Unpacking the black box: Empirical evidence to understand the human factor for effective rapid testing against SARS-CoV2 -
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+SARS-CoV-2 rapid antigen point-of-care (PoC) and home tests are available to laypeople. This raises questions regarding the drivers and barriers of people’s willingness to use tests, their understanding of test results and the psychological and behavioural consequences of positive and negative test results. Four cross-sectional data collections, including survey items, open text answers and three experiments, were therefore conducted between December 2020 and March 2021, involving 4,026 German participants. The majority was willing to use PoC or home tests. People will be more likely to use tests when they are inexpensive and easy to use or when they are a necessary (given low infection rates) for obtaining access to public and social life. However, people urgently need information about what a test result means and how they should behave. Recommendations based on the present findings could make rapid testing a successful pillar of pandemic management.
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Risk of Developing Posttraumatic Stress Disorder in Severe COVID-19 Survivors, their Families and Frontline Healthcare Workers: What Should Mental Health Specialists Prepare For? -
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+Given the high coronavirus disease 2019 (COVID-19) mortality, this disease may be a life-threatening event, especially for individuals at high risk of complications. Therefore, in the article we try to answer two questions that are relevant to public mental health: Can we define groups who are at higher risk of developing pandemic-related PTSD? How can health specialists prepare for it? Given the results of previous research on PTSD in epidemic (e.g. SARS) survivors, we suggest that mental health professionals in countries touched by the pandemic should prepare for an increase in the PTSD prevalence, specifically in: individuals who have had severe COVID-19; family members of these patients and of patients who have died; and frontline healthcare workers witnessing COVID-19 patients’ sudden deaths, or numerous life-threatening situations. We postulate that these groups at risk should be routinely screened for PTSD in primary medical and pediatric care. Mental health services should prepare for providing therapeutic interventions for individuals with PTSD in the vulnerable groups, and support to their families, especially children.
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Interpreting vaccine efficacy trial results for infection and transmission -
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+Randomized controlled trials (RCTs) have shown high efficacy of multiple vaccines against SARS-CoV-2 disease (COVID-19), and recent studies have shown the vaccines are also effective against infection. Evidence for the effect of each of these vaccines on ability to transmit the virus is also beginning to emerge. We describe an approach to estimate these vaccines9 effects on viral positivity, a prevalence measure which under the reasonable assumption that vaccinated individuals who become infected are no more infectious than unvaccinated individuals forms a lower bound on efficacy against transmission. Specifically, we recommend separate analysis of positive tests triggered by symptoms (usually the primary outcome) and cross-sectional prevalence of positive tests obtained regardless of symptoms. The odds ratio of carriage for vaccine vs. placebo provides an unbiased estimate of vaccine effectiveness against viral positivity, under certain assumptions, and we show through simulations that likely departures from these assumptions will only modestly bias this estimate. Applying this approach to published data from the RCT of the Moderna vaccine, we estimate that one dose of vaccine reduces the potential for transmission by at least 61%, possibly considerably more. We describe how these approaches can be translated into observational studies of vaccine effectiveness.
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Stillbirths in Germany: On the rise, but no additional increases during the first COVID-19 lockdown -
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+Abstract Background A growing body of studies on the indirect effect of the COVID-19 pandemic on stillbirths shows mixed and context-dependent evidence, even within high-income countries. We examined possible changes in the stillbirth rate in Germany during the first COVID-19 lockdown. Methods We used population-level data on live and stillbirths occurring between January 1995 and July 2020 and applied negative binomial regression to estimate the yearly and monthly stillbirth rate in this period. We compared the actual stillbirth rate to the expected figure for the first seven months of 2020, based on prediction intervals derived from the detected time trend. Findings We detected a steady increase in stillbirths in Germany since 2013, which was preceded by a declining (1995-2004), and then plateauing (2005-2012) stillbirth rate. The stillbirth rate for January 2020 through July 2020 (4·148) was slightly lower than the stillbirth rate in the same period in 2019 (4·242). Furthermore, all monthly stillbirth rates during the first half of 2020 lie inside the 95% prediction interval of expected stillbirth rates for this period. Thus, stillbirths in Germany have neither increased nor decreased during the country’s first COVID-19 lockdown period. Interpretation In contrast to other European countries, stillbirth rates have been on the rise in Germany in the last decade. However, stillbirth rates during the first seven months of 2020 were not higher than expected. Our results suggest that stillbirth rates have neither increased nor decreased during the first-wave COVID-19 lockdown in this high-income setting. Further studies on the causes of the increasing stillbirth trend in Germany are needed, however. Funding statement No external funding was received for this research.
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The human factor between airborne pollen concentrations and COVID-19 disease dynamics -
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+In their seminal paper, Damialis and colleagues (2021, PNAS) report that, in early 2020, higher airborne pollen concentrations were related to higher COVID-19 infection rates. As a mechanism, the authors propose that “pollen exposure weakens the immunity … by diminishing the antiviral interferon response.” Although they assume an effect for the whole population, they speculate that it could be stronger for those with allergies. As a limitation, they acknowledge that they did not account for the countries’ testing strategies. As allergic people may be more likely to show symptoms that may be mistaken for those of COVID-19 (runny nose, headache, increased temperature), we explored whether people with allergies were more prone to get a rapid SARS-CoV-2 antigen test. Moreover, we assessed whether the test result was more likely to be positive among those with allergies.
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+Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-{kappa}B activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-{kappa}B signaling. Nsp14 caused the nuclear translocation of NF-{kappa}B p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation was further confirmed in lung tissue samples from COVID-19 patients. A previous proteomic screen identified the putative interaction of Nsp14 with host Inosine-5’-monophosphate dehydrogenase 2 (IMPDH2) protein, which is known to regulate NF-{kappa}B signaling. We confirmed the Nsp14-IMPDH2 protein interaction and found that IMPDH2 knockdown or chemical inhibition using ribavirin (RIB) and mycophenolic acid (MPA) abolishes Nsp14-mediated NF-{kappa}B activation and cytokine induction. Furthermore, IMDPH2 inhibitors (RIB, MPA) efficiently blocked SARS-CoV-2 infection, indicating that IMDPH2, and possibly NF-{kappa}B signaling, is beneficial to viral replication. Overall, our results identify a novel role of SARS-CoV-2 Nsp14 in causing the activation of NF-{kappa}B.
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Variable Induction of Pro-inflammatory Cytokines by Commercial SARS CoV-2 Spike Protein Reagents: Potential Impacts of LPS on In Vitro Modeling and Pathogenic Mechanisms In Vivo -
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+Proinflammatory cytokine production following infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is associated with poor clinical outcomes. Like SARS CoV-1, SARS CoV-2 enters host cells via its spike protein, which attaches to angiotensin-converting enzyme 2 (ACE2). As SARS CoV-1 spike protein is reported to induce cytokine production, we hypothesized that this pathway could be a shared mechanism underlying pathogenic immune responses. We herein compared the capabilities of Middle East Respiratory Syndrome (MERS), SARS CoV-1 and SARS CoV-2 spike proteins to induce cytokine expression in human peripheral blood mononuclear cells (PBMC). We observed that only specific commercial lots of SARS CoV-2 induce cytokine production. Surprisingly, recombinant SARS CoV-2 spike proteins from different vendors and batches exhibited different patterns of cytokine induction, and these activities were not inhibited by blockade of spike protein-ACE2 binding using either soluble ACE2 or neutralizing anti-S1 antibody. Moreover, commercial spike protein reagents contained varying levels of endotoxin, which correlated directly with their abilities to induce cytokine production. The lipopolysaccharide (LPS) inhibitor, polymyxin B, blocked this cytokine induction activity. In addition, SARS CoV-2 spike protein avidly bound soluble LPS in vitro, rendering it a cytokine inducer. These results not only suggest caution in monitoring the purity of SARS CoV-2 spike protein reagents, but they indicate the possibility that interactions of SARS CoV-2 spike protein with LPS from commensal bacteria in virally infected mucosal tissues could promote pathogenic inflammatory cytokine production.
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Evidence of neutralizing antibodies against SARS-CoV-2 in domestic cats living with owners with a history of COVID-19 in Lima, Peru -
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+SARS-CoV-2 can infect a variety of wild and domestic animals worldwide. Of these, domestic cats are highly susceptible species and potential viral reservoirs. As such, it is important to investigate disease exposure in areas with active community transmission and high disease prevalence. In this report we demonstrate the presence of serum neutralizing antibodies against the receptor binding-domain (RBD) of the SARS-CoV-2 in cats whose owners had been infected with SARS-CoV-2 in Lima, Peru, using a commercial competitive ELISA SARS-CoV-2 Surrogate Virus Neutralization Test. Out of 41 samples, 17.1% (7/41) and 31.7% (13/41) were positive, using the cut-off inhibition value of 30% and 20%, respectively. Not all cats living in a single house had detectable neutralizing antibodies showing that heterogenous exposure and immune among cohabiting animals. This is the first report of SARS-COV-2 exposure of domestic cats in Lima, Peru. Further studies are required to ascertain the prevalence of SARS-COV-2 exposure among domestic cats of Lima, Peru.
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Multi-level multi-state modelling applied to hospital admission in mexican patients with COVID-19 -
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+Since the beginning of the SARS-CoV 2 pandemic, healthcare authorities have made clear that it is crucial to track and identify COVID-19 symptoms and seek medical attention in the presence of the first warning signs, as immediate medical attention can improve the patient9s prognosis. Therefore the present work aims to analyze the risks associated with the time between the patient9s first symptoms and hospitalization followed by death. A cross-sectional study was performed among Mexican population diagnosed with COVID-19 and hospitalized from March to January 2021. Four different Bayesian models were developed to asses the risk associated with different patient trajectories: symptoms-hospitalization and hospitalization-death. Comorbidities that could worsen the patient outcome were included as linear predictions; these analyses were further broken down to the different states of the Mexican Republic and the healthcare providers within. Model III was chosen as the best performance through a validation of leaving one out (LOO). Increased risk for hospitalization was observed at the global population level for chronic renal disease, whereas for death such was the case for COPD and the interaction of diabetes:hypertension:obesity. Our results show that there are differences in mortality between the states without accounting for institution and it is related to the prompt time of death or viceversa. Regarding the 6 healthcare providers included in the analysis differences were also found. While state-managed hospitals and private sector showed lower risks, in contrast the IMSS seems to be the one with the highest risk. The proposed modelling can be helpful to improve healthcare assistance at a regional level, additionally it could inform statistical parameter inference in epidemiological models.
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Frailty variation models for susceptibility and exposure to SARS-CoV-2 -
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+Individual variation in susceptibility and exposure is subject to selection by force of infection, accelerating the natural acquisition of immunity, and reducing herd immunity thresholds and epidemic final sizes. This is a manifestation of a wider population phenomenon known as “frailty variation” in demography. Despite this theoretical understanding, public health policies continue to be guided by mathematical models that leave out most of the relevant variation and as a result inflate projected infection burdens. Here we focus on the trajectories of the coronavirus disease (COVID-19) pandemic in England and Scotland. We fit models to series of daily deaths and estimate relevant epidemiological parameters, including coefficients of variation which we find in agreement with direct measurements based on published contact surveys. Our estimates are robust to whether the data series encompass one or two pandemic waves. We conclude that herd immunity thresholds are being reached with a larger contribution of vaccination in Scotland than in England, where naturally acquired immunity is higher. These results are relevant to global vaccination policies.
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Effective prophylaxis of COVID-19 in rhesus macaques using a combination of two parentally-administered SARS-CoV-2 neutralizing antibodies -
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+SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.
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Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence -
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+SARS-CoV-2 has infected over 160 million and caused more than 3 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive activation, including an early cellular and proteomic signature that correlated with the amplitude of virus-specific humoral responses after day 30. We characterized signals associated with recovery and convalescence to define a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).
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Impaired function and delayed regeneration of dendritic cells in COVID-19 -
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+Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DC) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute disease to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage- HLADR+ cells lacking DC markers. Increased frequency of the recently discovered CD163+ CD14+ DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of PD-L1 in conventional DC (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naive CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.
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REGEN-COV protects against viral escape in preclinical and human studies -
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+Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. As rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of minor virus variants in SARS-COV-2 isolates found in COVID-19 patients or identified from preclinical in vitro and in vivo studies. This study demonstrates that a combination of non-competing antibodies, REGEN-COV, not only provides full coverage against current variants of concern/interest but also protects against emergence of new such variants and their potential seeding into the population in a clinical setting.
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Multispecific DARPin(R) therapeutics demonstrate very high potency against SARS-CoV-2 variants in vitro -
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+The SARS-CoV-2 virus responsible for the COVID-19 pandemic has so far infected more than 160 million people globally, and continues to undergo genomic evolution. Emerging SARS-CoV-2 variants show increased infectivity and may lead to resistance against immune responses of previously immunized individuals or existing therapeutics, especially antibody-based therapies. Several monoclonal antibody therapeutics authorized for emergency use or in development have been shown to lose potency against some SARS-CoV-2 variants. Cocktails of two different monoclonal antibodies constitute a promising approach to protect against novel emerging variants as long as both antibodies are potent, but come with increased development complexity and therefore cost. As an alternative, we developed two multi-specific DARPin(R) therapeutics, each combining three independent DARPin(R) domains binding the SARS-CoV-2 spike protein in one molecule, to potently neutralize the virus and overcome virus escape. Here, we show in a panel of in vitro studies that the multispecific DARPin(R) therapeutic design incorporated in our clinical candidate ensovibep (MP0420) achieved high neutralization potencies against the circulating SARS-CoV-2 variants B.1.1.7 (UK variant), B.1.351 (South African variant), P.1 (Brazilian variant), B.1.429 (South Californian variant), B.1.526 (New York variant), R.1 (Japanese variant), A.23.1 (Ugandan variant), and B.1.617 (Indian variant), and there is strong evidence that ensovibep also potently neutralizes the Indian variant B.1.618 based on the analysis of the key point mutations in the spike protein of this variant. Additionally, viral passaging experiments show potent protection by ensovibep and MP0423 against development of escape mutations. Finally, we demonstrate that the cooperative binding of the individual modules in a multispecific DARPin(R) antiviral is key for potent virus inhibition and protection from escape variants. These results, combined with the relatively small size and high production yields of DARPin(R) molecules, suggest that ensovibep is a highly valuable alternative to monoclonal antibody cocktails for global supply and demonstrate the strength of the DARPin(R) platform for achieving potent and lasting virus inhibition for SARS-CoV-2 and possibly other viruses.
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Study to Evaluate a Single Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With COVID-19 - Condition: Covid19 Interventions: Drug: COVI-DROPS; Drug: Placebo Sponsor: Sorrento Therapeutics, Inc. Not yet recruiting
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Low-Dose Radiation Therapy to Lungs in Moderate COVID-19 Pneumonitis: A Case-Control Pilot Study - Condition: COVID-19 Pneumonia Intervention: Radiation: Low dose radiotherapy Sponsor: Mahatma Gandhi Institute of Medical Sciences Not yet recruiting
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Study to Evaluate the Effects of RO7496998 (AT-527) in Non-Hospitalized Adult and Adolescent Participants With Mild or Moderate COVID-19 - Condition: COVID-19 Interventions: Drug: RO7496998; Drug: Placebo Sponsors: Atea Pharmaceuticals, Inc.; Hoffmann-La Roche Recruiting
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Using Text Messages to Improve COVID-19 Vaccination Uptake - Condition: Covid19 Intervention: Behavioral: Text message content Sponsors: Imperial College Healthcare NHS Trust; Central London CCG; Imperial College Health Partners; Institute for Global Health Innovations; The Behavioural Insights Team Not yet recruiting
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Prophylaxis for COVID-19: Ivermectin in Close Contacts of COVID-19 Cases (IVERNEX-TUC) - Condition: Covid19 Interventions: Drug: Ivermectin; Other: Placebo Sponsor: Ministry of Public Health, Argentina Recruiting
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Mix and Match of the Second COVID-19 Vaccine Dose for Safety and Immunogenicity - Condition: COVID-19 Interventions: Biological: mRNA-1273 SARS-CoV-2 vaccine; Biological: BNT162b2; Biological: ChAdOx1-S [recombinant]; Other: 0, 28 day schedule; Other: 0, 112 day schedule Sponsors: Canadian Immunization Research Network; Canadian Center for Vaccinology; BC Children’s Hospital Research Institute; Children’s Hospital Research Institute of Manitoba; CHU de Quebec-Universite Laval; Ottawa Hospital Research Institute; Northern Alberta Clinical Trials + Research Centre; Ontario Agency for Health Protection and Promotion; University of Toronto; Massachusetts General Hospital Not yet recruiting
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CISCO-21 Prevent and Treat Long COVID-19. - Condition: Covid19 Intervention: Other: Resistance Exercise Sponsors: NHS Greater Glasgow and Clyde; University of Glasgow; Chief Scientist Office of the Scottish Government Not yet recruiting
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Leronlimab in Moderatelly Ill Patients With COVID-19 Pneumonia - Condition: COVID-19 Pneumonia Interventions: Drug: Leronlimab; Drug: Placebo Sponsors: Hospital Israelita Albert Einstein; CytoDyn, Inc. Not yet recruiting
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Amantadine for COVID-19 - Condition: Covid19 Interventions: Drug: Amantadine; Drug: Lactose monohydrate Sponsors: Copenhagen University Hospital, Hvidovre; University of Copenhagen Not yet recruiting
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Leronlimab in Critically Ill Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation - Condition: COVID-19 Pneumonia Interventions: Drug: Leronlimab; Drug: Placebo Sponsors: Hospital Israelita Albert Einstein; CytoDyn, Inc. Not yet recruiting
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The Role of High Dose Co-trimoxazole in Severe Covid-19 Patients - Condition: COVID-19 Pneumonia Interventions: Drug: Co-trimoxazole; Drug: Placebo Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh Not yet recruiting
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Anti COVID 19 Intravenous Immunoglobulin (C-IVIG) Therapy for Severe COVID-19 Patients - Condition: Covid19 Intervention: Biological: Anti COVID 19 Intravenous Immunoglobulin (C-IVIG) Sponsors: Dow University of Health Sciences; Higher Education Commission (Pakistan) Recruiting
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CRP-Apheresis for Attenuation of Pulmonary, MYocardial and/or Kidney Injury in COvid-19 - Condition: Covid19 Intervention: Device: CRP-apheresis Sponsor: University Hospital, Essen Recruiting
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A Proof of Concept Study for the DNA Repair Driven by the Mesenchymal Stem Cells in Critical COVID-19 Patients - Condition: COVID-19 Pneumonia Intervention: Biological: Mesenchymal Stem Cells Transplantation Sponsors: SBÜ Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi; Istinye University; Liv Hospital (Ulus) Completed
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A Global Phase III Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) - Condition: COVID-19 Interventions: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Other: Placebo control Sponsors: Jiangsu Province Centers for Disease Control and Prevention; WestVac Biopharma Co., Ltd.; West China Hospital Not yet recruiting
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From PubMed
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Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp - Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against…
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Interplay of the ubiquitin proteasome system and the innate immune response is essential for the replication of infectious bronchitis virus - Infectious bronchitis virus (IBV) is the only coronavirus known to infect poultry. The replication and pathogenesis of IBV are poorly understood, mainly because of the unavailability of a robust cell culture system. Here, we report that an active ubiquitin proteasome system (UPS) is necessary for efficient replication of IBV in Vero cells. Synthesis of IBV-specific RNA as well as viral protein is hampered in the presence of chemical inhibitors specific for the UPS. Like other coronaviruses, IBV…
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Coronavirus PEDV nucleocapsid protein interacts with p53 to induce cell cycle arrest in S-phase and promotes viral replication - Subversion of the host cell cycle to facilitate viral replication is a common feature of coronavirus infections. Coronavirus nucleocapsid (N) protein could modulate host cell cycle, but the mechanistic details remain largely unknown. Here, we investigated manipulation of porcine epidemic diarrhea virus (PEDV) N protein on cell cycle and its influence on viral replication. Results indicated that PEDV N-induced Vero E6 cell cycle arrest at S-phase, which promoted viral replication (P < 0.05)….
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Artificial intelligence as a fundamental tool in management of infectious diseases and its current implementation in COVID-19 pandemic - The world has never been prepared for global pandemics like the COVID-19, currently posing an immense threat to the public and consistent pressure on the global healthcare systems to navigate optimized tools, equipments, medicines, and techno-driven approaches to retard the infection spread. The synergized outcome of artificial intelligence paradigms and human-driven control measures elicit a significant impact on screening, analysis, prediction, and tracking the currently infected individuals,…
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Studying the prominence effect amid the COVID-19 crisis: implications for public health policy decision-making - The novel coronavirus disease 2019 (COVID-19) has brought with it crucial policy- and decision-making situations, especially when making judgments between economic and health concerns. One particularly relevant decision-making phenomenon is the prominence effect, where decision-makers base their decisions on the most prominent attribute of the object at hand (e.g., health concerns) rather than weigh all the attributes together. This bias diminishes when the decision-making mode inhibits…
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Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion - An ongoing pandemic of coronavirus disease 2019 (COVID-19) is now the greatest threat to global public health. Herbal medicines and their derived natural products have drawn much attention in the treatment of COVID-19, but the detailed mechanisms by which natural products inhibit SARS-CoV-2 have not been elucidated. Here, we show that platycodin D (PD), a triterpenoid saponin abundant in Platycodon grandiflorum (PG), a dietary and medicinal herb commonly used in East Asia, effectively blocks the…
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Long non-coding RNAs in Epstein-Barr virus-related cancer - Epstein Barr-virus (EBV) is related to several cancers. Long non-coding RNAs (lncRNAs) act by regulating target genes and are involved in tumourigenesis. However, the role of lncRNAs in EBV-associated cancers is rarely reported. Understanding the role and mechanism of lncRNAs in EBV-associated cancers may contribute to diagnosis, prognosis and clinical therapy in the future. EBV encodes not only miRNAs, but also BART lncRNAs during latency and the BHLF1 lncRNA during both the latent and lytic…
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A ‘deep dive’ into the SARS-Cov-2 polymerase assembly: identifying novel allosteric sites and analyzing the hydrogen bond networks and correlated dynamics - Replication of the SARS-CoV-2 genome is a fundamental step in the virus life cycle and inhibiting the SARS-CoV2 replicase machinery has been proven recently as a promising approach in combating the virus. Despite this recent success, there are still several aspects related to the structure, function and dynamics of the CoV-2 polymerase that still need to be addressed. This includes understanding the dynamicity of the various polymerase subdomains, analyzing the hydrogen bond networks at the…
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Time-dependent viral interference between influenza virus and coronavirus in the infection of differentiated porcine airway epithelial cells - Coronaviruses and influenza viruses are circulating in humans and animals all over the world. Co-infection with these two viruses may aggravate clinical signs. However, the molecular mechanisms of co-infections by these two viruses are incompletely understood. In this study, we applied air-liquid interface (ALI) cultures of well-differentiated porcine tracheal epithelial cells (PTECs) to analyze the co-infection by a swine influenza virus (SIV, H3N2 subtype) and porcine respiratory coronavirus…
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Sulforaphane inhibits the expression of interleukin-6 and interleukin-8 induced in bronchial epithelial IB3-1 cells by exposure to the SARS-CoV-2 Spike protein - CONCLUSION: The control of the cytokine storm is one of the major issues in the management of COVID-19 patients. Our study suggests that SFN can be employed in protocols useful to control hyperinflammatory state associated with SARS-CoV-2 infection.
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Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study - Coronaviruses are deadly and contagious pathogens that affects people in different ways. Researchers have increased their efforts in the development of antiviral agents against coronavirus targeting M^(pro) protein (main protease) as an effective drug target. The present study explores the inhibitory potential of characteristic and non-characteristic Withania somnifera (Indian ginseng) phytochemicals (n ≈ 100) against SARS-Cov-2 M^(pro) protein. Molecular docking studies revealed that certain W….
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Penetrating the Blood-Brain Barrier with New Peptide-Porphyrin Conjugates Having anti-HIV Activity - Passing through the blood-brain barrier (BBB) to treat neurological conditions is one of the main hurdles in modern medicine. Many drugs with promising in vitro profiles become ineffective in vivo due to BBB restrictive permeability. In particular, this includes drugs such as antiviral porphyrins, with the ability to fight brain-resident viruses causing diseases such as HIV-associated neurocognitive disorders (HAND). In the last two decades, BBB shuttles, particularly peptide-based ones, have…
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Antibodies: what makes us stronger - Neutralizing antibodies are the basis of almost all approved prophylactic vaccines and the foundation of effective protection from pathogens, including the recently emerging SARS Coronavirus 2 (SARS-CoV-2). However, the contribution of antibodies to protection and to the course of the disease during first-time exposure to a pathogen is unknown. We analyzed the antibodies and B cell responses in severe and mild COVID-19 patients. Despite our primary assumption that high antibody titers contribute…
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Virtual screening of quinoline derived library for SARS-COV-2 targeting viral entry and replication - The COVID-19 pandemic infection has claimed many lives and added to the social, economic, and psychological distress. The contagious disease has quickly spread to almost 218 countries and territories following the regional outbreak in China. As the number of infected populations increases exponentially, there is a pressing demand for anti-COVID drugs and vaccines. Virtual screening provides possible leads while extensively cutting down the time and resources required for ab-initio drug design….
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Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19 - Profound endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. In the quiescent state, the endothelial surface is anticoagulant, a property maintained at least in part via constitutive signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from activated endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is…
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From Patent Search
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METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA) - - link
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IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR - - link
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DEEP LEARNING BASED SYSTEM FOR DETECTION OF COVID-19 DISEASE OF PATIENT AT INFECTION RISK - The present invention relates to Deep learning based system for detection of covid-19 disease of patient at infection risk. The objective of the present invention is to solve the problems in the prior art related to technologies of detection of covid-19 disease using CT scan image processing. - link
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A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - link
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UBIQUITOUS COMPUTING SYSTEM FOR MENTAL HEALTH MONITORING OF PERSON DURING THE PANDEMIC OF COVID-19 - - link
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USE OF IMINOSUGAR COMPOUND IN PREPARATION OF ANTI-SARS-COV-2 VIRUS DRUG - - link
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一种高灵敏SARS-CoV-2中和抗体的检测方法、检测试剂盒 - 本发明公开了一种高灵敏SARS‑CoV‑2中和抗体的检测方法、检测试剂盒，属于生物医学检测技术领域，本发明试剂盒包括层析试纸、卡壳和样本稀释液，所述层析试纸包括底板、样品垫、结合垫、NC膜和吸水垫，所述NC膜上依次设置有捕获线、检测线和质控线，所述捕获线包被有ACE2蛋白，所述检测线包被有RBD蛋白，所述结合垫设置有RBD蛋白标记物；本发明采用阻断法加夹心法原理提高检测中和抗体的灵敏度，通过添加捕获线的方式，将靶向RBD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。 - link
+
逆转录酶突变体及其应用 - 本发明提供一种MMLV逆转录酶突变体，在野生型MMLV逆转录酶氨基酸序列（如SEQ ID No.1序列所示）中进行七个氨基酸位点的突变，氨基酸突变位点为：R205H；V288T；L304K；G525D；S526D；E531G；E574G。该突变体可以降低MMLV逆转录酶对Taq DNA聚合酶的抑制作用，大大提高了一步法RT‑qPCR的灵敏度。 - link
+
Konstruktion einer elektrochemischen Atemmaske zum aktiven Schutz vor Coronavirus -
+
+
Konstruktion einer elektrochemischen medizinischen Atemmaske (1) für den aktiven Schutz gegen Infektion mit Coronaviren dadurch gekennzeichnet, dass ein elektrochemischer Effekt durch eine allgemein positives Magnetfeld der Maske erzeugbar ist, das die positiv geladenen Coronavirus-Mikroorganismen von der Person vertreibt, indem eine aktive elektrochemische Atemmaske (1) aus einem zweischichtigen Material verwendet wird, umfassend eine äußeren Schicht (2) aus einer hochmolekularen Verbindung aus Bambus in Mischung mit Kupfer-, Silber- oder Goldmetallfasern und einer inneren Schicht (3) aus einem Vliesstoff auf Basis von Polypropylenfasern SMS oder SNS, wobei der Maskenkörper aus zwei in der Mitte der Gesichtssymmetrie genähten Elementen gebildet ist, um die Kontur der Gesichtskurven so weit wie möglich zu wiederholen, ausgestattet mit einem Atemfilter (9) mit einem Einsatz aus zwei Schichten ferromagnetischen Metallgewebes, wobei das Filter (9) hat eine herausnehmbare SMS- oder SNS-Vlieskartusche in einem Kunststoffrand (14) und eine Öse zur Fixierung im Filtergehäuse umfasst, wobei die Maske (1) jeweils einen Nasen- und Kinnbügel aus einem flexiblen Einschubstreifen zwischen den beiden Lagen des Maskengewebes aufweist, die eine Fixierung auf Basis von doppelseitig klebendem Silikonklebeband in den Maskenseitenkanten sowie Nacken- und Kopfbefestigungsschlaufen ermöglichen.
Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link
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+ 27 May, 2021
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+Daily-Dose
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George Floyd, the Tulsa Massacre, and Memorial Days - The two tragedies make for easy inferences about the importance of commemoration. But this is not how trauma works. - link
+
Great Britain Needs a Vacation - A nation of devoted international travellers has been bottled up by the coronavirus. - link
+
Bitcoin’s Troubles Go Far Beyond Elon Musk - Recent moves by China have exposed the vulnerability of the cryptocurrency. - link
+
Is Online Test-Monitoring Here to Stay? - Despite students’ complaints and the coming return to in-person learning, Proctorio and its rivals are betting on a lucrative future. - link
+
Big Oil’s Bad, Bad Day - Crushing blows to three of the world’s largest oil companies have made it clear that the arguments many have been making for decades have sunk in at the highest levels. - link
+
+
From Vox
+
+
Who wins Instagram giveaways? An investigation. -
+
+
+
+Who is actually winning cash and prizes from Instagram giveaways? | Getty Images/fStop
+
+
+
+Influencers and marketing firms keep teaming up to give you cars, cash, and more. No one ever seems to win.
+
+
+In 1851, the inventor and entrepreneur Benjamin T. Babbitt began traveling around the United States in a wagon, offering consumers free lithographic prints with the purchase of baking soda. According to historian Wendy A. Woloson, this new mode of marketing inspired enterprising salesmen to launch their own prize giveaways, many of which ended up being scams. We can trace the history of the giveaway from the 1850s right up through March 23, 2021, when Kris Jenner, the matriarch of the Kardashian family known fondly for working harder than Satan, posted a photograph of herself on her Instagram page sitting on a grand staircase surrounded by thousands of dollars’ worth of Louis Vuitton luggage.
+
+
+“Who wants a 20k USD preloaded credit card + the luxury purses pictured here with me,” she asked, adding a credit card emoji, four exclamation points, and two notices that the post was an #ad. (An ad for what, exactly? It’s complicated.) All entrants had to do, said Jenner, was follow a few dozen other Instagram accounts and comment on Jenner’s post.
+
+
+Peering at the display, I wondered: Who wins these things? The answer has been difficult to ascertain.
+
+
+“It takes 90 seconds”
+
+
+I started paying attention to Instagram giveaways such as Jenner’s last year, when I was spending [redacted] hours per day on my couch, scrolling through Instagram. All of the Kardashians, save for Rob, have participated in one at some time or another, tempting their followers with Saint Laurent handbags, luxury baby strollers, and credit cards “preloaded” with thousands of dollars. (“Girl this looks like a scam,” said one commenter on a Kylie Jenner giveaway post from November 2020. “No one ever wins these,” said another.)
+
+Plenty of lesser influencers have gotten in on the action, too. Last month, erstwhile Vanderpump Rules star Stassi Schroeder offered her followers the chance to win a MacBook Air, a Canon camera, a Gucci purse, and a $1,500 prepaid Visa gift card, so long as they turned around and followed the 55 accounts that the marketing firm @socialstance was following. Among these accounts were even lesser influencers and fledgling brands, including an organic cosmetics company, a self-described “wellness hacker,” and a boutique that sells those oversize bows that people like to make their babies wear now.
+
+
+This kind of suspicious marketing is what’s known as a “loop” giveaway: The lesser influencers and brands pay a marketing firm like Social Stance to be on the must-follow list, and Social Stance pays the featured influencer, like Schroeder, to post about the giveaway. Overnight, the influencers and brands that bought in can gain thousands of followers. (The cost to participate in such a scheme reportedly ranges from a few hundred dollars to tens of thousands.)
+
+
+Social Stance, the company that administered the Schroeder giveaway, has also partnered with personalities like the actress Lucy Hale, Keeping Up With the Kardashians star Malika Haqq, and several former contestants on The Bachelor. The company, which did not respond to a request for an interview, describes its business this way on its website: “We partner with celebrities, cultural icons and established business’ [sic] to drive large scale influence and rapid growth of brands.” On its “Results” page, it claims that the Schroeder giveaway led to 9,400 new followers for participants.
+
+
+The benefit to the average contest entrant is less clear. The company does not disclose how it picks the lucky Instagram user to win the Canon and the MacBook and the Gucci. A few days after Schroeder first advertised the giveaway, she deleted the post without announcing a winner.
+
+
+When the Kardashians advertise giveaways, they work primarily with Curated Businesses, a marketing firm based in Australia. On the FAQ page on the company’s website, the first question is “Is this real?” and the answer is “Yes!”
+
+Reading this, I was undoubtedly reassured, but still I wondered: Who wins? Curated Businesses is slightly more forthcoming, at least, about how it conducts its giveaways, though it also did not respond to a request for an interview, so I’m unable to confirm that the following is true. On the same FAQ page, the company claims that it obtains the “necessary government issued lottery permits for our campaigns and the final draw is conducted by an independent third party and overseen by a certified scrutineer.”
+
+
+A certified scrutineer! Despite this official-sounding surveillance mechanism, entering one of these contests still feels a bit like writing your name on a piece of paper and throwing it into the street in the hope that someone will find it and bring you a million dollars. Has this worked for anyone?
+
+
+“If I see 10,000 comments, I’m not bothering”
+
+
+Unlike most digital agencies dedicated to the project of giving away luxury items on Instagram, Curated Businesses does make a point to announce at least some winners after its contests conclude. The company has a separate Instagram page, @cbwinners, where it shares the Instagram handles, and sometimes the photos, of people who have allegedly won those prepaid Visas and designer bags. The winners tend to be young women, probably because the people inclined to enter such contests tend to be young women. They look real enough, but I could not independently confirm their identities or their wins — I contacted over a dozen of them on Instagram, and no one responded.
+
+
+
+
+
+Occasionally, Curated Businesses posts Instagram-DM testimonials from winners, which offer some insight into what it’s like to win a prize. In February, the firm shared a missive from a young man who said winning a Kendall Jenner giveaway “changed my outlook on life in so many ways.” I thought perhaps he would be open to elaborating, but he also did not respond to a request for an interview.
+
+
+But Curated Businesses is just one marketing firm among many. Plenty of smaller giveaway schemes have proliferated on Instagram, some of them orchestrated by influencers themselves. Last May, several groups of fashion and fitness influencers joined forces to give away Peloton bikes — lots and lots of Peloton bikes — in multiple different loop giveaways. One team of influencers, made up of former reality stars like Jade Roper and mommy bloggers like Peyton Baxter, upped the ante: They bought a 2020 Hyundai Accent SE car to give away to a (randomly selected?) follower. (The scheme was later investigated by Instagram.)
+
+
+With each new day, it seems there is another chance to (possibly, maybe, who knows) win something by “Liking” and following and commenting. Among these more casual, haphazard giveaways, I found someone who did.
+
+
+This lucky individual did not win a collection of luxury handbags or an overpriced exercise bike or thousands of dollars in cash, but she did win something. Lauren McDowell, a 36-year-old living in Houston, Texas, said she won a collection of high-end soaps and candles from a giveaway organized by Joya Studio, a perfumery in Brooklyn, New York.
+
+
+How did she do it? In this case, the randomness of the universe bent in her favor, and also she kind of knows what she’s doing on Instagram, given that she is a marketing professional herself. She co-owns a small communications company in Houston and is familiar with the many ways brands can market themselves on the app. The Joya Studio giveaway was not the first one she entered — she said she keeps an eye out for giveaways from smaller brands and influencers that do not have the same reach as, say, a Kardashian. If she sees only a couple hundred comments on a giveaway post, she thinks, Hey, I could win that.
+
+
+Her sister, she said, does not employ the same strategy: She’s always participating in the big-time influencer giveaways, which she does not win. Waste of time, said McDowell. “If I see 10,000 comments, I’m not bothering.”
+
+
+
+
+
+
+
+
+
+The Joya Studio giveaway fit her qualifications: To enter, she had to follow seven brands on Instagram, including the perfumery D.S. & Durga and the soap company Malin + Goetz. She also had to tag a friend in the comments. She chose her sister, because “I know that I can reliably tag her and she’ll tag me on giveaway posts, and I don’t have to feel bad inconveniencing a friend where they’re like, what is this?”
+
+
+A few days went by, and McDowell forgot about her entry. But then she got a DM from Joya Studio telling her she had won. The company sent a prize package to both her and her sister.
+
+
+“I feel really good about the brand now, which is the whole point of the thing,” she said.
+
+
+“Another lucky winner”
+
+
+As happy as I was to learn that someone somewhere won something on Instagram, I still wondered about the Louis Vuitton handbags and $20,000 preloaded credit card that Kris Jenner advertised on her Instagram in March. Did anyone win them? And what do you do with a $20,000 preloaded gift card? Can you use it at a grocery store or a gas station? Do you have to pay taxes on it?
+
+
+
+
+
+To answer that last question, I talked to my accountant, Ben Sargent, who works with some influencers. He said that, oh, yes, you have to pay taxes on it.
+
+
+“Many winners are surprised to find that they owe taxes on the new car, vacation, or other prize that they won when they receive a form 1099 reporting the income to them,” he explained. “Winning a $60,000 new car could mean you end up with a roughly $20,000 tax bill that you don’t have the extra cash to pay, leading many people to instead take the lower ‘cash’ option for prizes, or to sell the car for cash.”
+
+
+Sargent said this applies even if the company administering the prize is based in, say, Australia.
+
+
+On April 1, @curatedbusinesses posted about the Kris Jenner giveaway. “Remember: Winners are chosen randomly by a government audited organisation,” it said. “They are not chosen based on anyone’s financial status, skin colour, location or follower number … It could be you next!!”
+
+
+The company announced that this time, Instagram user @luvnlyte was the winner. She did not respond to a request for comment.
+
+
+
Here’s who owns everything in Big Media today -
+
+
+
+Rani Molla
+
+
+
+It probably won’t look like this for long.
+
+
+The media landscape used to be straightforward: Content companies (studios) made stuff (TV shows and movies) and sold it to pay TV distributors, who sold it to consumers.
+
+
+Now things are up for grabs: Netflix buys stuff from the studios, but it’s making its own stuff, too, and it’s selling it directly to consumers. That’s one of the reasons older media companies are trying to compete by consolidating. Disney, for example, bought much of 21st Century Fox — though much of the early success of its Disney+ streaming service looks like it’s a result of earlier purchases of Lucasfilm, Marvel, and Pixar. Meanwhile, distributors like AT&T, which bought Time Warner, and Verizon, which bought AOL and Yahoo, thought they wanted to become media companies — and have now done an about-face and are bailing out of those acquisitions.
+
+
+Giant tech companies like Google, Amazon, and Apple that used to be on the sidelines are getting closer and closer to the action — and now Amazon has jumped in with both feet, with a plan to buy MGM, the studio that makes James Bond movies and TV shows like Shark Tank. If regulators approve, Amazon will pay $8.5 billion (including debt) for MGM, with the hopes of turning brands and characters like Rocky and the Pink Panther into new shows and movies.
+
+
+To help sort this all out, we’ve created a diagram that organizes distributors, content companies, and internet video companies by market cap — the value investors assign to the companies — and their main lines of business.
+
+
+Here’s what the Big Media universe currently looks like. We will update it periodically:
+
+
+
+
+
+
+
+
+This article originally appeared on Recode.net.
+
+
A Quiet Place Part II takes a good premise and extends it -
+
+
+
+Emily Blunt and Noah Jupe in A Quiet Place Part II. | Paramount Pictures
+
+
+
+The sequel to the 2018 hit is a fun, taut tease for an expanded universe.
+
+
+When A Quiet Place appeared in theaters in April 2018, it was a worldwide smash hit, and I’ve spent a while since then trying to figure out why. Setting aside its star power (namely, Emily Blunt and John Krasinski), it was not obviously poised for success more than any other horror film.
+
+
+The premise is simple: A family of five lives alone in the woods. The world outside their home is stalked by alien-monsters who are triggered into murderous rage by noise of any kind. They’re just trying to survive.
+
+
+It’s a remarkably restrained film, mostly taking place over the course of one day, filling in only the barest background details, and letting us focus singularly on the terror of staying alive, and protecting vulnerable children, too. And I think that’s why it was such a hit: It delivers some excellent jump scares and whittles down a common theme in horror — keeping your kids alive in a world that’s trying to kill them — to its essence. It’s sincere and bittersweet, and it clearly tapped into something that moved audiences.
+
+
+
+If the first Quiet Place movie was efficient horror storytelling, A Quiet Place Part II expands a little into the post-apocalyptic, answering some questions about what happened before the invasion and also setting the table for what will happen next. (It’s definitely meant to be, at minimum, the middle part of a trilogy; it’s also easy to imagine a TV series, not that one should.) The characters move around a bit more than in the previous film, and the outlines of the world they used to inhabit start to fill in. A Quiet Place was uneven in spots, but still felt like a startling discovery, which means its sequel has a lot to live up to.
+
+
+And, for the most part, it does. A Quiet Place Part II starts in the story’s past. On day one of the rest of their lives — not in a good way — the Abbott family are in their quiet New England hamlet with their neighbors, watching a Little League baseball game. There’s no threat, yet. Evelyn (Blunt) and Lee (Krasinski) keep tabs on their three kids: daring Regan (Millicent Simmonds), who is deaf; timid Marcus (Noah Jupe), swinging away at home plate; and curious Beau (Dean Woodward), hanging onto the fence and watching his big brother play. Nearby on the bleachers, gruff neighbor Emmett (Cillian Murphy) hangs onto his radio and watches his kids play.
+
+
+ Paramount Pictures
+
+Emily Blunt in A Quiet Place Part II.
+
+
+
+Suddenly, fireballs from the sky crash onto the field, and havoc breaks loose. The opening sequences of A Quiet Place Part II feel obviously influenced by Spielbergian visions of apocalyptic catastrophe (there are echoes of War of the Worlds everywhere). And they’re skillfully executed. Krasinski returns to this sequel as director and sole writer (he co-wrote the first film), and he has a good sense of how to build tension in what we’re seeing and what we’re hearing.
+
+
+Or not hearing. Soon we jump forward in time, to the moments after A Quiet Place ended, and pick up the story from there. I’m reluctant to reveal many details since suspense is so vital to a film like this, but there’s plenty else of note. Blunt remains one of Hollywood’s most reliably interesting action performers, swinging between the extremes of vulnerability and boldness that make perfect sense for a terrified, bereaved mother of three.
+
+
+Jupe is stuck with the hard work — playing the kid who’s terrified all the time — but Simmonds (who, like her character, is deaf) also extends her run of great, emotionally resonant performances, turning into a bit of an action hero herself. The pair are two of the best teen actors working today, and their sibling chemistry is enough to carry the whole movie without any adults.
+
+
+Murphy also figures largely into this installment, and boy, did I miss seeing Cillian Murphy in movies. (He’s been around, but mostly busy with TV’s Peaky Blinders.) Few actors are quite as skilled at keeping the audience on edge; he can walk a fine line between heroic and deranged, unsettling and secure, and in this role, those possibilities play to his advantage.
+
+
+The performances in A Quiet Place Part II make it very watchable, when combined with some heart-pounding action scenes that deploy the presence or absence of sound to ramp up the anxiety. The movie sticks the landing, too, even if that landing clearly leads into some future sequel. Filmmakers sometimes struggle to know where to pull back, but Krasinski seems to sense that less is more, and turns in a confident, capable sequel. (Plus, it’s just so nice to see a summer blockbuster — even a sequel — that’s based on an original story, rather than endlessly recycled IP fare.)
+
+
+ Paramount Pictures
+
+Millicent Simmonds in A Quiet Place Part II.
+
+
+
+The heart of AQuiet Place Part II remains the same as that of its predecessor, and, to be honest, it will probably resonate more now than it would have in early March 2020, when it was originally scheduled for release. Parents seeking to protect their kids from a vengeful, baffling, indiscriminate threat to their lives by staying quietly at home? Mourning the world that was and hoping for respite, a place to live freely that is once again safe? Well, that’s pretty relatable at this point in time.
+
+
+Yet as with all of the eerily “relatable” movies that came out during the pandemic — none of which could have anticipated what was next — A Quiet Place Part II feels relevant because the pandemic exacerbated what was already going on in our lives, agitating feelings we already had. The world feels dangerous, whether or not you’re a parent. We simultaneously need and fear our neighbors in a society where everyone’s out only for themselves.
+
+
+A Quiet Place Part II retains the horrorof its predecessor, butstarts to raise the questions that post-apocalyptic entertainment often asks best. In the wake of earth-shattering catastrophes and unspeakable loss, how does a culture rebuild itself? Can a society find a new and better way to live? Or will we simply fall back on the old ways? As we approach the first big summer weekend of 2021, that question couldn’t be more resonant. A Quiet Place Part II is one place to start thinking about it.
+
+
+A Quiet Place Part II opens in theaters on May 28.
+
+
+
From The Hindu: Sports
+
+
Kerala’s chess players mobilise to checkmate COVID-19 - Chess Kerala organises online tournaments to raise funds for the COVID-19 vaccine drive in the State
+
Real Madrid says Zidane stepping down as team’s coach - He had a contract through June 2022
+
Rashford faces racist abuse on social media after final loss - “For those working to make me feel any worse than I already do, good luck trying.”
+
Citing mental health concerns, Naomi Osaka says she won’t do press at French Open - Expecting players to answer questions after losses amounted to “kicking a person while they’re down,” she said.
+
It felt like I beat the virus: Shiva Thapa talks about record 5th Asian medal - “I never thought I would be the first to do something like this.”
+
+
From The Hindu: National News
+
+
Toolkit | Twitter refusing to cooperate, says Delhi Police - Only courts can judge and ‘adjudicate the truth’, says statement.
+
Coronavirus | Sons of deceased Hurriyat leader test positive in custody: kin - The family of two jailed sons of Tehreek-e-Hurriyat (TeH) chairman Ashraf Sehrai, who died in the custody on May 5, on Thursday claimed that the duo h
+
KEAM entrance exams on July 24 - The Commissioner for Entrance Examinations has decided to conduct the KEAM 2021 entrance examinations for engineering and pharmacy courses on July 24.
+
Coronavirus | Despite dip in cases, Maharashtra to extend lockdown-like restrictions after May 31 - While the Maharashtra government may consider easing some curbs, the current lockdown-like restrictions are to remain in force after May 31, informed
+
Covid-19 | Following workers’ protests, Ford suspends operations in Chennai plant for three days - The workers’ demands include a compensation of ₹1 crore each to the kin of two Covid victms and covering the medical expenses of those testing positive.
+
+
From BBC: Europe
+
+
Belarus: I’m ready to beg for help, says mother of detained woman - The mother of Sofia Sapega, who was arrested when her flight was grounded in Minsk, speaks to the BBC.
+
Nexta: The journalists taking on Belarus’ regime - The BBC visits the colleagues of Roman Protasevich, the journalist arrested off the diverted Ryan Air flight.
+
Azerbaijan captures six Armenian troops on border - The six were surrounded by Azeri troops who foiled a sabotage mission, Azerbaijan says.
+
Macron asks Rwanda to forgive France over 1994 genocide role - At a memorial to the 1994 genocide in Rwanda’s capital President Macron admits French mistakes.
+
Zinedine Zidane leaves Real Madrid for second time as manager - Zinedine Zidane resigns as Real Madrid manager after their first season without a trophy since 2010.
+
+
From Ars Technica
+
+
We got our first ride in the electric Lucid Air sedan - The stylish and spacious electric sedan goes into production later this year. - link
+
Sony lists PC version of Uncharted 4 in investor report - Listed under “more PC releases planned” amid strong returns for Horizon’s port. - link
+
Scientists induced hallucinations in mice to learn more about human psychosis - Study uncovered a surprising link between how human and mouse minds malfunction. - link
+
Windows 10 21H1 available now, improves document load times - The changes in 21H1 are mostly minor—much bigger things are coming in October. - link
+
These offline, disc-based games require an online check-in on Xbox Series X - One-time connection required for configuration on Xbox One and Smart Delivery discs. - link
+
+
From Jokes Subreddit
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+
Dad, a girl invited me over to her house -
+
+
+“Oh that is great, Billy. But you should be careful, you are young and an STD or unwanted pregnancy is going to be devastating. Please, remember to wear a condom if the situation arises… Actually, no. I don’t trust you, son. Put it on right now, because at the heat of the moment you will forget.”
+
+
+And so Billy did. And he head over to the girl’s place. After a chat and some drinks, things got saucy.
+
+
+" Wait" she said, “In order to continue, you have to pass a test.” She then removed her shirt, proclaiming “My breasts! Pure and untouched. Only the sun on beach days had ever had a feel of them”
+
+
+She then removed her skirt. “My thighs. Pure and touched by no one. Only the wind on breezy days has ever felt their softness.”
+
+
+Finally, she removed her panties. “And last, my vagina, pure and untouched. No one has ever felt its warmth, nor the wind nor the sun. So tell me, Billy, should I let you feel my body? Are you capable to match my purity?”
+
+
+“Sure”, he claims as he pulls downs his pants, “I am so pure and untouched, my willy is still in the the wrapper”
+
A guy walks into a bar, notices a “free beer for life challenge” on the front door. -
+
+
+A guy walks into a bar, notices a “free beer for life challenge” on the front door.
+
+
+He goes inside, and asks the bartender what he needs to do to receive free beer for life. The bartender reaches under the bar and pulls out a bottle of vodka, " First, drink this whole bottle in one go, no crying, breathing, or puking allowed." The man grabs the bottle and starts chugging.
+
+
+He slams the bottle on the counter, burps, and asks what’s next. The bartender, totally aloof says, " Alright, there’s an alligator outside with a loose tooth, go pull it for me. Next, there’s a woman upstairs who has never had an orgasm, go up there and give her one." The man, visibly worried steps outside, the bar room falls silent. The bartender hears screaming and rustling in the bushes outside.
+
+
+After a few minutes the man comes inside, all bloodied with ripped clothes he asks, " Okay, where is that lady with the loose tooth again?"
+
A horny gorilla sees a lion bent over a small stream, taking a drink. [NSFW] -
+
+
+A horny gorilla sees a lion bent over a small stream, taking a drink.
+
+
+The gorilla runs up behind the lion, grabs on, and has his way with him. The gorilla then takes off running, with the very angry lion on his heels. As they run through the jungle, the gorilla gets a bit of a lead, and sees a British safari camp ahead.
+
+
+The gorilla enters the camp, grabs some khakis that are hung out to dry, and puts on pants, a shirt, and a hat. He sits on a chair by the campfire and grabs a copy of the local paper, pretending to read, to hide his face.
+
+
+The lion enters the campsite and lets out a huge roar. He yells, “did anyone see a gorilla run through here?”
+
+
+The gorilla, in full disguise, calls out, “you mean the one that fucked the lion up the ass?”
+
+
+The lion exclaims, “oh my god! It’s in the paper already?”
+
+
+
+/cdn.vox-cdn.com/uploads/chorus_asset/file/22538489/aqp2_08341r.jpg)
Paramount Pictures
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Paramount Pictures
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