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1. Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohortResearch in context

Author

Peter D. Kirwan, Victoria J. Hall, Sarah Foulkes, Ashley D. Otter, Katie Munro, Dominic Sparkes, Anna Howells, Naomi Platt, Jonathan Broad, David Crossman, Chris Norman, Diane Corrigan, Christopher H. Jackson, Michelle Cole, Colin S. Brown, Ana Atti, Jasmin Islam, Anne M. Presanis, Andre Charlett, Daniela De Angelis, Susan Hopkins, Tracy Lewis, Steve Bain, Rebeccah Thomas, John Geen, Carla Pothecary, Sean Cutler, John Northfield, Cathy Price, Johanne Tomlinson, Sarah Knight, Emily Macnaughton, Ekaterina Watson, Rajeka Lazarus, Aaran Sinclair, Joanne Galliford, Bridgett Masunda, Tabitha Mahungu, Alison Rodger, Esther Hanison, Simon Warren, Swati Jain, Mariyam Mirfenderesky, Natasha Mahabir, Rowan Pritchard-Jones, Diane Wycherley, Claire Gabriel, Elijah Matovu, Philippa Bakker, Simantee Guha, S. Gormley, James Pethick, Georgina Butt, Stacey Pepper, Luke Bedford, Paul Ridley, Jane Democratis, Manjula Meda, Anu Chawla, Fran Westwell, Nagesh Kalakonda, Sheena Khanduri, Allison Doel, Sumita Pai, Christian Hacon, Davis Nwaka, Veronica Mendez Moro, A. Moody, Cressida Auckland, Stephanie Prince, Thushan de Silva, Helen Shulver, A. Shah, C. Jones, Banerjee Subhro-Osuji, Angela Houston, Tim Planche, Martin Booth, Christopher Duff, Jonnie Aeron-Thomas, Ray Chaudhuri, David Hilton, Hannah Jory, Zehra'a Al-Khafaji, Philippa Kemsley, Ruth Longfellow, David Boss, Simon Brake, Louise Coke, Ngozi Elumogo, Scott Latham, Chinari Subudhi, Ina Hoad, Claire Thomas, Nihil Chitalia, Tracy Edmunds, Helen Ashby, John Elliott, Beverley Wilkinson, Abby Rand, Catherine Thompson, K. Agwuh, Anna Grice, Kelly Moran, Vijayendra Waykar, Yvonne Lester, Lauren Sach, Kathryn Court, Nikki White, Clair Favager, Kyra Holliday, Jayne Harwood, Brendan Payne, Karen Burns, Lynda Fothergill, Alejandro Arenas-Pinto, Abigail Severn, Kerryanne Brown, Katherine Gray, Jane Dare, Qi Zheng, Kathryn Hollinshead, Robert Shorten, Alun Roebuck, Christopher Holmes, Martin Wiselka, Barzo Faris, Liane Marsh, Clare McAdam, Lisa Ditchfield, Zaman Qazzafi, G. Boyd, N. Wong, Sarah Brand, Jack Squires, John Ashcroft, Ismaelette Del Rosario, Joanne Howard, Emma Ward, Gemma Harrison, Joely Morgan, Claire Corless, Ruth Penn, Nick Wong, Manny Bagary, Nadezda Starkova, Mandy Beekes, Mandy Carnahan, Shivani Khan, Shekoo Mackay, Keneisha Lewis, Graham Pickard, Joy Dawson, Lauren Finlayson, Euan Cameron, Anne Todd, Sebastien Fagegaltier, Sally Mavin, Alexandra Cochrane, Andrew Gibson, Sam Donaldson, Kate Templeton, Martin Malcolm, Beth Smith, Devesh Dhasmana, Susan Fowler, Antonia Ho, Michael Murphy, Claire Beith, Manish Patel, Elizabeth Boyd, Val Irvine, Alison Grant, Rebecca Temple-Purcell, Clodagh Loughrey, Elinor Hanna, Frances Johnston, Angel Boulos, Fiona Thompson, Yuri Protaschik, Susan Regan, Tracy Donaghy, Maurice O'Kane, Omolola Akinbami, Paola Barbero, Tim Brooks, Meera Chand, Ferdinando Insalata, Palak Joshi, Anne-Marie O'Connell, Mary Ramsay, Ayoub Saei, Maria Zambon, Ezra Linley, Simon Tonge, Enemona Adaji, Omoyeni Adebiyi, Nick Andrews, Joanna Conneely, Paul Conneely, Angela Dunne, Simone Dyer, Hannah Emmett, Nipunadi Hettiarachchi, Nishanthan Kapirial, Jameel Khawam, Edward Monk, Sophie Russell, Andrew Taylor-Kerr, Jean Timeyin, Silvia D'Arcangelo, Cathy Rowe, Amanda Semper, Eileen Gallagher, Robert Kyffin, Lisa Cromey, Desmond Areghan, Jennifer Bishop, Melanie Dembinsky, Laura Dobbie, Josie Evans, David Goldberg, Lynne Haahr, Annelysse Jorgenson, Ayodeji Matuluko, Laura Naismith, Desy Nuryunarsih, Alexander Olaoye, Caitlin Plank, Lesley Price, Nicole Sergenson, Sally Stewart, Andrew Telfer, Jennifer Weir, Ellen De Lacy, Yvette Ellis, Susannah Froude, Guy Stevens, Linda Tyson, Susanna Dunachie, Paul Klenerman, Chris Duncan, Rebecca Payne, Lance Turtle, Alex Richter, Thushan De Silva, Eleanor Barnes, Daniel Wootton, Oliver Galgut, Jonathan Heeney, Helen Baxendale, Javier Castillo-Olivares, Rupert Beale, Edward Carr, Wendy Barclay, Maya Moshe, Massimo Palmarini, Brian Willett, John Kenneth Baillie, Jennie Evans, and Erika Aquino

Subjects
SARS-CoV-2, Vaccine effectiveness, Asymptomatic, Symptomatic, Healthcare worker, Cohort study, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

Published
2024
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2. Four key challenges in infectious disease modelling using data from multiple sources

Author

Daniela De Angelis, Anne M. Presanis, Paul J. Birrell, Gianpaolo Scalia Tomba, and Thomas House

Subjects
Evidence synthesis, Bayesian, Statistical inference, Multiple sources, Epidemics, Complex models, Infectious and parasitic diseases, RC109-216
Abstract

Public health-related decision-making on policies aimed at controlling epidemics is increasingly evidence-based, exploiting multiple sources of data. Policy makers rely on complex models that are required to be robust, realistically approximating epidemics and consistent with all relevant data. Meeting these requirements in a statistically rigorous and defendable manner poses a number of challenging problems. How to weight evidence from different datasets and handle dependence between them, efficiently estimate and critically assess complex models are key challenges that we expound in this paper, using examples from influenza modelling.

Published
2015
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3. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Author

Harry D Wilson, Elaine O'Toole, Andrew Bassett, Moritz U. G. Kraemer, Beth Blane, Scott Goodwin, Giri Shankar, Joseph Hughes, Lucy R. Frost, Alicia Thornton, Scott Elliott, Tammy V Merrill, Sheila Waugh, Alexander Adams, Peter Muir, Graciela Sluga, Rebecca Williams, Hannah Dent, Christophe Fraser, Shavanthi Rajatileka, John C. Hartley, Luke B Snell, Benjamin J Cogger, Lance Turtle, Alex Makunin, John A. Todd, Victoria Wright, Daniela De Angelis, James McKenna, Dinesh Aggarwal, Jonathan K. Ball, Jillian Durham, Garren Scott, Thushan I de Silva, Veena Raviprakash, Hannah M Pymont, Jason Coombes, Anita Lucaci, Luke R. Green, Leigh M Jackson, Hermione J. Webster, Louis du Plessis, David A. Jackson, Minal Patel, Áine O'Toole, Ravi Gupta, Marc Niebel, Garry Scarlett, Rajiv Shah, Guy Mollett, Kathy Li, Rory Gunson, Matthew Bashton, Carl Jones, Sara Kumziene-Summerhayes, Zoltan Molnar, Siona Silveira, Malte L Pinckert, Catherine Ludden, Angeliki Karamani, Leanne Kane, Brendan A I Payne, Alan McNally, Clare M. McCann, Holli Carden, Mohammad Raza, Alison E. Mather, Kate B. Cook, Amy Gaskin, David J. Williams, Shaun R. Seaman, Christopher I. Jones, Gilberto Betancor, Matthew T. G. Holden, Jennifier Liddle, Meera Unnikrishnan, Angie Green, Ben Taylor, Kelly Bicknell, Alexander J. Trotter, Emma Meader, Leanne M Kermack, Nathaniel Storey, Michelle Cronin, Sally Forrest, Sarah Jeremiah, Asad Zaidi, M Morgan, Alasdair MacLean, Thomas R. Connor, Johnathan M Evans, Rachael Stanley, Ryan P George, Nadine Holmes, Richard H. Myers, Christine Sambles, Bernardo Gutierrez, Jeffrey K. J. Cheng, Tim Wyatt, Natasha Jesudason, Lindsay Coupland, Monika Pusok, Manon Ragonnet-Cronin, Jenifer Mason, Joshua Maksimovic, Russell Hope, Alison Holmes, David Simpson, Radoslaw Poplawski, Amelia Joseph, Erwan Acheson, James Bonfield, Mara K. N. Lawniczak, Sascha Ott, Lesley-Anne Williams, Jessica Lynch, Graham P. Taylor, Anita Kenyon, Elizabeth Wastenge, Megan Mayhew, Adhyana I K Mahanama, Stavroula F Louka, Chloe Bishop, Esther Robinson, Darren Smith, Anne M. Presanis, Matthew Carlile, Thomas D Stanton, Dennis Wang, Katerina Galai, Adam P Westhorpe, Flavia Flaviani, Michelle Wantoch, Max Whiteley, Yann Bourgeois, Matthew Gemmell, Mary Ramsay, A Lloyd, Simon Thelwall, Hannah C. Howson-Wells, Joseph G. Chappell, Steve Paterson, Gary Eltringham, Robert Impey, Siddharth Mookerjee, Steven Platt, Emma Swindells, Laura Letchford, Alex Alderton, Lee Graham, Safiah Afifi, David C. Lee, Cassie Breen, Melisa Louise Fenton, Benita Percival, Adrian W Signell, Tanya Golubchik, Ian B Vipond, Eleri Wilson-Davies, Angie Lackenby, Laura Atkinson, Sarojini Pandey, Nazreen F. Hadjirin, Michael A Chapman, Huw Gulliver, Joana Dias, Grant Hall, Antony D Hale, Hassan Hartman, Alp Aydin, Louise Smith, Ashok Dadrah, Johnny Debebe, Sarah Walsh, Stephanie W. Lo, Andrew Bosworth, Bridget Knight, Hannah E Bridgewater, Nadua Bayzid, Gemma L. Kay, Richard Gregory, Sally Kay, Ellena Brooks, Andre Charlett, Georgina M McManus, Riaz Jannoo, Victoria Blakey, Carol Scott, Rachel Nelson, Liz Ratcliffe, Gerry Tonkin-Hill, Verity Hill, Joanne D. Stockton, Danielle Leek, Steven Leonard, Stephanie Hutchings, Jonathan D. Moore, Kathryn Ann Harris, Sophie Jones, Venkat Sivaprakasam, Amy Plimmer, Tanzina Haque, Katherine L. Bellis, Khalil Abudahab, Dianne Irish-Tavares, Gaia Nebbia, Kathryn A Jackson, Stephen W Attwood, Daniel Mair, Sreenu Vattipally, Susanne Stonehouse, Ian Merrick, Lucille Rainbow, Mathew A. Beale, Angela Helen Beckett, Ember Hilvers, Thomas Helmer, Jenna Nichols, Giselda Bucca, Salman Goudarzi, Christopher Ruis, Surendra Parmar, Angela Cowell, Alberto C Cerda, Divya K. Shah, Judith Heaney, E. Thomson, Kyriaki Nomikou, Nicole Pacchiarini, Katherine L Harper, Fatima Downing, M. Estée Török, Michelle L Michelsen, Aaron R. Jeffries, Jennifer Collins, Christopher Williams, Katie F. Loveson, Steven Rudder, Theocharis Tsoleridis, Robert Davies, David Robertson, Katherine Smollett, Kathryn McCluggage, Liam Crawford, Inigo Martincorena, Charlotte Beaver, Oliver Megram, Karla Spellman, Sam Haldenby, Emma Betteridge, William D. Fuller, Will P. M. Rowe, Cherian Koshy, Tim E. A. Peto, Alison Cox, Natasha Johnson, Tanya Curran, Sharif Shaaban, Tamyo Mbisa, Cordelia Langford, Eric Witele, Andrew J. Page, Christoph Puethe, Nicola Reynolds, Paul W Bird, Louise Aigrain, Ronan Lyons, Amy Trebes, Sally Corden, Steven Rushton, Jack Cd Lee, Jane Greenaway, Hibo Asad, Amanda Bradley, Mohammed O Hassan-Ibrahim, Shane McCarthy, Fei Sang, Matthew Loose, Hannah Jones, Keith D. James, Chloe L Fisher, Chrystala Constantinidou, Alex G. Richter, Jane A. H. Masoli, Michael Gallagher, Vicki M. Fleming, Anna Price, Amy Ash, Michaela John, Alex Zarebski, Fenella D. Halstead, John Danesh, Christine Kitchen, Aminu S Jahun, Mark Whitehead, Julianne R Brown, Catherine Bresner, Marius Cotic, Stefanie V Lensing, Nick Levene, Louissa R Macfarlane-Smith, Wendy Hogsden, Cressida Auckland, Eleanor Drury, Richard Eccles, Jennifer Hart, Seema Nickbakhsh, Alisha Davies, David M. Aanensen, Shirelle Burton-Fanning, Ben Farr, Buddhini Samaraweera, Sarah Wyllie, Hannah Lowe, Richard J. Orton, Martin D. Curran, Carol Churcher, Karen Oliver, Elihu Aranday-Cortes, Wen Yew, Thanh Le-Viet, Matthew Parker, Katherine A Twohig, Shahjahan Miah, Samuel M. Nicholls, G MacIntyre-Cockett, Tranprit Saluja, Charlotte Nelson, Vicki Chalker, Roberto Amato, Ellen Higginson, Timothy M. Freeman, Christopher W Holmes, Yasmin Chaudhry, Elias Allara, Alec Birchley, Iraad Bronner, Emma Moles-Garcia, Angus I. Best, Anna L. Casey, Audrey Farbos, Nicholas W Machin, David W Eyre, Tim Boswell, Charlotte A Williams, Elen De Lacy, Matthew J. Bull, Matilde Mori, Carmen F. Manso, Peijun Zhang, Sahar Eldirdiri, Dimitris Grammatopoulos, Corin Yeats, Claudia Wierzbicki, David G Partridge, Kordo Saeed, Nichola Duckworth, David J. Studholme, Harmeet K Gill, Juan Ledesma, Thomas R. A. Davis, Sushmita Sridhar, Clive Graham, Husam Osman, Julian A. Hiscox, Helen Adams, Christopher Fearn, Fabrícia F. Nascimento, Ulf Schaefer, James W. Harrison, Andrew J. Nelson, Joshua Quick, Mohammad Tauqeer Alam, Liam Prestwood, Nikos Manesis, Julian Tang, Justin O'Grady, Sophia T Girgis, Louise Berry, Gemma Clark, Marina Escalera Zamudio, Karlie Fallon, Tim J Sloan, Joanne Watkins, Clare Pearson, Andrew D Beggs, Rachel Williams, Luke Bedford, Trevor Robinson, Nicholas M Redshaw, Richard Hopes, Mirko Menegazzo, Katherine Twohig, Gabrielle Vernet, Steven Liggett, Mariateresa de Cesare, Derrick W. Crook, Dominic P. Kwiatkowski, Mark Kristiansen, Miren Iturriza-Gomara, Christopher I. Moore, Claire Cormie, Olivia Boyd, Nikki Smith, Noel Craine, Kathleen A. Williamson, John Boyes, Sian Ellard, Cristina V. Ariani, Wendy Chatterton, David Bonsall, Kevin Lewis, David Jorgensen, Ian Harrison, Christopher Jackson, Martin P McHugh, Danni Weldon, Michael A. Quail, Amita Patel, Lily Geidelberg, Myra Hosmillo, Judith Breuer, Cariad Evans, Edward Barton, Trudy Workman, Derek Fairley, Vineet Patel, Daniel Bradshaw, Robin Manley, Scott Aj Thurston, John Sillitoe, Monique Andersson, Sharon J. Peacock, Jamie Lopez-Bernal, Thomas Thompson, Nabil-Fareed Alikhan, Ben Temperton, Paul Baker, Robin J Moll, Laura Gifford, Nicholas J. Loman, Jayna Raghwani, Jacqui Prieto, Andrew Hesketh, Oliver G. Pybus, Adela Alcolea-Medina, David Buck, Gregory R Young, Alistair C. Darby, Sónia Gonçalves, Aileen G. Rowan, Tabitha Mahungu, Nicholas Ellaby, Jon-Paul Keatley, Lily Tong, Robert Beer, Martyn Guest, Lisa J Levett, Ali R Awan, Iliana Georgana, Paul E Brown, Li Xu-McCrae, Stephen P. Kidd, Sara Rey, Shazaad Ahmad, Danielle C. Groves, Tetyana I. Vasylyeva, David F. Bibby, Nathan Moore, Fiona Ashcroft, Igor Starinskij, Hannah Paul, Claire McMurray, Michael Spencer Chapman, Carlos Balcazar, Joanna Warwick-Dugdale, Pinglawathee Madona, Edith Vamos, Lesley Shirley, Kate Templeton, Luke Foulser, Igor Siveroni, Ewan M. Harrison, Sian Morgan, Diana Rajan, S Taylor, Laia Fina, Naomi Park, Sarah J. O'Brien, Alessandro M Carabelli, Angela Marchbank, Sunando Roy, Leonardo de Oliveira Martins, Steve Palmer, Jonathan Hubb, Alexander J Keeley, Francesc Coll, Malorie Perry, Paul J. Parsons, Anthony Underwood, Patawee Asamaphan, William L Hamilton, Tommy Nyberg, Sophie Palmer, Amanda Symmonds, Anoop Chauhan, Robert Johnson, Christopher J. R. Illingworth, James Shepherd, Wendy Smith, Rich Livett, Rachel Blacow, Margaret Hughes, Jeremy Mirza, Joanne Watts, Jonathan D. Edgeworth, Sarah François, Sue Edwards, Adrienn Angyal, Thomas N. Williams, Marta Gallis, Lauren Gilbert, Paul Randell, Kate Johnson, Eileen Gallagher, Nick Cortes, Yusri Taha, Leah Ensell, Emanuela Pelosi, Stefan Rooke, Michelle Lister, Ana da Silva Filipe, Cassandra S Malone, Themoula Charalampous, Benjamin B Lindsey, Natalie Groves, Colin Smith, Ross J Harris, Rebekah E Wilson, Stephen Bonner, Richard Stark, Sharon Campbell, Nicola Sheriff, Helen L Lowe, Rachel Jones, Ben Warne, Rose K Davidson, Declan Bradley, Ian Johnston, Jeffrey C. Barrett, Joshua B Singer, Shirin Aliabadi, Andrew Whitwham, Patrick McClure, Samuel Robson, Sharon Glaysher, Robert J. Munn, Emma L. Wise, Laura Baxter, Kim S Smith, Catherine Moore, Bree Gatica-Wilcox, Alice Broos, Sarah Essex, David Baker, Manjinder Khakh, Dorota Jamrozy, Rachel Tucker, Ian Goodfellow, S.E. Moses, Nicola Cumley, Robin Howe, Meera Chand, James I. Price, Marina Gourtovaia, Debra Padgett, Jaime Tovar-Corona, Stephen L. Michell, Matthew J. Dorman, Lizzie Meadows, David Heyburn, Iona Willingham, Rocio Martinez Nunez, Grace Taylor-Joyce, Claire M Bewshea, Anita Justice, Simon Cottrell, Rebecca C H Brown, Jamie Young, Gavin Dabrera, Matthew Wyles, Stephen Carmichael, Lisa Berry, Frances Bolt, Andrew Rambaut, Samir Dervisevic, Erik M. Volz, Rahul Batra, Caoimhe McKerr, Samantha McGuigan, Katie Jones, Mailis Maes, Rebecca Dewar, Mary Sinnathamby, Joel Southgate, and Lynn Monaghan

Subjects
medicine.medical_specialty, business.industry, Proportional hazards model, Public health, Hazard ratio, Attendance, C500, Vaccination, Infectious Diseases, Relative risk, Internal medicine, Cohort, medicine, business, Cohort study
Abstract

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Published
2022

4. Four key challenges in infectious disease modelling using data from multiple sources

Author

Gianpaolo Scalia Tomba, Anne M. Presanis, Paul J Birrell, Thomas House, Daniela De Angelis, Presanis, Anne [0000-0003-3078-4427], Birrell, Paul [0000-0001-8131-4893], and Apollo - University of Cambridge Repository

Subjects
Computer science, Epidemiology, Bayesian probability, Statistics as Topic, Bayesian, Complex models, Epidemics, Evidence synthesis, Multiple sources, Statistical inference, computer.software_genre, Microbiology, Communicable Diseases, Article, lcsh:Infectious and parasitic diseases, Virology, Humans, lcsh:RC109-216, Data collection, Models, Statistical, Data Collection, Public Health, Environmental and Occupational Health, Data science, Settore MAT/06 - Probabilita' e Statistica Matematica, 3. Good health, Infectious Diseases, Infectious disease (medical specialty), Parasitology, Data mining, computer
Abstract

Highlights • Health decision making increasingly uses models and data from multiple sources. • Inference on model parameters using a multiplicity of data sources is challenging. • Key challenges include more thoughtful model specification and criticism. • Addressing these problems rigorously will require better use of existing tools. • Challenges in epidemic models may motivate new statistical methods., Public health-related decision-making on policies aimed at controlling epidemics is increasingly evidence-based, exploiting multiple sources of data. Policy makers rely on complex models that are required to be robust, realistically approximating epidemics and consistent with all relevant data. Meeting these requirements in a statistically rigorous and defendable manner poses a number of challenging problems. How to weight evidence from different datasets and handle dependence between them, efficiently estimate and critically assess complex models are key challenges that we expound in this paper, using examples from influenza modelling.

Published
2015

5. Dynamic predictions from longitudinal CD4 count measures and time to death of HIV/AIDS patients using a Bayesian joint model

Author

Feysal Kemal Muhammed, Denekew Bitew Belay, Anne M Presanis, and Aboma Temesgen Sebu

Subjects
Joint model, Dynamic predictions, Longitudinal, Time-to-event, and Bayesian model averaging, Science
Abstract

A Bayesian joint modeling approach to dynamic prediction of HIV progression and mortality allows individualized predictions to be made for HIV patients, based on monitoring of their CD4 counts. This study aims to provide predictions of patient-specific trajectories of HIV disease progression and survival. Longitudinal data on 254 HIV/AIDS patients who received ART between 2009 and 2014, and who had at least one CD4 count observed, were employed in a Bayesian joint model of disease progression. Different forms of association structure that relate the longitudinal CD4 biomarker and time to death were assessed; and predictions were averaged over the different models using Bayesian model averaging. The individual follow-up times ranged from 1 to 120 months, with a median of 22 months and IQR 7–39 months. The estimates of the association structure parameters from two of the three models considered indicated that the HIV mortality hazard at any time point is associated with the rate of change in the underlying value of the CD4 count. Model averaging the dynamic predictions resulted in only one of the hypothesized association structures having non-zero weight in almost all time points for each individual, with the exception of twelve patients, for whom other association structures were preferred at a few time points. The predictions were found to be different when we averaged them over models than when we derived them from the highest posterior weight model alone. The model with highest posterior weight for almost all time points for each individual gave an estimate of the association parameter of −0.02 implying that for a unit increase in the CD4 count, the hazard of HIV mortality decreases by a factor (hazard ratio) of 0.98. Functional status and alcohol intake are important contributing factors that affect the mean square root of CD4 measurements.

Published
2023
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6. Trends in undiagnosed HIV prevalence in England and implications for eliminating HIV transmission by 2030: an evidence synthesis model

Author

Anne M Presanis, PhD, Ross J Harris, PhD, Peter D Kirwan, BSc, Ada Miltz, PhD, Sara Croxford, PhD, Ellen Heinsbroek, PhD, Christopher H Jackson, PhD, Hamish Mohammed, PhD, Alison E Brown, PhD, Valerie C Delpech, MBBS, O Noel Gill, ProfMBBCh, and Daniela De Angelis, ProfPhD

Subjects
Public aspects of medicine, RA1-1270
Abstract

Summary: Background: A target to eliminate HIV transmission in England by 2030 was set in early 2019. This study aimed to estimate trends from 2013 to 2019 in HIV prevalence, particularly the number of people living with undiagnosed HIV, by exposure group, ethnicity, gender, age group, and region. These estimates are essential to monitor progress towards elimination. Methods: A Bayesian synthesis of evidence from multiple surveillance, demographic, and survey datasets relevant to HIV in England was used to estimate trends in the number of people living with HIV, the proportion of people unaware of their HIV infection, and the corresponding prevalence of undiagnosed HIV. All estimates were stratified by exposure group, ethnicity, gender, age group (15–34, 35–44, 45–59, or 60–74 years), region (London, or outside of London) and year (2013–19). Findings: The total number of people living with HIV aged 15–74 years in England increased from 83 500 (95% credible interval 80 200–89 600) in 2013 to 92 800 (91 000–95 600) in 2019. The proportion diagnosed steadily increased from 86% (80–90%) to 94% (91–95%) during the same time period, corresponding to a halving in the number of undiagnosed infections from 11 600 (8300–17 700) to 5900 (4400–8700) and in undiagnosed prevalence from 0·29 (0·21–0·44) to 0·14 (0·11–0·21) per 1000 population. Similar steep declines were estimated in all subgroups of gay, bisexual, and other men who have sex with men and in most subgroups of Black African heterosexuals. The pace of reduction was less pronounced for heterosexuals in other ethnic groups and people who inject drugs, particularly outside London; however, undiagnosed prevalence in these groups has remained very low. Interpretation: The UNAIDS target of diagnosing 90% of people living with HIV by 2020 was reached by 2016 in England, with the country on track to achieve the new target of 95% diagnosed by 2025. Reductions in transmission and undiagnosed prevalence have corresponded to large scale-up of testing in key populations and early diagnosis and treatment. Additional and intensified prevention measures are required to eliminate transmission of HIV among the communities that have experienced slower declines than other subgroups, despite having very low prevalences of HIV. Funding: UK Medical Research Council and Public Health England.

Published
2021
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