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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 150,124 papers from 632,984 authors.

Most tweeted biology preprints, last 24 hours

*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.

83 results found. For more information, click each entry to expand.

1: Effectiveness of COVID-19 vaccines against variants of concern in Ontario, Canada
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Posted 03 Jul 2021

Effectiveness of COVID-19 vaccines against variants of concern in Ontario, Canada
156 tweets medRxiv public and global health

Sharifa Nasreen, Hannah Chung, Siyi He, Kevin A. Brown, Jonathan B Gubbay, Sarah A Buchan, Deshayne B Fell, Peter C Austin, Kevin L Schwartz, Maria E. Sundaram, Andrew Calzavara, Branson Chen, Mina Tadrous, Kumanan Wilson, Sarah E. Wilson, Jeffrey C Kwong

Background: SARS-CoV-2 variants of concern (VOC) are more transmissible and have the potential for increased disease severity and decreased vaccine effectiveness. We sought to estimate the effectiveness of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and ChAdOx1 (AstraZeneca) vaccines against symptomatic SARS-CoV-2 infection and severe outcomes (COVID-19 hospitalization or death) caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) VOCs during December 2020 to May 2021. Methods: We conducted a test-negative design study using linked population-wide vaccination, laboratory testing, and health administrative databases in Ontario, Canada. Findings: Against symptomatic infection caused by Alpha, vaccine effectiveness with partial vaccination ([≥]14 days after dose 1) was higher for mRNA-1273 (83%) than BNT162b2 (66%) and ChAdOx1 (64%), and full vaccination ([≥]7 days after dose 2) increased vaccine effectiveness for BNT162b2 (89%) and mRNA-1273 (92%). Protection against symptomatic infection caused by Beta/Gamma was also higher with partial vaccination for mRNA-1273 (77%) than BNT162b2 (60%) and ChAdOx1 (48%), and full vaccination increased effectiveness for BNT162b2 (84%). Against Delta, vaccine effectiveness after partial vaccination tended to be lower compared to Alpha for mRNA-1273 (72% vs. 83%) and BNT162b2 (56% vs. 66%), but was similar to Alpha for ChAdOx1 (67% vs. 64%). Full vaccination with BNT162b2 increased protection against Delta (87%) to levels comparable to Alpha (89%) and Beta/Gamma (84%). Vaccine effectiveness against hospitalization or death caused by all VOCs was generally higher than for symptomatic infection after partial vaccination for all three vaccines. Interpretation: Our findings suggest that even a single dose of these 3 vaccines provide substantial protection against these 4 VOCs, and 2 doses likely provide higher protection. Jurisdictions facing vaccine supply constraints might consider delaying second doses to more rapidly achieve greater overall population protection.

2: The potential impact of vaccine passports on inclination to accept COVID-19 vaccinations in the United Kingdom: evidence from a large cross-sectional survey and modelling study
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Posted 01 Jun 2021

The potential impact of vaccine passports on inclination to accept COVID-19 vaccinations in the United Kingdom: evidence from a large cross-sectional survey and modelling study
59 tweets medRxiv health policy

Alex de Figueiredo, Heidi J Larson, Stephen D Reicher

Background: Four vaccines against the novel coronavirus 2019 disease (COVID-19) caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2) have currently been approved for use in the United Kingdom. As of 30 April 2021, over 34 million adults have received at least one dose of a COVID-19 vaccine. The UK Government is considering the introduction of vaccine passports for domestic use and to facilitate international travel for UK residents. Although vaccine incentivisation has been cited as a motivating factor for vaccine passports, it is currently unclear whether vaccine passports are likely to increase inclination to accept a COVID-19 vaccine. Methods: We conducted a large-scale national survey in the UK of 17,611 adults between 9 and 27 April 2021. Bayesian multilevel regression and poststratification is used to provide unbiased national-level estimates of the impact of the introduction of vaccine passports on inclination to accept COVID-19 vaccines among all respondents who have not yet had two vaccination doses. Multilevel regressions identify the differential impact of the likely impact of vaccine passports on uptake intent between socio-demographic groups. Gibbs sampling was used for Bayesian model inference, with 95% highest posterior density intervals used to capture uncertainty in all parameter estimates. Findings: We find that the introduction of vaccine passports will likely lower inclination to accept a COVID-19 vaccine once baseline vaccination intent has been adjusted for. Notably, this decrease is larger if passports were required for domestic use rather than for facilitating international travel. The impact of passports while controlling for baseline vaccination intent differentially impacts individuals by socio-demographic status, with being male (OR 0.87, 0.76 to 0.99) and having degree qualifications (OR 0.84, 0.72 to 0.94) associated with a decreased inclination to vaccinate if passports were required for domestic use, while Christians (OR 1.23, 1.08 to 1.41) have an increased inclination over atheists or agnostics. There is a strong association between change in vaccination inclination if passports were introduced and baseline vaccination intent: stated change in vaccination inclination is thus lower among Black or Black British respondents (compared to Whites), younger age groups, and non-English speakers. We find notable sub-national trends, for example, that passports could increase inclination among students and Jewish respondents in London compared to those in full-time education or atheists or agnostics, respectively. Interpretation: To our knowledge, this is the first quantitative assessment of the potential impact of the introduction of vaccine passports on COVID-19 vaccine intention. Our findings should be interpreted in light of sub-national trends in current uptake rates across the UK, as our results suggest that vaccine passports may induce a lower vaccination inclination in socio-demographic groups that cluster geographically in large urban areas. Caution should therefore be exercised in introducing passports as they may result in less positive health-seeking behaviours for the COVID-19 vaccine (as well as other existing or future vaccinations) and may contribute to concentrated areas of low vaccinate uptake, which is an epidemic risk. We call for further evidence on the impact of vaccine certification on confidence in COVID-19 vaccines and in routine immunisations in wider global settings and, in particular, in countries with low overall trust in vaccinations or in authorities that administer or recommend vaccines.

3: Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2
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Posted 10 May 2021

Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2
24 tweets medRxiv infectious diseases

Katherine Laiton-Donato, Carlos Franco-Munoz, Diego Alejandro Alvarez-Diaz, Hector Ruiz-Moreno, Jose Usme-Ciro, Diego Prada, Jhonnatan Reales, Sheryll Corchuelo, Maria Teresa Herrera-Sepulveda, Julian Naizaque, Gerardo Santamaria, Jorge Rivera, Paola Rojas, Andres Cardona Rios, Juan Hernandez-Ortiz, Diana Malo, Franklin Prieto, Fernando Ruiz-Gomez, Magdalena Wiesner, Martha Lucia Ospina-Martinez, Marcela Mercado-Reyes

The SARS-CoV-2 genetic diversification has a potential impact in the virus escape from natural infection- or vaccine-elicited neutralizing antibodies and higher transmissibility. Here we report the emergence of novel B.1.621 variant of interest with the insertion 145N in the N-terminal domain and amino acid change N501Y, E484K, and P681H in the Receptor Binding Domain of the Spike protein. Further studies in vitro biological assays and epidemiologic analysis will allow evaluating the public health impact of B.1.621 variant.

4: Phylogenetic reconstruction of ancestral ecological networks through time for pierid butterflies and their host plants
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Posted 05 Feb 2021

Phylogenetic reconstruction of ancestral ecological networks through time for pierid butterflies and their host plants
9 tweets bioRxiv ecology

Mariana P Braga, Niklas Janz, Sören Nylin, Fredrik Ronquist, Michael J Landis

The study of herbivorous insects underpins much of the theory that concerns the evolution of species interactions. In particular, Pieridae butterflies and their host plants have served as a model system for studying evolutionary arms-races. To learn more about the coevolution of these two clades, we reconstructed ancestral ecological networks using stochastic mappings that were generated by a phylogenetic model of host-repertoire evolution. We then measured if, when, and how two ecologically important structural features of the ancestral networks (modularity and nestedness) evolved over time. Our study shows that as pierids gained new hosts and formed new modules, a subset of them retained or recolonized the ancestral host(s), preserving connectivity to the original modules. Together, host-range expansions and recolonizations promoted a phase transition in network structure. Our results demonstrate the power of combining network analysis with Bayesian inference of host-repertoire evolution to understand changes in complex species interactions over time.

5: SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques
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Posted 23 Feb 2021

SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques
9 tweets bioRxiv neuroscience

Ingrid H.C.H.M. Philippens, Kinga P. Boszormenyi, Jacqueline A. Wubben, Zahra C Fagrouch, Nikki van Driel, Amber Q. Mayenburg, Diana Lozovagia, Eva Roos, Bernadette Schurink, Marianna Bugiani, Ronald E Bontrop, Jinte Middeldorp, Willy M Bogers, Lioe-Fee de Geus-Oei, Jan A.M. Langermans, Marieke A Stammes, Babs E Verstrepen, Ernst J Verschoor

SARS-CoV-2 may cause acute respiratory disease, but the infection can also initiate neurological symptoms. Here we show that SARS-CoV-2 infection causes brain inflammation in the macaque model. An increased metabolic activity in the pituitary gland of two macaques was observed by longitudinal positron emission tomography-computed tomography (PET-CT). Post-mortem analysis demonstrated infiltration of T-cells and activated microglia in the brain, and viral RNA was detected in brain tissues from one animal. We observed Lewy bodies in brains of all rhesus macaques. These data emphasize the virus' capability to induce neuropathology in this nonhuman primate model for SARS-CoV-2 infection. As in humans, Lewy body formation is an indication for the development of Parkinson's disease, this data represents a warning for potential long-term neurological effects after SARS-CoV-2 infection.

6: A Bayesian model selection approach for mediation analysis
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Posted 20 Jul 2021

A Bayesian model selection approach for mediation analysis
9 tweets bioRxiv genetics

Wesley L Crouse, Gregory R Keele, Madeleine S Gastonguay, Gary A Churchill, William Valdar

Mediation analysis is a powerful tool for discovery of causal relationships. We describe a Bayesian model selection approach to mediation analysis that is implemented in our bmediatR software. Using simulations, we show that bmediatR performs as well or better than established methods including the Sobel test, while allowing greater flexibility in both model specification and in the types of inference that are possible. We applied bmediatR to genetic data from mice and human cell lines to demonstrate its ability to derive biologically meaningful findings. The Bayesian model selection framework is extensible to support a wide variety of mediation models.

7: Necessity of COVID-19 Vaccination in Previously Infected Individuals: A Retrospective Cohort Study
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Posted 04 Jun 2021

Necessity of COVID-19 Vaccination in Previously Infected Individuals: A Retrospective Cohort Study
8 tweets medRxiv infectious diseases

Nabin K. Shrestha, Patrick C. Burke, Amy S. Nowacki, Paul Terpeluk, Steven M. Gordon

Background: There are good reasons to expect natural infection to provide protection against future infection with SARS-CoV-2. The purpose of this study was to evaluate the necessity of COVID-19 vaccination in persons previously infected with SARS-CoV-2. Methods: Employees of the Cleveland Clinic Health System working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Any subject who tested positive for SARS-CoV-2 at least 42 days earlier was considered previously infected. One was considered vaccinated 14 days after receipt of the second dose of a SARS-CoV-2 mRNA vaccine. The cumulative incidence of SARS-CoV-2 infection over the next four months, among previously infected subjects who received the vaccine, was compared with those of previously infected subjects who remained unvaccinated, previously uninfected subjects who received the vaccine, and previously uninfected subjects who remained unvaccinated. Results: Among the 52238 included employees, 1220 (47%) of 2579 previously infected subjects received the vaccine, compared with 29461 (59%) of 49659 not previously infected. The cumulative incidence of SARS-CoV-2 infection did not differ among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, and was much lower than that of previously uninfected subjects who remained unvaccinated. Not one of the 1359 previously infected subjects who remained unvaccinated had a SARS-CoV-2 infection over the duration of the study. Conclusion: Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before.

8: Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada
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Posted 07 Jul 2021

Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada
7 tweets medRxiv infectious diseases

David Fisman, Ashleigh Tuite

Background: The period from February to June 2021 was one during which initial wild-type SARS-CoV-2 strains were supplanted in Ontario, Canada, first by variants of concern (VOC) with the N501Y mutation (Alpha/B1.1.17, Beta/B.1.351 and Gamma/P.1 variants), and then by the Delta/B.1.617 variant. The increased transmissibility of these VOCs has been documented but data for increased virulence is limited. We used Ontario COVID-19 case data to evaluate the virulence of these VOCs compared to non-VOC SARS-CoV-2 infections, as measured by risk of hospitalization, intensive care unit (ICU) admission, and death. Methods: We created a retrospective cohort of people in Ontarios testing positive for SARS-CoV-2 and screened for VOCs, with dates of test report between February 7 and June 22, 2021 (n=211,197). We constructed mixed effects logistic regression models with hospitalization, ICU admission, and death as outcome variables. Models were adjusted for age, sex, time, comorbidities, and pregnancy status. Health units were included as random intercepts. Results: Compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 59% (49-69%) for hospitalization; 105% (82-134%) for ICU admission; and 61% (40-87%) for death. Increases with Delta variant were more pronounced: 120% (93-153%) for hospitalization; 287% (198-399%) for ICU admission; and 137% (50-230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-2 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred in the absence of VOC emergence.

9: Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel
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Posted 24 Apr 2021

Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel
6 tweets medRxiv epidemiology

Yair Goldberg, Micha Mandel, Yonatan Woodbridge, Ronen Fluss, Ilya Novikov, Rami Yaari, Arnona Ziv, Laurence Freedman, Amit Huppert

Worldwide shortage of vaccination against SARS-CoV-2 infection while the pandemic is still uncontrolled leads many states to the dilemma whether or not to vaccinate previously infected persons. Understanding the level of protection of previous infection compared to that of vaccination is critical for policy making. We analyze an updated individual-level database of the entire population of Israel to assess the protection efficacy of both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with COVID-19, severe disease, and death due to COVID-19. Vaccination was highly effective with overall estimated efficacy for documented infection of 92.8% (CI: [92.6, 93.0]); hospitalization 94.2% (CI: [93.6, 94.7]); severe illness 94.4% (CI: [93.6, 95.0]); and death 93.7% (CI: [92.5, 94.7]). Similarly, the overall estimated level of protection from prior SARS-CoV-2 infection for documented infection is 94.8% (CI: [94.4, 95.1]); hospitalization 94.1% (CI: [91.9, 95.7]); and severe illness 96.4% (CI: [92.5, 98.3]). Our results question the need to vaccinate previously-infected individuals.

10: α-Synuclein facilitates clathrin assembly in synaptic vesicle endocytosis
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Posted 30 Apr 2020

α-Synuclein facilitates clathrin assembly in synaptic vesicle endocytosis
5 tweets bioRxiv neuroscience

Karina J. Vargas, P L Colosi, Eric Girardi, Jae-Min Park, Sreeganga S Chandra

-Synuclein and family members {beta}-, and {gamma}-synuclein, are presynaptic proteins that sense and generate membrane curvature, properties important for synaptic vesicle (SV) cycling. {beta}{gamma}-synuclein triple knockout (KO) neurons exhibit SV endocytosis (SVE) deficits. Here, we investigate how SVE is regulated by -synuclein. Immuno-electron microscopy (EM) of synaptosomes reveals that -synuclein relocalizes from SVs to the synaptic membrane upon stimulation, allowing -synuclein to function on presynaptic membranes during or after stimulation. On cell membranes, we observe that -synuclein is colocalized with clathrin and its adaptor AP180. Clathrin patches that contain both -synuclein and AP180 were significantly larger than clathrin patches containing either protein alone. We also find that recruitment of clathrin and AP180 recruitment to membranes are altered in the absence of synucleins. Visualizing clathrin assembly on membranes using an in vitro endocytosis reconstitution system reveals that -synuclein increases clathrin patch size and enhances clathrin lattice curvature, facilitating normal clathrin coated pit maturation. Thus, -synuclein is an endocytic accessory protein that acts at early stages of SVE to controls the size and curvature of clathrin structures on the membrane.

11: Children with SARS-CoV-2 in the National COVID Cohort Collaborative (N3C)
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Posted 22 Jul 2021

Children with SARS-CoV-2 in the National COVID Cohort Collaborative (N3C)
4 tweets medRxiv pediatrics

Blake Martin, Peter E DeWitt, Seth Russell, Adit Anand, Katie R Bradwell, Carolyn Bremer, Davera Gabriel, Andrew T Girvin, Janos G Hajagos, Julie A McMurry, Andrew J Neumann, Emily R Pfaff, Anita Walden, Jacob T Wooldridge, Yun Jae Yoo, Joel Saltz, Ken R Gersing, Christopher G Chute, Melissa A Haendel, Richard Moffitt, Tellen D Bennett

Importance: SARS-CoV-2 Objective: To determine the characteristics, changes over time, outcomes, and severity risk factors of SARS-CoV-2 affected children within the National COVID Cohort Collaborative (N3C) Design: Prospective cohort study of encounters with end dates before May 27th, 2021. Setting: 45 N3C institutions Participants: Children < 19-years-old at initial SARS-CoV-2 testing Main Outcomes and Measures: Case incidence and severity over time, demographic and comorbidity severity risk factors, vital sign and laboratory trajectories, clinical outcomes, and acute COVID-19 vs MIS-C contrasts for children infected with SARS-CoV-2. Results: 728,047 children in the N3C were tested for SARS-CoV-2; of these, 91,865 (12.6%) were positive. Among the 5,213 (6%) hospitalized children, 685 (13%) met criteria for severe disease: mechanical ventilation (7%), vasopressor/inotropic support (7%), ECMO (0.6%), or death/discharge to hospice (1.1%). Male gender, African American race, older age, and several pediatric complex chronic condition (PCCC) subcategories were associated with higher clinical severity (p [&le;] 0.05). Vital signs (all p [&le;] 0.002) and many laboratory tests from the first day of hospitalization were predictive of peak disease severity. Children with severe (vs moderate) disease were more likely to receive antimicrobials (71% vs 32%, p < 0.001) and immunomodulatory medications (53% vs 16%, p < 0.001). Compared to those with acute COVID-19, children with MIS-C were more likely to be male, Black/African American, 1-to-12-years-old, and less likely to have asthma, diabetes, or a PCCC (p < 0.04). MIS-C cases demonstrated a more inflammatory laboratory profile and more severe clinical phenotype with higher rates of invasive ventilation (12% vs 6%) and need for vasoactive-inotropic support (31% vs 6%) compared to acute COVID-19 cases, respectively (p <0.03). Conclusions: In the largest U.S. SARS-CoV-2-positive pediatric cohort to date, we observed differences in demographics, pre-existing comorbidities, and initial vital sign and laboratory test values between severity subgroups. Taken together, these results suggest that early identification of children likely to progress to severe disease could be achieved using readily available data elements from the day of admission. Further work is needed to translate this knowledge into improved outcomes.

12: SARS-CoV-2 spike P681R mutation, a hallmark of the Delta variant, enhances viral fusogenicity and pathogenicity
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Posted 17 Jun 2021

SARS-CoV-2 spike P681R mutation, a hallmark of the Delta variant, enhances viral fusogenicity and pathogenicity
4 tweets bioRxiv microbiology

Akatsuki Saito, Takashi Irie, Rigel Suzuki, Tadashi Maemura, Hesham Nasser, Keiya Uriu, Yusuke Kosugi, Kotaro Shirakawa, Kenji Sadamasu, Izumi Kimura, Jumpei Ito, Jiaqi Wu, Kiyoko Iwatsuki-Horimoto, Mutsumi Ito, Seiya Yamayoshi, Seiya Ozono, Erika P Butlertanaka, Yuri L Tanaka, Ryo Shimizu, Kenta Shimizu, Kumiko Yoshimatsu, Ryoko Kawabata, Takemasa Sakaguchi, Kenzo Tokunaga, Isao Yoshida, Hiroyuki Asakura, Mami Nagashima, Yasuhiro Kazuma, Ryosuke Nomura, Yasuhito Horisawa, Kazuhisa Yoshimura, Akifumi Takaori-Kondo, Masaki Imai, The Genotype to Phenotype Japan (G2P-Japan) Consortium, So Nakagawa, Terumasa Ikeda, Takasuke Fukuhara, Yoshihiro Kawaoka, Kei Sato

During the current SARS-CoV-2 pandemic, a variety of mutations have been accumulated in the viral genome, and currently, four variants of concerns (VOCs) are considered as the hazardous SARS-CoV-2 variants to the human society1. The newly emerging VOC, the B.1.617.2/Delta variant, closely associates with a huge COVID-19 surge in India in Spring 20212. However, its virological property remains unclear. Here, we show that the B.1.617.2/Delta variant is highly fusogenic, and notably, more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates the spike protein cleavage and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity than the parental virus. Our data suggest that the P681R mutation is a hallmark that characterizes the virological phenotype of the B.1.617.2/Delta variant and is closely associated with enhanced pathogenicity.

13: Fast transcriptional activation of developmental signalling pathways during wound healing of the calcareous sponge Sycon ciliatum
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Posted 23 Jul 2021

Fast transcriptional activation of developmental signalling pathways during wound healing of the calcareous sponge Sycon ciliatum
3 tweets bioRxiv developmental biology

Cuneyt Caglar, Alexander Ereskovsky, Mary Laplante, Daria Tokina, Sven Leininger, Ilya Borisenko, Genevieve Aisbett, Di Pan, Marcin Adamski, Maja Adamska

Background: The ability to regenerate lost or damaged body parts is an ancient animal characteristic with a wide yet variable distribution across all phyla. Sponges, likely the sister group to all other animals, have remarkable regenerative abilities including whole body regeneration and re-development from dissociated cells. The calcareous sponge Sycon ciliatum has been subject to various regeneration studies since the beginning of the last century. However, the early steps of wound healing of S. ciliatum have not been addressed from the molecular perspective. Results: In this study, we combined electron microscopy with gene expression analysis to investigate wound healing after transverse sectioning of S. ciliatum. Microscopic analysis revealed massive transdifferentiation and collective migration behaviour of choanocytes and pinacocytes early upon injury (6-12h) as the main mechanisms for quick closure of the wound surface. RNA-sequencing identified upregulation of components of the conserved metazoan Wnt and TGF{beta} signalling pathways within 3h, preceding morphologically detectable wound healing events. De novo upregulation after a decline in expression coincides with morphologically visible polarity establishment. Moreover, by integrating the new wound healing data set with previously published data derived from intact sponge, we demonstrate similarity between gene activity during early wound healing and osculum maintenance. Whole mount in situ hybridisation of the TGF{beta} signalling pathway ligand SciTGF{beta}U and signal transducer SciSmadRa show that the early activation of both is initially encompassing a large area surrounding the cut surface with gradual restriction to the edge of the forming regenerative membrane as wound healing progresses. While SciTGF{beta}U transcripts are localised to exo- and endopinacocytes, SciSmadRa expression appears across all cell types. Using an EdU cell proliferation assay, we found that a global increase in cell proliferation is not visible before 12h into wound healing. Hence, the initial stages to cover the injury site including cell transdifferentiation and migration seem to be executed by cells remaining after injury. Gene expression clustering coupled with GO term enrichment analysis confirmed that expression of genes involved in processes related to cell proliferation, DNA repair as well as apoptotic processes at 3 and 6h of wound healing was not upregulated. On the other hand, genes associated with positive regulation of transcription, signal transduction, actin filament and chromatin organisation, as well as the Wnt signalling pathway are upregulated at early wound healing stages. Conclusion: We have analysed wound healing in the calcareous sponge Sycon ciliatum using microscopic and genomic methods. This study highlights a remarkable mechanism of interplay between cell transdifferentiation and collective migration we hypothesise to be regulated by conserved metazoan developmental pathways and numerous taxonomically restricted genes. Expression of these genes in regenerating and intact sponges sheds light on the long-standing question whether embryonic developmental pathways are redeployed in regeneration.

14: Effectiveness of the CoronaVac vaccine in the elderly population during a P.1 variant-associated epidemic of COVID-19 in Brazil: A test-negative case-control study
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Posted 21 May 2021

Effectiveness of the CoronaVac vaccine in the elderly population during a P.1 variant-associated epidemic of COVID-19 in Brazil: A test-negative case-control study
3 tweets medRxiv infectious diseases

Otavio T. Ranzani, Matt Hitchings, Murilo Dorion Neto, Tatiana Lang D'Agostini, Regiane Cardoso de Paula, Olivia Ferreira Pereira de Paula, Edlaine Faria de Moura Villela, Mario Sergio Scaramuzzini Torres, Silvano Barbosa de Oliveira, Wade L Schulz, Maria Almiron, Rodrigo Said, Roberto Dias de Oliveira, Patricia Vieira da Silva, Wildo Navegantes de Araujo, Jean Carlo Gorinchteyn, Jason R Andrews, Derek A.T. Cummings, Albert Ko, Julio Croda

Objective To estimate the effectiveness of the inactivated whole-virus vaccine, CoronaVac, against symptomatic COVID-19 in the elderly population of Sao Paulo State, Brazil during widespread circulation of the Gamma variant. Design Test negative case-control study. Setting Health-care facilities in Sao Paulo State, Brazil. Participants 43,774 adults aged 70 years or older who were residents of Sao Paulo State and underwent SARS-CoV-2 RT-PCR testing from January 17 to April 29, 2021. 26,433 cases with symptomatic COVID-19 and 17,622 symptomatic, test negative controls were selected into 7,950 matched pairs, according to age, sex, self-reported race, municipality of residence, prior COVID-19 status and date of RT-PCR testing. Intervention Vaccination with a two-dose regimen of CoronaVac. Main outcome measures RT-PCR confirmed symptomatic COVID-19 and COVID-19 associated hospitalizations and deaths. Results Adjusted vaccine effectiveness against symptomatic COVID-19 was 18.2% (95% CI, 0.0 to 33.2) in the period 0-13 days after the second dose and 41.6% (95% CI, 26.9 to 53.3) in the period >=14 days after the second dose. Adjusted vaccine effectiveness against hospitalisations was 59.0% (95% CI, 44.2 to 69.8) and against deaths was 71.4% (95% CI, 53.7 to 82.3) in the period >=14 days after the second dose. Vaccine effectiveness >=14 days after the second dose declined with increasing age for the three outcomes, and among individuals aged 70-74 years it was 61.8% (95% CI, 34.8 to 77.7) against symptomatic disease, 80.1% (95% CI, 55.7 to 91.0) against hospitalisations and 86.0% (95% CI, 50.4 to 96.1) against deaths. Conclusions Vaccination with CoronaVac was associated with a reduction in symptomatic COVID-19, hospitalisations and deaths in adults aged 70 years or older in a setting with extensive Gamma variant transmission. However, significant protection was not observed until completion of the two-dose regimen, and vaccine effectiveness declined with increasing age amongst this elderly population.

15: A decision-tree approach to treat platelet hyperactivity and anomalous blood clotting in acute COVID-19 patients
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Posted 07 Jul 2021

A decision-tree approach to treat platelet hyperactivity and anomalous blood clotting in acute COVID-19 patients
3 tweets medRxiv cardiovascular medicine

Gert J Laubscher, Petrus J Lourens, Chantelle Venter, Lize M Grobbelaar, Douglas B Kell, Etheresia Pretorius

The coronavirus disease 2019 (COVID-19) (SARS-Cov-2) has caused a worldwide, sudden and substantial increase in hospitalizations for pneumonia with multiorgan problems. An important issue is also that there is still no unified standard for the diagnosis and treatment of COVID-19. Substantial vascular events are significant accompaniments to lung complications in COVID-19 patients. Various papers have now also shown the significance of thromboelastrography (TEG(R)) as point-of-care technology to determine the levels of coagulopathy (both clotting and bleeding) in COVID-19, in managing COVID-19 patients. Here we present two treatment protocols that may used to treat thrombotic and bleeding or thrombocytopenia pathologies. We also present a case study, where the thrombotic pathology was successfully treated with the thrombotic protocol. Both the protocols use clinical parameters like D-dimer and CRP, as well as the TEG(R), to closely follow the daily clotting propensity of COVID-19 patients. We conclude by suggesting that the treatment of COVID-19 patients, should be based on a combination of blood biomarkers, and results from point-of-care analyses like the TEG(R). Such a combination approach closely follow the physiological responses of the immune system, the haematological, as well as the coagulation system, in real-time.

16: A SIMPLE, HOME-THERAPY ALGORITHM TO PREVENT HOSPITALIZATION FOR COVID-19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL MATCHED-COHORT STUDY
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Posted 26 Mar 2021

A SIMPLE, HOME-THERAPY ALGORITHM TO PREVENT HOSPITALIZATION FOR COVID-19 PATIENTS: A RETROSPECTIVE OBSERVATIONAL MATCHED-COHORT STUDY
3 tweets medRxiv infectious diseases

Fredy Suter, Elena Consolaro, Stefania Pedroni, Chiara Moroni, Elena Pasto, Maria Vittoria Paganini, Grazia Prevettoni, Umberto Cantarelli, Nadia Rubis, Norberto Perico, Annalisa Perna, Tobia Peracchi, Piero Ruggenenti, Giuseppe Remuzzi

Background. Effective simple, home-treatment algorithms implemented on the basis of a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalization of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health care providers. Methods. This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians from October 2020 to January 2021 according to the proposed recommendation algorithm with those of 90 age-, sex-, and comorbidities- matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalization. Analyses were by intention-to-treat. Findings. All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the recommended schedule cohort and 14 [7-30] days in the matched control cohort (p=0.033). Minor symptoms persisted in a lower percentage of patients in the recommended than in the control cohort (23.3% versus 73.3%, respectively, p<0.0001) and for a shorter period (p=0.0107). Two patients in the recommended cohort were hospitalized compared to 13 (14.4%) controls (Log-rank test, p=0.0038). Prevention algorithm abated the days and cumulative costs of hospitalization by >90% (from 481 to 44 days and from 296 to 28 thousand Euros, respectively. 1.2 patients had to be treated to save one hospitalization event. Interpretation. Implementation of an early, home-treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but almost blunted the risk of hospitalization and related treatment costs.

17: Efficacy of Proxalutamide in Hospitalized COVID-19 Patients: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial
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Posted 22 Jun 2021

Efficacy of Proxalutamide in Hospitalized COVID-19 Patients: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial
3 tweets medRxiv infectious diseases

Flavio A Cadegiani, Daniel N Fonseca, John McCoy, Ricardo A. Zimerman, Fatima N Mirza, Michael N Correia, Renan N Barros, Dirce C Onety, Karla Cristina P Israel, Brenda G Almeida, Emilyn O Guerreiro, Jose Enrique M Medeiros, Raquel N Nicolau, Luiza FM Nicolau, Rafael X Cunha, Maria Fernanda R Barroco, Patricia S da Silva, Gabriel S. Ferreira, Flavio Renan PC Alcantara, Angelo M Ribeiro, Felipe O de Almeida, Adailson A de Souza, Suzyane S do Rosario, Raysa WS Paulain, Alessandra Reis, Marissa Li, Claudia E Thompson, Gerald J Nau, Carlos Gustavo Wambier, Andy Goren

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is mediated by the androgen-promoted protease, transmembrane protease, serine 2 (TMPRSS2). Previously, we have shown that treatment with proxalutamide, a non-steroidal androgen receptor antagonist, accelerates viral clearance and clinical remission in outpatients with coronavirus disease 2019 (COVID-19) compared to placebo. The effects in hospitalized COVID-19 patients were unknown. Methods: Men and women hospitalized but not requiring mechanical ventilation were randomized (1:1 ratio) to receive 300 mg of proxalutamide per day or placebo for 14 days. The study was conducted at eight sites in the state of Amazonas, Brazil. The primary outcome measure was the clinical status (8-point ordinal scale) at 14-days post-randomization. The primary efficacy endpoint was the 14-day recovery ratio (alive hospital discharge [scores 1, 2]). Findings: A total of 645 patients were randomized (317 received proxalutamide, 328 placebo) and underwent intention-to-treat analysis. The 14-day median ordinal scale score in the proxalutamide group was 1 (interquartile range [IQR]=1-2) versus 7 (IQR=2-8) for placebo, P<0.001. The 14-day recovery rate was 81.4% for proxalutamide and 35.7% for placebo (recovery ratio, 2.28; 95% CI 1.95-2.66 [P<0.001]). The 28-day all-cause mortality rate was 11.0% for proxalutamide versus 49.4% for placebo (hazard ratio, 0.16; 95% CI 0.11-0.24). The median post-randomization time to recovery was 5 days (IQR=3-8) for proxalutamide versus 10 days (IQR=6-15) for placebo. Interpretation: Hospitalized COVID-19 patients not requiring mechanical ventilation receiving proxalutamide had a 128% higher recovery rate than those treated with placebo. All-cause mortality was reduced by 77.7% over 28 days. (ClinicalTrials.gov number, NCT04728802).

18: Viral Load of SARS-CoV-2 in Respiratory Aerosols Emitted by COVID-19 Patients while Breathing, Talking, and Singing
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Posted 19 Jul 2021

Viral Load of SARS-CoV-2 in Respiratory Aerosols Emitted by COVID-19 Patients while Breathing, Talking, and Singing
3 tweets medRxiv infectious diseases

Kristen K. Coleman, Douglas Jie Wen Tay, Kai Sen Tan, Sean Wei Xiang Ong, Than The Son, Ming Hui Koh, Yi Qing Chin, Haziq Nasir, Tze Minn Mak, Justin Jang Hann Chu, Donald K. Milton, Vincent T.K. Chow, Paul Anantharajah Tambyah, Mark Chen, Tham Kwok Wai

Background: Multiple SARS-CoV-2 superspreading events suggest that aerosols play an important role in driving the COVID-19 pandemic. However, the detailed roles of coarse (>5m) and fine ([&le;]5m) respiratory aerosols produced when breathing, talking, and singing are not well-understood. Methods: Using a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing. Results: Among the 22 study participants, 13 (59%) emitted detectable levels of SARS-CoV-2 RNA in respiratory aerosols, including 3 asymptomatic patients and 1 presymptomatic patient. Viral loads ranged from 63 - 5,821 N gene copies per expiratory activity. Patients earlier in illness were more likely to emit detectable RNA, and loads differed significantly between breathing, talking, and singing. The largest proportion of SARS-CoV-2 RNA copies was emitted by singing (53%), followed by talking (41%) and breathing (6%). Overall, fine aerosols constituted 85% of the viral load detected in our study. Virus cultures were negative. Conclusions: Fine aerosols produced by talking and singing contain more SARS-CoV-2 copies than coarse aerosols and may play a significant role in the transmission of SARS-CoV-2. Exposure to fine aerosols should be mitigated, especially in indoor environments where airborne transmission of SARS-CoV-2 is likely to occur. Isolating viable SARS-CoV-2 from respiratory aerosol samples remains challenging, and whether this can be more easily accomplished for emerging SARS-CoV-2 variants is an important enquiry for future studies.

19: AI for radiographic COVID-19 detection selects shortcuts over signal
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Posted 14 Sep 2020

AI for radiographic COVID-19 detection selects shortcuts over signal
2 tweets medRxiv radiology and imaging

Alex J. DeGrave, Joseph D Janizek, Su-In Lee

Artificial intelligence (AI) researchers and radiologists have recently reported AI systems that accurately detect COVID-19 in chest radiographs. However, the robustness of these systems remains unclear. Using state-of-the-art techniques in explainable AI, we demonstrate that recent deep learning systems to detect COVID-19 from chest radiographs rely on confounding factors rather than medical pathology, creating an alarming situation in which the systems appear accurate, but fail when tested in new hospitals. We observe that the approach to obtain training data for these AI systems introduces a nearly ideal scenario for AI to learn these spurious "shortcuts." Because this approach to data collection has also been used to obtain training data for detection of COVID-19 in computed tomography scans and for medical imaging tasks related to other diseases, our study reveals a far-reaching problem in medical imaging AI. In addition, we show that evaluation of a model on external data is insufficient to ensure AI systems rely on medically relevant pathology, since the undesired "shortcuts" learned by AI systems may not impair performance in new hospitals. These findings demonstrate that explainable AI should be seen as a prerequisite to clinical deployment of ML healthcare models.

20: Effects of non-pharmaceutical interventions on COVID-19: A Tale of Three Models
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Posted 27 Jul 2020

Effects of non-pharmaceutical interventions on COVID-19: A Tale of Three Models
2 tweets medRxiv health policy

Vincent Chin, John Ioannidis, Martin Tanner, Sally Cripps

Objective: To compare the inference regarding the effectiveness of the various non-pharmaceutical interventions (NPIs) for COVID-19 obtained from different SIR models. Study design and setting: We explored two models developed by Imperial College that considered only NPIs without accounting for mobility (model 1) or only mobility (model 2), and a model accounting for the combination of mobility and NPIs (model 3). Imperial College applied models 1 and 2 to 11 European countries and to the USA, respectively. We applied these models to 14 European countries (original 11 plus another 3), over two different time horizons. Results: While model 1 found that lockdown was the most effective measure in the original 11 countries, model 2 showed that lockdown had little or no benefit as it was typically introduced at a point when the time-varying reproductive number was already very low. Model 3 found that the simple banning of public events was beneficial, while lockdown had no consistent impact. Based on Bayesian metrics, model 2 was better supported by the data than either model 1 or model 3 for both time horizons. Conclusions: Inferences on effects of NPIs are non-robust and highly sensitive to model specification. Claimed benefits of lockdown appear grossly exaggerated.

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