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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 166,567 papers from 692,091 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.

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

1: Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals
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Posted 24 Nov 2021

Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals
120 tweets medRxiv epidemiology

Stijn P. Andeweg, Harry Vennema, Irene Veldhuijzen, Naomi Smorenburg, Dennis Schmitz, Florian Zwagemaker, SeqNeth Molecular surveillance group, RIVM COVID-19 Molecular epidemiology group, Arianne B. van Gageldonk-Lafeber, Susan JM Hahne, Chantal Reusken, Mirjam J. Knol, Dirk Eggink

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) break through infection- or vaccine-induced immunity is not well understood. Here, we analyze 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We find evidence for an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared to the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14-59 days after complete vaccination compared to 60 days and longer. In contrast to vaccine-induced immunity, no increased risk for reinfection with Beta, Gamma or Delta variants relative to Alpha variant was found in individuals with infection-induced immunity.

2: The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines
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Posted 23 Aug 2021

The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines
81 tweets bioRxiv microbiology

Yafei Liu, Noriko Arase, Jun-ichi Kishikawa, Mika Hirose, Songling Li, Asa Tada, Sumiko Matsuoka, Akemi Arakawa, Kanako Akamatsu, Chikako Ono, Hui Jin, Kazuki Kishida, Wataru Nakai, Masako Kohyama, Atsushi Nakagawa, Yoshiaki Yamagishi, Hironori Nakagami, Atsushi Kumanogoh, Yoshiharu Matsuura, Daron M Standley, Takayuki Kato, Masato Okada, Manabu Fujimoto, Hisashi Arase

mRNA-based vaccines provide effective protection against most common SARS-CoV-2 variants. However, identifying likely breakthrough variants is critical for future vaccine development. Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity. Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity. Given the fact that a Delta variant with three similar RBD mutations has already emerged according to the GISAID database, it is necessary to develop vaccines that protect against such complete breakthrough variants.

3: Artemisia annua hot-water extracts show potent activity in vitro against Covid-19 variants including delta
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Posted 08 Sep 2021

Artemisia annua hot-water extracts show potent activity in vitro against Covid-19 variants including delta
73 tweets bioRxiv microbiology

Manoj S. Nair, Yaoxing Huang, David A. Fidock, Melissa Towler, Pamela Weathers

Ethnopharmacological relevance: For millennia in Southeast Asia, Artemisia annua L. was used to treat fever. This medicinal plant is effective against numerous infectious microbial and viral diseases and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria. Aim of the Study: The SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants. Materials and Methods: Using Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-water A. annua extracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five fully infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1). Results: In addition to being effective against the original wild type WA1, A. annua cultivars A3, BUR, MED and SAM were also potent against all five variants. IC50 and IC90 values based on measured artemisinin content ranged from 0.3-8.4 M and 1.4-25.0 M, respectively. The IC50 and IC90 values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0-67.7 g DW and 59.5-160.6 g DW, respectively. Cell toxicity was insignificant at a leaf dry weight of [≤]50 g in the extract of any cultivar. Conclusions: Results suggest that oral consumption of A. annua hot-water extracts (tea infusions), could provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.

4: The Tabula Sapiens: a multiple organ single cell transcriptomic atlas of humans
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Posted 20 Jul 2021

The Tabula Sapiens: a multiple organ single cell transcriptomic atlas of humans
70 tweets bioRxiv cell biology

The Tabula Sapiens Consortium, Stephen R. Quake

Molecular characterization of cell types using single cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. While most work has focused on specific organs, there is a need for a reference which enables comparisons of cell types between organs and tissues. We present a human single cell transcriptomic atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This allows us to control for individual variation and enables characterization of more than 400 cell types, their distribution across tissues and tissue specific variation in gene expression. From this we identify the clonal distribution of T cells between tissues, the tissue specific mutation rate in B cells, and analyze the cell cycle state and proliferative potential of shared cell types across tissues. Finally, we characterize cell type specific RNA splicing and how such splicing varies across tissues within an individual.

5: Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections
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Posted 25 Aug 2021

Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections
36 tweets medRxiv infectious diseases

Sivan Gazit, Roei Shlezinger, Galit Perez, Roni Lotan, Asaf Peretz, Amir Ben-Tov, Dani Cohen, Khitam Muhsen, Gabriel Chodick, Tal Patalon

Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.

6: Thrombocytopenia and splenic platelet directed immune responses after intravenous ChAdOx1 nCov-19 administration
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Posted 29 Jun 2021

Thrombocytopenia and splenic platelet directed immune responses after intravenous ChAdOx1 nCov-19 administration
17 tweets bioRxiv immunology

Leo Nicolai, Alexander Leunig, Kami Pekayvaz, Afra Anjum, Eva Riedlinger, Luke Eivers, Marie-Louise Hoffknecht, Dario Rossaro, Raphael Escaig, Rainer Kaiser, Vivien Polewka, Anna Titova, Karsten Spiekermann, Matteo Iannacone, Konstantin Stark, Steffen Massberg

Vaccines against SARS-CoV-2 are based on a range of novel vaccine platforms, with adenovirus-based approaches (like ChAdOx1 nCov-19) being one of them. Recently a rare and novel complication of SARS-CoV-2 targeted adenovirus vaccines has emerged: thrombosis with thrombocytopenia syndrome (TTS). TTS is characterized by low platelet counts, clot formation at unusual anatomic sites and platelet-activating PF4-polyanion antibodies reminiscent of heparin-induced thrombocytopenia. Here, we employ in vitro and in vivo models to characterize the possible mechanisms of this platelet-targeted autoimmunity. We show that intravenous but not intramuscular injection of ChAdOx1 nCov-19 triggers platelet-adenovirus aggregate formation and platelet activation. After intravenous injection, these aggregates are phagocytosed by macrophages in the spleen and platelet remnants are found in the marginal zone and follicles. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelets. Our work contributes to the understanding of TTS and highlights accidental intravenous injection as potential mechanism for post-vaccination TTS. Hence, safe intramuscular injection, with aspiration prior to injection, could be a potential preventive measure when administering adenovirus-based vaccines.

7: Safety Monitoring of mRNA Vaccines Administered During the Initial 6 Months of the U.S. COVID-19 Vaccination Program: Reports to Vaccine Adverse Events Reporting System (VAERS) and v-safe
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Posted 27 Oct 2021

Safety Monitoring of mRNA Vaccines Administered During the Initial 6 Months of the U.S. COVID-19 Vaccination Program: Reports to Vaccine Adverse Events Reporting System (VAERS) and v-safe
17 tweets medRxiv infectious diseases

Hannah G. Rosenblum, Julianne M. Gee, Ruiling Liu, Paige L. Marquez, Bicheng Zheng, Penelope Strid, Winston E. Abara, Michael M. McNeil, Tanya R. Myers, Anne M. Hause, John R. Su, Bethany Baer, David Menschik, Lauri E. Markowitz, Tom T. Shimabukuro, David K Shay

Background: In December 2020, two mRNA-based COVID-19 vaccines were authorized for use in the United States. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system, and v-safe, an active surveillance system. Methods: VAERS and v-safe data during December 14, 2020-June 14, 2021 were analyzed. VAERS reports were categorized as non-serious, serious, or death; reporting rates were calculated. Rates of reported deaths were compared to expected mortality rates by age. Proportions of v-safe participants reporting local and systemic reactions or health impacts the week following doses 1 and 2 were determined. Findings: During the analytic period, 298,792,852 doses of mRNA vaccines were administered in the United States. VAERS processed 340,522 reports; 92.1% were non-serious; 6.6%, serious, non-death; and 1.3%, death. Over half of 7,914,583 v-safe participants self-reported local and systemic reactogenicity, more frequently after dose 2. Injection-site pain, fatigue, and headache were commonly reported during days 0-7 following vaccination. Reactogenicity was reported most frequently one day after vaccination; most reactions were mild. More reports of being unable to work or do normal activities occurred after dose 2 (32.1%) than dose 1 (11.9%); <1% of participants reported seeking medical care after vaccination. Rates of deaths reported to VAERS were lower than expected background rates by age group. Interpretation: Safety data from >298 million doses of mRNA COVID-19 vaccine administered in the first 6 months of the U.S. vaccination program show the majority of reported adverse events were mild and short in duration.

8: No Significant Difference in Viral Load Between Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Groups Infected with SARS-CoV-2 Delta Variant
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Posted 29 Sep 2021

No Significant Difference in Viral Load Between Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Groups Infected with SARS-CoV-2 Delta Variant
14 tweets medRxiv infectious diseases

Charlotte B. Acharya, John Schrom, Anthea M Mitchell, David A Coil, Carina Marquez, Susana Rojas, Chung Yu Wang, Jamin Liu, Genay Pilarowski, Leslie Solis, Elizabeth Georgian, Maya Petersen, Joseph DeRisi, Richard Michelmore, Diane Havlir

We found no significant difference in cycle threshold values between vaccinated and unvaccinated, asymptomatic and symptomatic groups infected with SARS-CoV-2 Delta. Given the substantial proportion of asymptomatic vaccine breakthrough cases with high viral levels, interventions, including masking and testing, should be considered for all in settings with elevated COVID-19 transmission.

9: Diagnostic Efficacy of Rapid Antigen Testing for SARS-CoV-2: The COVid-19 AntiGen (COVAG) study
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Posted 07 Aug 2021

Diagnostic Efficacy of Rapid Antigen Testing for SARS-CoV-2: The COVid-19 AntiGen (COVAG) study
14 tweets medRxiv public and global health

Christoph Wertenauer, Geovana Brenner-Michael, Alexander Dressel, Caroline Pfeifer, Ulrike Hauser, Eberhard Wieland, Christian Mayer, Caren Mutschmann, Martin Roskos, Hans-Joerg Wertenauer, Winfried Maerz

Abstract Background: Widely available rapid testing is pivotal to the fight against COVID-19. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) remains the gold standard. We compared two frequently used commercial rapid diagnostic tests (RDTs) for SARS-CoV-2-antigens, the SD Biosensor SARS-CoV-2 Rapid Antigen Test (Roche Diagnostics) and the Panbio COVID-19 Ag Rapid Test (Abbott Diagnostics), against rRT-PCR for SARS-CoV-2 detection. Methods: We compared the tests in 2215 all-comers at a diagnostic centre between February 1 and March 31, 2021. rRT-PCR-positive samples were examined for SARS-CoV-2 variants. Findings: 338 participants (15%) were rRT-PCR-positive for SARS-CoV-2. The sensitivities of Roche-RDT and Abbott-RDT were 60.4% and 56.8% (P<0.0001) and specificities 99.7% and 99.8% (P=0.076), respectively. Sensitivity inversely correlated with rRT-PCR-derived Ct values. Unadjusted, the RDTs had higher sensitivities in individuals referred by treating physicians and health departments than those tested for other reasons, in persons without comorbidities compared to those with comorbidities, in individuals with symptoms suggesting COVID-19, and in the absence of SARS-CoV-2 variants compared to Alpha variant carriers. The associations of sensitivity with clinical symptoms and the SARS-CoV-2 genotype were robust against adjustment for Ct values. Assuming that 10 000 symptomatic individuals are tested, 500 of which are truly positive, the RDTs would generate 38 false-positive and 124 false-negative results. Assuming that 10 000 asymptomatic individuals are tested, including 50 true positives, 18 false-positives and 34 false- negatives would be generated. Interpretation: The sensitivities of the two RDTs are unsatisfactory. This calls into question whether their widespread use is effective in the ongoing SARS-CoV-2 pandemic. Funding: SYNLAB Holding Deutschland GmbH Key words COVID-19, SARS-Cov-2, antibodies, rapid detection, antigen testing

10: Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview
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Posted 13 Jul 2021

Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview
14 tweets medRxiv epidemiology

Cathrine Axfors, John Ioannidis

Background: The infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) varies widely according to age and residence status. Purpose: Estimate the IFR of COVID-19 in community-dwelling elderly populations and other age groups from seroprevalence studies. Study protocol: https://osf.io/47cgb. Data Sources: Seroprevalence studies done in 2020 and identified by any of four existing systematic reviews. Study Selection: SARS-CoV-2 seroprevalence studies with [&ge;]1000 participants aged [&ge;]70 years that presented seroprevalence in elderly people; aimed to generate samples reflecting the general population; and whose location had available data on cumulative COVID-19 deaths in elderly (primary cutoff [&ge;]70 years; [&ge;]65 or [&ge;]60 also eligible). Data Extraction: We extracted the most fully adjusted (if unavailable, unadjusted) seroprevalence estimates and sampling procedure details. We also extracted age- and residence-stratified cumulative COVID-19 deaths (until 1 week after the seroprevalence sampling midpoint) from official reports, and population statistics, to calculate IFRs corrected for unmeasured antibody types. Sample size-weighted IFRs were estimated for countries with multiple estimates. Secondary analyses examined data on younger age strata from the same studies. Data Synthesis: Twenty-three seroprevalence surveys representing 14 countries were included. Across all countries, the median IFR in community-dwelling elderly and elderly overall was 2.4% (range 0.3%-7.2%) and 5.5% (range 0.3%-12.1%). IFR was higher with larger proportions of people >85 years. Younger age strata had low IFR values (median 0.0027%, 0.014%, 0.031%, 0.082%, 0.27%, and 0.59%, at 0-19, 20-29, 30-39, 40-49, 50-59, and 60-69 years). Limitations: Biases in seroprevalence and mortality data. Conclusions: The IFR of COVID-19 in community-dwelling elderly people is lower than previously reported. Very low IFRs were confirmed in the youngest populations.

11: A chemical-genetic map of the pathways controlling drug potency in Mycobacterium tuberculosis
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Posted 27 Nov 2021

A chemical-genetic map of the pathways controlling drug potency in Mycobacterium tuberculosis
11 tweets bioRxiv microbiology

Shuqi Li, Nicholas C Poulton, Jesseon S Chang, Zachary A Azadian, Michael A Dejusus, Nadine Ruecker, Matthew D. Zimmerman, Kathryn Eckartt, Barbara Bosch, Curtis A. Engelhart, Daniel Sullivan, Martin Gengenbacher, Véronique A Dartois, Dirk Schnappinger, Jeremy M. Rock

Mycobacterium tuberculosis infection is notoriously difficult to treat. To define the bacterial determinants that limit treatment efficacy, we developed a CRISPRi chemical genetics platform to titrate the expression of nearly all Mtb genes and quantify bacterial fitness in the presence of different drugs. Mining this dataset, we discovered diverse mechanisms of intrinsic drug resistance, unveiling hundreds of potential targets for synergistic drug combinations. Combining our data with comparative genomics of Mtb clinical isolates, we further identified new mechanisms of acquired drug resistance, one of which is associated with the emergence of a multidrug-resistant tuberculosis (TB) outbreak in South America. Lastly, we make the unexpected discovery of loss-of-function mutations in the intrinsic resistance factor whiB7 in an entire Mtb sublineage endemic to Southeast Asia, presenting an opportunity to repurpose macrolides to treat TB. This chemical-genetic map provides a rich resource to understand drug efficacy and guide future TB drug development and treatment.

12: X chromosomes show a faster evolutionary rate and complete somatic dosage compensation across Timema stick insect species
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Posted 28 Nov 2021

X chromosomes show a faster evolutionary rate and complete somatic dosage compensation across Timema stick insect species
11 tweets bioRxiv evolutionary biology

Darren J Parker, Kamil S Jaron, Zoé Dumas, Marc Robinson-Rechavi, Tanja Schwander

Sex chromosomes have evolved repeatedly across the tree of life. As they are present in different copy numbers in males and females, they are expected to experience different selection pressures than the autosomes, with consequences including a faster rate of evolution, increased accumulation of sexually antagonistic alleles, and the evolution of dosage compensation. Whether these consequences are general or linked to idiosyncrasies of specific taxa is not clear as relatively few taxa have been studied thus far. Here we use whole-genome sequencing to identify and characterize the evolution of the X chromosome in five species of Timema stick insects with XX:X0 sex determination. The X chromosome had a similar size (approximately 11% of the genome) and gene content across all five species, suggesting that the X chromosome originated prior to the diversification of the genus. Genes on the X showed evidence of a faster evolutionary rate than genes on the autosomes, likely due to less effective purifying selection. Genes on the X also showed almost complete dosage compensation in somatic tissues (heads and legs), but dosage compensation was absent in the reproductive tracts. Contrary to prediction, sex-biased genes showed little enrichment on the X, suggesting that the advantage X-linkage provides to the accumulation of sexually antagonistic alleles is weak. Overall, we found the consequences of X-linkage on gene sequences and expression to be similar across Timema species, showing the characteristics of the X chromosome are surprisingly consistent over 30 million years of evolution.

13: Protection Across Age Groups of BNT162b2 Vaccine Booster against Covid-19
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Posted 07 Oct 2021

Protection Across Age Groups of BNT162b2 Vaccine Booster against Covid-19
10 tweets medRxiv epidemiology

Yinon M. Bar-On, Yair Goldberg, Micha Mandel, Omri Bodenheimer, Laurence Freedman, Sharon Alroy-Preis, Nachman Ash, Amit Huppert, Ron Milo

BACKGROUND Following administration to persons 60+ years of age, the booster vaccination campaign in Israel was gradually expanded to younger age groups who received a second dose >5 months earlier. We study the booster effect on COVID-19 outcomes. METHODS We extracted data for the period July 30, 2021 to October 5, 2021 from the Israeli Ministry of Health database regarding 4,616,994 persons. We compared confirmed Covid-19 infections, severe illness, and death of those who received a booster [&ge;]12 days earlier (booster group) with a nonbooster group. In a secondary analysis, we compared the rates 3-7 days with [&ge;]12 days after receiving the booster dose. We used Poisson regressions to estimate rate ratios after adjusting for possible confounding factors. RESULTS Confirmed infection rates were {approx}10-fold lower in the booster versus nonbooster group (ranging 8.8-17.8 across five age groups) and 4.7-11.4 fold lower in the secondary analysis. Severe illness rates in the primary and secondary analysis were 19.1-fold (95% CI, 15.9-23) and 6.5-fold (95% CI, 5.1-8.4) lower for ages 60+, and 20.7-fold (95% CI, 9.7-44.2) and 2.9-fold (95% CI, 1-8.8) lower for ages 40-60. For ages 60+, COVID-19 associated death rates were 13.9-fold (95% CI, 8.8-22) lower in the primary analysis and 4.6-fold (95% CI, 2.7-7.9) lower in the secondary analysis. CONCLUSIONS Across all age groups, rates of confirmed infection and severe illness were substantially lower among those who received a booster dose of the BNT162b2 vaccine.

14: Impact of the COVID-19 Pandemic on Early Child Cognitive Development: Initial Findings in a Longitudinal Observational Study of Child Health
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Posted 11 Aug 2021

Impact of the COVID-19 Pandemic on Early Child Cognitive Development: Initial Findings in a Longitudinal Observational Study of Child Health
9 tweets medRxiv pediatrics

Sean Deoni, Jennifer Beauchemin, Alexandra Volpe, Viren D'Sa

Since the first reports of novel coronavirus in the 2020, public health organizations have advocated preventative policies to limit virus, including stay-at-home orders that closed businesses, daycares, schools, playgrounds, and limited child learning and typical activities. Fear of infection and possible employment loss has placed stress on parents; while parents who could work from home faced chal-lenges in both working and providing full-time attentive childcare. For pregnant individuals, fear of at-tending prenatal visits also increased maternal stress, anxiety, and depression. Not surprising, there has been concern over how these factors, as well as missed educational opportunities and reduced interaction, stimulation, and creative play with other children might impact child neurodevelopment. Lev-eraging a large on-going longitudinal study of child neurodevelopment, we examined general childhood cognitive scores in 2020 and 2021 vs. the preceding decade, 2011-2019. We find that children born during the pandemic have significantly reduced verbal, motor, and overall cognitive performance com-pared to children born pre-pandemic. Moreover, we find that males and children in lower socioeconom-ic families have been most affected. Results highlight that even in the absence of direct SARS-CoV-2 infection and COVID-19 illness, the environmental changes associated COVID-19 pandemic is signifi-cantly and negatively affecting infant and child development.

15: Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike protein D614, mutants D614G, N501Y, K417N and E484K in vitro
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Posted 19 Mar 2021

Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike protein D614, mutants D614G, N501Y, K417N and E484K in vitro
9 tweets bioRxiv microbiology

Hoai Thi Thu Tran, Nguyen Phan Khoi Le, Michael Gigl, Corinna Dawid, Evelyn Lamy

On 11th March 2020, coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, was declared as a global pandemic by the World Health Organization (WHO). To date, there are rapidly spreading new "variants of concern" of SARS-CoV-2, the United Kingdom (B.1.1.7), the South African (B.1.351) or Brasilian (P.1) variant. All of them contain multiple mutations in the ACE2 receptor recognition site of the spike protein, compared to the original Wuhan sequence, which is of great concern, because of their potential for immune escape. Here we report on the efficacy of dandelion (Taraxacum officinale) to block protein-protein interaction of spike S1 to the human ACE2 cell surface receptor. This could be shown for the original spike D614, but also for its mutant forms (D614G, N501Y, and mix of K417N, E484K, N501Y) in human HEK293-hACE2 kidney and A549-hACE2-TMPRSS2 lung cells. High molecular weight compounds in the water-based extract account for this effect. Infection of lung cells using SARS-CoV-2 spike pseudotyped lentivirus particles was efficiently prevented by the extract and so was virus-triggered pro-inflammatory interleukin 6 secretion. Modern herbal monographs consider the usage of this medicinal plant as safe. Thus, the in vitro results reported here should encourage further research on the clinical relevance and applicability of the extract as prevention strategy for SARS-CoV-2 infection.

16: Insights from an autism imaging biomarker challenge: promises and threats to biomarker discovery
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Posted 26 Nov 2021

Insights from an autism imaging biomarker challenge: promises and threats to biomarker discovery
9 tweets medRxiv radiology and imaging

Nicolas Traut, Katja Heuer, Guillaume Lemaitre, Anita Beggiato, David Germanaud, Monique Elmaleh, Alban Bethegies, Laurent Bonasse-Gahot, Weidong Cai, Stanislas Chambon, Freddy Cliquet, Ayoub Ghriss, Nicolas Guigui, Amicie de Pierrefeu, Meng Wang, Valentina Zantedeschi, Alexandre Boucaud, Joris van den Bossche, Balazs Kegl, Richard Delorme, Thomas Bourgeron, Roberto Toro, Gael Varoquaux

MRI has been extensively used to identify anatomical and functional differences in Autism Spectrum Disorder (ASD). Yet, many of these findings have proven difficult to replicate because studies rely on small cohorts and are built on many complex, undisclosed, analytic choices. We conducted an international challenge to predict ASD diagnosis from MRI data, where we provided preprocessed anatomical and functional MRI data from > 2,000 individuals. Evaluation of the predictions was rigorously blinded. 146 challengers submitted prediction algorithms, which were evaluated at the end of the challenge using unseen data and an additional acquisition site. On the best algorithms, we studied the importance of MRI modalities, brain regions, and sample size. We found evidence that MRI could predict ASD diagnosis: the 10 best algorithms reliably predicted diagnosis with AUC~0.80, far superior to what can be currently obtained using genotyping data in cohorts 20-times larger. We observed that functional MRI was more important for prediction than anatomical MRI, and that increasing sample size steadily increased prediction accuracy, providing an efficient strategy to improve biomarkers. We also observed that despite a strong incentive to generalise to unseen data, model development on a given dataset faces the risk of overfitting: performing well in cross-validation on the data at hand, but not generalising. Finally, we were able to predict ASD diagnosis on an external sample added after the end of the challenge (EU-AIMS), although with a lower prediction accuracy (AUC=0.72). This indicates that despite being based on a large multisite cohort, our challenge still produced biomarkers fragile in the face of dataset shifts.

17: Analysis of 8000 proteins and reduced carry over significantly increase the throughput of single-shot proteomics
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Posted 28 Nov 2021

Analysis of 8000 proteins and reduced carry over significantly increase the throughput of single-shot proteomics
8 tweets bioRxiv biochemistry

Karel Stejskal, Jeff Op de Beeck, Manuel Matzinger, Gerhard Duernberger, Oleksandr Boychenko, Paul Jacobs, Karl Mechtler

In the field of LC-MS based proteomics, increases in sampling depth and proteome coverage have mainly been accomplished by rapid advances in mass spectrometer technology. The comprehensiveness and quality of data that can be generated do however also depend on the performance provided by nano liquid chromatography (nanoLC) separations. Proper selection of reversed-phase separation columns can be of paramount importance to provide the MS instrument with peptides at the highest possible concentration and separated at the highest possible resolution. As an alternative to traditional packed bed LC column technology that uses beads packed into capillary tubing, we present a novel LC column format based on photolithographic definition and Deep Reactive Ion Etching (DRIE) into silicon wafers. With a next generation pillar array column designed for universal use in bottom-up proteomics, the critical dimensions of the stationary phase support structures have been reduced by a factor of 2 to provide further increases in separation power. To demonstrate the potential for single-shot proteomics workflows, we report on a series of optimization and benchmarking experiments where we combine LC separation on a new generation of pillar array columns using Vanquish Neo UHPLC with fast Orbitrap Tribrid MS data-dependent acquisition (DDA) and High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS). In addition to providing superior proteome coverage, robust operation over more than 1 month with a single nanoESI emitter and reduction of the column related sample carry over are additional figures of merit that can help improve proteome research sensitivity, productivity and standardization.

18: Does the brain care about averages? A simple test.
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Posted 28 Nov 2021

Does the brain care about averages? A simple test.
8 tweets bioRxiv neuroscience

Alejandro Tlaie, Katharine A Shapcott, Paul Tiesinga, Marieke Schölvinck, Martha N Havenith

Trial-averaged metrics, e.g. in the form of tuning curves and population response vectors, are a basic and widely accepted way of characterizing neuronal activity. But how relevant are such trial-averaged responses to neuronal computation itself? Here we present a simple test to estimate whether average responses reflect aspects of neuronal activity that contribute to neuronal processing in a specific context. The test probes two assumptions inherent in the usage of average neuronal metrics: 1) Reliability: Neuronal responses repeat consistently enough across single stimulus instances that the average response template they relate to remains recognizable to downstream regions. 2) Behavioural relevance: If a single-trial response is more similar to the average template, this should make it easier for the animal to identify the correct stimulus or action. We apply this test to a large publicly available data set featuring electrophysiological recordings from 42 cortical areas in behaving mice. In this data set, we show that single-trial responses were less correlated to the average response template than one would expect if they simply represented discrete versions of the template, down-sampled to a finite number of spikes. Moreover, single-trial responses were barely stimulus-specific -- they could not be clearly assigned to the average response template of one stimulus. Most importantly, better-matched single-trial responses did not predict accurate behaviour for any of the recorded cortical areas. We conclude that in this data set, average responses do not seem particularly relevant to neuronal computation in a majority of brain areas, and we encourage other researchers to apply similar tests when using trial-averaged neuronal metrics.

19: Using AnnoTree to get more assignments, faster, in DIAMOND+MEGAN microbiome analysis
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Posted 24 Nov 2021

Using AnnoTree to get more assignments, faster, in DIAMOND+MEGAN microbiome analysis
7 tweets bioRxiv bioinformatics

Anupam Gautam, Hendrik Felderhoff, Caner Bagci, Daniel H. Huson

In microbiome analysis, one main approach is to align metagenomic sequencing reads against a protein-reference database such as NCBI-nr, and then to perform taxonomic and functional binning based on the alignments. This approach is embodied, for example, in the standard DIAMOND+MEGAN analysis pipeline, which first aligns reads against NCBI-nr using DIAMOND and then performs taxonomic and functional binning using MEGAN. Here we propose the use of the AnnoTree protein database, rather than NCBI-nr, in such alignment-based analyses to determine the prokaryotic content of metagenomic samples. We demonstrate a 2-fold speedup over the usage of the prokaryotic part of NCBI-nr, and increased assignment rates, in particular, assigning twice as many reads to KEGG. In addition to binning to the NCBI taxonomy, MEGAN now also bins to the GTDB taxonomy.

20: A third COVID-19 vaccine shot markedly boosts neutralizing antibody potency and breadth
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Posted 18 Aug 2021

A third COVID-19 vaccine shot markedly boosts neutralizing antibody potency and breadth
7 tweets medRxiv infectious diseases

Sho Iketani, Lihong Liu, Manoj S. Nair, Hiroshi Mohri, Maple Wang, Yaoxing Huang, David D Ho

COVID-19 (coronavirus disease 2019) vaccines have been rapidly developed and deployed globally as a measure to combat the disease. These vaccines have been demonstrated to confer significant protection, but there have been reports of temporal decay in antibody titer. Furthermore, several variants have been identified with variable degrees of antibody resistance. These two factors suggest that a booster vaccination may be worthy of consideration. While such a booster dose has been studied as a series of three homologous vaccines in healthy individuals, to our knowledge, information on a heterologous regimen remains unreported, despite the practical benefits of such a scheme. Here, in this observational study, we investigated the serological profile of four healthy individuals who received two doses of the BNT162b2 vaccine, followed by a third booster dose with the Ad26.COV2.S vaccine. We found that while all individuals had spike-binding antibodies at each of the timepoints tested, there was an appreciable drop in titer by four months following the second vaccination. The third vaccine dose robustly increased titers beyond that of two vaccinations, and these elicited antibodies had neutralizing capability against all SARS-CoV-2 strains tested in both a recombinant vesicular stomatitis virus-based pseudovirus assay and an authentic SARS-CoV-2 assay, except for one individual against B.1.351 in the latter assay. Thus, a third COVID-19 vaccine dose in healthy individuals promoted not just neutralizing antibody potency, but also induced breadth against dominant SARS-CoV-2 variants.

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