potential to significantly hamper the Covid-19 pandemic across the world.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/tm2f7/" target="_blank">A Generic Deep Learning Based Cough Analysis System from Clinically Validated Samples for Point-of-Need Covid-19 Test and Severity Levels</a>
</div></li>
<li><strong>Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality</strong> -
<div>
The precise molecular mechanisms behind severe life-threatening lung abnormalities during severe SARS-CoV-2 infections are still unclear. To address this challenge, we performed whole transcriptome sequencing of lung autopsies from 31 patients suffering from severe COVID-19 related complications and 10 uninfected controls. Using a metatranscriptome analysis of lung tissue samples we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant “classical” signature (n=23) showed upregulation of unfolded protein response, steroid biosynthesis and complement activation supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) potentially representing “Cytokine Release Syndrome” (CRS) showed upregulation of IL1 cytokines such CCL19 but absence of complement activation and muted inflammation. Further, dissecting expression of individual genes within enriched pathways for patient signature suggests heterogeneity in host response to the primary infection. We found that the majority of patients cleared the SARS-CoV-2 infection, but all suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Gordonia bronchialis in “classical” patients and Staphylococcus warneri in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients that can be identified through the status of the complement activation, presence of specific cytokines and characteristic microbiome. This information can be used to design personalized therapy to treat COVID-19 related complications corresponding to patient signature such as using the identified drug molecules or mitigating specific secondary infections.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.08.467705v1" target="_blank">Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality</a>
</div></li>
<li><strong>SARS-COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity</strong> -
<div>
The SARS-CoV-2 B.1.617 lineage variants, Kappa (B.1.617.1) and Delta (B.1.617.2, AY) emerged during the second wave of infections in India, but the Delta variants have become dominant worldwide and continue to evolve. The spike proteins of B.1.617.1, B.1.617.2, and AY.1 variants have several substitutions in the receptor binding domain (RBD), including L452R+E484Q, L452R+T478K, and K417N+L452R+T478K, respectively, that could potentially reduce effectiveness of therapeutic antibodies and current vaccines. Here we compared B.1.617 variants, and their single and double RBD substitutions for resistance to neutralization by convalescent sera, mRNA vaccine-elicited sera, and therapeutic neutralizing antibodies using a pseudovirus neutralization assay. Pseudoviruses with the B.1.617.1, B.1.617.2, and AY.1 spike showed a modest 1.5 to 4.4-fold reduction in neutralization titer by convalescent sera and vaccine-elicited sera. In comparison, similar modest reductions were also observed for pseudoviruses with C.37, P.1, R.1, and B.1.526 spikes, but seven- and sixteen-fold reduction for vaccine-elicited and convalescent sera, respectively, was seen for pseudoviruses with the B.1.351 spike. Four of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.2 pseudoviruses due to the L452R substitution, whereas six of twenty-three therapeutic neutralizing antibodies showed either complete or partial loss of neutralization against B.1.617.1 pseudoviruses due to either the E484Q or L452R substitution. Against AY.1 pseudoviruses, the L452R and K417N substitutions accounted for the loss of neutralization by four antibodies and one antibody, respectively, whereas one antibody lost potency that could not be fully accounted for by a single RBD substitution. The modest resistance of B.1.617 variants to vaccine-elicited sera suggest that current mRNA-based vaccines will likely remain effective in protecting against B.1.617 variants, but the therapeutic antibodies need to be carefully selected based on their resistance profiles. Finally, the spike proteins of B.1.617 variants are more efficiently cleaved due to the P681R substitution, and the spike of Delta variants exhibited greater sensitivity to soluble ACE2 neutralization, as well as fusogenic activity, which may contribute to enhanced spread of Delta variants.
</div>
<div class="article-link article- html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.05.467523v1" target="_blank">SARS- COV-2 Delta variant displays moderate resistance to neutralizing antibodies and spike protein properties of higher soluble ACE2 sensitivity, enhanced cleavage and fusogenic activity</a>
</div></li>
<li><strong>Accelerated decline of genome heterogeneity in the SARS-CoV-2 coronavirus</strong> -
<div>
In the brief time since the outbreak of the COVID 19 pandemic, and despite its proofreading mechanism, the SARS- CoV-2 coronavirus has accumulated a significant amount of genetic variability through recombination and mutation events. To test evolutionary trends that could inform us on the adaptive process of the virus to its human host, we summarize all this variability in the Sequence Compositional Complexity (SCC), a measure of genome heterogeneity that captures the mutational and recombinational changes accumulated by a nucleotide sequence along time. Despite the brief time elapsed, we detected many differences in the number and length of compositional domains, as well as in their nucleotide frequencies, in more than 12,000 high-quality coronavirus genomes from across the globe. These differences in SCC are phylogenetically structured, as revealed by significant phylogenetic signal. Phylogenetic ridge regression shows that SCC followed a generalized decreasing trend along the ongoing process of pathogen evolution. In contrast, SCC evolutionary rate increased with time, showing that it accelerates toward the present. In addition, a low rate set of genomes was detected in all the genome groups, suggesting the existence of a stepwise distribution of rates, a strong indication of selection in favor of different dominant strains. Coronavirus variants reveal an exacerbation of this trend: non-significant SCC regression, low phylogenetic signal and, concomitantly, a threefold increase in the evolutionary rate. Altogether, these results show an accelerated decline of genome heterogeneity along with the SARS CoV 2 pandemic expansion, a process that might be related to viral adaptation to the human host, perhaps paralleling the transformation of the current pandemic to epidemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.06.467547v1" target="_blank">Accelerated decline of genome heterogeneity in the SARS-CoV-2 coronavirus</a>
</div></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structural basis of main proteases of coronavirus bound to drug candidate PF-07321332</strong> -
<div>
The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genus of coronaviruses is the substrate binding site of the main protease (Mpro or 3CLpro), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332 developed by Pfizer is the first orally administered inhibitor targeting the main protease of SARS-CoV-2, which also has shown potency against other coronaviruses. Here we report three crystal structures of main protease of SARS-CoV-2, SARS-CoV and MERS-CoV bound to the inhibitor PF-07321332. The structures reveal a ligand-binding site that is conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, providing insights into the mechanism of inhibition of viral replication. The long and narrow cavity in the cleft between domains I and II of main protease harbors multiple inhibitor binding sites, where PF-07321332 occupies subsites S1, S2 and S4 and appears more restricted compared with other inhibitors. A detailed analysis of these structures illuminated key structural determinants essential for inhibition and elucidated the binding mode of action of main proteases from different coronaviruses. Given the importance of main protease for the treatment of SARS-CoV-2 infection, insights derived from this study should accelerate the design of safer and more effective antivirals.
</div></li>
</ul>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.05.467529v1" target="_blank">Structural basis of main proteases of coronavirus bound to drug candidate PF-07321332</a>
</div>
<ul>
<li><strong>Ethnicity and outcomes in COVID-19 in the United Kingdom: a systematic review and meta-analysis</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
This systematic review and meta-analysis evaluated the clinical outcomes of COVID-19 disease in the ethnic minorities of the UK in comparison to the White ethnic group. Medline, Embase, Cochrane, MedRxiv, and Prospero were searched for articles published between May 2020 to April 2021. PROSPERO ID: CRD42021248117. Fourteen studies (767177 participants) were included in the review. In the adjusted analysis, the pooled Odds Ratio (OR) for the mortality outcome was higher for the Black (1.83, 95% CI: 1.21-2.76), Asian (1.16, 95% CI: 0.85-1.57), and Mixed and Other (MO) groups (1.12, 95% CI: 1.04-1.20) compared to the White group. The adjusted and unadjusted ORs of intensive care admission were more than double for all ethnicities (OR Black 2.32, 95% CI: 1.73-3.11, Asian 2.34, 95% CI: 1.89-2.90, MO group 2.26, 95% CI: 1.64-3.11). In the adjusted analysis of mechanical ventilation need the ORs were similarly significantly raised (Black group 2.03, 95% CI: 1.80-2.29, Asian group 1.84, 95% CI: 1.20-2.80, MO 2.09, 95% CI: 1.35-3.22). This review confirmed that all ethnic groups in the UK suffered from increased disease severity and mortality with regards to COVID-19. This has urgent public health and policy implications to reduce the health disparities.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.07.21266027v1" target="_blank">Ethnicity and outcomes in COVID-19 in the United Kingdom: a systematic review and meta-analysis</a>
</div></li>
<li><strong>Surveillance of COVID-19 in a Vaccinated Population: A Rapid Literature Review</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Objectives: With the availability of COVID-19 vaccines, public health focus is shifting to post-vaccination surveillance to identify breakthrough infections in vaccinated populations. Therefore, the objectives of these reviews are to identify scientific evidence and international guidance on surveillance and testing approaches to monitor the presence of the virus in a vaccinated population. Method: We searched Ovid MEDLINE, including Epub Ahead of Print, In- Process &amp; Other Non-Indexed Citations, Embase, EBM Reviews - Cochrane Central Register of Controlled Trials, and EBM Reviews - Cochrane Database of Systematic Reviews. We also searched the Web of Science Core Collection. A grey literature search was also conducted. This search was limited to studies conducted since December 2020 and current to June 13th, 2021. There were no language limitations. COVID-19 surveillance studies that were published after December 2020 but did not specify whether they tested a vaccinated population were also considered for inclusion. For the international guidance review, a grey literature search was conducted, including a thorough search of Google, websites of international government organizations (e.g., Center for Disease Control and Prevention [CDC], World Health Organization [WHO]), and McMaster Health Forum (CoVID-END). This search was primarily examining surveillance guidance published since December 2020 (to capture guidance specific to vaccinations) and any relevant pre-December 2020 guidance. Results: Thirty-three studies were included for data synthesis of scientific evidence on surveillance of COVID-19. All the studies were published between April and June 2021. Twenty-one studies were from peer-reviewed journals. Five approaches to monitoring post-vaccination COVID-19 cases and emerging variants of concern were identified, including screening with reverse transcriptase polymerase chain reaction (RT-PCR) and/or a rapid antigen test, genomic surveillance, wastewater surveillance, metagenomics, and testing of air filters on public buses. For population surveillance, the following considerations and limitations were observed: variability in person-to-person testing frequency; lower sensitivity of antigen tests; timing of infections relative to PCR testing can result in missed infections; large studies may fail to identify local variations; and loss of interest in testing by participants in long follow-up studies. Through comprehensive grey literature searching, 68 international guidance documents were captured for full-text review. A total of 26 documents met the inclusion criteria and were included in our synthesis. Seven overarching surveillance methods emerged in the literature. PCR-testing was the most recommended surveillance method, followed by genomic screening, serosurveillance, wastewater surveillance, antigen testing, health record screening, and syndromic surveillance. Conclusion: Evidence for post-vaccination COVID-19 surveillance was derived from studies in partially or fully vaccinated populations. Population PCR screening, supplemented by rapid antigen tests, was the most frequently used surveillance method and also the most commonly recommended across jurisdictions. Most recent guidance on COVID-19 surveillance is not specific to vaccinated individuals, or it is in effect but has not yet been updated to reflect that. Therefore, more evidence-informed guidance on testing and surveillance approaches in a vaccinated population that incorporates all testing modalities is required.
</p>
</div>
<div class="article-link article- html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.05.21265763v1" target="_blank">Surveillance of COVID-19 in a Vaccinated Population: A Rapid Literature Review</a>
</div></li>
<li><strong>Effect of the Neutralizing SARS-CoV-2 Antibody Sotrovimab in Preventing Progression of COVID-19: A Randomized Clinical Trial</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Importance: Older patients and those with underlying comorbidities infected with SARS-CoV-2 may be at increased risk of hospitalization and death from COVID-19. Sotrovimab is a neutralizing antibody designed for treatment of high- risk patients to prevent COVID-19 progression. Objective: To evaluate the efficacy and safety of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease. Design: Randomized, double-blind, multicenter, placebo-controlled, phase 3 study. Setting: 57 centers in 5 countries. Participants: Nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for disease progression. Intervention: Patients were randomized (1:1) to an intravenous infusion of sotrovimab 500 mg or placebo. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with COVID-19 progression, defined as all-cause hospitalization longer than 24 hours for acute illness management or death through day 29. Key secondary outcomes included the proportion of patients with COVID-19 progression, defined as emergency room visit, hospitalization of any duration, or death, and proportion of patients developing severe/critical respiratory COVID-19 requiring supplemental oxygen. Results: Among 1057 patients randomized (sotrovimab, 528; placebo, 529), all-cause hospitalization longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) by 79% (95% CI, 50% to 91%; P&lt;.001). Secondary outcome results further demonstrated the effect of sotrovimab in reducing emergency room visits, hospitalization of any duration, or death, which was reduced by 66% (95% CI, 37% to 81%; P&lt;.001), and severe/critical respiratory COVID-19, which was reduced by 74% (95% CI, 41% to 88%; P=.002). No patients receiving sotrovimab required high-flow oxygen, oxygen via nonrebreather mask, or mechanical ventilation compared with 14 patients receiving placebo. The proportion of patients reporting adverse events was similar between treatment groups; sotrovimab was well tolerated, and no safety concerns were identified. Conclusions and Relevance: Among nonhospitalized patients with mild to moderate COVID-19, a single 500-mg intravenous dose of sotrovimab prevented progression of COVID-19, with a reduction in hospitalization and need for supplemental oxygen. Sotrovimab is a well-tolerated, effective treatment option for patients at high risk for severe morbidity and mortality from COVID-19.
</p>
</div>
<div class="article-link article-html- link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.03.21265533v1" target="_blank">Effect of the Neutralizing SARS-CoV-2 Antibody Sotrovimab in Preventing Progression of COVID-19: A Randomized Clinical Trial</a>
</div></li>
<li><strong>Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalized children: a multicenter cohort study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Importance: Children are less likely than adults to have severe outcomes from SARS-CoV-2 infection and the corresponding risk factors are not well established. Objective: To identify risk factors for severe disease in symptomatic children hospitalized for PCR-positive SARS-CoV-2 infection. Design: Cohort study, enrollment from February 1, 2020 until May 31, 2021 Setting 15 children9s hospitals in Canada, Iran, and Costa Rica Participants: Patients &lt;18 years of age hospitalized with symptomatic SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C) Exposures: Variables assessed for their association with disease severity included patient demographics, presence of comorbidities, clinical manifestations, laboratory parameters and chest imaging findings. Main Outcomes and Measures: The primary outcome was severe disease defined as a WHO COVID-19 clinical progression scale of ≥6, i.e., requirement of non-invasive ventilation, high flow nasal cannula, mechanical ventilation, vasopressors, or death. Multivariable logistic regression was used to evaluate factors associated with severe disease. Results: We identified 403 hospitalizations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Severe disease occurred in 33.8% (102/403). In multivariable analyses, presence of multiple comorbidities (adjusted odds ratio 2.24, 95% confidence interval 1.04-4.81), obesity (2.87, 1.19-6.93), neurological disorder (3.22, 1.37-7.56), anemia, and/or hemoglobinopathy (5.88, 1.30-26.46), shortness of breath (4.37, 2.08-9.16), bacterial and/or viral coinfections (2.26, 1.08-4.73), chest imaging compatible with COVID-19 (2.99, 1.51-5.92), neutrophilia (2.60, 1.35-5.02), and MIS-C diagnosis (3.86, 1.56-9.51) were independent risk factors for severity. Comorbidities, especially obesity (40.9% vs 3.9%, p&lt;0.001), were more frequently present in adolescents ≥12 years of age. Neurological disorder (3.16, 1.19-8.43) in children &lt;12 years of age and obesity (3.21, 1.15-8.93) in adolescents were the specific comorbidities associated with disease severity in age-stratified adjusted analyses. Sensitivity analyses excluding the 81 cases with MIS-C did not substantially change the identified risk factors. Conclusions and Relevance: Pediatric risk factors for severe SARS-CoV-2 infection vary according to age and can potentially guide vaccination programs and treatment approaches in children.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.10.28.21265616v2" target="_blank">Risk factors for severe PCR- positive SARS-CoV-2 infection in hospitalized children: a multicenter cohort study</a>
</div></li>
<li><strong>Stable Cell Clones Harboring Self-Replicating SARS-CoV-2 RNAs for Drug Screen</strong> -
<div>
The development of antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been hampered by the lack of efficient cell-based replication systems that are amenable to high-throughput screens in biosafety level 2 laboratories. Here we report that stable cell clones harboring autonomously replicating SARS-CoV-2 RNAs without S, M, E genes can be efficiently derived from the baby hamster kidney (BHK-21) cell line when a pair of mutations were introduced into the non-structural protein 1 (Nsp1) of SARS-CoV-2 to ameliorate cellular toxicity associated with virus replication. In a proof-of-concept experiment we screened a 273-compound library using replicon cells and identified three compounds as novel inhibitors of SARS-CoV-2 replication. Altogether, this work establishes a robust, cell-based system for genetic and functional analyses of SARS-CoV-2 replication and for the development of antiviral drugs. IMPORTANCE: SARS-CoV-2 replicon systems that have been reported up to date were unsuccessful in deriving stable cell lines harboring non-cytopathic replicons. The transient expression of viral sgmRNA or a reporter gene makes it impractical for industry-scale screening of large compound libraries using these systems. Here, for the first time, we derived stable cell clones harboring the SARS-CoV-2 replicon. These clones may now be conveniently cultured in a standard BSL-2 laboratory for high throughput screen of compound libraries. This achievement represents a ground-breaking discovery that will greatly accelerate the pace of developing treatments for COVID-19.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.04.467291v1" target="_blank">Stable Cell Clones Harboring Self- Replicating SARS-CoV-2 RNAs for Drug Screen</a>
</div></li>
<li><strong>Immunogenicity and adverse events of priming with inactivated whole SARS-CoV-2 vaccine (CoronaVac) followed by boosting the ChAdOx1 nCoV-19 vaccine</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Responding to SARS-CoV-2 Delta variants escaped the vaccine-induced immunity and waning immunity from the inactivated whole virus vaccine, Thailand recently proposed a heterologous inactivated whole virus vaccine (CoronaVac) viral vector vaccine (ChAdOx1 nCoV-19) prime-boost vaccine regimen(I/V). This study aims to evaluate the immunogenicity and adverse events of this regimen by comparison with homologous CoronaVac, ChAdOx1 nCoV-19, and convalescent serum. Method: Immunogenicity was evaluated by the level of IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (S1 subunit) (anti-S RBD). At 2 weeks following the second dosage, a selection of random samples was tested for plaque reduction neutralisation (PRNT) and Pseudotype-Based Microneutralization test (PVNT) against SARS-CoV-2 variants of concern (VOCs). The safety profile of heterologous CoronaVac-ChAdOx1 nCoV-19 prime-boost vaccine regimen was described by interviewing at the 1-month visit. Result: Between April to August 2021,426 participants were included in the study, with 155 obtaining CoronaVac-ChAdOx1 nCoV-19(I/V),32 obtaining homologous CoronaVac(I/I),47 obtaining homologous ChAdOx1 nCoV-19(V/V),169 with history covid-19 infection. Geometric mean titers (GMTs) of anti-S RBD level in the I/V group compare 2wks and 4 wks ( 873.9 vs 639,p=0.00114).At 4 wks, GMTs of anti-S RBD level in I/V group was 639, 95% CI 63-726,and natural infection group 177.3, 95% CI 42-221, and V/V group 211.1, 95% CI 77-152 ,and I/I group 108.2 ,95% CI 77-152 ; all p&lt;0.001).At 2 wks, The GMTs of 50%PRNT of 19 sampling from the I/V group is 434.5, 95% CI 326-579, against wild type and 80.4, 95% CI 56-115, against alpha and 67.4, 95% CI 48-95, against delta and 19.8, 95% CI 14-30, against beta; all p&lt;0.001. At 2 wks, The GMTs of 50%PVNT of 15 sampling from the I/V group is 597.8, 95% CI 368-970, against wild type and 163.9, 95% CI 89-301, against alpha and 157.7, 95% CI 66-378, against delta. The AEs in the I/V schedule were well tolerated and generally unremarkable. Conclusion: The I/V vaccination is a mixed regimen that induced higher immunogenicity and shall be considered for responding to Delta Variants when only inactivated whole virus vaccine and viral vector vaccine was available.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.05.21264700v1" target="_blank">Immunogenicity and adverse events of priming with inactivated whole SARS-CoV-2 vaccine (CoronaVac) followed by boosting the ChAdOx1 nCoV-19 vaccine</a>
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<li><strong>Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY</strong> -
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Background While the vaccines against COVID-19 are considered to be highly effective, COVID-19 vaccine breakthrough is likely and a small number of people will still fall ill, be hospitalised, or die from COVID-19, despite being fully vaccinated. With the continued increase in numbers of positive SARS-CoV-2 tests, describing the characters of individuals who have experienced a COVID-19 vaccine breakthrough could be hugely important in helping to determine who may be at greatest risk. Method We conducted a retrospective cohort study using routine clinical data from the OpenSAFELY TPP database of fully vaccinated individuals, linked to secondary care and death registry data, and described the characteristics of those experiencing a COVID-19 vaccine breakthrough. Results As of 30th June 2021, a total of 10,782,870 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 43 days (IQR: 23-64). From within this population, a total of 16,815 (0.1%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate was ​​12.33 (95% CI 12.14-12.51). There were 955 COVID-19 hospital admissions and 145 COVID-19-related deaths; corresponding incidence rates of 0.70 (95% CI 0.65-0.74) and 0.12 (95% CI 0.1-0.14), respectively. When broken down by the initial priority group, higher rates of hospitalisation and death were seen in those in care homes. Comorbidities with the highest rates of breakthrough COVID-19 included renal replacement therapy, organ transplant, haematological malignancy, and immunocompromised. Conclusion The majority of COVID-19 vaccine breakthrough cases in England were mild with relatively few fully vaccinated individuals being hospitalised or dying as a result. However, some concerning differences in rates of breakthrough cases were identified in several clinical and demographic groups, The continued increase in numbers of positive SARS- CoV-2 tests are concerning and, as numbers of fully vaccinated individuals increases and follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, aimed at identifying individuals at higher risk, are therefore required.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.08.21265380v1" target="_blank">Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY</a>
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<li><strong>Association between long working hours and psychological distress: The effect of sick leave criteria in the workplace during the COVID-19 pandemic</strong> -
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Objective: This study investigated the effect of sick leave criteria on the association between long working hours and psychological distress. Methods: We conducted a cross-sectional survey in December 2020, and 27,032 workers completed the questionnaire. First, after testing the interaction effect of overtime work hours and sick leave criteria on psychological distress, we conducted stratified analyses using sick leave criteria. Results: A significant interaction effect was found. When we conducted stratified analyses, the odds ratios increased with longer working hours, both with and without sick leave criteria groups; however, the risk was greater in the without sick leave criteria group, compared with the criteria group. Conclusion: We revealed that working without sick leave criteria could strengthen the association between long working hours and psychological distress during the COVID-19 pandemic.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.07.21266036v1" target="_blank">Association between long working hours and psychological distress: The effect of sick leave criteria in the workplace during the COVID-19 pandemic</a>
</div></li>
<li><strong>SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2</strong> -
<div>
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<b>Background.</b> The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. <b>Methods.</b> We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine. We conducted five surveys on day 1, day 15, day 29 (seven days after the second dose), day 61, and days 82-96 following the first dose. <b>Results.</b> SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. <b>Conclusions.</b> This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These early immune responses are sustained for approximately six-ten weeks following the second vaccination dose.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.06.21265632v1" target="_blank">SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2</a>
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<li><strong>Preventing the Transmission of COVID-19 in Older Adults Aged 60 Years and Above Living in Long-Term Care: Rapid Review Update</strong> -
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Objectives: The objective of this study was to examine the effect of measures of control and management of COVID-19, Middle East Respiratory Syndrome (MERS), and severe acute respiratory syndrome (SARS) in adults 60 years or above living in long-term care facilities. This is an update of previous work done by Rios et al. Methods: A rapid review was conducted in accordance with the Rapid Review Guide for Health Policy and Systems Research. Literature search of databases MEDLINE, Cochrane library, and pre-print servers (biorxiv/medrxiv) was conducted from July 31, 2020 to October 9, 2020. EMBASE was searched from July 31, 2020 until October 18, 2020. Titles and abstracts from public archives were identified for screening using Gordon V. Cormack and Maura R. Grossmans Continuous Active Learning (CAL) tool, which uses supervised machine learning. Results: Five observational studies and one clinical practice guideline were identified. Infection prevention measures identified in this rapid review included: social distancing and isolation, personal protective equipment (PPE) use and hygiene practices, screening, training and staffing policies. The use of PPE, laboratory screening tests, sick pay to staff, self-confinement of staff within the LTCFs for 7 or more days, maintaining maximum resident occupancy, training and social distancing significantly reduced the prevalence of COVID-19 infection among residents and/or staff of LTCFs (p&lt;0.05). Practices such as hiring of temporary staff, not assigning staff to care separately for infected and uninfected residents, inability to isolate sick residents and infrequent cleaning of communal areas significantly increased the prevalence of infection among residents and/or staff of LTCFs (p&lt;0.05). Conclusion: The available studies are limited to only three countries despite the global nature of the disease. The majority of these studies showed that infection control measures such as favourable staffing policies, training, screening, social distancing, isolation and use of PPE significantly improved residents and staff related outcomes. More studies exploring the effects infection prevention and control practices in long term care facilities are required.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.05.21265759v1" target="_blank">Preventing the Transmission of COVID-19 in Older Adults Aged 60 Years and Above Living in Long-Term Care: Rapid Review Update</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>BREATHE: Virtual Self-management for Long COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: BREATHE<br/><b>Sponsor</b>:  <br/>
University of Calgary<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>the Safety and Efficacy of Meplazumab in Patients With COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Meplazumab for Injection;   Drug: Sterile normal saline (0.9%)<br/><b>Sponsor</b>:   Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Health Information Technology for COVID-19 Testing in Schools (SCALE-UP Counts)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Text Messaging (TM);   Behavioral: Text Messaging + Health Navigation (TM+HN)<br/><b>Sponsors</b>:   University of Utah;   Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)<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>Hypertonic Saline Nasal Irrigation and Gargling (HSNIG) for Suspected COVID-19 in Pakistan</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: Hypertonic Saline Nasal Irrigation and Gargles (HSNIG)<br/><b>Sponsors</b>:   The Allergy and Asthma Institute, Pakistan;   University of Edinburgh<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>Clinical Validation of Breath Analyser Tests for Diagnosis of COVID-19.</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Diagnostic Test: Breath Sample analysis<br/><b>Sponsor</b>:   Tera Group<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>Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With EV71 Vaccine (Vero Cell)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Experimental Group<br/><b>Sponsor</b>:  <br/>
Sinovac Biotech Co., Ltd<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate Safety &amp; Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: SARS-CoV-2 DNA Vaccine;   Biological: Matching placebo<br/><b>Sponsors</b>:   The University of Hong Kong;   Immuno Cure 3 Limited<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV2 Infection<br/><b>Interventions</b>:   Biological: Ad5-triCoV/Mac;   Biological: ChAd-triCoV/Mac<br/><b>Sponsors</b>:   McMaster University;   Canadian Institutes of Health Research (CIHR)<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>Homeopathic Treatment of Post-acute COVID-19 Syndrome</strong> - <b>Condition</b>:   Post-acute Covid-19 Syndrome<br/><b>Interventions</b>:   Drug: Homeopathic Medication;   Other: Placebo<br/><b>Sponsors</b>:   Southwest College of Naturopathic Medicine;   Samueli Institute for Information Biology<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>Effect of PBM on Functional Capacity and Fatigability in Post Covid-19 Elderly</strong> - <b>Condition</b>:   Post Covid-19 Elderly<br/><b>Interventions</b>:   Radiation: photobiomodulation;   Other: placebo intervention by photobiomodulation device<br/><b>Sponsor</b>:   Cairo University<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Vaccine (IN-B009) in Healthy Adults (COVID-19)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: IN-B009 (Low-dose);   Biological: IN-B009 (High- dose)<br/><b>Sponsor</b>:   HK inno.N Corporation<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>Effectiveness of Interactive Voice Response for COVID-19 Vaccination Training in the Democratic Republic of the Congo</strong> - <b>Conditions</b>:   COVID-19 Vaccine Knowledge;   COVID-19 Vaccine Beliefs and Behaviors<br/><b>Interventions</b>:   Behavioral: COVID-19 Vaccine IVR Training;   Behavioral: Control Condition<br/><b>Sponsors</b>:  <br/>
Stanford University;   Viamo<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>Lot-to-lot Consistency of an Inactivated SARS-CoV-2 Vaccine Between Different Workshops in Healthy Children Aged 3-17 Years</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 2 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 3 of the workshop 2;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 2 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 3 of the workshop 3;   Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell) Lot 1 of the workshop 1<br/><b>Sponsor</b>:   Sinovac 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>The Potential Use of Nebulized Hydroxychloroquine for the Treatment of COVID-19</strong> - <b>Condition</b>:   2019 Novel Coronavirus<br/><b>Interventions</b>:   Drug: HCQ01;   Other: standard of care (SOC) for COVID-19<br/><b>Sponsors</b>:   Ministry of Health Jordan;   King Hussein Cancer Center;   ACDIMA Biocenter;   Amman Pharmaceutical Industries;   Sana Pharmaceutical Industry<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>Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01) Booster Study</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Interventions</b>:   Biological: Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01);   Biological: Blank Preparation of Recombinant SARS-CoV-2 Fusion Protein Vaccine (V-01)<br/><b>Sponsor</b>:   Livzon Pharmaceutical Group Inc.<br/><b>Not yet 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>Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2</strong> - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented in human history. As a major structural protein, nucleocapsid protein (NPro) is critical to the replication of SARS-CoV-2. In this work, 17 NPro-targeting phenanthridine derivatives were rationally designed and synthesized, based on the crystal structure of NPro. Most of these compounds can interact with SARS-CoV-2 NPro tightly and inhibit the replication of SARS-CoV-2 in vitro….</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>Probiotic supplementation: A prospective approach in the treatment of COVID-19</strong> - Background: Despite strategies based on social distancing, the coronavirus disease 2019 (COVID-19) expands globally, and so far, many attempts have been made to achieve effective treatment for patients with COVID-19. This disease infects the lower respiratory tract and may lead to severe acute respiratory syndrome coronavirus (SARS-CoV). COVID-19 also can cause gastrointestinal infections. Therefore, COVID-19 patients with gastrointestinal symptoms are more likely to be complicated by SARS-CoV….</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>IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19</strong> - No abstract</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>ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics</strong> - The COVID-19 pandemic that began in late 2019 continues with new challenges arising due to antigenic drift as well as individuals who cannot or choose not to take the vaccine. There is therefore an urgent need for additional therapies that complement vaccines and approved therapies such as antibodies in the fight to end or slow down the pandemic. SARS- CoV-2 initiates invasion of the human target cell through direct contact between the receptor-binding domain of its Spike protein and its cellular…</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-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection</strong> - BACKGROUND: The duration of immunity in SARS-CoV-2 infected people remains unclear. Neutralizing antibody responses are the best available correlate of protection against re-infection. Recent studies estimated that the correlate of 50% protection from re-infection was 20% of the mean convalescent neutralizing antibody titre.</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>Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium</strong> - Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of…</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>Measurement of serum ACE status may potentially improve the diagnosis of SARS-CoV-2 infection</strong> - The severity of SARS-CoV-2 infection is associated with underlying cardiovascular or pulmonary pathological conditions. The fatality rate of this typical pneumonia has superseded the two previous coronavirus epidemics combined. Thus far, comprehensive diagnosis of SARS-CoV-2 remains essential for effective screening, detection, and disease monitoring. This allows employment of different life-saving interventions to lower the spread and mortality, whilst the development of labelled therapeutics…</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 Hydrogen: A Promising Adjunctive Strategy for the Treatment of the COVID-19</strong> - Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has no specific and effective treatment. The pathophysiological process of the COVID-19 is an excessive inflammatory response after an organism infects with a virus. Inflammatory storms play an important role in the development of the COVID-19. A large number of studies have confirmed that hydrogen has a therapeutic effect on many diseases via…</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>Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays</strong> - SARS-CoV-2 main protease (M^(pro)) is one of the most extensively exploited drug targets for COVID-19. Structurally disparate compounds have been reported as M^(pro) inhibitors, raising the question of their target specificity. To elucidate the target specificity and the cellular target engagement of the claimed M^(pro) inhibitors, we systematically characterize their mechanism of action using the cell-free FRET assay, the thermal shift-binding assay, the cell lysate Protease-Glo luciferase…</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>Epidemiological and Virological Surveillance of Seasonal Influenza Viruses - China, 2020-2021</strong> - CONCLUSIONS: Influenza activity has gradually increased in the mainland of China in 2021, although the intensity of activity is still lower than before the COVID-19 pandemic. The diversity of circulating influenza types/subtypes decreased, with the vast majority being B/Victoria lineage viruses. The surveillance data from this study suggest that we should strengthen influenza surveillance during the upcoming traditional influenza season. It also provided evidence for vaccine recommendations 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>In silico study of potential anti-SARS cell entry phytoligands from Phlomis aurea: a promising avenue for prophylaxis</strong> - Aim: The severity of COVID-19 has raised a great public health concern evoking an urgency for developing multitargeted therapeutics. Phlomis species was ethno-pharmacologically practiced for respiratory ailments. Materials &amp; methods: An array of 15 phytoligands previously isolated from Phlomis aurea were subjected to molecular docking to explore their potential SARS-CoV-Spike-angiotensin-converting enzyme 2 complex inhibition, that is essential for virus entry to host cell. Results: Acteoside…</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>Complex Pathophysiological Mechanisms and the Propose of the Three-Dimensional Schedule For Future COVID-19 Treatment</strong> - At present, the global COVID-19 epidemic is still in a state of anxiety, and increasing the cure rate of critically ill patients is an important means to defeat the virus. From an immune perspective, ARDS driven by an inflammatory storm is still the direct cause of death in severe COVID-19 patients. Although some experience has been gained in the treatment of COVID-19, and intensive COVID-19 vaccination has been carried out recently, it is still effective to save lives to develop more effective…</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>Non-Randomized Trial of Dornase Alfa for Acute Respiratory Distress Syndrome Secondary to Covid-19</strong> - CONCLUSION: Treatment with dornase alfa was associated with improved oxygenation and decreased DNA : MPO complexes in BALF. The positive effects, however, were limited to the time of drug delivery. These data suggest that degradation of extracellular DNA associated with NETs or other structures by inhaled dornase alfa can be beneficial. We propose a more extensive clinical trial is warranted.</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 coupled dynamics of information dissemination and SEIR-based epidemic spreading in multiplex networks</strong> - The outbreak of coronavirus disease 2019 (COVID-19) threatens the health and safety of all humanity. This disease has a prominent feature: the presymptomatic and asymptomatic viral carriers can spread the disease. It is crucial to estimate the impact of this undetected transmission on epidemic outbreaks. Currently, disease-related information has been widely disseminated by the mass media. To investigate the impact of both individuals and mass media information dissemination on the epidemic…</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>Design of New Bis-triazolyl Structure for Identification of Inhibitory Activity on COVID-19 Main Protease by Molecular Docking Approach</strong> - In the rapidly growing COVID-19 pandemic, designing of new drugs and evaluating their inhibitory action against main targets of corona virus could be an effective strategy to accelerate the drug discovery process and their efficacy towards corona virus disease. Herein, we design new bis-triazolyl probe for an investigation of inhibitory activity towards COVID-19 main protease by Molecular docking approach. The formulated compound has been thoroughly characterized by elemental analysis, NMR (¹H…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-SARS-CoV-2 antibodies and uses thereof I</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU339290405">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-SARS-CoV-2 antibodies and uses thereof II</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU339290406">link</a></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>휴대용 자화 육각수물 발생기</strong> - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.</p></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -&gt; 통증 -&gt; 극심한 통증 -&gt; 석회화, 섬유화, 암 까지 발병 한다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR338655754">link</a></p>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>휴대용 자화 육각수물 발생기</strong> - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -&gt; 통증 -&gt; 극심한 통증 -&gt; 석회화, 섬유화, 암 까지 발병 한다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR338650904">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>用于检测新冠病毒的配对抗体及其应用</strong> - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN339127990">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒</strong> - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN338723529">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>基于决策树模型与逻辑回归模型组合的感染筛查方法</strong> - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN339127711">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>病毒中和抗体与非中和抗体联合检测方法、检测卡及应用</strong> - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN338613501">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法</strong> - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示，其检测方法为：采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR，对PCR产物进行变性退火后，加入T7EI内切酶孵育，再进行PCR扩增，并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN339334235">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>多肽及其在新型冠状病毒检测中的应用</strong> - 本发明涉及生物医学领域，具体而言，涉及一种多肽及其在新型冠状病毒检测中的应用。所述多肽包括如下部分：S——Linker——N——avi‑tag。通过经过优化的刚性linker序列把S蛋白和N蛋白串联起来，使得这两个蛋白即具备相对独立的空间构象，又增加了许多优势表位，很大程度上提高了灵敏度和信号值；此外，融合蛋白引入Avi‑tag，使得重组蛋白可以通过固定的位点被固相化，降低包被过程所带来的空间位阻的影响。由此，该多肽能够达到很高的灵敏度和特异性，并且不易发生漏检。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN339334229">link</a></p></li>
</ul>
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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>The Trial of Kyle Rittenhouse Begins with Gruesome Videos and a Plea for Fact-Finding</strong> - The rifle-wielding teen-ager killed two men and grievously wounded a third during racial-justice protests in Kenosha, Wisconsin. - <a href="https://www.newyorker.com/news/news-desk/the-trial-of-kyle-rittenhouse-begins-with-gruesome-videos-and-a-plea-%20for-fact-finding">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Running Out of Time at the U.N. Climate Conference</strong> - To really appreciate America’s fecklessness, you have to go back to the meeting that preceded all the bad COPs—the so- called Earth Summit, in 1992. - <a href="https://www.newyorker.com/magazine/2021/11/15/running-out-of-time-at-the-un-climate-conference-cop26">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is This the Worst Place to Be Poor and Charged with a Federal Crime?</strong> - The Southern District of Georgia does remarkably little to provide for indigent defendants. - <a href="https://www.newyorker.com/news/us-journal/is-this-the-worst-place-to-be-poor-and-charged-with-a-federal-crime">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>“Uppercase Print,” Reviewed: The Terrifying Absurdities of the Surveillance State</strong> - The pursuit and persecution of a young freethinker are revealed by way of the archives of the Romanian secret police. - <a href="https://www.newyorker.com/culture/the-front-row/uppercase-print-reviewed-the-terrifying-absurdities-of-the-%20surveillance-state">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Splendid Uncoolness of “Sex, Love &amp; Goop”</strong> - Gwyneth Paltrow’s new Netflix series, which follows couples who are struggling with sexual dysfunction, is unexpectedly real, and genuinely moving. - <a href="https://www.newyorker.com/culture/on-television/the-splendid-uncoolness-of-sex-love-and-goop">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Why the US nursing crisis is getting worse</strong> -
<figure>
<img alt="A nurse leaning over a gurney in a hospital hallway." src="https://cdn.vox-
cdn.com/thumbor/TbEOMkNPBjUX02aBsZY_MhbVs_s=/0x0:4631x3473/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70111676/GettyImages_1334895267.0.jpg"/>
<figcaption>
An emergency room nurse tends to a patient at Houston Methodist The Woodlands Hospital in August. | Brandon Bell/Getty Images
</figcaption></figure></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Burnout, vaccine hesitancy, and plum traveling gigs are making it harder for hospitals to hire the nurses they need.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8Fz0A9">
Covid-19 may no longer be surging widely across the United States, but America’s hospitals are still experiencing <a href="https://www.vox.com/2020/3/26/21192191/coronavirus-us-new-york-hospitals-
doctors-nurses">a staffing crisis</a> that is putting critical care for patients in jeopardy.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U1xeGy">
Hospitals all over the country are struggling, especially those in lower-population areas. A new survey of rural hospitals from the Chartis Group, provided to Vox in advance of publication, reveals how deep the problem runs. Nearly 99 percent of rural hospitals surveyed said they were experiencing a staffing shortage; 96 percent of them said they were having the most difficulty finding nurses.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="aWgjIf">
Almost half of the hospitals in the survey said staffing problems had prevented them from accepting new patients in the past 60 days. One in four hospitals said that a lack of nurses had forced them to suspend certain services, including, according to Michael Topchik, national leader of the Chartis Center for Rural Health: newborn delivery, chemotherapy, and colonoscopies. Another one in five said they were considering it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Yu2wa8">
“The pandemic has maxed out these hospitals,” Topchik told me, “which means they are unable to provide services vital to the community.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G7FzLZ">
Hospitals have gotten a lot better at handling Covid-19 surges. They have more weapons at their disposal — antiviral drugs and monoclonal antibodies — and better understand which techniques are effective at preventing the disease from getting worse. Roberta Schwartz, chief innovation officer at Houston Methodist Hospital, told me while her hospital started shutting down services immediately during the first pandemic wave, they were able to absorb more than 700 Covid-19 patients during the most recent summer wave without compromising their other operations.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="img8L4">
But as flu season looms and cold weather threatens <a href="https://www.vox.com/22712737/covid-19-cases-deaths-2021-winter-wave">another Covid-19 surge</a>, two trends that would fill up hospital beds again, the staffing crisis isn’t easing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qikDEM">
According to <a href="https://www.aha.org/system/files/media/file/2021/09/AHA-KH-Ebook-Financial-Effects-of-COVID-Outlook-9-21-21.pdf">a September study</a> commissioned by the American Hospital Association, the average cost of labor expenses for each discharged patient has grown by 14 percent in 2021 — even as the number of full-time employees has dropped by 4 percent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6LCBte">
Hospitals, both rural and urban, are feeling the squeeze. Their workforces are burned out. Some staff members are still reluctant to take the Covid-19 vaccine, even as some facilities start to impose mandates. And they are facing competition from traveling nursing companies that are offering better and better benefits to lure nurses away from permanent full-time jobs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GvFAFz">
With some services being shut down, patients in underserved areas may have to travel hours to larger facilities — hospitals that are experiencing their own staffing challenges and often run at near 100 percent capacity already.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TTGha1">
“There are nursing shortages nationwide, which means many hospitals can’t staff all their beds,” Karen Joynt Maddox, assistant professor of medicine at Washington University in St. Louis, told me. “The big referral centers … chronically operate at or above capacity, so any bumps in volume put additional strain on the system.”
</p>
<h3 id="nyVwSQ">
Why many American hospitals have a staffing crisis
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eXxiyx">
Burnout among the health care workforce remains acute 20 months into the pandemic. About half of medical workers <a href="https://www.ama-assn.org/practice-management/physician-health/half-health-
workers-report-burnout-amid-covid-19">reported</a> feeling burnout during 2020, according to a study from the American Medical Association. Almost half of ICU nurses <a href="https://www.cnbc.com/2021/05/31/covid-is-driving-an-exodus-
among-health-care-workers.html">said</a> in another survey earlier this year that they were considering leaving the profession.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pZ2dIV">
Nine in 10 rural hospital leaders said their concerns about staff burnout had increased over the course of 2021. In other words, the staffing crisis is getting worse, not better.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xuNWQc">
“The workforce is burnt out. The workforce is leaving,” said Beth Feldpush, senior vice president at America’s Essential Hospitals. “The human capacity is more of an issue than physical capacity.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="c38PgK">
The average age of a nurse in the United States <a href="https://www.aacnnursing.org/news-information/fact-sheets/nursing-shortage">is 50</a>; some of those workers decided to retire early rather than push on through the most difficult working conditions of their career.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AqmgPu">
”This is mental anguish,” Schwartz said. “We have an aging workforce. Some of them might have worked another year or two, but with a pandemic, nope.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MtlPGs">
Vaccine hesitancy could end up making this difficult situation worse. Only about 25 percent of the rural hospitals surveyed by Chartis are instituting a vaccine mandate (some of which have not yet taken effect), but, among those, about one in four expect a significant percentage of their staff — 5 percent or more — not to comply with the mandate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FkZEDp">
For some of them, that would mean an automatic termination and another job opening that the hospital needs to fill.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sWn83f">
But that’s when the third problem squeezing hospitals complicates things: It’s getting harder to hire and retain nurses because many of them can earn a higher salary working as a traveling nurse, hired for a temporary period by a hospital facing a staffing crunch — and willing to pay the rising prices commanded by those workers.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AVth7U">
As NBC News <a href="https://www.nbcnews.com/business/business-news/rural-hospitals-losing-hundreds-staff-high-paid-traveling-
nurse-jobs-n1279199">reported</a> last month, permanent nurses at rural hospitals make on average about $1,200 per week. These days, some travel nursing firms are offering their workers more than $5,000 per week.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="56yEOF">
“This has been a huge shift for many folks,” Mary Beth Kingston, chief nursing officer at a health system serving Illinois and Wisconsin, said in a panel discussion on the staffing crisis hosted by the AHA. “People are leaving their place of employment because this is a chance to increase their salary in a major way.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="1VwptB">
Traveling nurses have played an important role in the pandemic. Hospital leaders say that, in essence, they needed to increase their workforce by 20 percent to handle Covid-19 surges, and the travel firms helped to supply that excess staffing. In the Chartis survey, more than half of the hospitals said their use of travel nurses had increased “significantly” during the pandemic, even though most of them used those workers only “rarely” prior to the current crisis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eXm0N1">
But that increase in demand has allowed travel nursing firms to offer those higher salaries and more generous benefits, which can lure nurses away from permanent employment. Hospital leaders describe a situation in which full-time nurses and traveling nurses are sitting side by side at a nursing station, with the latter telling the former how much money they are making in this new role.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4rzKUP">
In the Chartis survey of rural health systems, hospital leaders named “more financially lucrative opportunities” as the No. 1 reason for their nurses leaving, followed by pandemic burnout and retirement.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7DPFAW">
There isn’t an easy solution to the nursing crisis. The worrisome trends actually predate the pandemic; in 2018, <a href="https://pubmed.ncbi.nlm.nih.gov/29183169/">a study in the <em>American Journal of Medical Quality</em></a> projected more nursing shortages to appear from 2016 to 2030, concentrated particularly in the South and the West.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="77HBm1">
The aging workforce is part of the problem, and not enough students are enrolling in nursing school to offset those losses, according to <a href="https://www.aacnnursing.org/news-
information/fact-sheets/nursing-shortage">the American Association of Colleges of Nursing</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iHu7F3">
There are some provisions in Democrats’ pending <a href="https://www.vox.com/2021/10/28/22748554/biden-budget-build-back-
better-democrats-child-care-taxes">Build Back Better legislation</a> to support the health care workforce by forgiving loans for medical education, incentivizing more doctors and nurses to practice in underserved areas, and providing more funding to hospitals that run graduate education programs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZCRuyN">
But hospitals don’t believe it will be enough. They are preparing for a world in which Covid-19 is endemic, a regular part of the medical calendar — and their staffs are still overstretched.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mo2DhV">
“They are concerned with the overlap of a winter surge and more flu circulating,” Feldpush said. “They do not expect to see any alleviation in staffing shortages or costs.”
</p>
<ul>
<li><strong>The paradox of American freedom</strong> -
<figure>
<img alt="" src="https://cdn.vox-
cdn.com/thumbor/XDsee8lWsoNHW1z3tzdKNoSaffY=/46x0:574x396/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70111566/gettyimages_671636508_594x594.0.jpg"/>
<figcaption>
Author Sebastian Junger at a book signing during the Palm Beach Book Festival in 2017 in Palm Beach, Florida. | Mychal Watts/Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“The idea that we can enjoy the benefits of society while owing nothing in return is literally infantile. Only children owe nothing.” —Sebastian Junger
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NWNB9y">
America is uniquely obsessed with “freedom.” You can see it in our politics. You can hear it in our discourse. But we’re also, strangely, a country full of fortunate people who are constantly fretting about their lack of freedom.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DG2j5u">
Why is that?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yMsrnn">
There isn’t a single answer to a question like this, or even a good one, but a recent book by Sebastian Junger called <a href="https://www.simonandschuster.com/books/Freedom/Sebastian-
Junger/9781982153410"><em>Freedom</em></a> searches for one anyway.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VpD61G">
The book orbits around a long walk Junger and a few friends took several years ago. They hiked hundreds of miles of East Coast railroad lines, carrying everything they needed on their backs and sleeping wherever they could. Everyone involved had experienced combat (Junger’s a longtime war reporter who embedded with an infantry unit in Afghanistan while shooting the documentaries <em>Restrepo</em> and <em>Korengal</em>), and they were all looking for ways to process that trauma. Junger later documented the trip in a 2014 film, <a href="https://www.hbo.com/documentaries/the-last-patrol"><em>The Last Patrol</em></a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PTmZKj">
Junger’s book weaves the account of the hike with various stories from history — everything from labor strikes to women’s resistance movements to bloody battles with Apache raiders — and in the end, it all comes back to a meditation on human freedom and all the ways we seek and defend it, especially in a country as divided and unequal as America.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TnBYWp">
I reached out to Junger for this week’s episode of <a href="https://podcasts.apple.com/us/podcast/vox-conversations/id1081584611"><em>Vox Conversations</em></a> to talk about what he learned out there on the railroad lines. Like the book, we cover a lot of ground — the meaning of personal freedom, what we owe other people, and why these things are bound up with each other. We also talk about becoming parents, and how that experience changed the way we thought about freedom and responsibility in our own lives.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wQKDPy">
Below is an excerpt from our conversation, edited for length and clarity. As always, there’s much more in the full podcast, so subscribe to <em>Vox Conversations</em> on <a href="https://apps.apple.com/us/app/vox-
conversations/id1215557536">Apple Podcasts</a>, <a href="https://podcasts.google.com/search/vox%20conversations">Google Podcasts</a>, <a href="https://open.spotify.com/show/6NOJ6IkTb2GWMj1RpmtnxP">Spotify</a>, <a href="https://www.stitcher.com/show/vox-conversations">Stitcher</a>, or wherever you listen to podcasts.
</p>
<div id="hRXax5">
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="uUv3Hy">
</p>
<hr class="p-entry-hr" id="mSoTOi"/>
<h4 id="Tli9C2">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YpmQzM">
I know your goal in this book and elsewhere isn’t to weight conservative notions of freedom against liberal notions of freedom. I understand, as a writer, why you want to avoid that. But I do think we can address this in a nonpolitical way. I think there’s a really crucial tension that we have to touch. The tension is this paradoxical relationship between freedom and obligation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OD4w0y">
You write: “For most of human history, freedom had to be at least suffered for if not died for. That raised its value to something almost sacred. In modern democracies, however, an ethos of public sacrifice is rarely needed because freedom and survival are more or less guaranteed.” Shortly after that, you say, “The idea that we can enjoy the benefits of society while owing nothing in return is literally infantile. Only children owe nothing.” Why did you think it was so important to make that point?
</p>
<h4 id="ONAwkE">
Sebastian Junger
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6PmTbu">
Because I feel like there’s a strange idea in American society right now, and I think it’s because we’re not under any direct threat, and because we’re not under a direct outside threat, it’s possible to imagine our own government as a threat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AqDZ7p">
There’s this idea that’s sort of arisen, that you can live your life without ever being told in any way what you can and can’t do. It’s complete nonsense. Humans have never lived like that. Even people that think that, they, like good little doobies, drive on the right-hand side of the road, and they know they can’t drive on the left-hand side of the road. At a red light, they stop, because they know if they don’t, they might kill somebody. If they don’t care about that, they might kill themselves. If they don’t do that, they might get a ticket. Everyone is very carefully obeying all these rules, but some people think that the government actually doesn’t have a right to regulate and to enforce and to create strategies that benefit the greater good.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TwVwK0">
The great thing about a democracy is if you think that the government is overreaching — and the government’s great at overreaching … I mean, it’s not like it doesn’t do that. I get it. — But if you think that that’s the case, you have recourse. You can go to the courts or you can vote the bastards out. You can go to the polling booth.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="FBh95f">
But the one thing you can’t do in a democracy is use violence to change an outcome. As soon as you use violence to change that outcome, you’re actually creating the opposite of a democracy. You are on the road to fascism.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P6aNYQ">
The one exception that I actually think I might want to insist on is that there is a history in this country of protest movements that have sometimes turned violent. These movements, they’re groups of people insisting on their basic rights. The labor movement of 100 years ago, the civil rights movement, these protests sometimes were violent, but sometimes it takes violence to get the attention of an immoral government that’s not interested in acting in a free and fair way.
</p>
<div class="c-float-right">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/AY2yPQiEpDCpQWTMU8TdnsRPWgA=/800x0/filters:no_upscale()/cdn.vox-
cdn.com/uploads/chorus_asset/file/22985706/Freedom_cropped.jpg"/>
</figure>
</div>
<h4 id="07kvEn">
Sean Illing
</h4></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mGxGtR">
I guess I’ve always thought of freedom as an activity, not a condition. There’s a tendency, especially in our culture, to think of freedom as “freedom from.” To be free is to not be tyrannized by some outside power, and that’s fine, but it’s incomplete. You can be free of tyranny, but if you’re destitute, if you’re abandoned, if you don’t have agency because your most immediate needs aren’t being met, you’re not free in any meaningful sense. I say all that because it’s why I think we’re obliged to care about the condition of other people if we believe in freedom as a universal right.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K37N8w">
Ok, that’s the end of my rant, I promise.
</p>
<h4 id="mJBwU0">
Sebastian Junger
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Q4R4pf">
No, you’re absolutely right. I didn’t go into these contemporary issues in America in my book, because the issue of freedom, it doesn’t change that much over the ages. I was trying to write a book about what allows humans to maintain their autonomy in the face of a more powerful group. Throughout history, very disempowered and often very mobile groups were able to evade or outfight larger dominant groups that wanted to oppress them. The extraordinary thing about humans, unlike any other mammal, is that a smaller individual or a smaller group can actually outfight a larger one. I wanted to understand how that worked. How do we maintain our autonomy in the face of a more powerful group?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eD2EvK">
Sometimes that more powerful group is your own government. The labor movement 100 years ago, there were totally disenfranchised foreign workers working in the textile mills in Massachusetts, and they faced down the National Guard and the corporations and the government, and they got the laws changed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8CFKOJ">
One of the ways they did that was incorporating women into their ranks. Once you put women on the front line of a protest, the cops often do not dare use mass violence. They’re way more willing to do that against men. As one frustrated policeman said in Lawrence, Massachusetts, in 1912, he said, “One good cop can handle 10 men. But it takes 10 cops to handle one woman.” That changed the tactical dynamic on the streets that allowed those protests to succeed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="l1j1JP">
But let me just add to that: What I was saying about freedom from an enemy or freedom from oppression within your own society, those are the classic conservative and liberal concerns. Conservatives are concerned with an outside threat, and liberals, they’re much less worried about outsiders. In fact, they’re often quite open to them culturally. What they’re worried about is internal unfairness. If you take those two concerns and you marry them together in one society, you have a society that can both protect itself and run a fairly equitable system. Either one by itself wouldn’t work very well.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="TX8xWS">
There’s actually a lot of data. There’s a wonderful book, I’m looking at it right now on my bookshelf, <a href="https://www.amazon.com/Our-Political-Nature-Evolutionary-Origins/dp/1616148233"><em>Our Political Nature</em></a>, by Avi Tuschman. Maybe you know it. He collects all the studies that show that our political predilections are partly hereditary. About 50 percent of the variance of our political opinion comes from our genetics, it’s inherited. That to me means that a basically conservative or liberal viewpoint had to have been adaptive in our evolutionary past. When they’re in roughly equal measure within a society, you’re at this sort of sweet spot where you can defend yourself and you’re running a society that’s fair and therefore stable.
</p>
<h4 id="xeqZn0">
Sean Illing
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LdRRXq">
This theme of the importance of groups, of community, of solidarity, was at the heart of your last book, <a href="https://www.amazon.com/Tribe-Homecoming-Belonging-Sebastian-Junger/dp/144344958X"><em>Tribe</em></a>, which was about combat soldiers and the transition back to “normal” life. Soldiers come home and that intensity is gone, the sense of immediate and overwhelming purpose is gone. Even the title of your documentary about the hike, <a href="https://www.hbo.com/documentaries/the-last-patrol"><em>The Last Patrol</em></a>, gestures at this longing to recapture the emotional intensity of war. Was that something that was clear to you from the outset, or did this part of it become clear once you were out there on the road?
</p>
<h4 id="eWG4Ht">
Sebastian Junger
</h4>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SxsuDu">
No, I knew how it would work out there. I mean, listen, the interesting thing about having to find water is that it creates the proper value for water. If you can just get water by turning on a faucet, it doesn’t have any value. If you have to go looking for it, suddenly water has value. Suddenly being warm has value, being safe has value.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cNL2yi">
I know that the only way to survive and function effectively in a raw environment like that, particularly the semi- industrial one that we were in, which had all kinds of social threats as well, it was to be in a small group that was quite loyal to itself, and where people were willing to do very hard things to make sure everyone was okay.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mpK5hG">
Since I wrote <em>Tribe</em>, I had this thought: “How do you define ‘tribe’?” It’s one of those elusive words, like freedom. You try to define it, and then it sort of squirts to the side and you’re like, “No, that’s not it either.” You can’t quite pin it down. And I was like, “This is ‘tribe.’ I will make sure that whatever happens to you will happen to me too. We’re going through this together.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cSRVw1">
This small group that I walked with along the railroad lines, that’s very much how we were. At one point we had a 110-degree heat index, and one guy really started falling out. We were all carrying 50, 60 pounds on our back, even 70 sometimes if we were loaded up with food. We had to get where we were going. One of us said to the guy who was falling out, “Listen, man, I’ll take your pack.” He put 60 pounds on top of 60 pounds, and strapped it on and walked that way until the guy who was having trouble felt a little better and took his pack back. That’s “what happens to you, happens to me.” We’re in this together.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BtLJBS">
What I would say about <em>Tribe</em>, in the third chapter, I talk about soldiers because that’s the most immediate current topic that the public is familiar with. But actually, in the beginning of the book, I’m talking about how community works, and why the tribal community has always been so appealing.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U5IIiP">
Along the American frontier, there are many, many cases of young people, young Americans, absconding to the Natives. Running off to join the Natives. As Benjamin Franklin himself lamented, there were no examples of Native peoples going in the other direction. This is a white Christian society that thinks it’s superior, but people were sort of voting with their feet, as it were, and all of the migration was towards the tribal. You didn’t have the church breathing down your neck, you weren’t behind the plow 12 hours a day plowing up some rocky field. You didn’t have these awful sexual and social mores of colonial society.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4so8sE">
Interestingly, all the way on the other side of the world, the Great Wall of China has always been thought of as having been built to keep out that sort of barbarian horde, the nomads on the steppe that invaded mainland China, invaded the Chinese empire and didn’t destroy everything. Obviously that was an element, but what many historians now think is that the wall was also there to keep people, impoverished Chinese farmers, from fleeing to nomadic society.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="GCYhmW">
Nomadic society is always more equitable, more egalitarian than sedentary, agricultural society, where you can accumulate wealth and pass it on through generations. The beginnings of class structure start with agriculture. What the early Chinese were trying to do is keep their own people from absconding to the native peoples across the wall as well.
</p>
<hr class="p-entry-hr" id="EUBHTt"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="VR7RjK">
<em>To hear the rest of the conversation, </em><a href="https://open.spotify.com/episode/2VlEBYdYRhV6gwzGa6GJHu?si=IiN2MLctQBGe6lW2ORbNag"><em>click here</em></a><em>, and be sure to subscribe to </em>Vox Conversations<em> on </em><a href="https://apps.apple.com/us/app/vox-
conversations/id1215557536"><em>Apple Podcasts</em></a><em>, </em><a href="https://podcasts.google.com/search/vox%20conversations"><em>Google Podcasts</em></a><em>, </em><a href="https://open.spotify.com/show/6NOJ6IkTb2GWMj1RpmtnxP"><em>Spotify</em></a><em>, </em><a href="https://www.stitcher.com/show/vox-conversations"><em>Stitcher</em></a><em>, or wherever you listen to podcasts.</em>
</p>
<ul>
<li><strong>People still can’t get enough of Princess Diana</strong> -
<figure>
<img alt="" src="https://cdn.vox-
cdn.com/thumbor/4aYeVdBqJ4KKjt5Hrw36c2qYdjY=/0x0:768x576/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70111448/2._SPENCER_Second_Look._Kristen_Stewart_as_Princess_Diana._Photo_by_Pablo_Larrai_n.0.jpeg"/>
<figcaption>
Kristen Stewart as Princess Diana in Spencer. | Neon
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
From Spencer to The Crown to Diana: The Musical, Princess Diana is all over our screens once more.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G3oviJ">
Time to go Diana-watching again. The People’s Princess is once again back on our screens, and one of the most beloved sports on both sides of the pond is back in season. All the classic iconography is there, again and again. The sapphire engagement ring, the black sheep sweater, the dashing blonde haircut; in Pablo Larraín’s <em>Spencer</em>, in <em>The Crown</em>, in <em>Diana: The Musical</em> (which is streaming on Netflix and soon to reopen on Broadway): there she is, there she is, there she is.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Yj7P9y">
As all of these Diana stories are happy to remind you, Princess Diana, who married Prince Charles in 1981 and divorced him in 1996, died in a car crash in 1997. You would be forgiven for wondering why, then, she seems to be suddenly inescapable 24 years later. Yet here she is, over and over again, on screen after screen, ducking her head and smiling shyly up at the camera lens, lovely and tragic and doomed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ohcHW3">
Something about Diana seems to strike us, just now, as perfect for revisitation. In <em>Spencer</em>, Diana is a gothic heroine, wandering around the queen’s moldering country seat in the lonely splendor of her white evening gown, palpably aware that she has been imprisoned by her own beauty. In <em>The Crown</em>, she’s part innocent naif, part calculating manipulator, roller skating through the palace with her headphones on. In <em>Diana: The Musical</em>, she’s a put-upon girlboss, striving for global celebrity and adoration in the face of obstacle after obstacle from the recalcitrant royal family. Always, she becomes a metaphor for femininity writ large: its glamours and seductions, the way it traps and limits with its queasily close embrace.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OG3zRT">
Here are three of the big reasons Princess Diana is so inescapable just now.
</p>
<h3 id="oljvUL">
Diana fits the classic cultural archetype of the virgin sacrifice
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2PKpWF">
From the very beginning of her fame, back when she was just Prince Charles’s girlfriend, Diana has been an object of fascination because she fits a particular cultural trope. She was one of those blondes who seems to be simultaneously very innocent and very sexy, and whose innocence works to render her sexiness nonthreatening: It’s safe to desire her, because she does not realize that she is desirable. (Marilyn Monroe and Britney Spears fit the same archetype.) “I have never seen such a strong charge of innocently provocative sex,” one of Diana’s wedding guests wrote in his diary the night of the wedding.
</p>
<aside id="1vkCF8">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oTC4fG">
I call this pop cultural trope <a href="https://www.vox.com/culture/21593569/princess-diana-explainer-crown-netflix-marilyn-monroe-
britney-spears-innocence">the virgin sacrifice</a>. The name fits first because we are usually fascinated by the virginity or lack thereof of the women who fit the trope, and second because we tend to devour these women alive at the merest hint that they might not be as innocent as they seem: that they might wield their charisma intentionally, as a weapon; that they might not be virgins after all. The contradiction seems to continually fuel both obsession and outrage, driving us to pant lasciviously after tabloid coverage. We seem to long to see the innocent virgin at the heights of her desirability, and at her most fallen and desperate.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yU3fSN">
Diana embodied this binary with considerable style within her lifetime, which is part of why she was one of the most discussed and photographed women in the world at the time. But to look at why she’s having another moment <em>right now</em>, we’ll have to look at two of today’s big cultural conversations.
</p>
<h3 id="D6EAYp">
We’re currently fascinated by looking back at wronged women
</h3></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tXnVpJ">
As a culture, <a href="https://www.vox.com/culture/22350286/2000s-pop-culture-misogyny-britney-spears-
janet-jackson-whitney-houston-monica-lewinsky">we are currently obsessed with looking back at the stories of the wronged women of the ’90s and the ’00s</a>. The revisitation is sometimes pegged to the premiere of <a href="https://www.vox.com/culture/22276585/framing-britney-spears-us-weekly-perez-hilton-daniel-ramos"><em>Framing Britney Spears</em></a>, the New York Times documentary that argued earlier this year that Spears was unfairly targeted by a predatory media, but it would be more accurate to say that <em>Framing Britney Spears</em> is the culmination of a longer, ongoing trend of looking backward.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QLw1Cd">
The popular podcast <a href="https://yourewrongabout.com/"><em>You’re Wrong About</em></a>, which began in 2018, built its name in part on debunking cultural myths about women like Anna Nicole Smith and Monica Lewinsky. <a href="https://www.vox.com/culture/2017/9/14/16301552/i-tonya-harding-kerrigan-review-tiff">Tonya Harding was the subject of an Oscar-winning film in 2017</a>, and <a href="https://www.nytimes.com/2019/01/30/arts/television/lorena-bobbitt-
documentary-jordan-peele.html">an acclaimed 2019 documentary revisited Lorena Bobbitt</a>. Hardly a month seems to go by these days <a href="https://www.gawker.com/media/the-cultural-revisionism-industry">without a cultural artifact informing us that we all got it badly wrong</a> when we made one particular woman the butt of a global joke 20 years ago.
</p>
<aside id="konl91">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O5w6K9">
Part of this reconsideration seems to come from how drastically the cultural norms around feminism and misogyny have shifted over the past few<strong> </strong>decades, especially after the tumultuous upheaval brought on by the Me Too movement in 2017 and 2018. We veered out of one decade where snickering over nonconsensual upskirt photos was a perfectly normal late-night comedy joke into another in which revenge porn has a name and a criminal sentence attached to it. It’s natural, in the wake of such a rapid shift, to want to look back with wide and blinking eyes: Wow. We really all said some things then that we never would today, didn’t we?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0lCuo4">
And as the baby boomers begin to age out of their long-held positions as cultural gatekeepers, millennials have begun to take their place. With that changing of the guard comes enough accumulated cultural power that those who grew up in the ’90s and ’00s can indulge in a preoccupation with the decades of their childhood, and with how retrograde they can appear in hindsight.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OAq70r">
“For me, it was kind of a rite of passage to look at stories that I remembered adults reporting on when I was a child and then seeing just how bad of a job they’ve done some of the time,” <a href="https://www.vox.com/culture/22350286/2000s-pop-culture-misogyny-britney-spears-janet-jackson-
whitney-houston-monica-lewinsky">Sarah Marshall, co-host of <em>You’re Wrong About</em>, told Vox earlier this year</a>. “We just abused women for sport in the media, and I feel like that’s generationally something important to look at. What was in the media and the bloodstream when you were a child? How were the adults who were in charge of the culture then maybe not doing as good a job as you would like to try and do now?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="G2MxcY">
Enter Diana, <a href="https://www.history.com/topics/british-history/princess-dianas-death#section_3">literally hounded to her death by a ravenous tabloid press</a>. The tragedy of Diana’s story makes her a perfect fit for our current moment of reexamination. But there’s an added wrinkle to Diana’s story that no one else has, one that makes her especially ripe for revisitation this year.
</p>
<h3 id="OuYYsj">
Meghan Markle is a walking, talking reminder of Diana’s legacy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6di0MJ">
One of the signs that Diana is having a moment is that the women’s retailer Anthropologie has what is clearly<strong> </strong>a full Diana-themed section on its website this fall, complete with a Diana-look-alike model. But interspersed among all the photographs of shaggy blonde pageboy haircuts and classic English riding boots, there are photos of another model whom Anthropologie seems to believe goes with Diana: a woman who bears a striking resemblance to Meghan Markle, the daughter-in-law Diana would never live to see.
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<figure class="e-image">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><img alt=" " src="https://cdn.vox-cdn.com/thumbor/JG-3be7duT4MoniVENjm6fZ_HCY=/800x0/filters:no_upscale()/cdn.vox-
cdn.com/uploads/chorus_asset/file/22988371/FB_BWulXEAc5x8F.jpeg"/> <cite>Anthropologie</cite></p>
<figcaption>
Anthropologie’s Diana section features a Meghan Markle look-alike model.
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</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tetdcV">
Meghan Markle, who knows her way around a publicity narrative as well as Diana did, <a href="https://www.vox.com/culture/22323456/harry-meghan-markle-diana-oprah-interview-cbs">has repeatedly aligned herself with Princess Diana</a> in the time since she and her husband Prince Harry left the royal family in 2020. In <a href="https://www.vox.com/culture/22323456/harry-meghan-markle-diana-oprah-interview-cbs">a much-discussed interview with Oprah this March</a>, Meghan and Harry explained that much like Diana, Meghan had faced intense mental health struggles upon joining the royal family.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2jZqEb">
“What I was seeing was history repeating itself,” Harry said, adding, “When I’m talking about history repeating itself, I’m talking about my mother. When you can see something happening in the same kind of way, anybody would ask for help.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KI2MO3">
The pair said they relied on the money Harry inherited from Diana to support themselves as they withdrew from the royal family, and Meghan compared their decision to talk to Oprah to <a href="https://www.bbc.com/news/explainers-57163815">Diana’s infamous choice</a> to go public about her discontent with her marriage to Prince Charles. Throughout the interview, Meghan wore a diamond bracelet that had belonged to Diana.
</p>
<aside id="diaT6D">
<div>
</div>
</aside>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="IzCqID">
Meghan and Harry offer a potent reminder of the power of the Diana story: the tale of a beautiful princess trapped within an unfeeling royal system, driven slowly toward despair, is a killer narrative arc in any decade. But they also offer a valuable new twist on the old tale.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qXn1wd">
Diana was caught in a loveless marriage, and Charles was both unable and unwilling to support her in the way she needed to be supported. But Meghan and Harry have made it clear that they are facing their own trials and tribulations together, as partners — so when Meghan needed to leave the royal family, Harry left with her.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="r8FQcw">
They’re offering the public a rare chance to redeem the memory of the virgin sacrifice whose life we destroyed. So while pop culture remains committed to constantly revisiting the details of what happened to Diana and why, Harry and Meghan offer us a chance to retell the Diana story yet again — this time with a happy ending at last.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0pEKST">
</p>
<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>Iron Age and Chancellor catch the eye</strong> - Iron Age and Chancellor caught the eye when the horses were exercised here on Tuesday (Nov. 9) morning.Sand track: 600m: Fassbinder (Zervan) 39. easy.</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>ICC Twenty20 World Cup | Hasan Ali, Fakhar Zaman big match players, will fire in semifinals, says Babar Azam</strong> - Pakistan, the only unbeaten team in the tournament, has played nothing like the unpredictable tag associated with them for years</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>India-Pak clash most viewed T20 international match: Star India</strong> - The match created history by clocking a record reach of 167 million viewers, says the event broadcaster</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>T20WC: X-factor loaded England face ever consistent New Zealand in first semifinal</strong> - The absence of Jason Roy, who suffered a calf injury against the Proteas, is a big blow to the team heading into the semifinals</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sanjay Bangar elevated as RCB’s head coach</strong> - Bangar comes with vast experience having served as the batting coach of the Indian men’s senior team for five years from</li>
</ul>
<ol start="2014" type="1">
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<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>COVID ex gratia: special cell created for registration</strong> - A special cell was set up at the District Medical and Health Office here for the registration of families next to those who succumbed to the COVID-19</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 | U.K. to add India’s Covaxin to approved list from November 22</strong> - The move follows the World Health Organisation’s Emergency Use Listing for Covaxin, which is the second most used formulation in India</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>GMC for looking at common challenges and forging tangible solutions to key issues: Navy Chief</strong> - Seas permit free flow of commerce and ideas, says Admiral Karambir Singh</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>Rafale scam trail ends at PM’s door, says Congress</strong> - Despite evidence since 2018, govt. has not initiated action against middleman Gupta, says Oppn</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>Shillong Sikhs seek agenda-based invitation from Government</strong> - Meghalaya Government wants to shift them out of a prime location to outskirts</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>Belarus migrants: Poland fears armed border escalation</strong> - The warning comes after hundreds of migrants tried to cut a fence to enter Poland illegally.</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>REvil: Day of reckoning for notorious cyber gang</strong> - A global police operation has dealt a major blow to one of the most prolific cyber gangs in history.</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 Mafia: ’Ndrangheta members convicted as Italy begins huge trial</strong> - More than 350 alleged mobsters will face court in the biggest mafia trial in decades.</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>NI 100: Michael Collins’ diaries donated to Irish state</strong> - The family of the Irish revolutionary leader lend five of his diaries to the National Archives.</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>Brexit: UK-EU trade deal could collapse over NI row, says Coveney</strong> - The UK is laying foundations to suspend parts of the NI Protocol, says the Irish foreign minister.</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>Crew Dragon lands safely, despite one parachute inflating slowly [Updated]</strong> - We’re going to miss Thomas Pesquet’s spicy memes from space. - <a href="https://arstechnica.com/?p=1811085">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What the physics of crowds can tell us about the tragic deaths at Astroworld</strong> - 8 people were killed and 25 were hospitalized in a crush during Travis Scott’s set - <a href="https://arstechnica.com/?p=1811035">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rodgers is wrong—NFL says league docs never talked to him about vaccine</strong> - Health org dropped Rodgers and State Farm cut ads after widely panned anti-vaccine rant. - <a href="https://arstechnica.com/?p=1811353">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A brief love letter to Xbox’s new colorful, cool-looking Forza gamepad</strong> - No new features, but it runs aesthetic circles around the competition. - <a href="https://arstechnica.com/?p=1811305">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hacking group says it has found encryption keys needed to unlock the PS5</strong> - Fail0verflow announcement suggests a private exploit to expose system’s secure kernel. - <a href="https://arstechnica.com/?p=1811284">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>Professor X asks a girl, “what is your mutant power?”</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Girl replies: “I can guess how many pulls to turn a ceiling fan off on the first try!”
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She points up and says: “3 pulls”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Professor X stands up and pulls 3 times. After the third pull the fan turns off.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Professor X: “Yeah thats cool and all, but not really a super power…”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Girl: “Yeah I was jut kidding, I can heal paraplegics”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Professor X, still standing: “Oh my god”
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/rep_phantom"> /u/rep_phantom </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/qq0sb0/professor_x_asks_a_girl_what_is_your_mutant_power/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/qq0sb0/professor_x_asks_a_girl_what_is_your_mutant_power/">[comments]</a></span></p></li>
<li><strong>3 brothers own a cow, which suddenly dies.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The cow being almost a part of their family and a major income source for the family, the 3 brothers become very heartbroken and decide to commit suicide in the river. So they approach the river and are almost about to jump in when a fairy comes out of the river.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Fairy: “If anyone of you is able to satisfy me sexually, I’ll bring the cow back from the dead.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Brother 1 takes her into the jungle and comes back with her after 1 hour. The fairy says she’s not impressed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Brother 2 takes her into the jungle and comes back with her after 3 hours. The fairy says she’s still not impressed.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Now brother 3 takes her into the jungle and comes back with her the next day after almost 24 hours.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The fairy clearly exhausted and almost dead, says to the other 2 brothers, “I’m giving your cow back. Your brother is just insane. I haven’t seen such raw sexual stamina before.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Well”, one of the brother replies, “How do you think the cow died?”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/punekar-reddit"> /u/punekar-reddit </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/qpvd1y/3_brothers_own_a_cow_which_suddenly_dies/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/qpvd1y/3_brothers_own_a_cow_which_suddenly_dies/">[comments]</a></span></p></li>
<li><strong>What’s purple and doesn’t fit anymore?</strong> - <!-- SC_OFF -->
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A dead epileptic
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MartynAndJasper"> /u/MartynAndJasper </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/qppkg4/whats_purple_and_doesnt_fit_anymore/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/qppkg4/whats_purple_and_doesnt_fit_anymore/">[comments]</a></span></p></li>
<li><strong>I call my girlfriend Bambi. She thinks it’s because she’s cute.</strong> - <!-- SC_OFF -->
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I just really hope her mom gets shot.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MikeNoble91"> /u/MikeNoble91 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/qpv4br/i_call_my_girlfriend_bambi_she_thinks_its_because/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/qpv4br/i_call_my_girlfriend_bambi_she_thinks_its_because/">[comments]</a></span></p></li>
<li><strong>A Nazi walks into a bar</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He goes up to the bartender and looks around seeing an older Jewish man sitting in a corner. He turns to the bartender and announces loudly: “A round of beer for everyone except that Jew over there!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Nazi turns to the Jew smiling nastily and is surprised to see him smiling warmly back. Somewhat miffed the Nazi turns back to the bartender and says “A round of your sweetest wine for everyone here except that Jew!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Once again while everyone is cheering he turns back to the Jew grinning evilly but is shocked to see the Jew still smiling warmly and even inclined his head in the Nazi’s direction.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Nazi turns to bartender and says as loud as he could through gritted teeth “A bottle of your most expensive drink for everyone in this bar except for that Jew”.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The Nazi satisfied turns around chuckling to himself and freezes gobsmacked seeing the Jew smiling broadly at him and waving.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Furiously the Nazi turns back to the bartender and says “What the hell is wrong with that Jew? Is he crazy or just plain stupid?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The bartender replies “Neither. He’s the owner of the bar.”
</p>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/SonGoku3557"> /u/SonGoku3557 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/qphp92/a_nazi_walks_into_a_bar/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/qphp92/a_nazi_walks_into_a_bar/">[comments]</a></span></p></li>
</ul>
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