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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>Success of prophylactic antiviral therapy for SARS-CoV-2: predicted critical efficacies and impact of different drug-specific mechanisms of action</strong> -
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Repurposed drugs that are safe and immediately available constitute a first line of defense against new viral infections. Despite limited antiviral activity against SARS-CoV-2, several drugs are being tested as medication or as prophylaxis to prevent infection. Using a stochastic model of early phase infection, we find that there exists a critical efficacy that a treatment must reach in order to block viral establishment. For a single drug this efficacy is 87%, whereas for a combination of drugs this efficacy is reduced. Below the critical efficacy of any treatment, establishment of infection can sometimes be prevented, most effectively with drugs blocking viral entry into cells or enhancing viral clearance. Even when a viral infection cannot be prevented, antivirals delay the time to detectable viral loads. This delay flattens the within-host viral dynamic curve, possibly reducing transmission and symptom severity. Thus, antiviral prophylaxis, even with reduced efficacy, could be efficiently used to prevent or alleviate infection in people at high risk.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.05.07.20092965v3" target="_blank">Success of prophylactic antiviral therapy for SARS-CoV-2: predicted critical efficacies and impact of different drug-specific mechanisms of action</a>
</div></li>
<li><strong>Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: A Systematic Review and Meta-analysis</strong> -
<div>
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Background: Nasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs. Methods: We systematically searched PubMed, Google Scholar, medRxiv, and bioRxiv (last retrieval October 1st, 2020) for comparative studies of alternative specimen types [saliva, oropharyngeal (OP), and nasal (NS) swabs] versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT). A logistic-normal random-effects meta-analysis was performed to calculate % positive alternative-specimen, % positive NP, and % dual positives overall and in sub-groups. The QUADAS 2 tool was used to assess bias. Results: From 1,253 unique citations, we identified 25 saliva, 11 NS, 6 OP, and 4 OP/NS studies meeting inclusion criteria. Three specimen types captured lower % positives [NS (0.82, 95% CI: 0.73-0.90), OP (0.84, 95% CI: 0.57-1.0), saliva (0.88, 95% CI: 0.81 -0.93)] than NP swabs, while combined OP/NS matched NP performance (0.97, 95% CI: 0.90-1.0). Absence of RNA extraction (saliva) and utilization of a more sensitive NAAT (NS) substantially decreased alternative-specimen yield. Conclusions: NP swabs remain the gold standard for diagnosis of SARS-CoV-2, although alternative specimens are promising. Much remains unknown about the impact of variations in specimen collection, processing protocols, and population (pediatric vs. adult, late vs. early in disease course) and head-to head studies of sampling strategies are urgently needed.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.12.20230748v1" target="_blank">Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: A Systematic Review and Meta-analysis</a>
</div></li>
<li><strong>SARS-CoV-2 serological tests can generate false positive results for samples from patients with chronic inflammatory diseases</strong> -
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Objectives: Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless the tests give false positive results. The aim of this study was to evaluate the specificity of SARS-Cov-2 serological assays with samples from patients with chronic inflammatory diseases collected before April 2019, thus defined as negative. Methods: Samples from patients with multiple sclerosis (MS, n=10), rheumatoid arthritis (RA, n=47) with or without rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP2) and RF +/- systemic lupus erythematosus (SLE, n=10), were tested with 17 commercially available lateral flow assays (LFA), two ELISA kits and one in-house developed multiplex bead-based assay. Results: Six LFA and the in-house IgG assay gave the correct negative results for all samples. However, the majority of assays (n=13), gave false positive signal with samples from patients with RA and SLE. This was most notable in RF positive RA samples. MS samples did not give any false positive in any of the assays. Conclusion: The majority of the verified serological assays were sensitive to interfering antibodies in samples from patients with chronic inflammatory diseases and therefore may have poor specificity in this context. For these patients, the risk of false positivity should be considered when interpreting results of the SARS-CoV-2 serological assays.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.13.20231076v1" target="_blank">SARS-CoV-2 serological tests can generate false positive results for samples from patients with chronic inflammatory diseases</a>
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<li><strong>Critical care workers have lower seroprevalence of SARS-CoV-2 IgG compared with non-patient facing staff in first wave of COVID19.</strong> -
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With the first 2020 surge of the COVID-19 pandemic, many health care workers (HCW) were re-deployed to critical care environments to support intensive care teams to look after high numbers of patients with severe COVID-19. There was considerable anxiety of increased risk of COVID19 for staff working in these environments. Using a multiplex platform to assess serum IgG responses to SARS-CoV-2 N, S and RBD proteins, and detailed symptom reporting, we screened over 500 HCW (25% of the total workforce) in a quaternary level hospital to explore the relationship between workplace and evidence of exposure to SARS-CoV-2. Whilst 45% of the cohort reported symptoms that they consider may have represented COVID-19, overall seroprevalence was 14% with anosmia and fever being the most discriminating symptoms for seropositive status. There was a significant difference in seropositive status between staff working in clinical and non-clinical roles (9% patient facing critical care, 15% patient facing non-critical care, 22% nonpatient facing). In the seropositive cohort, symptom severity increased with age for men and not for women. In contrast, there was no relationship between symptom severity and age or sex in the seronegative cohort reporting possible COVID-19 symptoms. Of the 12 staff screened PCR positive (10 symptomatic), 3 showed no evidence of seroconversion in convalescence. Conclusion: The current approach to Personal Protective Equipment (PPE) appears highly effective in protecting staff from patient acquired infection in the critical care environment including protecting staff managing interhospital transfers of COVID-19 patients. The relationship between seroconversion and disease severity in different demographics warrants further investigation. Longitudinally paired virological and serological surveillance, with symptom reporting are urgently required to better understand the role of antibody in the outcome of HCW exposure during subsequent waves of COVID-19 in health care environments.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.12.20145318v1" target="_blank">Critical care workers have lower seroprevalence of SARS-CoV-2 IgG compared with non-patient facing staff in first wave of COVID19.</a>
</div></li>
<li><strong>SARS-CoV-2 antigens expressed in plants detect antibody responses in COVID-19 patients</strong> -
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Background: The SARS-CoV-2 pandemic has swept the world and poses a significant global threat to lives and livelihoods, with over 16 million confirmed cases and at least 650 000 deaths from COVID-19 in the first 7 months of the pandemic. Developing tools to measure seroprevalence and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings. Methods: We established an indirect enzyme-linked immunosorbent assay (ELISA) using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana. We measured antibody responses in sera from South African patients (n=77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of six weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease. In addition, we tested the reactivity of pre-pandemic plasma (n=58) and compared the performance of our in-house ELISA with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva. Results: We demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies by a validated, high sensitivity commercial ELISA, and OD values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers. Conclusions: We demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody responses to SARS-CoV-2 in infected patients in our setting.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.08.04.20167940v2" target="_blank">SARS-CoV-2 antigens expressed in plants detect antibody responses in COVID-19 patients</a>
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<li><strong>Can a data driven obesity classification system identify those at risk of severe COVID-19 in the UK Biobank cohort study?</strong> -
<div>
In this short communication we demonstrate how an individual level classification built using a Whole Systems approach to an understanding of obesity can be used to profile individual’s exposure, treatment and mortality for COVID-19. The cohort is the UK Biobank and the information on COVID-19 test outcomes, hospitalisations and mortality are provided as part of this research initiative. We find that the cohort profiles accurately against the understood heightened risk factors for COVID-19, namely age, gender, ethnicity, obesity and deprivation. This confidence in these data then allows us to profile the participants in each of the classification clusters for these COVID-19 outcomes. We see that there is a large degree of differentiation between the classes. The article finishes by highlighting how this classification can help in prioritising care, treatments and vaccine delivery.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/2568p/" target="_blank">Can a data driven obesity classification system identify those at risk of severe COVID-19 in the UK Biobank cohort study?</a>
</div></li>
<li><strong>Traumatic Impact of the COVID-19 Pandemic in an International Sample: Contribution of Fatalism to Psychological Distress and Behavior Change</strong> -
<div>
This study aimed to assess the traumatic impact of the COVID-19 outbreak and to explore the contribution of fatalism to a) psychological distress and b) pandemic-related behavior change. Data for the study were collected via an anonymous online survey. The survey included questions about demographic characteristics, health status, pandemic-related stress, impact of COVID-19 on health and behavior, posttraumatic stress symptoms (PTSS), and fatalism. The sample included 465 participants from 30 countries (mean age = 36.87, SD = 13.39, age range = 18 – 76; 80% female). While none of the study participants have been diagnosed with COVID-19, almost 25% knew someone who had received the diagnosis. The overwhelming majority (79%) had to make changes to their daily routine, and 48.82% of the sample reported moderate to severe PTSS. Fatalism was found to be a statistically significant predictor of PTSS in a multiple regression model and was also associated with lack of behavior changes in response to the pandemic. Our findings indicate that the COVID-19 pandemic is a traumatic event with a potential to affect mental health and well-being of individuals and communities. Fatalism may contribute to severity of psychological distress and diminish individuals’ ability to engage in health-protective behaviors.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/an4k6/" target="_blank">Traumatic Impact of the COVID-19 Pandemic in an International Sample: Contribution of Fatalism to Psychological Distress and Behavior Change</a>
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<li><strong>Predictors of adverse outcome in patients with suspected COVID-19 managed in a virtual hospital setting: a cohort study</strong> -
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Objective: Identify predictors of adverse outcome in a Virtual Hospital (VH) setting for COVID 19. Design: Real-world prospective observational study. Setting: Virtual hospital remote assessment service in West Hertfordshire NHS Trust, UK. Participants: Patients with suspected COVID-19 illness enrolled directly from the community (post-accident and emergency (A&amp;E) or medical intake assessment) or post-inpatient admission. Main outcome measure: Death or (re-)admission to inpatient hospital care over 28 days. Results: 900 patients with a clinical diagnosis of COVID-19 (455 referred from A&amp;E or medical intake and 445 post-inpatient) were included in the analysis. 76 (8.4%) of these experienced an adverse outcome (15 deaths in admitted patients, 3 deaths in patients not admitted, and 58 additional inpatient admissions). Predictors of adverse outcome were increase in age (OR 1.04 [95%CI: 1.02, 1.06] per year of age), history of cancer (OR 2.87 [95%CI: 1.41, 5.82]), history of mental health problems (OR 1.76 [95%CI: 1.02, 3.04]), severely impaired renal function (OR for eGFR &lt;30 = 9.09 [95%CI: 2.01, 41.09]) and having a positive SARS-CoV-2 PCR result (OR Mike Moo]). Conclusions: These predictors may help direct intensity of monitoring for patients with suspected or confirmed COVID-19 who are being remotely monitored by primary or secondary care services. Further research is needed to identify the reasons for increased risk of adverse outcome associated with cancer and mental health problems.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.09.20228189v1" target="_blank">Predictors of adverse outcome in patients with suspected COVID-19 managed in a virtual hospital setting: a cohort study</a>
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<li><strong>Early medical abortion using telemedicine - acceptability to patients</strong> -
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Introduction The English government approved both stages of early medical abortion (EMA) for at-home use on 30th March 2020. MSI Reproductive Choices UK (MSUK), one of the largest service providers of abortion services in England, launched a telemedicine EMA pathway on 6th April 2020. Methods A sample of all MSUK9s telemedicine EMA patients between April and August 2020 were invited to opt in to a follow-up call to answer clinical and satisfaction questions. 1,243 (13.7% of all telemedicine EMAs) were successfully followed-up, on average within five days post-procedure. Responses were analysed quantitatively and descriptively. The sample was compared to the total telemedicine EMA population on nine sets of background characteristics to check sample validity, and all results were tested across the same nine characteristics for variation. Results Patients reported high confidence in telemedicine EMA and high satisfaction with the convenience, privacy and ease of managing their abortion at home. No patient reported that they were unable to consult privately. Over 80% of patients reported preferring the telemedicine pathway, and two-thirds that they would choose telemedicine again if COVID-19 were no longer an issue. Discussion Telemedicine EMA is a valued, private, convenient and easier option that is highly acceptable for patients seeking an abortion, especially those for whom in-clinic visits are logistically or emotionally challenging. Evidence that this pathway would be a first choice again in future for most patients supports the case to make access to telemedicine EMA permanent.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.11.20229377v1" target="_blank">Early medical abortion using telemedicine - acceptability to patients</a>
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<li><strong>Association of social distancing and masking with risk of COVID-19</strong> -
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Given the continued burden of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) disease (COVID-19) across the U.S., there is a high unmet need for data to inform decision-making regarding social distancing and universal masking. We examined the association of community-level social distancing measures and individual masking with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported masking was associated with a 63% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. In the current environment of relaxed social distancing mandates and practices, universal masking may be particularly important in mitigating risk of infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.11.20229500v1" target="_blank">Association of social distancing and masking with risk of COVID-19</a>
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<li><strong>The Use of Saliva as a Diagnostic Specimen for SARS CoV-2 Molecular Diagnostic Testing for Pediatric Patients</strong> -
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Background Children are an important population to test for COVID-19 infection, particularly because they may shed the virus without displaying symptoms. Testing children for COVID-19 via sensitive molecular methods is important, although collecting nasopharyngeal (NP) specimens can be challenging. A less invasive mode of specimen collection that yields test results comparable to those from NP specimens would be beneficial to simplify sample collection. Methods To demonstrate that saliva is a suitable specimen for collection from children, the clinical usability/acceptability and the analytic performance of saliva were compared to NP specimens suspended in viral transport medium. Four different FDA EUA-approved real-time RT-PCR assays and one EUA approved saliva collection device were investigated. Results The study population included 526 patients between the ages of 3 and 61 years, 461 (88%) were &lt;18 years, 425 were asymptomatic (81.1%), 92 were symptomatic (17.6%). Saliva mixed with saliva stabilizing buffer was found to yield comparable sensitivity to NP specimens when tested on the AllPlex SARS-CoV-2 molecular test (Seegene Inc). The analytic sensitivity of the AllPlex assay during testing of spiked saliva mixed with SpectrumDNA saliva stabilizer was found to be 250 genomic copies/mL. Conclusions Of the four FDA EUA-approved SARS-CoV-2 PCR assays studied, we found the AllPlex assay to be best suited for testing saliva specimens collected from children 5 years of age or older. The sensitivity of viral detection was equivalent to NP specimens when saliva specimens were mixed with the saliva stabilizer.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.11.20223800v1" target="_blank">The Use of Saliva as a Diagnostic Specimen for SARS CoV-2 Molecular Diagnostic Testing for Pediatric Patients</a>
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<li><strong>Mental Health of Keyworkers in the UK during the COVID-19 Pandemic: a Cross-sectional Analysis of a Community Cohort</strong> -
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Objectives: Previous pandemics have resulted in high levels of psychological morbidity among frontline workers. Here we report on the early mental health impact of the COVID-19 pandemic on keyworkers in the UK, as assessed during the first six weeks of nationwide social distancing measures being introduced. Comparisons are made with non-keyworkers, and psychological factors that may be protective to keyworkers mental health are explored. Design: Cross-sectional analysis of a community cohort study. Results: Keyworkers reported significantly higher depression, anxiety, and stress than pre-pandemic population norms. Compared to non-keyworkers, keyworkers were more likely to worry about COVID-19 and perceived they were at higher risk from the virus. This was particularly evident for health and social care keyworkers. Younger keyworkers and those in a clinically increased risk group were more likely to report poorer mental health. Lower positive mood, greater loneliness and worrying more about COVID-19 were all associated with poorer mental health outcomes amongst keyworkers. Conclusions: The mental health impact of the COVID-19 pandemic on keyworkers in the UK has been substantial. Worry about COVID-19 and perceived risk from COVID-19 in keyworkers are understandable given potential increased exposure to the virus. Younger and clinically vulnerable keyworkers may benefit most from any interventions that seek to mitigate the negative mental health impacts of the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.11.20229609v1" target="_blank">Mental Health of Keyworkers in the UK during the COVID-19 Pandemic: a Cross-sectional Analysis of a Community Cohort</a>
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<li><strong>A room, a bar and a classroom: how the coronavirus is spread through the air depends on heavily mask filtration efficiency</strong> -
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Background: Recently the US CDC acknowledged by that the COVID19 crisis is facilitated at least in part by aerosolized virus exhaled by symptomatic, asymptomatic, or pre-symptomatic infected individuals. Disposable N95 masks remain in short supply due to their use in healthcare settings during the Coronavirus pandemic, whereas NIOSH-approved elastomeric N95 (eN95) masks remain immediately available for use by essential workers and the general public. New reusable N95 mask options with symmetric filtration efficiency can be anticipated to be NIOSH approved in the coming months, today9s eN95 masks have asymmetric filtration efficiency upon inhalation (95%) and exhalation (well under 95%) but are available now during the Fall and Winter when Coronavirus cases are expected to peak. Methods: Based on the Wells-Riley model of infection risk, we examine how the rate of transmission of the virus from one infected person in a closed, congested room with poor ventilation to several other susceptible individuals is impacted by the filtration efficiency of the masks they are wearing. Three scenarios are modeled: a room (6 people, 12 foot x 20 foot x 10 foot), a bar (18 people, 20 foot x 40 foot x 10 foot), and a classroom (26 people, 20 foot x 30 foot x 10 foot) with one infectious individual and remaining susceptibles. By dynamically estimating the accumulation of virus in aerosols exhaled by the infected person in these congested spaces for four hours using a box model, we compare the transmission risk (probability) when susceptible people based on a realistic hypothesis of face mask protection during inhaling and exhaling e.g. using cloth masks or N95 respirators. Results: Across all three scenarios, cloth masks modeled with 30% symmetric filtration efficiency alone were insufficient to stop the spread (18% to 40% infection risk), whereas eN95 masks (modeled as 95% filtration efficiency on inhalation, 30% on exhalation) reduced the infection risk to 1.5% to 3.6%. Symmetric filtration of 80% reduces the risk to 1.7% to 4.1% and symmetric filtration of 95% would further reduce the risk to 0.11% to 0.26%. Conclusion: This modeling of mask filtration efficiency suggests that the pandemic could be readily controlled within several weeks if (in conjunction with sensible hygiene) a sufficiently large majority of people wear asymmetric but higher filtration masks (e.g. eN95) that also block aerosols whenever exposed to anyone else outside their household in order to completely stop inter household spread.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.10.20227710v1" target="_blank">A room, a bar and a classroom: how the coronavirus is spread through the air depends on heavily mask filtration efficiency</a>
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<li><strong>Non-COVID-19 patients in times of pandemic: decreased emergency department visits and increased out-of-hospital mortality in Northern Italy</strong> -
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Objective. The aim of this was to assess the short-term impact of the pandemic on non-COVID-19 patients living in a one-million inhabitants area in Northern Italy (Bologna Metropolitan Area-BMA), analyzing time trends of Emergency Department (ED) visits, hospitalizations and mortality. Methods. We conducted a retrospective observational study using data extracted from BMA healthcare informative systems. Weekly trends of ED visits, hospitalizations, in- and out-of-hospital, all-cause and cause-specific mortality between December 1st, 2019 to May 31st, 2020, were compared with those of the same period of the previous year, using Joinpoint regression models and incidence rate ratios. Results. Non-COVID-19 ED visits and hospitalizations showed a stable trend until the first Italian case of COVID-19 has been recorded, on February 19th, 2020, when they dropped simultaneously. The reduction of ED visits was observed in all age groups and across all severity and diagnosis groups. In the lockdown period a significant increase was found in overall out-of-hospital mortality (43.2%) and cause-specific out-of-hospital mortality related to neoplasms (76.7%), endocrine, nutritional and metabolic (79.5%) as well as cardiovascular (32.7%) diseases. Conclusions. The pandemic caused a sudden drop of ED visits and hospitalizations of non-COVID-19 patients during the lockdown period, and a concurrent increase in out-of-hospital mortality mainly driven by deaths for neoplasms, cardiovascular and endocrine diseases. The findings of this study might be useful to understand both the population reaction and the healthcare system response at the early phases of the pandemic in terms of reduced demand of care and systems capability in intercepting it.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.10.20229237v1" target="_blank">Non-COVID-19 patients in times of pandemic: decreased emergency department visits and increased out-of-hospital mortality in Northern Italy</a>
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<li><strong>Design and implementation of the multi-arm, multi-stage Therapeutics for Inpatients with COVID-19 (TICO) platform master protocol: An Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative</strong> -
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Background: The SARS-CoV-2 pandemic is a public health emergency. Safe and effective therapies are urgently needed. Methods: Therapeutics for Inpatients with COVID-19 (TICO), is a global multi-arm, multi-stage (MAMS) platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of candidate anti-viral therapeutic agents for adults hospitalized with COVID-19. The protocol design allows multiple therapeutic agents to be evaluated in an efficient and scientifically rigorous manner, with efficiencies delivered by the MAMS design, and began by studying neutralizing monoclonal antibodies. TICO employs an agile and robust approach to futility and safety evaluation at 300 patients enrolled (Stage 1), with subsequent expansion to full sample size and an expanded target population (Stage 2) if the agent shows an acceptable safety profile and evidence of efficacy. Two ordinal outcomes applied early (Day 5) determine the efficacy signals of the investigational agents(s) and progression to Stage 2. These ordinal outcomes assess both respiratory and other organ failure events, recognizing the broad range of COVID-19 morbidity. In Stage 2, overall efficacy is assessed using the primary outcome of time to sustained recovery, assessed over 90 days. This approach to early futility assessment using an early intermediate outcome and a primary endpoint out to 90 days allows the study team to make rapid decisions on safety and potential efficacy of novel agents while ultimately focusing on patient-centered, longer-term outcomes. The implementation of TICO across a global network allows for continued enrollment despite variations in geographic epidemiology. Study Status: The TICO master protocol moved from conception to first patient enrolled in approximately 9 weeks, a testament to the expedited regulatory and ethics review, coupled with flexible and responsive study operations. The first agent to be tested using this protocol, LY-CoV-555, enrolled N=326 participants before undergoing Stage 1 futility and safety assessment. Two additional agents will enter the study in November 2020, with other agents planned. Conclusion: The TICO MAMS platform trial has been implemented efficiently across a global network of sites and several trial networks. It will generate results rapidly for multiple novel neutralizing monoclonal antibodies and other therapeutics agents.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.11.08.20227876v2" target="_blank">Design and implementation of the multi-arm, multi-stage Therapeutics for Inpatients with COVID-19 (TICO) platform master protocol: An Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study Evaluating the Efficacy and Safety of CKD-314 in Hospitalized Adult Patients Diagnosed With COVID-19 Pneumonia</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Nafamostat Mesilate<br/><b>Sponsor</b>:   Chong Kun Dang Pharmaceutical<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 III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: AZD7442;   Drug: Placebo<br/><b>Sponsors</b>:   AstraZeneca;   QuintilesIMS<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 III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: AZD7442;   Drug: Placebo<br/><b>Sponsors</b>:   AstraZeneca;   QuintilesIMS<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness and Safety of Rhea Health Tone® as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Dietary Supplement: Rhea Health Tone®<br/><b>Sponsors</b>:   Universitas Padjadjaran;   PT. Rhea Pharmaceutical Sciences Indonesia;   Prodia Diacro Laboratories P.T.<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>Ultramicronized Palmitoylethanolamide (PEA) Treatment in Hospitalized Participants With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: FSD201;   Drug: Placebo<br/><b>Sponsor</b>:   FSD Pharma, Inc.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hyperimmune Plasma for Patients With COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Other: treated with hyperimmune plasma<br/><b>Sponsor</b>:   ANNA FALANGA<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>Intravenous Infusion of CAP-1002 in Patients With COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: CAP-1002;   Biological: Placebo<br/><b>Sponsor</b>:   Capricor Inc.<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clarithromycin Versus Azithromycin in Treatment of Mild COVID-19 Infection</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: Clarithromycin 500mg;   Drug: Azithromycin;   Drug: Placebo<br/><b>Sponsor</b>:   South Valley University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Probiotics in Reducing Duration and Symptoms of COVID-19 (PROVID-19)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Dietary Supplement: Probiotics (2 strains 10x10^9 UFC);   Dietary Supplement: Placebo (potato starch and magnesium stearate)<br/><b>Sponsors</b>:   Centre de recherche du Centre hospitalier universitaire de Sherbrooke;   Lallemand Health Solutions<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of ZnAg Liquid Solution to Treat COVID-19 Symptomatic Participants</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Drug: CNM-ZnAg;   Drug: Placebo<br/><b>Sponsors</b>:   Clene Nanomedicine;   ICL Pharma;   Azidus Brazil<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>Efficacy and Safety of Two Hyperimmune Equine Anti Sars-CoV-2 in COVID-19 Patients</strong> - <b>Condition</b>:   Covid19<br/><b>Intervention</b>:   Biological: Administration of Equine immunoglobulin anti SARS-CoV-2<br/><b>Sponsors</b>:   Caja Costarricense de Seguro Social;   Universidad de Costa Rica;   Ministry of Health Costa Rica<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>Mesenchymal Stem Cells in Patients Diagnosed With COVID-19</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Biological: MSC;   Drug: Control<br/><b>Sponsors</b>:   Hospital Reg. Lic. Adolfo Lopez Mateos;   Instituto de Terapia Celular: ITC<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>Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Against COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVI-VAC;   Other: Placebo<br/><b>Sponsor</b>:   Codagenix, Inc<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diagnostic Performance Evaluation of a Novel SARS-CoV-2 (COVID-19) Antigen Detection Test</strong> - <b>Conditions</b>:   Covid19;   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Diagnostic Test: RT-qPCR test;   Diagnostic Test: COVID-VIRO® test<br/><b>Sponsor</b>:   Centre Hospitalier Régional d’Orléans<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>plasmApuane CoV-2 : Efficacy and Safety of Immune Covid-19 Plasma in Covid-19 Pneumonia in Non ITU Patients</strong> - <b>Condition</b>:   Covid-19 Pneumonia<br/><b>Intervention</b>:   Biological: immune plasma<br/><b>Sponsor</b>:   Azienda USL Toscana Nord Ovest<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Therapeutic Approach against 2019-nCoV by Inhibition of ACE-2 Receptor</strong> - The continued spread of 2019-nCoV has prompted widespread concern around the world. WHO formally named COVID-19 and International Committee on Taxonomy called it Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to this viral attack, the whole world is in lockdown. Presently, there is no effective way to control it, except social distancing and hygienic activity. World class scientists and researchers are trying to make vaccine and discover the medicine against the control 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>Peptide modelling and screening against human ACE2 and spike glycoprotein RBD of SARS-CoV-2</strong> - Outbreak of Coronavirus Disease 2019 (COVID-19) has become a great challenge for scientific community globally. Virus enters cell through spike glycoprotein fusion with ACE2 (Angiotensin-Converting Enzyme 2) human receptor. Hence, spike glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a potential target for diagnostics, vaccines, and antibodies. Also, virus entry can be prevented by blocking ACE2 thus, ACE2 can be considered potential target for therapeutics. As…</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 targeting of vulnerable RNA sequences in SARS CoV-2: identifying clinical feasibility</strong> - Covid-19 (SARS CoV-2) has become a deadly, world-wide pandemic. Although most who are infected survive, complications from the virus can be pronounced and long-lasting. To date, of all the respiratory viruses including influenza and coronaviruses, only influenza has had a drug (i.e., Tamiflu) specifically targeted to treat and prevent infection. As a result, additional agents that specifically target viral production and are clinically feasible are needed to alleviate respiratory viral…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of a repurposed drug as an inhibitor of Spike protein of human coronavirus SARS-CoV-2 by computational methods</strong> - Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is an emerging new viral pathogen that causes severe respiratory disease. SARS-CoV-2 is responsible for the outbreak of COVID-19 pandemic worldwide. As there are no confirmed antiviral drugs or vaccines currently available for the treatment of COVID-19, discovering potent inhibitors or vaccines are urgently required for the benefit of humanity. The glycosylated Spike protein (S-protein) directly interacts with human…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The SKI complex is a broad-spectrum, host-directed antiviral drug target for coronaviruses, influenza, and filoviruses</strong> - The SARS-CoV-2 pandemic has made it clear that we have a desperate need for antivirals. We present work that the mammalian SKI complex is a broad-spectrum, host-directed, antiviral drug target. Yeast suppressor screening was utilized to find a functional genetic interaction between proteins from influenza A virus (IAV) and Middle East respiratory syndrome coronavirus (MERS-CoV) with eukaryotic proteins that may be potential host factors involved in replication. This screening identified the SKI…</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>Recent Advances in Discovery of Potent Proteases Inhibitors Targeting the SARS Coronaviruses</strong> - Across the globe, countries are being challenged by the SARS-CoV-2 (COVID-19) pandemic in ways they have never been before. Global outbreak of SARS-CoV-2 with an uncertain fatality rate has imposed extreme challenges on global health. The World Health Organization (WHO) has officially declared the outbreak of COVID-19 a pandemic, after the disease caused by the new coronavirus spread to more than 100 countries. To date, various therapeutic approaches has been proposed and are being implemented…</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>High-Throughput Screening of an FDA-Approved Drug Library Identifies Inhibitors against Arenaviruses and SARS-CoV-2</strong> - Arenaviruses are a large family of enveloped negative-strand RNA viruses that include several causative agents of severe hemorrhagic fevers. Currently, there are no FDA-licensed drugs to treat arenavirus infection except for the off-labeled use of ribavirin. Here, we performed antiviral drug screening against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) using an FDA-approved drug library. Five drug candidates were identified, including mycophenolic acid, benidipine…</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>Necrostatin-1 and necroptosis inhibition: pathophysiology and therapeutic implications</strong> - Necrostatin-1 (Nec-1) is a RIP1-targeted inhibitor of necroptosis, a form of programmed cell death discovered and investigated in recent years. There are already many studies demonstrating the essential role of necroptosis in various diseases, including inflammatory diseases, cardiovascular diseases and neurological diseases. However, the potential of Nec-1 in diseases has not received much attention. Nec-1 is able to inhibit necroptosis signaling pathway and thus ameliorate necroptotic cell…</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>Russelioside B; A Pregnane Glycoside for Treatment of Gastric Ulcer via Modulation of Heat Shock Protein-70 and Vascular Endothelial Growth Factor</strong> - Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n=8) 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 analysis of selected alkaloids against main protease (M(pro)) of COVID-19</strong> - In the present situation, COVID-19 has become the global health concern due to its high contagious nature. It initially appeared in December 2019 in Wuhan, China and now affected more than 190 countries. As of now preventive measures are the sole solution to stop this disease for further transmission from person to person transmissions as there is no effective treatment or vaccine available to date. Research and development of new molecule is a laborious process; therefore, drug repurposing can…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Quercetin and Its Metabolites Inhibit Recombinant Human Angiotensin-Converting Enzyme 2 (ACE2) Activity</strong> - Angiotensin-converting enzyme 2 (ACE2) is a host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inhibiting the interaction between the envelope spike glycoproteins (S-proteins) of SARS-CoV-2 and ACE2 is a potential antiviral therapeutic approach, but little is known about how dietary compounds interact with ACE2. The objective of this study was to determine if flavonoids and other polyphenols with B-ring 3’,4’-hydroxylation inhibit recombinant human (rh)ACE2 activity….</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>Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target</strong> - Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell…</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 Outbreak: Pathogenesis, Current Therapies, and Potentials for Future Management</strong> - At the end of 2019, a novel coronavirus (CoV) was found at the seafood market of Hubei province in Wuhan, China, and this virus was officially named coronavirus diseases 2019 (COVID-19) by World Health Organization (WHO). COVID-19 is mainly characterized by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) and creates public health concerns as well as significant threats to the economy around the world. Unfortunately, the pathogenesis of COVID-19 is unclear and there is no 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>Engineered trimeric ACE2 binds viral spike protein and locks it in “Three-up” conformation to potently inhibit SARS-CoV-2 infection</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>Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotoxin as M(Pro) inhibitors of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)</strong> - OBJECTIVES: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</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>AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 예방을 위한 mRNA기반 항원보강제 혼합물 합성 방법</strong> - 본 발명은 SARS-CoV-2(코로나 바이러스) 예방을 위한 mRNA 항원보강제에 관한 것으로 코로나 바이러스에 대한 백신으로서 상기의 항원에 대한 예방을 목적으로 하고 있다. 아이디어에는 보강제에 해당하는 완전프로인트항원보강제(CFA)와 불완전프로인트항원보강제(IFA), 번역과 안정성의 최적화가 된 mRNA, mRNA 운반체, 양이온성 지질 나노입자(lipid nanoparticles)로 구성되며 기존의 백신에 비해 효율성과 안정성의 측면에서 더 향상된 효과를 가지고 있다.</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>Methods for treating Arenaviridae and Coronaviridae virus infections</strong> - Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I:</p></li>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">wherein the ’ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Atemschutz-Baukastensystem</strong> -
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Atemschutz-Baukastensystem, das aufweist:</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">eine auf zumindest Mund und Nase einer Person aufsetzbare Maske (1), die einen Eingang (11) und einen Ausgang (12) aufweist, und</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">mindestens einen Schlauch (3, 31, 32),</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">wobei sämtliche Komponenten des Atemschutz-Baukastensystems modular ausgebildet und über Steckverbindungen oder Schraubverbindungen (115, 125, 155, 165, 175, 215, 315, 75, 915) miteinander verbindbar sind, um der Maske (1) Luft über deren Eingang (11) zuzuführen und/oder ausgeatmete Luft vom Ausgang (12) der Maske (1) wegzuführen.</li>
</ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vorrichtung zur Übergabe und Dekontamination von mit Krankheitserregern kontaminierten Gegenständen oder Erzeugnissen</strong> -
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Vorrichtung zur Übergabe von mit Krankheitserregern kontaminierten Gegenständen oder Erzeugnissen nach einer Dekontamination, umfassend eine Einrichtung zur Dekontamination der mit Krankheitserregern kontaminierten Gegenstände oder Erzeugnisse mit mindestens einer UV-Strahlungsquelle (24), eine Durchzugseinrichtung mit Ein- und/oder Ausgabebereichen für die kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse, dadurch gekennzeichnet, dass die Durchzugseinrichtung im Eingang bzw. im Ausgang zum Ein- und/oder Ausgabebereich angeordnete sich paarweise gegenüberliegende Walzen (17) und Räder (4) umfasst, die zum Einzug bzw. zur Ausgabe der kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse vorgesehen sind, wobei die Walzen (17) und die Räder (4) durch im Ein- und/oder Ausgabebereich angeordnete Sensoren (23) und einer elektronische Kontrolleinheit (27) in Bewegung bringbar sind, wobei die Gegenstände oder Erzeugnisse in den Bereich der Einrichtung zur Dekontamination förderbar sind, der zwischen den paarweise angeordneten Walzen (17) und Rädern (4) vorgesehen ist, welcher sich gegenüberliegende Platten (25) aus Quarzglas oder einem UV-transparenten Polymermaterial, wie Graphen oder Kunstglas umfasst, über bzw. unter welchen die UV-Strahlungsquelle (24) angeordnet ist, welche als UVC-LED-Leiste und/oder Modul mit mindestens einer LED-Lampe ausgebildet ist.</p></li>
</ul>
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<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물</strong> - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. [화학식 1] .</p>
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48
135</code></pre></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>新型冠状病毒中和性抗体滴度检测ELISA试剂盒</strong> - 本发明提供一种新型冠状病毒中和性抗体滴度检测ELISA试剂盒，其中包括：包被有生物素‑链霉亲和素标记的人ACE2蛋白的酶标板、辣根过氧化酶标记的新型冠状病毒RBD蛋白、新型冠状病毒中和性抗体阳性对照、包被液、洗涤液、稀释液、封闭液、显色液和终止液等。该试剂盒具有成本低，操作简单，高灵敏度、高特异性、高准确度的特点，可用于新型冠状病毒中和抗体的批量、快速检测。</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>Zahnbürstenaufsatz, elektrische Versorgungseinheit einer elektrischen Zahnbürste, elektrische Zahnbürste mit einem Zahnbürstenaufsatz, Zahnbürste sowie Testaufsatz für eine elektrische Zahnbürste</strong> -</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
</p><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.</p></li>
</ul>
<img alt="embedded image" id="EMI-D00000"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Wasserpfeife mit Hygienefunktion</strong> -
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Hygiene-Mundstückelement (100), aufweisend einen ersten Endabschnitt (103), welcher ausgebildet ist zur Verbindung mit einem Griff-Mundstückelement (200) einer Wasserpfeife (400) und aufweisend einen zweiten Endabschnitt (104), welcher als mundseitiges, freies Ende ausgebildet ist, wobei das Hygiene-Mundstückelement (100) ein erstes Filterelement (101) aufweist, wobei das erste Filterelement (101) wenigstens ein adsorbierendes Material umfasst und/oder wobei das Hygiene-Mundstückelement (100) ein zweites Filterelement (102) aufweist, wobei das zweite Filterelement (102) Metalloxid und/oder elektrostatisch geladene Fasern umfasst.</p></li>
</ul>
<img alt="embedded image" id="EMI-D00000"/>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>알츠하이머병 혹은 뇌졸중의 뉴로인플라마섬의 치료제로서 디디에스 혹은 그 유도체</strong> - 목표 / 배경 :이 연구는 신경-정신과 증상을 측면과 구별하기 위해 2018 ‘NIA-AA 연구 프레임 워크’에 따라 뉴로인플라마섬 경쟁자로서 4, 4’- 디아미노디 페닐설폰(DDS, 디디에스)으로 치료받은 알츠하이머병(AD) 환자를 조사했습니다. 방법 : 서울 연구에서는 AD 진단 기준에 따라 2005 년 1 월부터 2020 년 6 월까지 보관된 소록도 국립병원 EDI 데이터베이스의 AD와 항AD약물(AAD)의 효과를 분석하여 ICD-9와 10 개의 코드를 이용하여 검색 하였습니다. 새로운 바이오마커 (D)를 사용하여 AAD로 인한 AD 증상과 신경정신병적 증상을 관리하여 수치 임상 병기를 분류했습니다. 우리는 서울 연구에서 뉴로인플라마섬 경쟁자로서 뇌경색 및 DDS 관련 사례를 보고합니다. 결과 : DDS는 DDS를 처방했거나 처방하지 않은 사람들과 AD의 비율을 비교할 때 뉴로인플라마섬 경쟁자였습니다. (D)를 도입함으로써, AD의 진행은 NCS 병기 결정을 통해 모니터링 하였습니다. AAD 또는 신경병리 증상을 구별하고 DDS로 치료했습니다. AD는 AAD에 의해 악화될 수 있고 DDS에 의해 경미한 인지 장애로 회복될 수 있습니다. 우리는 서울 연구에서 뇌경색이 발생하기 전과 후에 뉴로인플라마섬 경쟁자로서 DDS가 어떤 역할을 하는지를 임상적으로 확인했습니다. 결론 : DDS는 RBS 분할에 의한 정규/비정규적 우비퀴틴화, NLRP3 inflammasome 형성, Higgins의 캐스케이드 및 철이 풍부한 강자성 나노 입자를 차단하는 역할을 합니다. 바이오마커 (D)를 통하여 DDS로 AD를 예방하고 치료할 수 있습니다. AD에 대한 예방 및 치료 방법으로 뉴로인플라마섬을 치료하는 것을 수치 임상 병기(NCS, Numeric clinical staging)를 통하여 증명하고 있습니다.</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-apple-subreddit">From Apple Subreddit</a></li>
<li><a href="#from-hacker-news">From Hacker News</a></li>
<li><a href="#from-new-yorker">From New Yorker</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-apple-subreddit">From Apple Subreddit</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>‘AirTags’ appear to include privacy features to stop unwanted tracking</strong></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PSA: If your Mac suddenly just got very slow and is not opening apps, this is why</strong></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>iPhone 12 Pro Max Preview: The Camera Hardware Changes</strong></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Apple M1 interview with two vice presidents at Apple</strong></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Apple Joins Industry Group Working Towards 6G</strong></li>
</ul>
<h1 data-aos="fade-right" id="from-hacker-news">From Hacker News</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>So you’ve made a mistake and it’s public</strong> - <a href="https://news.ycombinator.com/item?id=25084506">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Transparency Report</strong> - <a href="https://news.ycombinator.com/item?id=25084415">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Durable Objects in Production</strong> - <a href="https://news.ycombinator.com/item?id=25084470">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DoorDash S-1</strong> - <a href="https://news.ycombinator.com/item?id=25082043">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The “Dying Seas” of the Anthropocene</strong> - <a href="https://news.ycombinator.com/item?id=25080998">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Xi Jinping personally halted Ant’s IPO after Jack Ma snubbed government leaders</strong> - <a href="https://news.ycombinator.com/item?id=25084953">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Less screen time and more sleep critical for preventing depression</strong> - <a href="https://news.ycombinator.com/item?id=25081952">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SLS vs. Starship</strong> - <a href="https://news.ycombinator.com/item?id=25081707">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dover (YC S19) is hiring engineers to build a truly modern recruiting agency</strong> - <a href="https://news.ycombinator.com/item?id=25085085">Comments</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Old Dogs, New Research and the Secrets of Aging</strong> - <a href="https://news.ycombinator.com/item?id=25083096">Comments</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</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>Georgia Republicans Turn Trump’s Baseless Claims of Voter Fraud Into an Electoral Strategy</strong> - In a pair of Senate runoffs, the incumbents, Kelly Loeffler and David Perdue, are clinging tightly to the lame-duck President, hoping his voters will turn out for them in January.</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 Seven Pillars of Biden’s Foreign Policy</strong> - The world wants a mensch to make America great again.</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 Work of Saving Democracy Must Go On After Trump</strong> - The emergency that roused so many ordinary Americans from their complacency has now ended, but the great uncertainty is what happens next to a country that seems irretrievably divided.</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 Kremlin Prepares for a Biden Presidency</strong> - Even in Moscow, there is accumulated disappointment and fatigue with Trump and all that his Presidency failed to deliver.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What My Ninety-Two-Year-Old Mother and Her Cohort Have Taught Us This Election</strong> - Her generation had a more visceral understanding of what was at stake than many of us did. They had seen men like Trump before.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Rohan Bopanna satisfied with his season</strong> - He is happy to have handled all the uncertainties with aplomb</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>Mthethwa threatens to de-recognise CSA</strong> - If members of council don’t recognise interim board immediately</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>West Indies squad clears final COVID test</strong> - Off to Queenstown for warm-up match</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>Hunker down — Low to team</strong> - Says it has to turn the page on its mediocre campaign so far</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>Still all to play for in the Nations League affected by the pandemic</strong> - Portugal-France the key match; Belgium in pole position; Poland, Italy, the Netherlands fighting it out</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<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>Nagorno-Karabakh: The families burning down their own homes</strong> - Fleeing ethnic Armenians are destroying their own homes so no Azerbaijanis can move in.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dutch police give ‘stop paedophile hunts’ warning after Arnhem death</strong> - A police chief warns against vigilantism after a retired teacher is beaten to death by teenagers.</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>Paris attacks: France remembers night of terror amid jihadist threat</strong> - On high alert, France is mourning the 130 people murdered in co-ordinated attacks five years ago.</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>Six-year-olds sketch rogue driver for German police</strong> - Children saw a driver smash through a barrier - and drew it for police in west Germany.</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>New Sentinel satellites to check the pulse of Earth</strong> - More satellites are ordered for the EU project that monitors the state of the planet.</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>Broadband power users explode, making data caps more profitable for ISPs</strong> - Usage increase “confirms the value” of data caps for ISP revenue, vendor says. - <a href="https://arstechnica.com/?p=1723177">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Elon Musk says he has tested positive for COVID-19</strong> - Musk took a rapid antigen test that has a substantial false negative rate. - <a href="https://arstechnica.com/?p=1723143">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Amazon begins shifting Alexa’s cloud AI to its own silicon</strong> - The amazon-designed Inferentia chips reduced cost and latency in text-to-speech. - <a href="https://arstechnica.com/?p=1723132">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Creeptastic Truth Seekers takes its horror seriously—but not too seriously</strong> - Showrunners Nick Saunders, James Serafinowicz on the key to balancing horror and comedy. - <a href="https://arstechnica.com/?p=1720223">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expansive White House COVID outbreak sidelines 10% of Secret Service</strong> - Spread linked to Trump’s campaign rallies and the White House itself. - <a href="https://arstechnica.com/?p=1723131">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The farmer</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A farmer walks upstairs to his bedroom with a chicken under his arm and stands before his wife.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“This is the pig I’ve been fucking”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
His wife rolls over and sees the farmer.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“You idiot that’s a chicken”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“SHUT THE FUCK UP IM TALKIN TO THE CHICKEN”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Adventurous_Celery28"> /u/Adventurous_Celery28 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/jtgigh/the_farmer/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/jtgigh/the_farmer/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What did Trump say to Biden in the hallway of the white house?</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Pardon me, please.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/murphanduncas"> /u/murphanduncas </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/jt7jwz/what_did_trump_say_to_biden_in_the_hallway_of_the/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/jt7jwz/what_did_trump_say_to_biden_in_the_hallway_of_the/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I got mugged by 6 dwarves today</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Not Happy.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/AndrewMacSydney"> /u/AndrewMacSydney </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/jtfgb7/i_got_mugged_by_6_dwarves_today/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/jtfgb7/i_got_mugged_by_6_dwarves_today/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A teenage girl was being intimate with her boyfriend</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
At her parents house. Her father after being woken by the noises goes upstairs to check it out, and walks in on them.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“Dad!” she exclaimed in a panic “…I’m sorry”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The dad being a dad replies “hi sorry, I’m Dad!”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He then turns to the boyfriend and asks “Are you fucking sorry?”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Iamthe_none"> /u/Iamthe_none </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/jsywad/a_teenage_girl_was_being_intimate_with_her/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/jsywad/a_teenage_girl_was_being_intimate_with_her/">[comments]</a></span></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>I want to speak to President Trump</strong> - <!-- SC_OFF --></p>
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
One sunny day in late January 2021 an old man approached the White House from across Pennsylvania Avenue, where he’d been sitting on a park bench. He spoke to the U.S. Marine standing guard and said, “I would like to go in and meet with President Trump.” The Marine looked at the man and said, “Sir, Mr Trump is no longer President and no longer resides here.” The old man said, “Okay”, and walked away.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The following day, the same man approached the White House and said to the same Marine, “I would like to go in and meet with President Trump.” The Marine repeated, “Sir, as I told you yesterday, Mr Trump is no longer President and no longer resides here.” The man thanked him and, again, just walked away.
</p>
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The third day, the old man approached the White House and spoke to the very same U.S. Marine, saying again, “I would like to go in and meet with President Trump.” The Marine, understandably irritated at this point, looked at the man and said, “Sir, this is the third day in a row you’ve been here asking to speak to Trump. I’ve told you each time that he’s no longer the President and no longer resides here. Don’t you get it?” The old man looked at the Marine and said, “Oh, I understand. I just love hearing it.”
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The Marine snapped to attention and said, “See you tomorrow, Sir!”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/brokendrumsticks"> /u/brokendrumsticks </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/jt5peu/i_want_to_speak_to_president_trump/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/jt5peu/i_want_to_speak_to_president_trump/">[comments]</a></span></p></li>
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