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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 150,603 papers from 634,740 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.

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

1: A connectomic study of a petascale fragment of human cerebral cortex
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Posted 30 May 2021

A connectomic study of a petascale fragment of human cerebral cortex
18 tweets bioRxiv neuroscience

Alexander Shapson-Coe, Michal Januszewski, Daniel R Berger, Art Pope, Yuelong Wu, Tim Blakely, Richard L. Schalek, Peter H Li, Shuohong Wang, Jeremy Maitlin-Shepard, Neha Karlupia, Sven Dorkenwald, Evelina Sjostedt, Laramie Leavitt, Dongil Lee, Luke Bailey, Angerica Fitzmaurice, Rohin Kar, Benjamin Field, Hank Wu, Julian Wagner-Carena, David Aley, Joanna Lau, Zudi Lin, Donglai Wei, Hanspeter Pfister, Adi Peleg, Viren Jain, Jeff W Lichtman

We acquired a rapidly preserved human surgical sample from the temporal lobe of the cerebral cortex. We stained a 1 mm3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at ~30 nm and imaged these sections using a high-speed multibeam scanning electron microscope. We used computational methods to render the three-dimensional structure of 50,000 cells, hundreds of millions of neurites and 133.7 million synaptic connections. The 1.4 petabyte electron microscopy volume, the segmented cells, cell parts, blood vessels, myelin, inhibitory and excitatory synapses, and 100 manually proofread cells are available to peruse online. Despite the incompleteness of the automated segmentation caused by split and merge errors, many interesting features were evident. Glia outnumbered neurons 2:1 and oligodendrocytes were the most common cell type in the volume. The E:I balance of neurons was 69:31%, similar to the ratio of excitatory versus inhibitory synapses in the volume, which was 63:37%. The E:I ratio of synapses was significantly higher on pyramidal neurons than inhibitory interneurons. We found that deep layer excitatory cell types can be classified into subsets, based on structural and connectivity differences, that chandelier interneurons not only innervate excitatory neuron initial segments as previously described, but also each others initial segments. Furthermore, among the thousands of weak connections established on each neuron, there exist rarer highly powerful axonal inputs that establish multi-synaptic contacts (up to ~20 synapses) with target neurons. Our analysis indicates that these strong inputs are specific, and allow small numbers of axons to have an outsized role in the activity of some of their postsynaptic partners.

2: SARS-CoV-2 reinfection in a cohort of 43,000 antibody-positive individuals followed for up to 35 weeks
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Posted 15 Jan 2021

SARS-CoV-2 reinfection in a cohort of 43,000 antibody-positive individuals followed for up to 35 weeks
14 tweets medRxiv epidemiology

Laith J Abu-Raddad, Hiam Chemaitelly, Peter Coyle, Joel A Malek, Ayeda A Ahmed, Yasmin A. Mohamoud, Shameem Younuskunju, Houssein H. Ayoub, Zaina Al Kanaani, Einas Al Kuwari, Adeel A Butt, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Hanan F. Abdul Rahim, Gheyath Nasrallah, HADI M. YASSINE, Mohamed G. Al Kuwari, Hamad Eid Al Romaihi, Mohamed H. Al-Thani, Abdullatif Al Khal, Roberto Bertollini

Background: Reinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. Risk and incidence rate of SARS-CoV-2 reinfection were assessed in a large cohort of antibody-positive persons in Qatar. Methods: All SARS-CoV-2 antibody-positive persons with a PCR-positive swab [≥]14 days after the first-positive antibody test were individually investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those antibody-negative. Results: Among 43,044 anti-SARS-CoV-2 positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab [≥]14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the risk of reinfection was estimated at 0.10% (95% CI: 0.08-0.11%). The incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), risk of infection was estimated at 2.15% (95% CI: 2.08-2.22%) and incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing. Conclusions: Reinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months.

3: 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
9 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.

4: 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
9 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.

5: Fatal neuroinvasion of SARS-CoV-2 in K18-hACE2 mice is partially dependent on hACE2 expression
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Posted 13 Jan 2021

Fatal neuroinvasion of SARS-CoV-2 in K18-hACE2 mice is partially dependent on hACE2 expression
8 tweets bioRxiv pathology

Mariano Carossino, Paige Montanaro, Aoife O'Connell, Devin Kenney, Hans Gertje, Kyle Grosz, Susanna Kurnick, Markus Bosmann, Mohsan Saeed, Udeni Balasuriya, Florian Douam, Nicholas A. Crossland

Animal models recapitulating the distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. However, the cause(s) and mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection for up to 14 days post-infection. Despite infection and moderate inflammation in the lungs, lethality was invariably associated with viral neuroinvasion and neuronal damage (including spinal motor neurons). Neuroinvasion occurred following virus transport through the olfactory neuroepithelium in a manner that was only partially dependent on hACE2. Interestingly, SARS-CoV-2 tropism was overall neither widespread among nor restricted to only ACE2-expressing cells. Although our work incites caution in the utility of the K18-hACE2 model to study global aspects of SARS-CoV-2 pathogenesis, it underscores this model as a unique platform for exploring the mechanisms of SARS-CoV-2 neuropathogenesis. SUMMARYCOVID-19 is a respiratory disease caused by SARS-CoV-2, a betacoronavirus. Here, we show that in a widely used transgenic mouse model of COVID-19, lethality is invariably associated with viral neuroinvasion and the ensuing neuronal disease, while lung inflammation remains moderate.

6: Mechanosensitivity of nucleocytoplasmic transport
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Posted 24 Jul 2021

Mechanosensitivity of nucleocytoplasmic transport
8 tweets bioRxiv biophysics

Ion Andreu, Ignasi Granero, Nimesh Chahare, Kessem Clein, Marc Molina Jordan, Amy E.M. Beedle, Alberto Elosegui-Artola, Xavier Trepat, Barak Raveh, Pere Roca-Cusachs

Mechanical force controls fundamental cellular processes in health and disease, and increasing evidence shows that the nucleus both experiences and senses applied forces. Here we show that nuclear forces differentially control both passive and facilitated nucleocytoplasmic transport, setting the rules for the mechanosensitivity of shuttling proteins. We demonstrate that nuclear force increases permeability across nuclear pore complexes, with a dependence on molecular weight that is stronger for passive than facilitated diffusion. Due to this differential effect, force leads to the translocation into or out of the nucleus of cargoes within a given range of molecular weight and affinity for nuclear transport receptors. Further, we show that the mechanosensitivity of several transcriptional regulators can be both explained by this mechanism, and engineered exogenously by introducing appropriate nuclear localization signals. Our work sets a novel framework to understand mechanically induced signalling, with potential general applicability across signalling pathways and pathophysiological scenarios.

7: Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) Up to 15 Months Post-Infection
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Posted 25 Jun 2021

Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) Up to 15 Months Post-Infection
7 tweets bioRxiv immunology

Bruce Patterson, Edgar B Francisco, Ram Yogendra, Emily Long, Amruta Pise, Hallison Rodrigues, Eric Hall, Monica Herrera, Purvi Parikh, Jose Guevara-Coto, Timothy Triche, Paul Scott, Saboor Hekmati, Dennis Maglinte, Xaiolan Chang, Rodrigo Rodriguez, Javier Mora

The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. Non-classical monocytes are capable of causing inflammation throughout the body in response to fractalkine/CX3CL1 and RANTES/CCR5.

8: Effectiveness of the BNT162b2 vaccine in preventing COVID-19 in the working age population - first results from a cohort study in Southern Sweden
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Posted 21 Apr 2021

Effectiveness of the BNT162b2 vaccine in preventing COVID-19 in the working age population - first results from a cohort study in Southern Sweden
7 tweets medRxiv infectious diseases

Jonas Björk, Malin Inghammar, Mahnaz Moghaddassi, Magnus Rasmussen, Ulf Malmqvist, Fredrik Kahn

Background Vaccine effectiveness against COVID-19 needs to be assessed in diverse real-world population settings. Methods A cohort study of 805 741 residents in Scania county, Southern Sweden, aged 18-64 years, of whom 26 587 received at least one dose of the BNT162b2 vaccine. Incidence rates of COVID-19 were estimated in sex- and age-adjusted analysis and stratified in two-week periods with substantial community spread of the disease. Results The estimated vaccine effectiveness in preventing infection >7 days after second dose was 86% (95% CI 72-94%) but only 42% (95% CI 14-63%) >14 days after a single dose. No difference in vaccine effectiveness was observed between females and males. Having a prior positive test was associated with 91% (95% CI 85 to 94%) effectiveness against new infection among the unvaccinated. Conclusion A satisfactory effectiveness of BNT162b2 after the second dose was suggested, but with possibly substantially lower effect before the second dose.

9: Identification of a new family of "megaphages" that are abundant in the marine environment
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Posted 26 Jul 2021

Identification of a new family of "megaphages" that are abundant in the marine environment
7 tweets bioRxiv microbiology

Slawomir Michniewski, Branko Rihtman, Ryan Cook, Michael Jones, William Wilson, Dave D Scanlan, Andrew Millard

Megaphages - bacteriophages harbouring extremely large genomes - have recently been found to be ubiquitous, being described from a variety of microbiomes ranging from the animal gut to soil and freshwater systems. However, no complete marine megaphage has been identified to date. Here, using both short and long read sequencing, we assembled >900 high-quality draft viral genomes from water in the English Channel. One of these genomes included a novel megaphage, Mar_Mega_1 at >650 Kb, making it one of the largest phage genomes assembled to date. Utilising phylogenetic and network approaches, we found this phage represents a new family of bacteriophages. Genomic analysis showed Mar_Mega_1 shares relatively few homologues with its closest relatives, but, as with other mega-phages Mar_Mega_1 contained a variety of auxiliary metabolic genes responsible for carbon metabolism and nucleotide biosynthesis, including isocitrate dehydrogenase [NADP] and nicotinamide-nucleotide amidohydrolase [PncC] which have not previously been identified in megaphages. The results of this study indicate that phages containing extremely large genomes can be found in abundance in the marine environment and augment host metabolism by mechanisms not previously described.

10: 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
4 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 ([≤]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.

11: The infection fatality rate of COVID-19 inferred from seroprevalence data
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Posted 19 May 2020

The infection fatality rate of COVID-19 inferred from seroprevalence data
4 tweets medRxiv infectious diseases

John Ioannidis

Objective To estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies. Methods Population studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of July 11, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Secondarily, results from national studies were also examined from preliminary press releases and reports whenever a country had no other data presented in full papers of preprints. Results 36 studies (43 estimates) were identified with usable data to enter into calculations and another 7 preliminary national estimates were also considered for a total of 50 estimates. Seroprevalence estimates ranged from 0.222% to 47%. Infection fatality rates ranged from 0.00% to 1.63% and corrected values ranged from 0.00% to 1.31%. Across 32 different locations, the median infection fatality rate was 0.27% (corrected 0.24%). Most studies were done in pandemic epicenters with high death tolls. Median corrected IFR was 0.10% in locations with COVID-19 population mortality rate less than the global average (<73 deaths per million as of July 12, 2020), 0.27% in locations with 73-500 COVID-19 deaths per million, and 0.90% in locations exceeding 500 COVID-19 deaths per million. Among people <70 years old, infection fatality rates ranged from 0.00% to 0.57% with median of 0.05% across the different locations (corrected median of 0.04%). Conclusions The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.

12: Breakthrough Symptomatic COVID-19 Infections Leading to Long Covid: Report from Long Covid Facebook Group Poll
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Posted 26 Jul 2021

Breakthrough Symptomatic COVID-19 Infections Leading to Long Covid: Report from Long Covid Facebook Group Poll
4 tweets medRxiv epidemiology

Daisy Massey, Diana Berrent, Harlan Krumholz

Vaccines have been shown to be extremely effective in preventing COVID-19 hospitalizations and deaths. However, a question remains whether vaccine breakthrough cases can still lead to Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as Long Covid. To address this question, the Survivor Corps group, a grassroots COVID-19 organization focused on patient support and research, posted a poll to its 169,900 members that asked about breakthrough cases, Long Covid, and hospitalizations. 1,949 people who self-report being fully vaccinated have responded to date. While robust data are needed in a larger, unbiased sample to extrapolate rates to the population, we analyzed the results of this public poll to determine what people were reporting regarding Long Covid after breakthrough infection and to prompt discussion of how breakthrough cases are measured. The poll was posted in the Survivor Corps Facebook group (~169,900 members). Of the 1,949 participants who responded to the poll, 44 reported a symptomatic breakthrough case and 24 of those reported that the case led to symptoms of Long Covid. 1 of these 24 cases was reported to have led to hospitalization in addition to Long Covid.

13: Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study
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Posted 21 Oct 2020

Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study
3 tweets medRxiv psychiatry and clinical psychology

Adam Hampshire, William Trender, Samuel R Chamberlain, Amy Jolly, Jon E. Grant, Fiona Patrick, Ndaba Mazibuko, Steve CR Williams, Joseph M Barnby, Peter J. Hellyer, Mitul A Mehta

Case studies have revealed neurological problems in severely affected COVID-19 patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of severity. We analysed cognitive test data from 84,285 Great British Intelligence Test participants who completed a questionnaire regarding suspected and biologically confirmed COVID-19 infection. People who had recovered, including those no longer reporting symptoms, exhibited significant cognitive deficits when controlling for age, gender, education level, income, racial-ethnic group and pre-existing medical disorders. They were of substantial effect size for people who had been hospitalised, but also for mild but biologically confirmed cases who reported no breathing difficulty. Finer grained analyses of performance support the hypothesis that COVID-19 has a multi-system impact on human cognition. Significance statementThere is evidence that COVID-19 may cause long term health changes past acute symptoms, termed long COVID. Our analyses of detailed cognitive assessment and questionnaire data from tens thousands of datasets, collected in collaboration with BBC2 Horizon, align with the view that there are chronic cognitive consequences of having COVID-19. Individuals who recovered from suspected or confirmed COVID-19 perform worse on cognitive tests in multiple domains than would be expected given their detailed age and demographic profiles. This deficit scales with symptom severity and is evident amongst those without hospital treatment. These results should act as a clarion call for more detailed research investigating the basis of cognitive deficits in people who have survived SARS-COV-2 infection.

14: M&Ms: A software for building realistic Microbial Mock communities
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Posted 22 Apr 2021

M&Ms: A software for building realistic Microbial Mock communities
3 tweets bioRxiv bioinformatics

Natalia García-García, Javier Tamames, Fernando Puente-Sánchez

Motivation: Advances in sequencing technologies have triggered the development of many bioinformatic tools aimed to analyze these data. As these tools need to be tested, it is important to simulate datasets that resemble realistic conditions. Although there is a large amount of software dedicated to produce reads from in silico microbial communities, often the simulated data diverge widely from real situations. Results: Here, we introduce M&Ms, a user-friendly open-source bioinformatic tool to produce realistic amplicon datasets from reference sequences, based on pragmatic ecological parameters. This tool creates sequence libraries for in silico microbial communities with user-controlled richness, evenness, microdiversity, and source environment. M&Ms allows the user to generate simple to complex read datasets based on real parameters that can be used in developing bioinformatic software or in benchmarking current tools. M&Ms also provides additional figures and files with extensive details on how each synthetic community is composed, so that users can make informed choices when designing their benchmarking pipelines. Availability: The source code of M&Ms is freely available from https://github.com/ggnatalia/MMs

15: Development of a pan-neuronal genetic driver in Aedes aegypti mosquitoes
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Posted 22 Aug 2020

Development of a pan-neuronal genetic driver in Aedes aegypti mosquitoes
3 tweets bioRxiv neuroscience

Zhilei Zhao, David Tian, Carolyn S McBride

The mosquito Aedes aegypti is the primary worldwide vector of arboviruses that infect humans, including dengue, Zika, chikungunya, and yellow fever. Recent advances in transgenic technology have yielded important new insight into the biology of this disease vector. The early development of neurogenetic tools, in particular, is beginning to shed light on the neural basis of behaviors that allow Ae. aegypti to thrive in human environments and find and bite human hosts. Despite these advances, a pan-neuronal expression driver remains elusive. Pan-neuronal drivers give researchers genetic access to all neurons and thus provide a critical entry point for circuit dissection. Here, we describe our efforts to generate pan-neuronal drivers in Ae. aegypti via targeted knock-in of in-frame reporter constructs to the native coding sequence of broadly expressed neural genes with CRISPR/Cas9. Two of five attempts were successful, resulting in a Syt1:GCaMP6s strain that expresses synaptically-localized GCaMP in all neurons and a brp-T2A-QF2w driver strain that can be used to drive and amplify expression of any effector in all neurons via the Q binary system. We show that both manipulations broadly and uniformly label the nervous system and have only mild effects on behavior. We envision that these strains will facilitate neurobiological research in Ae. aegypti mosquitoes and provide documentation of both successful and failed manipulations as a roadmap for similar tool development in other non-model species. ### Competing Interest Statement The authors have declared no competing interest.

16: 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)
2 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.

17: Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells
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Posted 27 Apr 2021

Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells
2 tweets medRxiv allergy and immunology

Kristen W Cohen, Susanne L. Linderman, Zoe Moodie, Julie Czartoski, Lilin Lai, Grace Mantus, Carson Norwood, Lindsay E. Nyhoff, Venkata Viswanadh Edara, Katharine Floyd, Stephen C De Rosa, Hasan Ahmed, Rachael Whaley, Shivan N. Patel, Brittany Prigmore, Maria P Lemos, Carl W Davis, Sarah Furth, James O'Keefe, Mohini P. Gharpure, Sivaram Gunisetty, Kathy A. Stephens, Rustom Antia, Veronika I Zarnitsyna, David S Stephens, Srilatha Edupuganti, Nadine Rouphael, Evan J. Anderson, Aneesh K. Mehta, Jens Wrammert, Mehul S. Suthar, Rafi Ahmed, M Juliana McElrath

Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. We evaluated 254 COVID-19 patients longitudinally from early infection and for eight months thereafter and found a predominant broad-based immune memory response. SARS-CoV-2 spike binding and neutralizing antibodies exhibited a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. In addition, there was a sustained IgG+ memory B cell response, which bodes well for a rapid antibody response upon virus re-exposure. Polyfunctional virus-specific CD4+ and CD8+ T cells were also generated and maintained with an estimated half-life of 200 days. Interestingly, the CD4+ T cell response equally targeted several SARS-CoV-2 proteins, whereas the CD8+ T cell response preferentially targeted the nucleoprotein, highlighting the importance of including the nucleoprotein as a potential vaccine antigen. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.

18: The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses
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Posted 06 May 2021

The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses
2 tweets medRxiv infectious diseases

F. Konstantin Föhse, Büsranur Geckin, Gijs Overheul, Josephine van de Maat, Gizem Kilic, Ozlem Bulut, Helga Dijkstra, Heidi Lemmers, S. Andrei Sarlea, Maartje Reijnders, Jacobien Hoogerwerf, Jaap ten Oever, Elles Simonetti, Frank L van de Veerdonk, Leo A.B. Joosten, Bart L. Haagmans, Reinout van Crevel, Yang Li, Ronald P. van Rij, Corine GeurtsvanKessel, Marien I. de Jonge, Jorge Domínguez-Andrés, Mihai G. Netea

The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.

19: The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape
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Posted 05 Mar 2021

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape
2 tweets medRxiv infectious diseases

Darren P Martin, Steven Weaver, Houryiah Tegally, Emmanuel James San, Stephen D. Shank, Eduan Wilkinson, Jennifer Giandhari, Sureshnee Naidoo, Yeshnee Pillay, Lavanya Singh, Richard J. Lessells, NGS-SA Consortium, COVID-19 Genomics UK (COG-UK) Consortium, Ravindra K Gupta, Joel O. Wertheim, Anton Nekturenko, Ben Murrell, Gordon W. Harkins, Philippe Lemey, Oscar MacLean, David L Robertson, Tulio de Oliveira, Sergei L Kosakovsky Pond

The emergence and rapid rise in prevalence of three independent SARS-CoV-2 '501Y lineages', B.1.1.7, B.1.351 and P.1, in the last three months of 2020 has prompted renewed concerns about the evolutionarily capacity of SARS-CoV-2 to adapt to both rising population immunity and public health interventions such as vaccines and social distancing. Viruses giving rise to the different 501Y lineages have, presumably under intense natural selection following a shift in host environment, independently acquired multiple unique and convergent mutations. As a consequence all have gained epidemiological and immunological properties that will likely complicate the control of COVID-19. Here, by examining patterns of mutations that arose in SARS-CoV-2 genomes during the pandemic we find evidence of a major change in the selective forces acting on immunologically important SARS-CoV-2 genes (such as N and S) that likely coincided with the emergence of the 501Y lineages. In addition to involving continuing sequence diversification, we find evidence that a significant portion of the ongoing adaptive evolution of the 501Y lineages also involves further convergence between the lineages. Our findings highlight the importance of monitoring how members of these known 501Y lineages, and others still undiscovered, are convergently evolving similar strategies to ensure their persistence in the face of mounting infection and vaccine induced host immune recognition.

20: 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
2 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.

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