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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 172,590 papers from 713,117 authors.

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

1: Association between vaccination status and reported incidence of post-acute COVID-19 symptoms in Israel: a cross-sectional study of patients tested between March 2020 and November 2021
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Posted 06 Jan 2022

Association between vaccination status and reported incidence of post-acute COVID-19 symptoms in Israel: a cross-sectional study of patients tested between March 2020 and November 2021
644 tweets medRxiv epidemiology

Paul Kuodi, Yanay Gorelik, Hiba Zayyad, Ofir Wertheim, Karine Beiruti Wiegler, Kamal Abu Jabal, Amiel Dror, Saleh Nazzal, Daniel Glikman, Michael Edelstein

Background: Long COVID is a post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection syndrome characterised by not recovering for several weeks or months following the acute episode. The effectiveness of COVID-19 vaccines against long-term symptoms of COVID-19 is not well understood. We determined whether vaccination was associated with the incidence of reporting long-term symptoms post-SARS-CoV-2 infection Methods: We invited individuals who were PCR tested for SARS-CoV-2 infection at participating hospitals between March 2020-November 2021 to fill an online questionnaire that included baseline demographics, details of their acute episode and information about symptoms they were currently experiencing. Using binomial regression, we compared vaccinated individuals with those unvaccinated and those uninfected in terms of self-reported symptoms post-acute infection. Results: We included 951 infected and 2437 uninfected individuals. Of the infected, 637(67%) were vaccinated. The most commonly reported symptoms were; fatigue (22%), headache (20%), weakness (13%), and persistent muscle pain (10%). After adjusting for follow-up time and baseline symptoms, those who received two doses less likely than unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68% respectively, (Risk ratios 0.36, 0.46, 0.43, 0.32, p<0.04 in the listed sequence). Those who received two doses were no more likely to report any of these symptoms than individuals reporting no previous SARS-CoV-2 infection. Conclusions: Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID-19 symptoms, bringing it back to baseline. Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.

2: 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
35 tweets medRxiv epidemiology

Cathrine Axfors, John P.A. Ioannidis

Objective: This mixed design synthesis aimed to estimate the infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) in community-dwelling elderly populations and other age groups from seroprevalence studies. Protocol: https://osf.io/47cgb. Methods and analyses: Eligible were seroprevalence studies done in 2020 and identified by any of four existing systematic reviews; with [&ge;]1000 participants aged [&ge;]70 years that presented seroprevalence in elderly people; that 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). We extracted the most fully adjusted (if unavailable, unadjusted) seroprevalence estimates. 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. Results: Twenty-five seroprevalence surveys representing 14 countries were included. Across all countries, the median IFR in community-dwelling elderly and elderly overall was 2.9% (range 0.2%-6.9%) and 4.9% (range 0.2%-16.8%) without accounting for seroreversion (2.4% and 4.0%, respectively, accounting for 5% monthly seroreversion). Multiple sensitivity analyses yielded similar results. IFR was higher with larger proportions of people >85 years. Younger age strata had low IFR values (median 0.0013%, 0.0088%, 0.021%, 0.042%, 0.14%, and 0.65%, at 0-19, 20-29, 30-39, 40-49, 50-59, and 60-69 years even without accounting for seroreversion). 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.

3: Vaccine effectiveness against SARS-CoV-2 infection with the Omicron or Delta variants following a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: A Danish cohort study
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Posted 21 Dec 2021

Vaccine effectiveness against SARS-CoV-2 infection with the Omicron or Delta variants following a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: A Danish cohort study
8 tweets medRxiv infectious diseases

Christian Holm Hansen, Astrid Blicher Schelde, Ida Rask Moustsen-Helms, Hanne-Dorthe Emborg, Tyra Grove Krause, Kåre Mølbak, Palle Valentiner-Branth, The Infectious Disease Preparedness Group at Statens Serum Institut

In this brief communication we are showing original research results with early estimates from Danish nationwide databases of vaccine effectiveness (VE) against the novel SARS-CoV-2 Omicron variant (B.1.1.529) up to five months after a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines. Our study provides evidence of protection against infection with the Omicron variant after completion of a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines; in particular, we found a VE against the Omicron variant of 55.2% (95% confidence interval (CI): 23.5 to 73.7%) and 36.7% (95% CI: -69.9 to 76.4%) for the BNT162b2 and mRNA-1273 vaccines, respectively, in the first month after primary vaccination. However, the VE is significantly lower than that against Delta infection and declines rapidly over just a few months. The VE is re-established upon revaccination with the BNT162b2 vaccine (54.6%, 95% CI: 30.4 to 70.4%).

4: Characterizing features of outbreak duration for novel SARS-CoV-2 variants of concern
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Posted 14 Jan 2022

Characterizing features of outbreak duration for novel SARS-CoV-2 variants of concern
7 tweets medRxiv epidemiology

Alex D. Washburne, Nathaniel Hupert, Nicole Kogan, William Hanage, Mauricio Santillana

Characterizing the dynamics of epidemic trajectories is critical to understanding the potential impacts of emerging outbreaks and to designing appropriate mitigation strategies. As the COVID-19 pandemic evolves, however, the emergence of SARS-CoV-2 variants of concern has complicated our ability to assess in real-time the potential effects of imminent outbreaks, such as those presently caused by the Omicron variant. Here, we report that SARS-CoV-2 outbreaks across regions exhibit strain-specific times from onset to peak, specifically for Delta and Omicron variants. Our findings may facilitate real-time identification of peak medical demand and may help fine-tune ongoing and future outbreak mitigation deployment efforts.

5: Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation
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Posted 16 Jan 2022

Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation
5 tweets bioRxiv cancer biology

Anna S. Nam, Neville Dusaj, Franco Izzo, Rekha Murali, Robert M. Myers, Tarek Mouhieddine, Jesus Sotelo, Salima Benbarche, Michael Waarts, Federico Gaiti, Sabrin Tahri, Ross Levine, Omar Abdel-Wahab, Lucy A. Godley, Ronan Chaligne, Irene M. Ghobrial, Dan Landau

Somatic mutations in cancer genes have been ubiquitously detected in clonal expansions across healthy human tissue, including in clonal hematopoiesis. However, mutated and wildtype cells are morphologically and phenotypically similar, limiting the ability to link genotypes with cellular phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing the mutation with transcriptomes and methylomes in stem and progenitors from individuals with DNMT3A R882 mutated clonal hematopoiesis. DNMT3A mutations resulted in myeloid over lymphoid bias, and in expansion of immature myeloid progenitors primed toward megakaryocytic-erythroid fate. We observed dysregulated expression of lineage and leukemia stem cell markers. DNMT3A R882 led to preferential hypomethylation of polycomb repressive complex 2 targets and a specific sequence motif. Notably, the hypomethylation motif is enriched in binding motifs of key hematopoietic transcription factors, serving as a potential mechanistic link between DNMT3A R882 mutations and aberrant transcriptional phenotypes. Thus, single-cell multi-omics pave the road to defining the downstream consequences of mutations that drive human clonal mosaicism.

6: Partial reprogramming restores youthful gene expression through transient suppression of cell identity
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Posted 23 May 2021

Partial reprogramming restores youthful gene expression through transient suppression of cell identity
4 tweets bioRxiv systems biology

Antoine Roux, Chunlian Zhang, Jonathan Paw, José-Zavalara Solorio, Twaritha Vijay, Ganesh Kolumam, Cynthia Kenyon, Jacob C Kimmel

Transient induction of pluripotent reprogramming factors has been reported to reverse some features of aging in mammalian cells and tissues. However, the impact of transient reprogramming on somatic cell identity programs and the necessity of individual pluripotency factors remain unknown. Here, we mapped trajectories of transient reprogramming in young and aged cells from multiple murine cell types using single cell transcriptomics to address these questions. We found that transient reprogramming restored youthful gene expression in adipocytes and mesenchymal stem cells but also temporarily suppressed somatic cell identity programs. We further screened Yamanaka Factor subsets and found that many combinations had an impact on aging gene expression and suppressed somatic identity, but that these effects were not tightly entangled. We also found that a transient reprogramming approach inspired by amphibian regeneration restored youthful gene expression in aged myogenic cells. Our results suggest that transient pluripotent reprogramming poses a neoplastic risk, but that restoration of youthful gene expression can be achieved with alternative strategies.

7: Standing genetic variation fuels rapid evolution of herbicide resistance in blackgrass
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Posted 16 Dec 2021

Standing genetic variation fuels rapid evolution of herbicide resistance in blackgrass
4 tweets bioRxiv evolutionary biology

Sonja Kersten, Jiyang Chang, Christian D Huber, Yoav Voichek, Christa Lanz, Timo Hagmaier, Patricia Lang, Ulrich Lutz, Insa Hirschberg, Jens Lerchl, Aimone Porri, Yves Van de Peer, Karl Schmid, Detlef Weigel, Fernando A. Rabanal

Repeated herbicide applications exert enormous selection on blackgrass (Alopecurus myosuroides), a major weed in cereal crops of the temperate climate zone including Europe. This inadvertent large-scale experiment gives us the opportunity to look into the underlying genetic mechanisms and evolutionary processes of rapid adaptation, which can occur both through mutations in the direct targets of herbicides and through changes in other, often metabolic, pathways, known as non-target-site resistance. How much either type of adaptation relies on de novo mutations versus pre-existing standing variation is important for developing strategies to manage herbicide resistance. We generated a chromosome-level reference genome for A. myosuroides for population genomic studies of herbicide resistance and genome-wide diversity across Europe in this species. Bulked-segregant analysis evidenced that non-target-site resistance has a complex genetic architecture. Through empirical data and simulations, we showed that, despite its simple genetics, target-site resistance mainly results from standing genetic variation, with only a minor role for de novo mutations.

8: 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
2 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.

9: Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions
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Posted 23 May 2020

Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions
2 tweets bioRxiv immunology

Divij Mathew, Josephine R. Giles, Amy E. Baxter, Allison R. Greenplate, Jennifer E Wu, Cecile Alanio, Derek A. Oldridge, Leticia Kuri-Cervantes, M. Betina Pampena, Kurt D’Andrea, Sasikanth Manne, Zeyu Chen, Yinghui Jane Huang, John P Reilly, Ariel R Weisman, Caroline A.G. Ittner, Oliva Kuthuru, Jeanette Dougherty, Kito Nzingha, Nicholas Han, Justin Kim, Ajinkya Pattekar, Eileen C. Goodwin, Elizabeth M Anderson, Madison E. Weirick, Sigrid Gouma, Claudia P Arevalo, Marcus J Bolton, Fang Chen, Simon F. Lacey, Scott E. Hensley, Sokratis A. Apostolidis, Alexander C Huang, Laura A. Vella, The UPenn COVID Processing Unit, Michael R. Betts, Nuala J. Meyer, E John Wherry

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines. ### Competing Interest Statement The authors have declared no competing interest.

10: Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron
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Posted 11 Jan 2022

Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron
2 tweets medRxiv infectious diseases

Olha Puhach, Kenneth Adea, Nicolas Hulo, Pascale Sattonnet-Roche, Camille Genecand, Anne Iten, Frederique Jacquerioz Bausch, Laurent Kaiser, Pauline Vetter, Isabella Eckerle, Benjamin Meyer

Abstract Background Viral load (VL) is one determinant of secondary transmission of SARS-CoV-2. Emergence of variants of concerns (VOC) Alpha and Delta was ascribed, at least partly, to higher VL. Furthermore, with parts of the population vaccinated, knowledge on VL in vaccine breakthrough infections is crucial. As RNA VL is only a weak proxy for infectiousness, studies on infectious virus presence by cell culture isolation are of importance. Methods We assessed nasopharyngeal swabs of COVID-19 patients for quantitative infectious viral titres (IVT) by focus-forming assay and compared to overall virus isolation success and RNA genome copies. We assessed infectious viral titres during the first 5 symptomatic days in a total of 384 patients: unvaccinated individuals infected with pre-VOC SARS-CoV-2 (n= 118) or Delta (n= 127) and vaccine breakthrough infections with Delta (n= 121) or Omicron (n=18). Findings Correlation between RNA copy number and IVT was low for all groups. No correlation between IVTs and age or sex was seen. We observed higher RNA genome copies in pre-VOC SARS-CoV-2 compared to Delta, but significantly higher IVTs in Delta infected individuals. In vaccinated vs. unvaccinated Delta infected individuals, RNA genome copies were comparable but vaccinated individuals have significantly lower IVTs, and cleared virus faster. Vaccinated individuals with Omicron infection had comparable IVTs to Delta breakthrough infections. Interpretation Quantitative IVTs can give detailed insights into virus shedding kinetics. Vaccination was associated with lower infectious titres and faster clearance for Delta, showing that vaccination would also lower transmission risk. Omicron vaccine breakthrough infections did not show elevated IVTs compared to Delta, suggesting that other mechanisms than increase VL contribute to the high infectiousness of Omicron. Funding This work was supported by the Swiss National Science Foundation 196644, 196383, NRP (National Research Program) 78 Covid-19 Grant 198412, the Fondation Ancrage Bienfaisance du Groupe Pictet and the Fondation Privee des Hopitaux Universitaires de Geneve.

11: Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine
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Posted 15 Jul 2021

Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine
2 tweets bioRxiv immunology

Suhas Sureshchandra, Sloan A. Lewis, Brianna Doratt, Allen Jankeel, Izabela Ibraim, Ilhem Messaoudi

mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used single-cell RNA sequencing and functional assays to compare humoral and cellular responses to two doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4 T cells, and robust antigen-specific polyfunctional CD4 T cell responses in all vaccinees. On the other hand, CD8 T cell responses were both weak and variable. Interestingly, clonally expanded CD8 T cells were observed in every vaccinee, as observed following natural infection. TCR gene usage, however, was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of larger CD8 T cell clones occupied distinct clusters, likely due to the recognition of a broader set of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response where early CD4 T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8 T cells, together capable of contributing to future recall responses.

12: SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis
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Posted 08 Sep 2021

SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis
2 tweets medRxiv epidemiology

Tracy Beth Hoeg, Allison Krug, Josh Stevenson, John Mandrola

Objectives: Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.

13: Deep-BGCpred: A unified deep learning genome-mining framework for biosynthetic gene cluster prediction
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Posted 16 Nov 2021

Deep-BGCpred: A unified deep learning genome-mining framework for biosynthetic gene cluster prediction
2 tweets bioRxiv bioinformatics

Ziyi Yang, Benben Liao, Changyu Hsieh, Chao Han, Liang Fang, Shengyu Zhang

Natural products produced by microorganisms constitute an important source of essential pharmaceuticals, including antimicrobial and anti-tumor drugs. These bioactive molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The rapid increase of microbial genomics resources, due to the availability of high-throughput sequencing technologies, has spurred the development of computational methods for microbial genome mining for BGC discovery. Current machine learning methods, however, have limited successes in uncovering novel BGCs due to an excessive number of false positives in their predictions. To this end, we propose Deep-BGCpred, a framework that effectively addresses the aforementioned issue by improving a deep learning model termed DeepBGC. The new model embeds multi-source protein family domains and employs a stacked Bidirectional Long Short-Term Memory model to boost accuracy for BGC identifications. In particular, it integrates two customized strategies, sliding window strategy and dual-model serial screening, to improve the model's performance stability and reduce the number of false positive in BGC predictions. We compare the proposed model against other well-established methods on common benchmarks and achieve new state-of-the-art results with convincing evidences. We expect that researchers working on genome mining for natural products may be greatly benefited from our newly proposed method, Deep-BGCpred.

14: Neutralization of ancestral SARS-CoV-2 and variants Alpha, Beta, Gamma, Delta, Zeta and Omicron by mRNA vaccination and infection-derived immunity through homologous and heterologous variants
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Posted 31 Dec 2021

Neutralization of ancestral SARS-CoV-2 and variants Alpha, Beta, Gamma, Delta, Zeta and Omicron by mRNA vaccination and infection-derived immunity through homologous and heterologous variants
2 tweets medRxiv infectious diseases

Meriem Bekliz, Kenneth Adea, Pauline Vetter, Christiane S Eberhardt, Krisztina Hosszu-Fellous, Diem-Lan Vu, Olha Puhach, Manel Essaidi-Laziosi, Sophie Waldvogel-Abramowski, Caroline Stephan, Arnaud L'Huillier, Claire-Anne Siegrist, Arnaud M Didierlaurent, Laurent M Kaiser, Benjamin Meyer, Isabella Eckerle

Emerging SARS-CoV-2 variants of concern/interest (VOC/VOI) raise questions about effectiveness of neutralizing antibodies derived from infection or vaccination. As the population immunity to SARS-CoV-2 has become more complex due to prior infection and/or vaccination, understanding the antigenic relationship between variants is needed. Here, we have assessed in total 104 blood specimens from convalescent individuals after infection with early-pandemic SARS-CoV-2 (pre-VOC) or with Alpha, Beta, Gamma or Delta, post-vaccination after double-dose mRNA-vaccination and break through infections due to Delta or Omicron. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, Omicron) was assessed by plaque-reduction neutralization assay. We found highest neutralization titers against the homologous (previously infecting) variant, with lower neutralization efficiency against heterologous variants. Significant loss of neutralization for Omicron was observed but to a varying degree depending on previously infecting variant (23.0-fold in Beta-convalescence up to 56.1-fold in Alpha-convalescence), suggesting that infection-derived immunity varies, but independent of the infecting variant is only poorly protective against Omicron. Of note, Zeta VOI showed also pronounced escape from neutralization of up to 28.2-fold in Alpha convalescent samples. Antigenic mapping reveals both Zeta and Omicron as separate antigenic clusters. Double dose vaccination showed robust neutralization for Alpha, Beta, Gamma, Delta and Zeta, with fold-change reduction of only 2.8 (for Alpha) up to 6.9 (for Beta). Escape from neutralization for Zeta was largely restored in vaccinated individuals, while Omicron still showed a loss of neutralization of 85.7-fold compared to pre-VOC SARS-CoV-2. Combined immunity from infection followed by vaccination or vaccine breakthrough infection showed highest titers and most robust neutralization for heterologous variants. Breakthrough infection with Delta showed only 12.5-fold reduced neutralization for Omicron, while breakthrough infection with Omicron showed only a 1.5-fold loss for Delta, suggests that infection with antigenically different variants can boost immunity for antigens closer to the vaccine strain. Antigenic cartography showed also a tendency towards broader neutralizing capacity for heterologous variants. We conclude that the complexity of background immunity needs to be taken into account when assessing new VOCs. Development towards separate serotypes such as Zeta was already observed before Omicron emergence, thus other factors than just immune escape must contribute to Omicrons rapid dominance. However, combined infection/vaccination immunity could ultimately lead to broad neutralizing capacity also against non-homologous variants.

15: The emergence of SARS-CoV-2 variants of concern is driven by acceleration of the evolutionary rate
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Posted 31 Aug 2021

The emergence of SARS-CoV-2 variants of concern is driven by acceleration of the evolutionary rate
1 tweet medRxiv infectious diseases

John H Tay, Ashleigh F. Porter, Wytamma Wirth, Sebastian Duchene

The ongoing SARS-CoV-2 pandemic has seen an unprecedented amount of rapidly generated genome data. These data have revealed the emergence of lineages with mutations associated to transmissibility and antigenicity, known as variants of concern (VOCs). A striking aspect of VOCs is that many of them involve an unusually large number of defining mutations. Current phylogenetic estimates of the evolutionary rate of SARS-CoV-2 suggest that its genome accrues around 2 mutations per month. However, VOCs can have around 15 defining mutations and it is hypothesised that they emerged over the course of a few months, implying that they must have evolved faster for a period of time. We analysed genome sequence data from the GISAID database to assess whether the emergence of VOCs can be attributed to changes in the evolutionary rate of the virus and whether this pattern can be detected at a phylogenetic level using genome data. We fit a range of molecular clock models and assessed their statistical fit. Our analyses indicate that the emergence of VOCs is driven by an episodic increase in the evolutionary rate of around 4-fold the background phylogenetic rate estimate that may have lasted several weeks or months. These results underscore the importance of monitoring the molecular evolution of the virus as a means of understanding the circumstances under which VOCs may emerge.

16: 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
1 tweet medRxiv infectious diseases

F. Konstantin Föhse, Büsranur Geckin, Gijs J. 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 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.

17: 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
1 tweet 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.

18: Shedding of Infectious SARS-CoV-2 Despite Vaccination
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Posted 31 Jul 2021

Shedding of Infectious SARS-CoV-2 Despite Vaccination
1 tweet medRxiv infectious diseases

Kasen K Riemersma, Brittany E Grogan, Amanda Kita-Yarbro, Peter Halfmann, Anna Kocharian, Kelsey R Florek, Ryan Westergaard, Allen Bateman, Gunnar E Jeppson, Yoshihiro Kawaoka, David H O'Connor, Thomas C Friedrich, Katarina M Grande

The SARS-CoV-2 Delta variant is highly transmissible and contains mutations that confer partial immune escape. We compared RT-PCR cycle threshold (Ct) data from 699 test-positive anterior nasal swab specimens from fully vaccinated (n = 310) or unvaccinated (n=389) individuals. We observed low Ct values (<25) in 212 of 310 fully vaccinated (68%) and 246 of 389 (63%) unvaccinated individuals. Testing a subset of these low-Ct samples revealed infectious SARS-CoV-2 in 15 of 17 specimens (88%) from unvaccinated individuals and 37 of 39 (95%) from vaccinated people. To determine whether infectious virus titers differed in vaccinated and unvaccinated persons, we performed plaque assays on an additional set of 48 samples with Ct <25, finding no difference in infectious virus titer between groups.

19: Longitudinal monitoring of SARS-CoV-2 RNA on high-touch surfaces in a community setting
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Posted 01 Nov 2020

Longitudinal monitoring of SARS-CoV-2 RNA on high-touch surfaces in a community setting
1 tweet medRxiv infectious diseases

Abigail P. Harvey, Erica R. Fuhrmeister, Molly Cantrell, Ana K. Pitol, Jenna M. Swarthout, Julie E. Powers, Maya L. Nadimpalli, Timothy R Julian, Amy Pickering

Environmental surveillance of surface contamination is an unexplored tool for understanding transmission of SARS-CoV-2 in community settings. We conducted longitudinal swab sampling of high-touch non-porous surfaces in a Massachusetts town during a COVID-19 outbreak from April to June 2020. Twenty-nine of 348 (8.3 %) surface samples were positive for SARS-CoV-2, including crosswalk buttons, trash can handles, and door handles of essential business entrances (grocery store, liquor store, bank, and gas station). The estimated risk of infection from touching a contaminated surface was low (less than 5 in 10,000), suggesting fomites play a minimal role in SARS-CoV-2 community transmission. The weekly percentage of positive samples (out of n=33 unique surfaces per week) best predicted variation in city-level COVID-19 cases using a 7-day lead time. Environmental surveillance of SARS-CoV-2 RNA on high-touch surfaces could be a useful tool to provide early warning of COVID-19 case trends.

20: Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAE
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Posted 22 Jul 2021

Gammaherpesvirus infection licenses age-associated B cells for pathogenicity in MS and EAE
1 tweet bioRxiv immunology

Isobel C. Mouat, Jessica R. Allanach, Vina Fan, Anna M. Girard, Iryna Shanina, Galina Vorobeychik, Marc S. Horwitz

While age-associated B cells (ABCs) are known to expand and persist following viral infection and during autoimmunity, their interactions are yet to be studied together in these contexts. Epstein-Barr virus (EBV) infection has long been implicated in multiple sclerosis (MS), and it is not known whether ABCs could play a role in mediating viral contribution to autoimmunity. Here, we show that the circulating ABC population is expanded in people with MS and that EBV infection and MS status differentially impact the circulating ABC phenotype. We then directly compared ABCs during viral infection and autoimmunity using mouse models of EBV, gammaherpesvirus 68 ({gamma}HV68), and MS, experimental autoimmune encephalomyelitis (EAE). We observed that splenic ABCs are expanded in a sex-biased manner during both latent virus infection and EAE, and each event drives the ABC population to opposing phenotypes. We have previously shown that latent {gamma}HV68 infection exacerbates EAE and here we show that mice lacking ABCs fail to display {gamma}HV68-enhanced disease. Collectively, these findings indicate that latent viral infection and central nervous system autoimmunity differentially impact the ABC population and suggests that viral infections such as EBV prime ABCs to contribute pathogenically in MS.

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