8,902 Matching Annotations
  1. Aug 2020
    1. 2020-08-12

    2. In this paper, we present an unsupervised graph-based approach for the detection of symptoms of COVID-19, the pathology of which seems to be evolving. More generally, the method can be applied to finding context-specific words and texts (e.g. symptom mentions) in large imbalanced corpora (e.g. all tweets mentioning #COVID-19). Given the novelty of COVID-19, we also test the proposed approach generalizes to the problem of detecting Adverse Drug Reaction (ADR). We find that the approach applied on Twitter data can detect symptom mentions much prior to their being reported by the Centers for Disease Control (CDC).
    3. Detecting Symptoms using Context-based Twitter Embeddings during COVID-19
    1. 2020-08-24

    2. Velásquez-Rojas, F., Ventura, P. C., Connaughton, C., Moreno, Y., Rodrigues, F. A., & Vazquez, F. (2020). Disease and information spreading at different speeds in multiplex networks. Physical Review E, 102(2), 022312. https://doi.org/10.1103/PhysRevE.102.022312

    3. 10.1103/PhysRevE.102.022312
    4. Nowadays, one of the challenges we face when carrying out modeling of epidemic spreading is to develop methods to control disease transmission. In this article we study how the spreading of knowledge of a disease affects the propagation of that disease in a population of interacting individuals. For that, we analyze the interaction between two different processes on multiplex networks: the propagation of an epidemic using the susceptible-infected-susceptible dynamics and the dissemination of information about the disease—and its prevention methods—using the unaware-aware-unaware dynamics, so that informed individuals are less likely to be infected. Unlike previous related models where disease and information spread at the same time scale, we introduce here a parameter that controls the relative speed between the propagation of the two processes. We study the behavior of this model using a mean-field approach that gives results in good agreement with Monte Carlo simulations on homogeneous complex networks. We find that increasing the rate of information dissemination reduces the disease prevalence, as one may expect. However, increasing the speed of the information process as compared to that of the epidemic process has the counterintuitive effect of increasing the disease prevalence. This result opens an interesting discussion about the effects of information spreading on disease propagation.
    5. Disease and information spreading at different speeds in multiplex networks
    1. 2020-08-24

    2. Nelson, N. C., Ichikawa, K., Chung, J., & Malik, M. (2020). Mapping the discursive dimensions of the reproducibility crisis: A mixed methods analysis [Preprint]. MetaArXiv. https://doi.org/10.31222/osf.io/sbv3q

    3. 10.31222/osf.io/sbv3q
    4. Addressing issues with the reproducibility of results is critical for scientific progress, but conflicting ideas about the sources of and solutions to irreproducibility are a barrier to change. Prior work has attempted to address this problem by creating analytical definitions of reproducibility. We take a novel empirical, mixed methods approach to understanding variation in reproducibility conversations, which yields a map of the discursive dimensions of these conversations. This analysis demonstrates that concerns about the incentive structure of science, the transparency of methods and data, and the need to reform academic publishing form the core of reproducibility discussions. We also identify three clusters of discussion that are distinct from the main group: one focused on reagents, another on statistical methods, and a final cluster focused the heterogeneity of the natural world. Although there are discursive differences between scientific and popular articles, there are no strong differences in how scientists and journalists write about the reproducibility crisis. Our findings show that conversations about reproducibility have a clear underlying structure, despite the broad scope and scale of the crisis. Our map demonstrates the value of using qualitative methods to identify the bounds and features of reproducibility discourse, and identifies distinct vocabularies and constituencies that reformers should engage with to promote change.
    5. Mapping the discursive dimensions of the reproducibility crisis: A mixed methods analysis
    1. 2020-08-24

    2. Fife, D., Lung, M., Sullivan, N., & Young, C. (2020). When Values Collide: Why Scientists Argue About Open Science and How to Move Forward [Preprint]. PsyArXiv. https://doi.org/10.31234/osf.io/q9d28

    3. 10.31234/osf.io/q9d28
    4. In the early/mid 20th century, scientists and philosophers advocated for a scientific framework that valued objectivity and certainty. This framework was committed to the value-free ideal, which held that social, political, ethical, and personal values are irrelevant to the process of science. This value system was adopted, both in science and public education systems. Indeed, the value of objectivity is thought to be synonymous with sound scientific practice. However, the “replication crisis” showed objectivity and certainty are illusory, and a value-system that favors objectivity may actually incentivize researchers to hide their biases. Over the last few years, a new value system is emerging, one that embraces uncertainty, encourages openness and transparency, and recognizes bias inherent in the scientific enterprise. These values conflict with those of the previous system, which creates discord among the scientific community. In this paper, we trace the origins of the existing value system and delineate new values emerging in the post-replication-crisis scientific community. This new set of values, objectified by the open science movement, recognizes the scientific process as a social enterprise. Neither set of values is inherently better, but both are reactions to the social environment in which researchers participate. What is important, however, is to recognize the significance of personal values in scientific discovery and to open dialogue about how to leverage these values. We conclude with recommendations about how to overcome both discord and the current incentive structure to increase the validity and reputability of science.
    5. When Values Collide: Why Scientists Argue About Open Science and How to Move Forward
    1. 2020-08-18

    2. Mishra, V., & Dexter, J. P. (2020). Comparison of Readability of Official Public Health Information About COVID-19 on Websites of International Agencies and the Governments of 15 Countries. JAMA Network Open, 3(8), e2018033–e2018033. https://doi.org/10.1001/jamanetworkopen.2020.18033

    3. We found that official information about COVID-19 exceeded the recommended reading level, exhibited complex syntax, and used technical terminology. The significant difference in use of difficult terms between the CDC and state resources may reflect the influence of federal oversight mandating government communication that is understandable to the public. Limitations included the focus on text, with no evaluation of multimedia communication, and lack of data about actual comprehension or relevant outcomes such as adherence to mitigation strategies. Nonadherence to readability standards may have a greater influence in communities with lower health literacy, potentially exacerbating the disparate effects of the pandemic. As such, efforts should focus on the urgent development of plain-language COVID-19 resources that conform to established guidelines for clear communication and are more accessible to all audiences.
    4. 10.1001/jamanetworkopen.2020.18033
    5. Comparison of Readability of Official Public Health Information About COVID-19 on Websites of International Agencies and the Governments of 15 Countries
    1. 2020-08-21

    2. Althouse, B. M., Wallace, B., Case, B., Scarpino, S. V., Berdahl, A. M., White, E. R., & Hebert-Dufresne, L. (2020). The unintended consequences of inconsistent pandemic control policies. ArXiv:2008.09629 [Physics, q-Bio]. http://arxiv.org/abs/2008.09629

    3. 2008.09629
    4. Controlling the spread of COVID-19 - even after a licensed vaccine is available - requires the effective use of non-pharmaceutical interventions: physical distancing, limits on group sizes, mask wearing, etc. To date, such interventions have neither been uniformly nor systematically implemented in most countries. For example, even when under strict stay-at-home orders, numerous jurisdictions granted exceptions and/or were in close proximity to locations with entirely different regulations in place. Here, we investigate the impact of such geographic inconsistencies in epidemic control policies by coupling search and mobility data to a simple mathematical model of SARS-COV2 transmission. Our results show that while stay-at-home orders decrease contacts in most areas of the US, some specific activities and venues often see an increase in attendance. Indeed, over the month of March 2020, between 10 and 30% of churches in the US saw increases in attendance; even as the total number of visits to churches declined nationally. This heterogeneity, where certain venues see substantial increases in attendance while others close, suggests that closure can cause individuals to find an open venue, even if that requires longer-distance travel. And, indeed, the average distance travelled to churches in the US rose by 13% over the same period. Strikingly, our model reveals that across a broad range of model parameters, partial measures can often be worse than none at all where individuals not complying with policies by traveling to neighboring areas can create epidemics when the outbreak would otherwise have been controlled. Taken together, our data analysis and modelling results highlight the potential unintended consequences of inconsistent epidemic control policies and stress the importance of balancing the societal needs of a population with the risk of an outbreak growing into a large epidemic.
    5. The unintended consequences of inconsistent pandemic control policies
    1. 2020-08-22

    2. Facebook, Twitter, options, S. more sharing, Facebook, Twitter, LinkedIn, Email, URLCopied!, C. L., & Print. (2020, August 22). Researchers show that COVID-19 racial disparities aren’t inevitable. Los Angeles Times. https://www.latimes.com/science/story/2020-08-22/researchers-show-that-covid-19-racial-disparities-arent-inevitable

    3. One of the hallmarks of the COVID-19 pandemic in the United States is that the disease disproportionately strikes people of color. But it doesn’t have to be that way, a new study suggests.Researchers analyzed more than 11,000 COVID-19 patients who were sick enough to seek treatment at a hospital and found that Black Americans in the study were no more likely to die of the disease than their white counterparts. Even when they zeroed in on the sickest patients — those who were admitted to an intensive care unit and who had to be put on ventilators — the results were the same.
    4. Researchers show that COVID-19 racial disparities aren’t inevitable
    1. 2020-08-20

    2. Preprint Servers Have Changed Research Culture in Many Fields. Will a New One for Education Catch On? - EdSurge News. (2020, August 20). EdSurge. https://www.edsurge.com/news/2020-08-20-preprint-servers-have-changed-research-culture-in-many-fields-will-a-new-one-for-education-catch-on

    3. a group of professors have built a preprint server for education research, with the hope of speeding up the pace of research and reaching communities of teachers and parents. The effort is called EdArXiv (pronounced “ed-archive”). The odd spelling follows the formula set by that pioneering physics preprint server, arXiv, and the new server uses the same underlying software. In disciplines where sharing papers on preprint website is routine—including physics, computer science and mathematics—papers that have early versions posted end up getting cited more widely once they hit official journals, says Amanda Montoya, assistant professor of psychology at UCLA, who is the vice chair of the EdArXiv steering committee.One win for education, she stresses, is that it is a field where a large number of people could benefit from freely accessible findings—teachers, parents and policymakers. “None of those people are people who have all the resources of a university library,” she says.
    4. Preprint Servers Have Changed Research Culture in Many Fields. Will a New One for Education Catch On?
    1. 2020-08-21

    2. Khanam, K. Z., Srivastava, G., & Mago, V. (2020). The Homophily Principle in Social Network Analysis. ArXiv:2008.10383 [Physics]. http://arxiv.org/abs/2008.10383

    3. 2008.10383
    4. In recent years, social media has become a ubiquitous and integral part of social networking. One of the major attentions made by social researchers is the tendency of like-minded people to interact with one another in social groups, a concept which is known as Homophily. The study of homophily can provide eminent insights into the flow of information and behaviors within a society and this has been extremely useful in analyzing the formations of online communities. In this paper, we review and survey the effect of homophily in social networks and summarize the state of art methods that has been proposed in the past years to identify and measure the effect of homophily in multiple types of social networks and we conclude with a critical discussion of open challenges and directions for future research.
    5. The Homophily Principle in Social Network Analysis
    1. 2020-08-21

    2. David Murphy—BPS Vice-President on Twitter. (n.d.). Twitter. Retrieved August 24, 2020, from https://twitter.com/ClinPsychDavid/status/1296732460672262146

    3. These NHS & care staff are the same ones who we were standing on our doorsteps clapping not long ago. Many of them are suffering themselves now &, in my opinion, deserve much better recognition, support & rehabilitation than they are currently receiving (6/6)
    4. What shocks me, however, is the apparent lack of attention nationally to the needs of the thousands of NHS staff suffering prolonged symptoms of Covid. How many NHS staff are currently off sick because of Covid? We don’t know. What support are they being offered? Very little. 5/6
    5. Its no surprise that many staff caring for pts with a highly infectious disease, often with inadequate PPE, contracted Covid. In April, @BPSOfficial guidance on Covid recovery predicted a significant % would experience prolonged symptoms. Sadly @LongCovidSOS bears this out (4/6)
    6. The massive increase in sickness could be a) staff contracting Covid or b) stress-related disorders due to working during the pandemic. However, data clearly shows it is the former, in fact, the proportion of sickness absence due to anxiety & depression actually went down. (3/6)
    7. In developing the NHS Covid Recovery programme, I’ve spoken to many people experiencing persistent effects of #Covid_19. I’ve been struck by how many are NHS staff themselves; analysis of newly released data clearly illustrates the scale of the impact of Covid on NHS Staff (1/6)
    8. The sickness rate for NHS Staff in London increased by >100% in April. Of course, the population sickness rate also went up, but the increase was ONLY in frontline NHS organizations & MUCH HIGHER in staff groups that were most likely to be in contact with Covid-19 patients. (2/6)
    1. 2020-08-21

    2. Peter English #FBPE on Twitter. (n.d.). Twitter. Retrieved August 24, 2020, from https://twitter.com/petermbenglish/status/1296730819420196864

    3. Now, tell me again. Who commissioned the laboratories? How much attention did they give to what would be needed (other than simply "ramping up testing" for political rather than public health reasons)? 17/17
    4. I'm not blaming the labs for this. The private sector is not a charity. They are doing what they were commissioned to do (and no more) - because they are answerable to their shareholders, to make a profit. 16/17
    5. That's if they decide it's commercially worthwhile at all. If they've set up a system that's making them rich, and it would be tricky and costly to start sharing Ct values, they might decide not to bother. They don't care if key workers are put off work unnecessarily. 15/17
    6. It will be the same with Ct values. "Not in our contract. We can do it if you like. It will cost [now, how much can we sting the suckers for, we know that Hancock will do anything to improve testing numbers, and the NHS and social care are desperate not to lose staff]." 14/17
    7. Instead, they just said "not covered by our contract - come and collect them if you want, otherwise we'll bin them". Which caused huge delays and expense. 13/17
    8. The lighthouse labs are commercial for-profit organisations. When we discovered swabs from a care home had gone to a lighthouse lab when they should have gone to a PHE one, they could easily have run the swabs at minimal cost - & absorbed the cost, or sent us a small bill. 12/17
    9. (Yes, it is PHE doing this work, not local authority public health - LA public health is doing a brilliant job, but not this). 11/17
    10. One of the private lighthouse labs (in Cambridge) apparently does record the Ct - but it won't routinely share it. So the PHE teams have no way of assessing whether these are true cases or prolonged RNA from previous infection - no risk at all. 10/17
    11. Which is where I come to the private "lighthouse" labs. Some of them don't record the Ct. They simply are unable to give use the information, because (they claim) they weren't commissioned to record these data. 9/17
    12. It is *extremely* disruptive otherwise. If we treat these positive cases as new infections, care homes have to be closed all the residents have to self-isolate for 14 days; key health and social care workers have to self-isolate for 10 days, and their contacts for 14. 8/17
    13. So… Now that we are seeing all of these people who had tested positive previously, we need to know if they are currently infected (and infectious), or simply showing residual RNA from a previous infection. 7/17
    14. These aren't "false positives" in the sense of being positive tests in the absence of viral RNA (there is RNA in the swab); but they are "false positives" in the sense that they do not show current infection or infectiousness. 6/17
    15. If there is current infection, there is likely to be a lot of RNA in the sample (and a low Ct value). If somebody has left-over RNA from a previous infection, there'll be less of it, and a high CT value. 5/17
    16. So the Ct value is a way of quantifying the amount of RNA. If there was very little RNA in the sample you'll have to double the amount more often - giving a higher Ct value. If there was a lot of RNA, you'll get a low Ct value. 4/17
    17. tldr: each time you run a "cycle" you double the amount of RNA in the sample. The number of times you do it is called the "cycle threshold" "Ct) ; the more often you have to do this before you can detect it, the less RNA there must have been in the original sample. 3/17
    18. Where these are genuine cases, this is good. The problem is many are being detected in people who had tested positive previously. And we don't know how to interpret them. This helps: https://cebm.net/covid-19/infectious-positive-pcr-test-result-covid-19/… 2/17
    19. A problem with privatisation of testing. Now that we are routinely testing lots of people - including care home staff and residents, and NHS staff - we are picking up positive results in asymptomatic people. 1/17
    1. 2020-08-21

    2. Page, M. L. (n.d.). How likely are you to be infected by the coronavirus on a flight? New Scientist. Retrieved August 24, 2020, from https://www.newscientist.com/article/2252152-how-likely-are-you-to-be-infected-by-the-coronavirus-on-a-flight/

    3. Is it safe to fly with the coronavirus still circulating? That depends partly on where you are. But while hard evidence is scarce, it appears the risk of being infected with the coronavirus during a flight is relatively low. “Overall, planes are probably safer than poorly ventilated pubs, where similar densities of people do not wear masks and talk a lot and loudly,” says Julian Tang at the University of Leicester in the UK.
    4. How likely are you to be infected by the coronavirus on a flight?
    1. 2020-01-07

    2. 10.31234/osf.io/t5dwg
    3. Psychology researchers are rapidly adopting open science practices, yet clear guidelines on how to apply these practices to meta-analysis remain lacking. In this tutorial, we describe why open science is important in the context of meta-analysis in psychology, and suggest how to adopt the three main components of open science: preregistration, open materials, and open data. We first describe how to make the preregistration as thorough as possible—and how to handle deviations from the plan. We then focus on creating easy-to-read materials (e.g., search syntax, R scripts) to facilitate reproducibility and bolster the impact of a meta-analysis. Finally, we suggest how to organize data (e.g., literature search results, data extracted from studies) that are easy to share, interpret, and update as new studies emerge. For each step of the meta-analysis, we provide example templates, accompanied by brief video tutorials, and show how to integrate these practices into the Open Science Framework (https://osf.io/q8stz/).
    4. Conducting a Meta-Analysis in the Age of Open Science: Tools, Tips, and Practical Recommendations
    1. 2020-08-03

    2. 10.1103/PhysRevE.102.022310
    3. The frequent emergence of diseases with the potential to become threats at local and global scales, such as influenza A(H1N1), SARS, MERS, and recently COVID-19 disease, makes it crucial to keep designing models of disease propagation and strategies to prevent or mitigate their effects in populations. Since isolated systems are exceptionally rare to find in any context, especially in human contact networks, here we examine the susceptible-infected-recovered model of disease spreading in a multiplex network formed by two distinct networks or layers, interconnected through a fraction q<math xmlns="http://www.w3.org/1998/Math/MathML"><mi>q</mi></math> of shared individuals (overlap). We model the interactions through weighted networks, because person-to-person interactions are diverse (or disordered); weights represent the contact times of the interactions. Using branching theory supported by simulations, we analyze a social distancing strategy that reduces the average contact time in both layers, where the intensity of the distancing is related to the topology of the layers. We find that the critical values of the distancing intensities, above which an epidemic can be prevented, increase with the overlap q<math xmlns="http://www.w3.org/1998/Math/MathML"><mi>q</mi></math>. Also we study the effect of the social distancing on the mutual giant component of susceptible individuals, which is crucial to keep the functionality of the system. In addition, we find that for relatively small values of the overlap q<math xmlns="http://www.w3.org/1998/Math/MathML"><mi>q</mi></math>, social distancing policies might not be needed at all to maintain the functionality of the system.
    4. Disease spreading with social distancing: A prevention strategy in disordered multiplex networks
    1. Sun, K., Wang, W., Gao, L., Wang, Y., Luo, K., Ren, L., Zhan, Z., Chen, X., Zhao, S., Huang, Y., Sun, Q., Liu, Z., Litvinova, M., Vespignani, A., Ajelli, M., Viboud, C., & Yu, H. (2020). Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2. MedRxiv, 2020.08.09.20171132. https://doi.org/10.1101/2020.08.09.20171132

    2. 2020-08-13

    3. A long-standing question in infectious disease dynamics is the role of transmission heterogeneities, particularly those driven by demography, behavior and interventions. Here we characterize transmission risk between 1,178 SARS-CoV-2 infected individuals and their 15,648 close contacts based on detailed contact tracing data from Hunan, China. We find that 80% of secondary transmissions can be traced back to 14% of SARS-CoV-2 infections, indicating substantial transmission heterogeneities. Regression analysis suggests a marked gradient of transmission risk scales positively with the duration of exposure and the closeness of social interactions, after adjusted for demographic and clinical factors. Population-level physical distancing measures confine transmission to families and households; while case isolation and contact quarantine reduce transmission in all settings. Adjusted for interventions, the reconstructed infectiousness profile of a typical SARS-CoV-2 infection peaks just before symptom presentation, with ~50% of transmission occurring in the pre-symptomatic phase. Modelling results indicate that achieving SARS-CoV-2 control would require the synergistic efforts of case isolation, contact quarantine, and population-level physical distancing measures, owing to the particular transmission kinetics of this virus.
    4. 10.1101/2020.08.09.20171132
    5. Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2
    1. 2020-08-15

    2. Conventional methods for viral genome sequencing largely use metatranscriptomic approaches or, alternatively, enrich for viral genomes by amplicon sequencing with virus-specific PCR or hybridization-based capture. These existing methods are costly, require extensive sample handling time, and have limited throughput. Here, we describe V-seq, an inexpensive, fast, and scalable method that performs targeted viral genome sequencing by multiplexing virus-specific primers at the cDNA synthesis step. We designed densely tiled reverse transcription (RT) primers across the SARS-CoV-2 genome, with a subset of hexamers at the 3’ end to minimize mis-priming from the abundant human rRNA repeats and human RNA PolII transcriptome. We found that overlapping RT primers do not interfere, but rather act in concert to improve viral genome coverage in samples with low viral load. We provide a path to optimize V-seq with SARS-CoV-2 as an example. We anticipate that V-seq can be applied to investigate genome evolution and track outbreaks of RNA viruses in a cost-effective manner. More broadly, the multiplexed RT approach by V-seq can be generalized to other applications of targeted RNA sequencing.
    3. 10.1101/2020.08.15.252510
    4. Rapid cost-effective viral genome sequencing by V-seq
    1. Rodda, L. B., Netland, J., Shehata, L., Pruner, K. B., Morawski, P. M., Thouvenel, C., Takehara, K. K., Eggenberger, J., Hemann, E. A., Waterman, H. R., Fahning, M. L., Chen, Y., Rathe, J., Stokes, C., Wrenn, S., Fiala, B., Carter, L. P., Hamerman, J. A., King, N. P., … Pepper, M. (2020). Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. MedRxiv, 2020.08.11.20171843. https://doi.org/10.1101/2020.08.11.20171843

    2. 2020-08-15

    3. The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. The majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that might contribute to herd immunity. Thus, we performed a longitudinal assessment of individuals recovered from mildly symptomatic COVID-19 to determine if they develop and sustain immunological memory against the virus. We found that recovered individuals developed SARS-CoV-2-specific IgG antibody and neutralizing plasma, as well as virus-specific memory B and T cells that not only persisted, but in some cases increased numerically over three months following symptom onset. Furthermore, the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-γ and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies. These findings demonstrate that mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks associated with antiviral protective immunity.
    4. 10.1101/2020.08.11.20171843
    5. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19
    1. 2020-08-12

    2. Wang, C., Wang, S., Chen, Y., Zhao, J., Han, S., Zhao, G., Kang, J., Liu, Y., Wang, L., Wang, X., Xu, Y., Wang, S., Huang, Y., Wang, J., & Zhao, J. (2020). Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection. BioRxiv, 2020.08.12.247338. https://doi.org/10.1101/2020.08.12.247338

    3. 10.1101/2020.08.12.247338
    4. The ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg−1 of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-acheive memrbane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19.
    5. Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection
    1. Chen, Y., Yang, W.-H., Huang, L.-M., Wang, Y.-C., Yang, C.-S., Liu, Y.-L., Hou, M.-H., Tsai, C.-L., Chou, Y.-Z., Huang, B.-Y., Hung, C.-F., Hung, Y.-L., Chen, J.-S., Chiang, Y.-P., Cho, D.-Y., Jeng, L.-B., Tsai, C.-H., & Hung, M.-C. (2020). Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro. BioRxiv, 2020.08.14.250258. https://doi.org/10.1101/2020.08.14.250258

    2. 2020-08-15

    3. 10.1101/2020.08.14.250258
    4. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mpro blocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mpro and diminishes its protease activity. Specifically, TFQ reduces the α-helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.
    5. Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro
    1. 2020-08-16

    2. Kreye, J., Reincke, S. M., Kornau, H.-C., Sánchez-Sendin, E., Corman, V. M., Liu, H., Yuan, M., Wu, N. C., Zhu, X., Lee, C.-C. D., Trimpert, J., Höltje, M., Dietert, K., Stöffler, L., Wardenburg, N. von, Hoof, S. van, Homeyer, M. A., Hoffmann, J., Abdelgawad, A., … Prüss, H. (2020). A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model. BioRxiv, 2020.08.15.252320. https://doi.org/10.1101/2020.08.15.252320

    3. The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.
    4. 10.1101/2020.08.15.252320
    5. A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
    1. 2020-08-12

    2. A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.
    3. 10.1101/2020.08.11.247395
    4. Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2
    1. 2020-08-14

    2. Addetia, A., Crawford, K. H., Dingens, A., Zhu, H., Roychoudhury, P., Huang, M., Jerome, K. R., Bloom, J. D., & Greninger, A. (2020). Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with high attack rate. MedRxiv, 2020.08.13.20173161. https://doi.org/10.1101/2020.08.13.20173161

    3. The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have only been performed in animal models and correlates of protection have not been established in humans. Here, we describe an outbreak of SARS-CoV-2 on a fishing vessel associated with a high attack rate. Predeparture serological and viral RT-PCR testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.5 days (range 18.8 to 50.5 days). A total of 104 individuals had an RT-PCR positive viral test with Ct <35 or seroconverted during the follow-up period, yielding an attack rate on board of 85.2% (104/122 individuals). Metagenomic sequencing of 39 viral genomes suggested the outbreak originated largely from a single viral clade. Only three crewmembers tested seropositive prior to the boat's departure in initial serological screening and also had neutralizing and spike-reactive antibodies in follow-up assays. None of these crewmembers with neutralizing antibody titers showed evidence of bona fide viral infection or experienced any symptoms during the viral outbreak. Therefore, the presence of neutralizing antibodies from prior infection was significantly associated with protection against re-infection (Fisher's exact test, p=0.002).
    4. 10.1101/2020.08.13.20173161
    5. Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with high attack rate
    1. Godfred-Cato, S. (2020). COVID-19–Associated Multisystem Inflammatory Syndrome in Children—United States, March–July 2020. MMWR. Morbidity and Mortality Weekly Report, 69. https://doi.org/10.15585/mmwr.mm6932e2

    2. 2020-08-14

    3. 10.15585/mmwr.mm6932e2external icon
    4. What is already known about this topic? Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition that has been reported approximately 2–4 weeks after the onset of COVID-19 in children and adolescents. What is added by this report? Most cases of MIS-C have features of shock, with cardiac involvement, gastrointestinal symptoms, and significantly elevated markers of inflammation, with positive laboratory test results for SARS-CoV-2. Of the 565 patients who underwent SARS-CoV-2 testing, all had a positive test result by RT-PCR or serology. What are the implications for public health practice? Distinguishing MIS-C from other severe infectious or inflammatory conditions poses a challenge to clinicians caring for children and adolescents. As the COVID-19 pandemic continues to expand in many jurisdictions, health care provider awareness of MIS-C will facilitate early recognition, early diagnosis, and prompt treatment.
    5. COVID-19–Associated Multisystem Inflammatory Syndrome in Children — United States, March–July 2020
    1. 2020-08-11

    2. Gaiha, S. M., Cheng, J., & Halpern-Felsher, B. (2020). Association Between Youth Smoking, Electronic Cigarette Use, and Coronavirus Disease 2019. Journal of Adolescent Health, 0(0). https://doi.org/10.1016/j.jadohealth.2020.07.002

    3. PurposeThis study aimed to assess whether youth cigarette and electronic cigarette (e-cigarette) use are associated with coronavirus disease 2019 (COVID-19) symptoms, testing, and diagnosis.MethodsAn online national survey of adolescents and young adults (n = 4,351) aged 13–24 years was conducted in May 2020. Multivariable logistic regression assessed relationships among COVID-19–related symptoms, testing, and diagnosis and cigarettes only, e-cigarettes only and dual use, sociodemographic factors, obesity, and complying with shelter-in-place.ResultsCOVID-19 diagnosis was five times more likely among ever-users of e-cigarettes only (95% confidence interval [CI]: 1.82–13.96), seven times more likely among ever-dual-users (95% CI: 1.98–24.55), and 6.8 times more likely among past 30-day dual-users (95% CI: 2.40–19.55). Testing was nine times more likely among past 30-day dual-users (95% CI: 5.43–15.47) and 2.6 times more likely among past 30-day e-cigarette only users (95% CI: 1.33–4.87). Symptoms were 4.7 times more likely among past 30-day dual-users (95% CI: 3.07–7.16).ConclusionsCOVID-19 is associated with youth use of e-cigarettes only and dual use of e-cigarettes and cigarettes, suggesting the need for screening and education.
    4. 10.1016/j.jadohealth.2020.07.002
    5. Association Between Youth Smoking, Electronic Cigarette Use, and Coronavirus Disease 2019