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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 166,810 papers from 692,906 authors.

Most tweeted biology preprints, last 24 hours

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

61: Molecular pathology of a cystic fibrosis mutation is explained by loss of a hydrogen bond
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Posted 21 Oct 2021

Molecular pathology of a cystic fibrosis mutation is explained by loss of a hydrogen bond
2 tweets bioRxiv biophysics

Márton A. Simon, LászlÓ Csanády

The phosphorylation-activated anion channel CFTR is gated by an ATP hydrolysis cycle at its two cytosolic nucleotide binding domains, and is essential for epithelial salt-water transport. A large number of CFTR mutations cause cystic fibrosis. Since recent breakthrough in targeted pharmacotherapy, CFTR mutants with impaired gating are candidates for stimulation by potentiator drugs. Thus, understanding the molecular pathology of individual mutations has become important. The relatively common R117H mutation affects an extracellular loop, but nevertheless causes a strong gating defect. Here we identify a hydrogen bond between the side chain of arginine 117 and the backbone carbonyl group of glutamate 1124 in the cryo-electronmicroscopic structure of phosphorylated, ATP-bound CFTR. We address the functional relevance of that interaction for CFTR gating using macroscopic and microscopic inside-out patch-clamp recordings. Employing thermodynamic double-mutant cycles, we systematically track gating-state dependent changes in the strength of the R117-E1124 interaction. We find that the H-bond is formed only in the open state, but neither in the short-lived "flickery" nor in the long-lived "interburst" closed state. Loss of this H-bond explains the entire gating phenotype of the R117H mutant, including robustly shortened burst durations and strongly reduced intraburst open probability. The findings may help targeted potentiator design.

62: A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2
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Posted 07 May 2021

A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2
2 tweets bioRxiv genomics

Damien Richard, Liam P. Shaw, Robert Lanfear, Russell Corbett-Detig, Yatish Turakhia, Angie S. Hinrichs, Jakob McBroome, Mislav Acman, Christopher Owen, Cedric C.S. Tan, Lucy van Dorp, Francois Balloux

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally to cause the COVID-19 pandemic. Despite the constant accumulation of genetic variation in the SARS-CoV-2 population, there was little evidence for the emergence of significantly more transmissible lineages in the first half of 2020. Starting around November 2020, several more contagious and possibly more virulent Variants of Concern (VoCs) were reported in various regions of the world. These VoCs share some mutations and deletions that haven arisen recurrently in distinct genetic backgrounds. Here, we build on our previous work modelling the association of mutations to SARS-CoV-2 transmissibility and characterise the contribution of individual recurrent mutations and deletions to estimated viral transmissibility. We then assess how patterns of estimated transmissibility in all SARS-CoV-2 clades have varied over the course of the COVID-19 pandemic by summing transmissibility estimates for all individual mutations carried by any sequenced genome analysed. Such an approach recovers the Delta variant (21A) as the most transmissible clade currently in circulation, followed by the Alpha variant (20I). By assessing transmissibility over the time of sampling, we observe a tendency for estimated transmissibility within clades to slightly decrease over time in most clades. Although subtle, this pattern is consistent with the expectation of a decay in transmissibility in mainly non-recombining lineages caused by the accumulation of weakly deleterious mutations. SARS-CoV-2 remains a highly transmissible pathogen, though such a trend could conceivably play a role in the turnover of different global viral clades observed over the pandemic so far.

63: Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals
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Posted 09 Apr 2021

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals
2 tweets medRxiv epidemiology

Talia Kustin, Noam Harel, Uriah Finkel, Shay Perchik, Sheri Harari, Maayan Tahor, Itamar Caspi, Rachel Levy, Michael Leschinsky, Shifra Ken Dror, Galit Bergerzon, Hala Gadban, Faten Gadban, Eti Eliassian, Orit Shimron, Loulou Saleh, Haim Ben-Zvi, Doron Amichay, Anat Ben-Dor, Dana Sagas, Merav Strauss, Yonat Shemer Avni, Amit Huppert, Eldad Kepten, Ran D. Balicer, Doron Nezer, Shay Ben-Shachar, Adi Stern

The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals. Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

64: Evidence for treatment with estradiol for women with SARS-CoV-2 infection
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Posted 24 Aug 2020

Evidence for treatment with estradiol for women with SARS-CoV-2 infection
2 tweets medRxiv epidemiology

Ute Seeland, Flaminia Coluzzi, Maurizio Simmaco, Cameron Mura, Philip E. Bourne, Max Heiland, Robert Preissner, Saskia Preissner

BACKGROUND Given that an individual's age and gender are strongly predictive of COVID-19 outcomes, do such factors imply anything about preferable therapeutic options? METHODS An analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in five-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds Ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15-49 years) and post-menopausal (>50 years). RESULTS The incidence of SARS-CoV-2 infection is higher in women than men (about +15%) and, in contrast, the fatality rate is higher in men (about +50%). Interestingly, the relationships between these quantities are also linked to age. Pre-adolescent girls had the same risk of infection and fatality rate as boys. Adult premenopausal women had a significantly higher risk of infection than men in the same five-year age stratum (about 16,000 vs. 12,000 cases). This ratio changed again in postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17{beta}-estradiol has a positive effect on expression of the human ACE2 protein--which plays an essential role for SARS-CoV-2 cellular entry--propensity score matching was performed for the women's sub-cohort, comparing users versus non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women >50 yrs receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95 % CI [0.18, 0.62] and the Hazard Ratio was 0.29, 95% CI [0.11,0.76]. For younger, pre-menopausal women (15-49 yrs), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels. CONCLUSIONS As of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone.

65: Six-month sequelae of post-vaccination SARS-CoV-2 infection: a retrospective cohort study of 10,024 breakthrough infections
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Posted 26 Oct 2021

Six-month sequelae of post-vaccination SARS-CoV-2 infection: a retrospective cohort study of 10,024 breakthrough infections
2 tweets medRxiv infectious diseases

Maxime Taquet, Quentin Dercon, Paul J Harrison

Background. Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Methods. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021). Associations with the number of vaccine doses (1 vs. 2) and age (< 60 vs. [&ge;] 60 years-old) were assessed. Findings. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p<.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those < 60 years-old, whereas no robust associations were observed in those [&ge;] 60 years-old. Interpretation. COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. These benefits of vaccination were clear in younger people but not in the over-60s. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae. Funding. National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.

66: Effect of vaccination on transmission of COVID-19: an observational study in healthcare workers and their households
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Posted 21 Mar 2021

Effect of vaccination on transmission of COVID-19: an observational study in healthcare workers and their households
2 tweets medRxiv public and global health

Anoop Shah, Ciara Gribben, Jennifer Bishop, Peter Hanlon, David Caldwell, Rachael Wood, Martin Reid, Jim McMenamin, David Goldberg, Diane Stockton, Sharon Hutchinson, Chris Robertson, Paul M McKeigue, Helen Colhoun, David McAllister

Background: The effect of vaccination for COVID-19 on onward transmission is unknown. Methods: A national record linkage study determined documented COVID-19 cases and hospitalizations in unvaccinated household members of vaccinated and unvaccinated healthcare workers from 8th December 2020 to 3rd March 2021. The primary endpoint was COVID-19 >= 14 days following the first dose. Results: The cohort comprised of 194,362 household members (mean age 31.1 years) and 144,525 healthcare workers (mean age 44.4 years). 113,253 (78.3%) of healthcare workers received at least one dose of the BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccine and 36,227 (25.1%) received a second dose. Household members of vaccinated healthcare workers had a lower risk of COVID-19 case compared to household members of unvaccinated healthcare worker (rate per 100 person-years 9.40 versus 5.93; HR 0.70, 95% confidence interval [CI] 0.63-0.78). The effect size for COVID-19 hospitalization was similar, with the confidence interval crossing the null (HR 0.77 [0.53-1.10]). The rate per 100 person years was lower in vaccinated compared to unvaccinated healthcare workers for documented (20.13 versus 8.51; HR 0.45 [0.42-0.49]) and hospitalized COVID-19 (0.97 versus 0.14; HR 0.16 [0.09-0.27]). Compared to the period before the first dose, the risk of documented COVID-19 case was lower at >= 14 days after the second dose for household members (HR 0.46 [0.30-0.70]) and healthcare workers (HR 0.08 [0.04-0.17]). Conclusion: Vaccination of health care workers was associated with a substantial reduction in COVID-19 cases in household contacts consistent with an effect of vaccination on transmission.

67: A Helicase-tethered ORC Flip Enables Bidirectional Helicase Loading
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Posted 06 Oct 2021

A Helicase-tethered ORC Flip Enables Bidirectional Helicase Loading
2 tweets bioRxiv molecular biology

Shalini Gupta, Larry J Friedman, Jeff Gelles, Stephen P Bell

Replication origins are licensed by loading two Mcm2-7 helicases around DNA in a head-to-head conformation poised to initiate bidirectional replication. This process requires ORC, Cdc6, and Cdt1. Although different Cdc6 and Cdt1 molecules load each helicase, whether two ORC proteins are required is unclear. Using colocalization single-molecule spectroscopy combined with FRET, we investigated interactions between ORC and Mcm2-7 during helicase loading. We demonstrate that a single ORC molecule can recruit both Mcm2-7/Cdt1 complexes via similar interactions that end upon Cdt1 release. Between the first and second helicase recruitment, we observe a rapid change in interactions between ORC and the first Mcm2-7. In quick succession ORC breaks the interactions mediating first Mcm2-7 recruitment, releases from its initial DNA-binding site, and forms a new interaction with the opposite face of the first Mcm2-7. This rearrangement requires release of the first Cdt1 and tethers ORC as it flips over the first Mcm2-7 to form an inverted Mcm2-7-ORC-DNA complex required for second-helicase recruitment. To ensure correct licensing, this complex is maintained until head-to-head interactions between the two helicases are formed. Our findings reconcile previous observations and reveal a highly-coordinated series of events through which a single ORC molecule can load two oppositely-oriented helicases.

68: SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations
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Posted 01 Oct 2021

SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations
2 tweets medRxiv infectious diseases

Elizabeth M Anderson, Theresa Eiloa, Eileen Goodwin, Marcus J Bolton, Sigrid Gouma, Rishi R Goel, Mark M Painter, Sokratis A. Apostolidis, Divij Mathew, Debora Dunbar, Danielle Fiore, Amanda Brock, JoEllen Weaver, John S. Millar, Stephanie DerOhannessian, The UPenn COVID Processing Unit, Allison R. Greenplate, Ian Frank, Daniel J Rader, E John Wherry, Scott E. Hensley

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines elicit higher levels of antibodies compared to natural SARS-CoV-2 infections in most individuals; however, the specificities of antibodies elicited by vaccination versus infection remain incompletely understood. Here, we characterized the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers and 23 participants who received mRNA-based SARS-CoV-2 vaccines. We found that infection and primary mRNA vaccination elicited S1 and S2-reactive antibodies, while secondary vaccination boosted mostly S1 antibodies. Using magnetic bead-based absorption assays, we found that SARS-CoV-2 infections elicited a large proportion of original antigenic sin-like antibodies that bound efficiently to common seasonal human coronaviruses but poorly to SARS-CoV-2. In converse, vaccination only modestly boosted antibodies reactive to common seasonal human coronaviruses and these antibodies bound efficiently to SARS-CoV-2. Our data indicate that SARS-CoV-2 mRNA vaccinations elicit fundamentally different antibody responses compared to SARS-CoV-2 infections.

69: Daily feeding rhythm linked to microbiome composition in two zooplankton species
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Posted 28 Oct 2021

Daily feeding rhythm linked to microbiome composition in two zooplankton species
2 tweets bioRxiv microbiology

Alaina C. Pfenning-Butterworth, Reilly Cooper, Clay Cressler

Host-associated microbial communities are impacted by external and within-host factors, i.e., diet and feeding behavior. For organisms known to have a circadian rhythm in feeding behavior, microbiome composition is likely impacted by the different rates of microbe introduction and removal across a daily cycle, in addition to any diet-induced changes in microbial interactions. Here, we measured feeding behavior and used 16S rRNA sequencing to compare the microbial community across a diel cycle in two distantly related species of Daphnia, that differ in their life history traits, to assess how daily feeding patterns impact microbiome composition. We find that Daphnia species reared under similar laboratory conditions have significantly different microbial communities. Additionally, we reveal that Daphnia have daily differences in their microbial composition that correspond with feeding behavior, such that there is greater microbiome diversity at night during the host's active feeding phase. These results highlight that zooplankton microbiomes are relatively distinct and are likely influenced by host phylogeny.

70: Hyaluronic Acid Fuels Pancreatic Cancer Growth
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Posted 15 Sep 2020

Hyaluronic Acid Fuels Pancreatic Cancer Growth
2 tweets bioRxiv cancer biology

Peter K. Kim, Christopher J. Halbrook, Samuel A Kerk, Stephanie Wisner, Daniel M. Kremer, Peter Sajjakulnukit, Sean W. Hou, Galloway Thurston, Abhinav Anand, Liang Yan, Lucia Salamanca-Cardona, Samuel D. Welling, Li Zhang, Matthew R Pratt, Kayvan R. Keshari, Haoqiang Ying, Costas A Lyssiotis

Rewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not impair tumor growth, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. Here, we show that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating N-acetyl-glucosamine (GlcNAc) and glucuronic acid sugars, can bypass GFAT1 to refuel the HBP via the GlcNAc salvage pathway. Furthermore, HA facilitates proliferation in nutrient-starved wild-type PDA. Together, these data show HA can serve as a nutrient fueling PDA metabolism beyond its previously appreciated structural and signaling roles. ### Competing Interest Statement CAL is an inventor on patents pertaining to Kras regulated metabolic pathways, redox control pathways in pancreatic cancer, and targeting the GOT1-pathway as a therapeutic approach. KRK serves on the scientific advisory board of NVision Imaging Technologies.

71: Using next generation matrices to estimate the proportion of cases that are not detected in an outbreak
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Posted 26 Feb 2021

Using next generation matrices to estimate the proportion of cases that are not detected in an outbreak
2 tweets medRxiv epidemiology

H Juliette T Unwin, Anne Cori, Natsuko Imai, Katy A. M. Gaythorpe, Sangeeta Bhatia, Lorenzo Cattarino, Christl A. Donnelly, Neil M. Ferguson, Marc Baguelin

Contact tracing, where exposed individuals are followed up to break ongoing transmission chains, is a key pillar of outbreak response for many infectious disease outbreaks, such as Ebola and SARS-CoV-2. Unfortunately, these systems are not fully effective, and cases can still go undetected as people may not know or remember all of their contacts or contacts may not be able to be traced. A large proportion of undetected cases suggests poor contact tracing and surveillance systems, which could be a potential area of improvement for a disease response. In this paper, we present a novel method for estimating the proportion of cases that are not detected during an outbreak. Our method uses next generation matrices that are parameterized by linked contact tracing and case line-lists. We use this method to investigate the proportion of undetected cases in two case studies: the SARS-CoV-2 outbreak in New Zealand during 2020 and the West African Ebola outbreak in Guinea during 2014. We estimate that only 6% of SARS-CoV-2 cases were not detected in New Zealand (95% credible interval: 1.31 - 16.7%), but over 60% of Ebola cases were not detected in Guinea (95% credible interval: 15 - 90%).

72: A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients.
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Posted 02 Jun 2020

A cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients.
2 tweets medRxiv infectious diseases

Chuen Wen Tan, Liam Pock Ho, Shirin Kalimuddin, Benjamin Pei Zhi Cherng, Yii Ean Teh, Siew Yee Thien, Hei Man Wong, Paul Jie Wen Tern, Jason Wai Mun Chay, Chandramouli Nagarajan, Rehena Sultana, Jenny Guek Hong Low, Heng Joo Ng

Objective: To determine the clinical outcomes of older COVID-19 patients who received DMB compared to those who did not. We hypothesized that fewer patients administered DMB would require oxygen therapy and/or intensive care support than those who did not. Methodology: Cohort observational study of all consecutive hospitalized COVID-19 patients aged 50 and above in a tertiary academic hospital who received DMB compared to a recent cohort who did not. Patients were administered oral vitamin D3 1000 IU OD, magnesium 150mg OD and vitamin B12 500mcg OD (DMB) upon admission if they did not require oxygen therapy. Primary outcome was deterioration post-DMB administration leading to any form of oxygen therapy and/or intensive care support. Results: Between 15 January and 15 April 2020, 43 consecutive COVID-19 patients aged [&ge;]50 were identified. 17 patients received DMB and 26 patients did not. Baseline demographic characteristics between the two groups was significantly different in age. In univariate analysis, age and hypertension showed significant influence on outcome while DMB retained protective significance after adjusting for age or hypertension separately in multivariate analysis. Fewer DMB patients than controls required initiation of oxygen therapy during their hospitalization (17.6% vs 61.5%, P=0.006). DMB exposure was associated with odds ratios of 0.13 (95% CI: 0.03 - 0.59) and 0.20 (95% CI: 0.04 - 0.93) for oxygen therapy and/or intensive care support on univariate and multivariate analyses respectively. Conclusions: DMB combination in older COVID-19 patients was associated with a significant reduction in proportion of patients with clinical deterioration requiring oxygen support and/or intensive care support. This study supports further larger randomized control trials to ascertain the full benefit of DMB in ameliorating COVID-19 severity.

73: A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease
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Posted 25 Sep 2021

A systematic review of COVID-19 vaccine efficacy and effectiveness against SARS-CoV-2 infection and disease
2 tweets medRxiv epidemiology

Melissa M Higdon, Brian Wahl, Carli B Jones, Joseph G Rosen, Shaun A Truelove, Anurima Baidya, Anjalika A Nande, Parisa A ShamaeiZadeh, Karoline K Walter, Daniel R Feikin, Minal K Patel, Maria Deloria Knoll, Alison L Hill

Billions of doses of COVID-19 vaccines have been administered around the world, dramatically reducing SARS-CoV-2 incidence in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. Here we conduct a systematic review of COVID-19 vaccines as of August 2021. We included efficacy data from Phase 3 clinical trials for 13 vaccines within the WHO Emergency Use Listing evaluation process and real-world effectiveness for 5 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include effects against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for both partial and complete vaccination, and against SARS-CoV-2 variants of concern. In addition, we review the epidemiological principles behind the design and interpretation of vaccine effects, and explain important sources of heterogeneity between studies.

74: Relating neural oscillations to laminar fMRI connectivity
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Posted 18 Sep 2020

Relating neural oscillations to laminar fMRI connectivity
2 tweets bioRxiv neuroscience

Rene Scheeringa, Mathilde Bonnefond, Tim van Mourik, Ole Jensen, David G Norris, Peter J Koopmans

Laminar fMRI holds the potential to study connectivity at the laminar level in humans. Here we analyze simultaneously recorded EEG and high resolution fMRI data to investigate how EEG power modulations, induced by a task with an attentional component, relate to changes in fMRI laminar connectivity between and within brain regions. Our results indicate that our task induced decrease in beta power relates to an increase in deep-to-deep layer coupling between regions and to an increase in deep/middle-to-superficial layer connectivity within brain regions. The attention-related alpha power decrease predominantly relates to reduced connectivity between deep and superficial layers within brain regions, since, unlike beta power, alpha power was found to be positively correlated to connectivity. We observed no strong relation between laminar connectivity and gamma band oscillations. These results indicate that especially beta band, and to a lesser extent alpha band oscillations relate to laminar specific fMRI connectivity. These differential effects for the alpha and beta bands suggest a complex picture of possibly co-occurring neural processes that can differentially affect laminar connectivity.

75: Lower probability and shorter duration of infections after Covid-19 vaccine correlate with anti-SARS-CoV-2 circulating IgGs
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Posted 27 Sep 2021

Lower probability and shorter duration of infections after Covid-19 vaccine correlate with anti-SARS-CoV-2 circulating IgGs
2 tweets medRxiv infectious diseases

Chiara Ronchini, Sara Gandini, Sebastiano Pasqualato, Luca Mazzarella, Federica Facciotti, Marina Mapelli, IEO Covid Team, Gianmaria Frige', Rita Passerini, Luca Pase, Silvio Capizzi, Fabrizio Mastrilli, Roberto Orecchia, Gioacchino Natoli, Pier Giuseppe Pelicci

The correlation between immune responses and protection from SARS-CoV-2 infections and its duration remains unclear. We performed a sanitary surveillance at the European Institute of Oncology (IEO) in Milan over a 27 months period. Pre-vaccination, in 1493 participants, we scored 266 infections (17.8%) and 8 possible reinfections (3%). Post-vaccination, we identified 30 infections in 2029 vaccinated individuals (1.5%). We report that the probability of infection post-vaccination is i) significantly lower compared to natural infection, ii) associated with a significantly shorter median duration of infection than that of first infection and reinfection, iii) anticorrelated with circulating antibody levels.

76: Durability of immune responses to the BNT162b2 mRNA vaccine
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Posted 30 Sep 2021

Durability of immune responses to the BNT162b2 mRNA vaccine
2 tweets bioRxiv immunology

Mehul S Suthar, Prabhu S Arunachalam, Mengyun Hu, Noah Reis, Meera Trisal, Olivia Raeber, Sharon Chinthrajah, Meredith E Davis-Gardner, Kelly Manning, Prakriti Mudvari, Sucheta Godbole, Eli Boritz, Amy R Henry, Daniel Douek, Kari Nadeau, Yoshihiro Kawaoka, Veronika I Zarnitsyna, Bali Pulendran, Peter Halfmann

The development of the highly efficacious mRNA vaccines in less than a year since the emergence of SARS-CoV-2 represents a landmark in vaccinology. However, reports of waning vaccine efficacy, coupled with the emergence of variants of concern that are resistant to antibody neutralization, have raised concerns about the potential lack of durability of immunity to vaccination. We recently reported findings from a comprehensive analysis of innate and adaptive immune responses in 56 healthy volunteers who received two doses of the BNT162b2 vaccination. Here, we analyzed antibody responses to the homologous Wu strain as well as several variants of concern, including the emerging Mu (B.1.621) variant, and T cell responses in a subset of these volunteers at six months (day 210 post-primary vaccination) after the second dose. Our data demonstrate a substantial waning of antibody responses and T cell immunity to SARS-CoV-2 and its variants, at 6 months following the second immunization with the BNT162b2 vaccine. Notably, a significant proportion of vaccinees have neutralizing titers below the detection limit, and suggest a 3rd booster immunization might be warranted to enhance the antibody titers and T cell responses.

77: Parasite co-opts a ubiquitin receptor to induce a plethora of developmental changes
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Posted 15 Feb 2021

Parasite co-opts a ubiquitin receptor to induce a plethora of developmental changes
2 tweets bioRxiv molecular biology

Weijie Huang, Allyson Marie MacLean, Akiko Sugio, Abbas Maqbool, Macro Busscher, Shu-Ting Cho, Sophien Kamoun, Chih-Horng Kuo, Richard G.H. Immink, Saskia A Hogenhout

Obligate parasites can induce complex and substantial phenotypic changes in their hosts in ways that favour their transmission to other trophic levels. However, mechanisms underlying these changes remain largely unknown. Here, we demonstrate how SAP05 protein effectors from insect-vectored plant pathogenic phytoplasmas take control of several plant developmental processes to simultaneously prolong host lifespan and induce witch's broom-like proliferations of leaf and sterile shoots, organs colonized by phytoplasmas and vectors. SAP05 acts by mediating the concurrent degradation of SPL and GATA developmental regulators via a process that uniquely relies on hijacking the plant ubiquitin receptor RPN10 independently of substrate lysine ubiquitination. RPN10 is highly conserved among eukaryotes, but SAP05 does not bind insect vector RPN10. A two-amino-acid substitution within plant RPN10 generates a functional variant that is resistant to SAP05 activities. Therefore, one effector protein enables obligate parasitic phytoplasmas to induce a plethora of developmental phenotypes in their hosts.

78: An insight into neurotoxic and toxicity of spike fragments SARS-CoV-2 by exposure environment: A threat to aquatic health?
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Posted 13 Jan 2021

An insight into neurotoxic and toxicity of spike fragments SARS-CoV-2 by exposure environment: A threat to aquatic health?
2 tweets bioRxiv molecular biology

Ives Charlie-Silva, Amanda Araujo, Abraao Guimaraes, Flavio Veras, Helyson Braz, Leticia Pontes, Roberta Jorge, Marco Belo, Bianca Fernandes, Rafael H. Nóbrega, Giovane Galdino, Antonio Condino-Neto, Jorge Galindo-Villegas, Glaucia Machodo-Santelli, Paulo Sanches, Rafael Rezende, Eduardo Cilli, Guilherme Malafaia

The Spike protein (S protein) is a critical component in the infection of the new coronavirus (SARS-CoV-2). The objective of this work was to evaluate whether peptides from S protein could cause negative impact in the aquatic animals. The aquatic toxicity of SARS-CoV-2 spike protein peptides derivatives has been evaluated in tadpoles (n = 50 tadpoles / 5 replicates of 10 animals) from species Physalaemus cuvieri (Leptodactylidae). After synthesis, purification, and characterization of peptides (PSDP2001, PSDP2002, PSDP2003) an aquatic contamination has been simulatedwith these peptides during 24 hours of exposure in two concentrations (100 and 500 ng/mL). The control group (C) was composed of tadpoles kept in polyethylene containers containing de-chlorinated water. Oxidative stress, antioxidant biomarkers and neurotoxicity activity were assessed. In both concentrations, PSPD2002 and PSPD2003 increased catalase and superoxide dismutase antioxidants enzymes activities, as well as oxidative stress (nitrite levels, hydrogen peroxide and reactive oxygen species). All three peptides also increased acetylcholinesterase activity in the highest concentration. These peptides showed molecular interactions in silico with acetylcholinesterase and antioxidant enzymes. Aquatic particle contamination of SARS-CoV-2 has neurotoxics effects in P. cuvieri tadpoles. These findings indicate that the COVID-19 can constitute environmental impact or biological damage potential.

79: S gene dropout patterns in SARS-CoV-2 tests suggest spread of the H69del/V70del mutation in the US.
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Posted 30 Dec 2020

S gene dropout patterns in SARS-CoV-2 tests suggest spread of the H69del/V70del mutation in the US.
2 tweets medRxiv infectious diseases

Nicole L Washington, Simon White, Kelly M Schiabor Barrett, Elizabeth T. Cirulli, Alexandre Bolze, James Lu

Recently, multiple novel strains of SARS-CoV-2 have been found to share the same deletion of amino acids H69 and V70 in the virus S gene. This includes strain B.1.1.7 / SARS-CoV-2 VUI 202012/01, which has been found to be more infectious than other strains of SARS-CoV-2, and its increasing presence has resulted in new lockdowns in and travel restrictions leaving the UK. Here, we analyze 2 million RT-PCR SARS-CoV-2 tests performed at Helix to identify the rate of S gene dropout, which has been recently shown to occur in tests from individuals infected with strains of SARS-CoV-2 that carry the H69del/V70del mutation. We observe a rise in S gene dropout in the US starting in early October, with 0.25% of our daily SARS-CoV-2-positive tests exhibiting this pattern during the first week. The rate of positive samples with S gene dropout has grown slowly over time, with last week exhibiting the highest level yet, at 0.5%. Focusing on the 14 states for which we have sufficient sample size to assess the frequency of this rare event (n>1000 SARS-CoV-2-positive samples), we see a recent expansion in the Eastern part of the US, concentrated in MA, OH, and FL. However, we cannot say from these data whether the S gene dropout samples we observe here represent the B.1.1.7. strain. Only with an expansion of genomic surveillance sequencing in the US will we know for certain the prevalence of the B.1.1.7 strain in the US.

80: Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism
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Posted 07 Mar 2020

Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism
2 tweets bioRxiv bioinformatics

Houcemeddine Othman, Zied Bouslama, Jean-Tristan Brandenburg, Jorge Emanuel Batista da Rocha, Yosr Hamdi, Kais Ghedira, Najet Srairi-Abid, Scott Hazelhurst

The spread of the COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor via which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with the phylogeny analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than mutation accumulation. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to hACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of human engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2. ### Competing Interest Statement The authors have declared no competing interest.

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