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  1. Article ; Online: Characterization and Evaluation of Bone-Derived Nanoparticles as a Novel pH-Responsive Carrier for Delivery of Doxorubicin into Breast Cancer Cells

    Sheikh Tanzina Haque / Rowshan Ara Islam / Siew Hua Gan / Ezharul Hoque Chowdhury

    International Journal of Molecular Sciences, Vol 21, Iss 6721, p

    2020  Volume 6721

    Abstract: Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as ... ...

    Abstract Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5–6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into ...
    Keywords goose bone ash (GBA) ; carbonated apatite ; breast cancer ; carbonate apatite (CA) ; pH responsive drug delivery ; cytotoxicity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Fe/Mg-Modified Carbonate Apatite with Uniform Particle Size and Unique Transport Protein-Related Protein Corona Efficiently Delivers Doxorubicin into Breast Cancer Cells

    Sheikh Tanzina Haque / Md. Emranul Karim / Syafiq Asnawi Zainal Abidin / Iekhsan Othman / Mark M. Banaszak Holl / Ezharul Hoque Chowdhury

    Nanomaterials, Vol 10, Iss 834, p

    2020  Volume 834

    Abstract: Breast cancer is the abnormal, uncontrollable proliferation of cells in the breast. Conventional treatment modalities like chemotherapy induce deteriorating side effects on healthy cells. Non-viral inorganic nanoparticles (NPs) confer exclusive ... ...

    Abstract Breast cancer is the abnormal, uncontrollable proliferation of cells in the breast. Conventional treatment modalities like chemotherapy induce deteriorating side effects on healthy cells. Non-viral inorganic nanoparticles (NPs) confer exclusive characteristics, such as, stability, controllable shape and size, facile surface modification, and unique magnetic and optical properties which make them attractive drug carriers. Among them, carbonate apatite (CA) particles are pH-responsive in nature, enabling rapid intracellular drug release, but are typically heterogeneous with the tendency to self-aggregate. Here, we modified the nano-carrier by partially substituting Ca 2+ with Mg 2+ and Fe 3+ into a basic lattice structure of CA, forming Fe/Mg-carbonate apatite (Fe/Mg-CA) NPs with the ability to mitigate self-aggregation, form unique protein corona in the presence of serum and efficiently deliver doxorubicin (DOX), an anti-cancer drug into breast cancer cells. Two formulations of Fe/Mg-CA NPs were generated by adding different concentrations of Fe 3+ and Mg 2+ along with a fixed amount of Ca 2+ in bicarbonate buffered DMEM (Dulbecco’s Modified Eagle’s Medium), followed by 30 min incubation at 37 °C. Particles were characterized by turbidity analysis, z-average diameter and zeta potential measurement, optical microscopy, field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), flame atomic absorption spectroscopy (FAAS), pH dissolution, drug binding, cellular uptake, thiazolyl blue tetrazolium bromide (MTT) assay, stability analysis, and protein corona study by LCMS (Liquid chromatography-mass spectrometry). Both formulations of Fe/Mg-CA displayed mostly uniform nano-sized particles with less tendency to aggregate. The EDX and FAAS elemental analysis confirmed the weight (%) of Ca, Fe and Mg, along with their Ca/P ratio in the particles. A constant drug binding efficiency was noticed with 5 μM to 10 μM of initial DOX concentration. A pH ...
    Keywords nanoparticles (NPs) ; inorganic NPs ; doxorubicin (DOX) ; breast cancer ; carbonate apatite (CA) ; Fe/Mg-carbonate apatite (Fe/Mg-CA) ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Cytomegalovirus viral load parameters associated with earlier initiation of pre-emptive therapy after solid organ transplantation.

    Sheila Lumley / Cameron Green / Hannah Rafferty / Colette Smith / Mark Harber / James O'Beirne / Gareth Jones / Douglas Thorburn / Aileen Marshall / Tina Shah / Mohamed Zuhair / Emily Rothwell / Sowsan Atabani / Tanzina Haque / Paul Griffiths

    PLoS ONE, Vol 14, Iss 1, p e

    2019  Volume 0210420

    Abstract: BACKGROUND:Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 ... ...

    Abstract BACKGROUND:Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT). METHODS:Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes. FINDINGS:In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p<0.0215) were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment (16/58; 27% versus 26/49; 53%). Median peak viral load increased significantly (2,103 to 3,934 genomes/ml, p<0.0249) in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup. INTERPRETATION:Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Comparison of automated chemiluminescence immunoassays with capture enzyme immunoassays for the detection of measles and mumps IgM antibodies in serum

    Haywood, Becky / Daniel Webster / Dianne Irish / Mauli Patel / Ruth Copping / Samantha Hurday / Tanzina Haque

    Journal of virological methods. 2014 Feb., v. 196

    2014  

    Abstract: Outbreaks of measles and mumps occur regularly in the UK. Rapid diagnosis of acute infection is important for both infection control and epidemiological purposes. The objective of this study was to compare the performance of an automated platform ( ... ...

    Abstract Outbreaks of measles and mumps occur regularly in the UK. Rapid diagnosis of acute infection is important for both infection control and epidemiological purposes. The objective of this study was to compare the performance of an automated platform (DiaSorin Liaison®, Saluggia, Italy) with a manual capture enzyme immunoassay (EIA; Microimmune, Hounslow, UK) for the detection of measles and mumps IgM antibodies in serum from symptomatic individuals. Ninety sera tested previously for measles (n=50) and mumps (n=40) IgM using the manual EIA were tested retrospectively using the DiaSorin Liaison® and the results compared. Sensitivity, specificity, inter-assay variability and intra-assay variability of the Liaison® assays were calculated. Sensitivity and specificity of the Liaison® assay for measles IgM were 92% and 100% respectively, with inter-assay variation of 14.1% and intra-assay variation of 12.5%. The sensitivity and specificity of the mumps IgM Liaison® assay were 88% and 95% respectively, with an inter-assay and intra-assay variation of 13.9% and 5.3% respectively. Both the measles and mumps IgM Liaison® assays gave fewer equivocal results than the EIA. Neither Liaison® IgM assay showed any cross-reactivity with sera positive against other viruses, however the measles IgM EIA cross-reacted with parvovirus IgM. The automated Liaison® assays are more specific, cheaper and less labour-intensive compared to the manual EIA. The Liaison® assays benefit from reduced number of equivocal results compared to the EIA for both measles and mumps IgM. This allows clinical decisions to be made accurately and in a timely manner.
    Keywords acute course ; antibodies ; automation ; blood serum ; chemiluminescence immunoassays ; cross reaction ; disease control ; enzyme immunoassays ; immunoglobulin M ; measles ; Protoparvovirus ; viruses ; United Kingdom
    Language English
    Dates of publication 2014-02
    Size p. 15-17.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2013.10.027
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Analysis of transmitted HIV-1 drug resistance using 454 ultra-deep-sequencing and the DeepChek®-HIV system

    Ana Garcia-Diaz / Adele McCormick / Clare Booth / Dimitri Gonzalez / Chalom Sayada / Tanzina Haque / Margaret Johnson / Daniel Webster

    Journal of the International AIDS Society , Vol 17, Iss 4(Suppl 3), Pp 1-

    2014  Volume 1

    Abstract: Introduction: Next-generation sequencing (NGS) is capable of detecting resistance-associated mutations (RAMs) present at frequencies of 1% or below. Several studies have found that baseline low-frequency RAMs are associated with failure to first-line ... ...

    Abstract Introduction: Next-generation sequencing (NGS) is capable of detecting resistance-associated mutations (RAMs) present at frequencies of 1% or below. Several studies have found that baseline low-frequency RAMs are associated with failure to first-line HAART. One major limitation to the expansion of this technology in routine diagnostics is the complexity and laboriousness integral to bioinformatics analysis. DeepChek (ABL, TherapyEdge) is a CE-marked software that allows automated analysis and resistance interpretation of NGS data. Objective: To evaluate the use of 454 ultra-deep-sequencing (Roche® 454, Life Sciences; 454-UDS) and DeepChek for routine baseline resistance testing in a clinical diagnostic laboratory. Methods: 107 newly diagnosed HIV-1-infected patients (subtypes: A, n=9; B, n=52; C, n=21; D, n=2; F, n=3; G, n=1; CRF01, n=7; CRF02, n=7; CRF06, n=1; CRF07, n=1; CRF10, n=1 and unassigned complex, n=2) with a median plasma viral load of 88,727 copies/mL (range: 1380–2,143,543) were tested by 454-UDS and Sanger sequencing for the detection of protease and reverse transcriptase RAMs. In addition, integrase RAMs were investigated in 57 of them. Sequence analysis and resistance interpretation were performed using DeepChek applying 1% and 20% thresholds for variant detections; filters applied were comparison between Sanger and 454-UDS, and Stanford and IAS list for resistance interpretation. Results: The time elapsed from generation of raw 454 data (between 2,000–5,000 sequences/sample) to elaboration of a resistance report was approximately 10 minutes per sample, equivalent to the time required for the same process using Sanger sequencing. Four patients (3.7%) showed baseline resistance by Sanger and 454-UDS at frequencies above 20%, which affected both NRTIs (n=2) and NNRTIs (n=2). In addition, 12 patients (11.2%) showed transmitted drug resistance (TDR) by 454-UDS at frequencies below 20% affecting NRTIs (n=9), NNRTIs (n=7) and PIs (n=2). Integrase resistance was not detected at baseline by 454-UDS or Sanger sequencing. Conclusions: DeepChek allowed easy and rapid analysis and interpretation of NGS data, thus facilitating the incorporation of this technology in routine diagnostics. The use of NGS considerably increased the detection rates of TDR to NRTI, NNRTIs and PIs. No transmitted resistance to integrase inhibitors was found in our population by Sanger sequencing or UDS.
    Keywords General Works ; A ; Medicine ; R ; Political science ; J ; Social Sciences ; H ; Immunologic diseases. Allergy ; RC581-607
    Subject code 630
    Language English
    Publishing date 2014-11-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men

    Judith Breuer / Catherine F Houlihan / David Partridge / Gaia Nebbia / Jacqui Prieto / Gee Yen Shin / Oliver Stirrup / Kenneth Laing / Rachel Williams / Helen Wheeler / Paul Randell / Ana da Silva Filipe / Tommy Rampling / Tabassum Khan / James Price / Sharon Glaysher / Scott Elliott / Helen Umpleby / Emanuela Pelosi /
    Emma Thomson / Cristina Venturini / Anna Riddell / Alison Cox / Andrew C Hayward / Malin Bergström / David Harrington / Charlotte Williams / Tanzina Haque / Dianne Irish / Adrienn Angyal / Marios Margaritis / Florencia Boshier / José Afonso Guerra-Assunção / Adela Alcolea-Medina / Angela Beckett / Themoula Charalampous / Raghavendran Kulasegaran Shylini / Beatrix Kele / Irene Monahan / Guy Mollett / Matthew Parker / Sunando Roy / Joshua Taylor / Sophie Weller / Eleri Wilson-Davies / Phillip Wade / Joseph Hughes / Tabitha Mahungu / Cassie Pope / Samuel Robson

    BMJ Open Respiratory Research, Vol 8, Iss

    multicentre cohort study

    2021  Volume 1

    Keywords Medicine ; R ; Diseases of the respiratory system ; RC705-779
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
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  7. Article ; Online: Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7

    Mark S Graham, PhD / Carole H Sudre, PhD / Anna May, MA / Michela Antonelli, PhD / Benjamin Murray, MSc / Thomas Varsavsky, MSc / Kerstin Kläser, MSc / Liane S Canas, PhD / Erika Molteni, PhD / Marc Modat, PhD / David A Drew, PhD / Long H Nguyen, MD / Lorenzo Polidori, MSc / Somesh Selvachandran, MSc / Christina Hu, MA / Joan Capdevila, PhD / Alexander Hammers, ProfPhD / Andrew T Chan, ProfMD / Jonathan Wolf, MA /
    Tim D Spector, ProfPhD / Claire J Steves, PhD / Sebastien Ourselin, ProfPhD / Cherian Koshy / Amy Ash / Emma Wise / Nathan Moore / Matilde Mori / Nick Cortes / Jessica Lynch / Stephen Kidd / Derek J Fairley / Tanya Curran / James P McKenna / Helen Adams / Christophe Fraser / Tanya Golubchik / David Bonsall / Mohammed O Hassan-Ibrahim / Cassandra S Malone / Benjamin J Cogger / Michelle Wantoch / Nicola Reynolds / Ben Warne / Joshua Maksimovic / Karla Spellman / Kathryn McCluggage / Michaela John / Robert Beer / Safiah Afifi / Sian Morgan / Angela Marchbank / Anna Price / Christine Kitchen / Huw Gulliver / Ian Merrick / Joel Southgate / Martyn Guest / Robert Munn / Trudy Workman / Thomas R Connor / William Fuller / Catherine Bresner / Luke B Snell / Amita Patel / Themoula Charalampous / Gaia Nebbia / Rahul Batra / Jonathan Edgeworth / Samuel C Robson / Angela H Beckett / David M Aanensen / Anthony P Underwood / Corin A Yeats / Khalil Abudahab / Ben EW Taylor / Mirko Menegazzo / Gemma Clark / Wendy Smith / Manjinder Khakh / Vicki M Fleming / Michelle M Lister / Hannah C Howson-Wells / Louise Berry / Tim Boswell / Amelia Joseph / Iona Willingham / Carl Jones / Christopher Holmes / Paul Bird / Thomas Helmer / Karlie Fallon / Julian Tang / Veena Raviprakash / Sharon Campbell / Nicola Sheriff / Victoria Blakey / Lesley-Anne Williams / Matthew W Loose / Nadine Holmes / Christopher Moore / Matthew Carlile / Victoria Wright / Fei Sang / Johnny Debebe / Francesc Coll / Adrian W Signell / Gilberto Betancor / Harry D Wilson / Sahar Eldirdiri / Anita Kenyon / Thomas Davis / Oliver G Pybus / Louis du Plessis / Alex E Zarebski / Jayna Raghwani / Moritz UG Kraemer / Sarah Francois / Stephen W Attwood / Tetyana I Vasylyeva / Marina Escalera Zamudio / Bernardo Gutierrez / M. Estee Torok / William L Hamilton / Ian G Goodfellow / Grant Hall / Aminu S Jahun / Yasmin Chaudhry / Myra Hosmillo / Malte L Pinckert / Iliana Georgana / Samuel Moses / Hannah Lowe / Luke Bedford / Jonathan Moore / Susanne Stonehouse / Chloe L Fisher / Ali R Awan / John BoYes / Judith Breuer / Kathryn Ann Harris / Julianne Rose Brown / Divya Shah / Laura Atkinson / Jack CD Lee / Nathaniel Storey / Flavia Flaviani / Adela Alcolea-Medina / Rebecca Williams / Gabrielle Vernet / Michael R Chapman / Lisa J Levett / Judith Heaney / Wendy Chatterton / Monika Pusok / Li Xu-McCrae / Darren L Smith / Matthew Bashton / Gregory R Young / Alison Holmes / Paul Anthony Randell / Alison Cox / Pinglawathee Madona / Frances Bolt / James Price / Siddharth Mookerjee / Manon Ragonnet-Cronin / Fabricia F. Nascimento / David Jorgensen / Igor Siveroni / Rob Johnson / Olivia Boyd / Lily Geidelberg / Erik M Volz / Aileen Rowan / Graham P Taylor / Katherine L Smollett / Nicholas J Loman / Joshua Quick / Claire McMurray / Joanne Stockton / Sam Nicholls / Will Rowe / Radoslaw Poplawski / Alan McNally / Rocio T Martinez Nunez / Jenifer Mason / Trevor I Robinson / Elaine O'Toole / Joanne Watts / Cassie Breen / Angela Cowell / Graciela Sluga / Nicholas W Machin / Shazaad S Y Ahmad / Ryan P George / Fenella Halstead / Venkat Sivaprakasam / Wendy Hogsden / Chris J Illingworth / Chris Jackson / Emma C Thomson / James G Shepherd / Patawee Asamaphan / Marc O Niebel / Kathy K Li / Rajiv N Shah / Natasha G Jesudason / Lily Tong / Alice Broos / Daniel Mair / Jenna Nichols / Stephen N Carmichael / Kyriaki Nomikou / Elihu Aranday-Cortes / Natasha Johnson / Igor Starinskij / Ana da Silva Filipe / David L Robertson / Richard J Orton / Joseph Hughes / Sreenu Vattipally / Joshua B Singer / Seema Nickbakhsh / Antony D Hale / Louissa R Macfarlane-Smith / Katherine L Harper / Holli Carden / Yusri Taha / Brendan AI Payne / Shirelle Burton-Fanning / Sheila Waugh / Jennifer Collins / Gary Eltringham / Steven Rushton / Sarah O'Brien / Amanda Bradley / Alasdair Maclean / Guy Mollett / Rachel Blacow / Kate E Templeton / Martin P McHugh / Rebecca Dewar / Elizabeth Wastenge / Samir Dervisevic / Rachael Stanley / Emma J Meader / Lindsay Coupland / Louise Smith / Clive Graham / Edward Barton / Debra Padgett / Garren Scott / Emma Swindells / Jane Greenaway / Andrew Nelson / Clare M McCann / Wen C Yew / Monique Andersson / Timothy Peto / Anita Justice / David Eyre / Derrick Crook / Tim J Sloan / Nichola Duckworth / Sarah Walsh / Anoop J Chauhan / Sharon Glaysher / Kelly Bicknell / Sarah Wyllie / Scott Elliott / Allyson Lloyd / Robert Impey / Nick Levene / Lynn Monaghan / Declan T Bradley / Tim Wyatt / Elias Allara / Clare Pearson / Husam Osman / Andrew Bosworth / Esther Robinson / Peter Muir / Ian B Vipond / Richard Hopes / Hannah M Pymont / Stephanie Hutchings / Martin D Curran / Surendra Parmar / Angie Lackenby / Tamyo Mbisa / Steven Platt / Shahjahan Miah / David Bibby / Carmen Manso / Jonathan Hubb / Meera Chand / Gavin Dabrera / Mary Ramsay / Daniel Bradshaw / Alicia Thornton / Richard Myers / Ulf Schaefer / Natalie Groves / Eileen Gallagher / David Lee / David Williams / Nicholas Ellaby / Ian Harrison / Hassan Hartman / Nikos Manesis / Vineet Patel / Chloe Bishop / Vicki Chalker / Juan Ledesma / Katherine A Twohig / Matthew T.G. 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    The Lancet Public Health, Vol 6, Iss 5, Pp e335-e

    an ecological study

    2021  Volume 345

    Abstract: Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease ... ...

    Abstract Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.
    Keywords Public aspects of medicine ; RA1-1270
    Subject code 150
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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