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  1. Article ; Online: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectivity by Viral Load, S Gene Variants and Demographic Factors, and the Utility of Lateral Flow Devices to Prevent Transmission.

    Lee, Lennard Y W / Rozmanowski, Stefan / Pang, Matthew / Charlett, Andre / Anderson, Charlotte / Hughes, Gareth J / Barnard, Matthew / Peto, Leon / Vipond, Richard / Sienkiewicz, Alex / Hopkins, Susan / Bell, John / Crook, Derrick W / Gent, Nick / Walker, A Sarah / Peto, Tim E A / Eyre, David W

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2021  Volume 74, Issue 3, Page(s) 407–415

    Abstract: Background: How severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources ... ...

    Abstract Background: How severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect clinical sensitivity is unknown.
    Methods: We combined SARS-CoV-2 testing and contact tracing data from England between 1 September 2020 and 28 February 2021. We used multivariable logistic regression to investigate relationships between polymerase chain reaction (PCR)-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using 1 of 4 LFDs.
    Results: In total, 231 498/2 474 066 (9%) contacts of 1 064 004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower cycle threshold [Ct] values), for example, 11.7% (95% confidence interval [CI] 11.5-12.0%) at Ct = 15 and 4.5% (95% CI 4.4-4.6%) at Ct = 30. B.1.1.7 infection increased PCR-positive results by ~50%, (eg, 1.55-fold, 95% CI 1.49-1.61, at Ct = 20). PCR-positive results were most common in household contacts (at Ct = 20.1, 8.7% [95% CI 8.6-8.9%]), followed by household visitors (7.1% [95% CI 6.8-7.3%]), contacts at events/activities (5.2% [95% CI 4.9-5.4%]), work/education (4.6% [95% CI 4.4-4.8%]), and least common after outdoor contact (2.9% [95% CI 2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5% (95% CI 89.4-89.6%) and 83.0% (95% CI 82.8-83.1%) of cases with PCR-positive contacts, respectively.
    Conclusions: SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ~50%. The best performing LFDs detect most infectious cases.
    MeSH term(s) COVID-19 ; COVID-19 Testing ; Child ; Family Characteristics ; Humans ; SARS-CoV-2 ; Viral Load
    Language English
    Publishing date 2021-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciab421
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission

    Lee, Lennard YW / Rozmanowski, Stefan / Pang, Matthew / Charlett, Andre / Anderson, Charlotte / Hughes, Gareth J / Barnard, Matthew / Peto, Leon / Vipond, Richard / Sienkiewicz, Alex / Hopkins, Susan / Bell, John / Crook, Derrick W / Gent, Nick / Walker, A Sarah / Peto, Tim EA / Eyre, David W

    medRxiv

    Abstract: Background: How SARS-CoV-2 infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect sensitivity is unknown. Methods: We ... ...

    Abstract Background: How SARS-CoV-2 infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect sensitivity is unknown. Methods: We combined SARS-CoV-2 testing and contact tracing data from England between 01-September-2020 and 28-February-2021. We used multivariable logistic regression to investigate relationships between PCR-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using one of four LFDs. Results: 231,498/2,474,066 (9%) contacts of 1,064,004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower Ct values) e.g., 11.7%(95%CI 11.5-12.0%) at Ct=15 and 4.5%(4.4-4.6%) at Ct=30. B.1.1.7 infection increased PCR-positive results by ~50%, (e.g. 1.55-fold, 95%CI 1.49-1.61, at Ct=20). PCR-positive results were most common in household contacts (at Ct=20.1, 8.7%[95%CI 8.6-8.9%]), followed by household visitors (7.1%[6.8-7.3%]), contacts at events/activities (5.2%[4.9-5.4%]), work/education (4.6%[4.4-4.8%]), and least common after outdoor contact (2.9%[2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5%(89.4-89.6%) and 83.0%(82.8-83.1%) of cases with PCR-positive contacts respectively. Conclusions: SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ~50%. The best performing LFDs detect most infectious cases.
    Keywords covid19
    Language English
    Publishing date 2021-04-05
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.03.31.21254687
    Database COVID19

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  3. Article ; Online: Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.

    Supasa, Piyada / Zhou, Daming / Dejnirattisai, Wanwisa / Liu, Chang / Mentzer, Alexander J / Ginn, Helen M / Zhao, Yuguang / Duyvesteyn, Helen M E / Nutalai, Rungtiwa / Tuekprakhon, Aekkachai / Wang, Beibei / Paesen, Guido C / Slon-Campos, Jose / López-Camacho, César / Hallis, Bassam / Coombes, Naomi / Bewley, Kevin R / Charlton, Sue / Walter, Thomas S /
    Barnes, Eleanor / Dunachie, Susanna J / Skelly, Donal / Lumley, Sheila F / Baker, Natalie / Shaik, Imam / Humphries, Holly E / Godwin, Kerry / Gent, Nick / Sienkiewicz, Alex / Dold, Christina / Levin, Robert / Dong, Tao / Pollard, Andrew J / Knight, Julian C / Klenerman, Paul / Crook, Derrick / Lambe, Teresa / Clutterbuck, Elizabeth / Bibi, Sagida / Flaxman, Amy / Bittaye, Mustapha / Belij-Rammerstorfer, Sandra / Gilbert, Sarah / Hall, David R / Williams, Mark A / Paterson, Neil G / James, William / Carroll, Miles W / Fry, Elizabeth E / Mongkolsapaya, Juthathip / Ren, Jingshan / Stuart, David I / Screaton, Gavin R

    Cell

    2021  Volume 184, Issue 8, Page(s) 2201–2211.e7

    Abstract: SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of ... ...

    Abstract SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.
    MeSH term(s) Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; CHO Cells ; COVID-19/epidemiology ; COVID-19/immunology ; Chlorocebus aethiops ; Cricetulus ; HEK293 Cells ; Humans ; Pandemics ; Protein Binding ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Structure-Activity Relationship ; Vero Cells
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-02-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.02.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Performance characteristics of five immunoassays for SARS-CoV-2

    Ainsworth, Mark / Andersson, Monique / Auckland, Kathryn / Baillie, J Kenneth / Barnes, Eleanor / Beer, Sally / Beveridge, Amy / Bibi, Sagida / Blackwell, Luke / Borak, Martyna / Bown, Abbie / Brooks, Tim / Burgess-Brown, Nicola A / Camara, Susana / Catton, Matthew / Chau, Kevin K. / Christott, Thomas / Clutterbuck, Elizabeth / Coker, Jesse /
    Cornall, Richard J / Cox, Stuart / Crawford-Jones, David / Crook, Derrick W / D'Arcangelo, Silvia / Dejnirattsai, Wanwisa / Dequaire, Julie M M / Dimitriadis, Stavros / Dingle, Kate E / Doherty, George / Dold, Christina / Dong, Tao / Dunachie, Susanna J / Ebner, Daniel / Emmenegger, Marc / Espinosa, Alexis / Eyre, David W / Fairhead, Rory / Fassih, Shayan / Feehily, Conor / Felle, Sally / Fernandez-Cid, Alejandra / Fernandez Mendoza, Maria / Foord, Thomas H / Fordwoh, Thomas / Fox McKee, Deborah / Frater, John / Gallardo Sanchez, Veronica / Gent, Nick / Georgiou, Dominique / Groves, Christopher J / Hallis, Bassam / Hammond, Peter M / Hatch, Stephanie B. / Harvala, Heli J / Hill, Jennifer / Hoosdally, Sarah J / Horsington, Bryn / Howarth, Alison / James, Tim / Jeffery, Katie / Jones, Elizabeth / Justice, Anita / Karpe, Fredrik / Kavanagh, James / Kim, David S / Kirton, Richard / Klenerman, Paul / Knight, Julian C / Koukouflis, Leonidas / Kwok, Andrew / Leuschner, Ullrich / Levin, Robert / Linder, Aline / Lockett, Teresa / Lumley, Sheila F / Marinou, Spyridoula / Marsden, Brian D / Martinez, Jose / Martins Ferreira, Lucas / Mason, Lara / Matthews, Philippa C / Mentzer, Alexander J / Mobbs, Alexander / Mongkolsapaya, Juthathip / Morrow, Jordan / Mukhopadhyay, Shubhashish M M / Neville, Matthew J / Oakley, Sarah / Oliveira, Marta / Otter, Ashley / Paddon, Kevin / Pascoe, Jordan / Peng, Yanchun / Perez, Elena / Perumal, Prem K / Peto, Timothy E A / Pickford, Hayleah / Ploeg, Rutger J / Pollard, Andrew J / Richardson, Anastasia / Ritter, Thomas G / Roberts, David J / Rodger, Gillian / Rollier, Christine S / Rowe, Cathy / Rudkin, Justine K / Screaton, Gavin / Semple, Malcolm G / Sienkiewicz, Alex / Silva-Reyes, Laura / Skelly, Donal T / Sobrino Diaz, Alberto / Stafford, Lizzie / Stockdale, Lisa / Stoesser, Nicole / Street, Teresa / Stuart, David I / Sweed, Angela / Taylor, Adan / Thraves, Hannah / Tsang, Hoi P / Verheul, Marije K / Vipond, Richard / Walker, Timothy M / Wareing, Susan / Warren, Yolanda / Wells, Charlie / Wilson, Clare / Withycombe, Kate / Young, Rebecca K

    The Lancet Infectious Diseases ; ISSN 1473-3099

    a head-to-head benchmark comparison

    2020  

    Keywords Infectious Diseases ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    DOI 10.1016/s1473-3099(20)30634-4
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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