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2. Mathematical models to evaluate the impact of increasing serotype coverage in pneumococcal conjugate vaccines

Author

Løchen, Alessandra, Anderson, Roy, and Croucher, Nicholas

Abstract

Of over 100 serotypes of Streptococcus pneumoniae, only 7 were included in the first pneumo- coccal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation. This thesis has four aims. First, to explore the limitations and assumptions of published pneu- mococcal models and the implications for future vaccine formulation and policy. Second, to conduct a trend analysis assembling all the available evidence for serotype replacement in Europe, North America and Australia to characterise invasive pneumococcal disease (IPD) caused by vaccine-type (VT) and non-vaccine-types (NVT) serotypes. The motivation behind this is to assess the patterns of relative abundance in IPD cases pre- and post-vaccination, to examine country-level differences in relation to the vaccines employed over time since introduction, and to assess the growth of the replacement serotypes in comparison with the serotypes targeted by the vaccine. The third aim is to use a Bayesian framework to estimate serotype-specific invasiveness, i.e. the rate of invasive disease given carriage. This is useful for dynamic transmission modelling, as transmission is through carriage but a majority of serotype-specific pneumococcal data lies in active disease surveillance. This is also helpful to address whether serotype replacement reflects serotypes that are more invasive or whether serotypes in a specific location are equally more invasive than in other locations. Finally, the last aim of this thesis is to estimate the epidemiological and economic impact of increas- ing serotype coverage in PCVs using a dynamic transmission model. Together, the results highlight that though there are key parameter uncertainties that merit further exploration, divergence in serotype replacement and inconsistencies in invasiveness on a country-level may make a universal PCV suboptimal.

Published
2022
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8. Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England

Author

Allen, Hester, primary, Tessier, Elise, additional, Turner, Charlie, additional, Anderson, Charlotte, additional, Blomquist, Paula, additional, Simons, David, additional, Løchen, Alessandra, additional, Jarvis, Christopher I., additional, Groves, Natalie, additional, Capelastegui, Fernando, additional, Flannagan, Joe, additional, Zaidi, Asad, additional, Chen, Cong, additional, Rawlinson, Christopher, additional, Hughes, Gareth J., additional, Chudasama, Dimple, additional, Nash, Sophie, additional, Thelwall, Simon, additional, Lopez-Bernal, Jamie, additional, Dabrera, Gavin, additional, Charlett, André, additional, Kall, Meaghan, additional, and Lamagni, Theresa, additional

Published
2023
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9. Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021

Author

Blomquist, Paula B, Bridgen, Jessica, Bray, Neil, O’Connell, Anne Marie, West, Daniel, Groves, Natalie, Gallagher, Eileen, Utsi, Lara, Jarvis, Christopher I, Hardstaff, Jo L, Byers, Chloe, Metelmann, Soeren, Simons, David, Zaidi, Asad, Twohig, Katherine A, Savagar, Bethan, Løchen, Alessandra, Wrenn, Katie, Saavedra-Campos, María, Abedin, Zahidul, Florence, Isaac, Cleary, Paul, Elson, Richard, Vivancos, Roberto, Lake, Iain R, Blomquist, Paula B, Bridgen, Jessica, Bray, Neil, O’Connell, Anne Marie, West, Daniel, Groves, Natalie, Gallagher, Eileen, Utsi, Lara, Jarvis, Christopher I, Hardstaff, Jo L, Byers, Chloe, Metelmann, Soeren, Simons, David, Zaidi, Asad, Twohig, Katherine A, Savagar, Bethan, Løchen, Alessandra, Wrenn, Katie, Saavedra-Campos, María, Abedin, Zahidul, Florence, Isaac, Cleary, Paul, Elson, Richard, Vivancos, Roberto, and Lake, Iain R

Abstract

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

Published
2022

10. Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021

Author

Blomquist, Paula B, primary, Bridgen, Jessica, additional, Bray, Neil, additional, O’Connell, Anne Marie, additional, West, Daniel, additional, Groves, Natalie, additional, Gallagher, Eileen, additional, Utsi, Lara, additional, Jarvis, Christopher I, additional, Hardstaff, Jo L, additional, Byers, Chloe, additional, Metelmann, Soeren, additional, Simons, David, additional, Zaidi, Asad, additional, Twohig, Katherine A, additional, Savagar, Bethan, additional, Løchen, Alessandra, additional, Ryan, Cian, additional, Wrenn, Katie, additional, Saavedra-Campos, María, additional, Abedin, Zahidul, additional, Florence, Isaac, additional, Cleary, Paul, additional, Elson, Richard, additional, Vivancos, Roberto, additional, and Lake, Iain R, additional

Published
2022
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14. Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England

Author

Allen, Hester, primary, Tessier, Elise, additional, Turner, Charlie, additional, Anderson, Charlotte, additional, Blomquist, Paula, additional, Simons, David, additional, Løchen, Alessandra, additional, Jarvis, Christopher I, additional, Groves, Natalie, additional, Capelastegui, Fernando, additional, Flannagan, Joe, additional, Zaidi, Asad, additional, Chen, Cong, additional, Rawlinson, Christopher, additional, Hughes, Gareth J., additional, Chudasama, Dimple, additional, Nash, Sophie, additional, Thelwall, Simon, additional, Lopez-Bernal, Jamie, additional, Dabrera, Gavin, additional, Charlett, André, additional, Kall, Meaghan, additional, and Lamagni, Theresa, additional

Published
2022
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17. Modelling intensive care unit capacity under different epidemiological scenarios of the COVID-19 pandemic in three Western European countries

Author

McCabe, Ruth, Kont, Mara D, Schmit, Nora, Whittaker, Charles, Løchen, Alessandra, Baguelin, Marc, Knock, Edward, Whittles, Lilith K, Lees, John, Brazeau, Nicholas F, Walker, Patrick Gt, Ghani, Azra C, Ferguson, Neil M, White, Peter J, Donnelly, Christl A, Hauck, Katharina, and Watson, Oliver J

Abstract

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020-2021 is essential. METHODS: An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff and ventilators under different epidemic scenarios in France, Germany and Italy across the 2020-2021 winter period. The effect of implementing lockdowns triggered by different numbers of COVID-19 patients in ICUs under varying levels of effectiveness is examined, using a 'dual-demand' (COVID-19 and non-COVID-19) patient model. RESULTS: Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource. Reactive lockdowns could lead to large improvements in ICU capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and sustained under a higher level of suppression. The success of such interventions also depends on baseline bed numbers and average non-COVID-19 patient occupancy. CONCLUSION: Reductions in capacity deficits under different scenarios must be weighed against the feasibility and drawbacks of further lockdowns. Careful, continuous decision-making by national policymakers will be required across the winter period 2020-2021.

Published
2021

18. Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: A mathematical modelling analysis

Author

Hogan, Alexandra B., primary, Winskill, Peter, additional, Watson, Oliver J., additional, Walker, Patrick G.T., additional, Whittaker, Charles, additional, Baguelin, Marc, additional, Brazeau, Nicholas F., additional, Charles, Giovanni D., additional, Gaythorpe, Katy A.M., additional, Hamlet, Arran, additional, Knock, Edward, additional, Laydon, Daniel J., additional, Lees, John A., additional, Løchen, Alessandra, additional, Verity, Robert, additional, Whittles, Lilith K., additional, Muhib, Farzana, additional, Hauck, Katharina, additional, Ferguson, Neil M., additional, and Ghani, Azra C., additional

Published
2021
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19. Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: a mathematical modelling analysis

Author

Hogan, Alexandra B, primary, Winskill, Peter, additional, Watson, Oliver J, additional, Walker, Patrick G T, additional, Whittaker, Charles, additional, Baguelin, Marc, additional, Brazeau, Nicholas F, additional, Charles, Giovanni D, additional, Gaythorpe, Katy A M, additional, Hamlet, Arran, additional, Knock, Edward, additional, Laydon, Daniel J, additional, Lees, John A, additional, Løchen, Alessandra, additional, Verity, Robert, additional, Whittles, Lilith K, additional, Muhib, Farzana, additional, Hauck, Katharina, additional, Ferguson, Neil M, additional, and Ghani, Azra C, additional

Published
2021
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20. Clinical Characteristics and Predictors of Outcomes of Hospitalized Patients With Coronavirus Disease 2019 in a Multiethnic London National Health Service Trust: A Retrospective Cohort Study

Author

Perez-Guzman, Pablo N, primary, Daunt, Anna, additional, Mukherjee, Sujit, additional, Crook, Peter, additional, Forlano, Roberta, additional, Kont, Mara D, additional, Løchen, Alessandra, additional, Vollmer, Michaela, additional, Middleton, Paul, additional, Judge, Rebekah, additional, Harlow, Christopher, additional, Soubieres, Anet, additional, Cooke, Graham, additional, White, Peter J, additional, Hallett, Timothy B, additional, Aylin, Paul, additional, Ferguson, Neil, additional, Hauck, Katharina, additional, Thursz, Mark R, additional, and Nayagam, Shevanthi, additional

Published
2020
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21. Additional file 3 of Adapting hospital capacity to meet changing demands during the COVID-19 pandemic

Author

McCabe, Ruth, Schmit, Nora, Christen, Paula, D’Aeth, Josh C., Løchen, Alessandra, Dheeya Rizmie, Shevanthi Nayagam, Miraldo, Marisa, Aylin, Paul, Bottle, Alex, Perez-Guzman, Pablo N., Ghani, Azra C., Ferguson, Neil M., White, Peter J., and Hauck, Katharina

Subjects
Computer Science::Operating Systems
Abstract

Additional file 3. Model equations. Equations used.

Published
2020
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22. Additional file 1 of Adapting hospital capacity to meet changing demands during the COVID-19 pandemic

Author

McCabe, Ruth, Schmit, Nora, Christen, Paula, D’Aeth, Josh C., Løchen, Alessandra, Dheeya Rizmie, Shevanthi Nayagam, Miraldo, Marisa, Aylin, Paul, Bottle, Alex, Perez-Guzman, Pablo N., Ghani, Azra C., Ferguson, Neil M., White, Peter J., and Hauck, Katharina

Subjects
Data_FILES, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Abstract

Additional file 1. Glossary. Definitions of key terms used.

Published
2020
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23. Additional file 2 of Adapting hospital capacity to meet changing demands during the COVID-19 pandemic

Author

McCabe, Ruth, Schmit, Nora, Christen, Paula, D’Aeth, Josh C., Løchen, Alessandra, Dheeya Rizmie, Shevanthi Nayagam, Miraldo, Marisa, Aylin, Paul, Bottle, Alex, Perez-Guzman, Pablo N., Ghani, Azra C., Ferguson, Neil M., White, Peter J., and Hauck, Katharina

Abstract

Additional file 2. Overview table of model inputs, assumptions and how this was quantified for the analysis. Model input values, assumptions, references to data sources and how inputs were quantified for the purpose of this analysis.

Published
2020
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24. Report 28 : Excess non-COVID-19 deaths in England and Wales between 29th February and 5th June 2020

Author

Forchini, Giovanni, Løchen, Alessandra, Hallett, Timothy, Aylin, Paul, White, Peter J., Donnelly, Christl, Ghani, Azra, Ferguson, Neil, Hauck, Katharina, Forchini, Giovanni, Løchen, Alessandra, Hallett, Timothy, Aylin, Paul, White, Peter J., Donnelly, Christl, Ghani, Azra, Ferguson, Neil, and Hauck, Katharina

Abstract

There were 189,403 deaths from any cause reported in England from 29th February to 5th June 2020 inclusive, and 11,278 all-cause deaths in Wales over the same period. Of those deaths, 44,736 (23.6%) registered COVID-19 on the death certificate in England, and 2,294 (20.3%) in Wales, while 144,667 (76.4%) were not recorded as having been due to COVID-19 in England, and 8,984 (79.7%) in Wales. However, it could be that some of the ‘non-COVID-19’ deaths have in fact also been caused by COVID-19, either as the direct cause of death, or indirectly through provisions for the pandemic impeding access to care for other conditions. There is uncertainty in how many of the non-COVID-19 deaths were directly or indirectly caused by the pandemic. We estimated the excess deaths that were not recorded as associated with COVID-19 in the death certificate (excess non-COVID-19 deaths) as the deaths for which COVID-19 was not reported as the cause, compared to those we would have expected to occur had the pandemic not happened. Expected deaths were forecast with an analysis of historic trends in deaths between 2010 and April 2020 using data by the Office of National Statistics and a statistical time series model. According to the model, we expected 136,294 (95% CI 133,882 - 138,696) deaths in England, and 8,983 (CI 8,051 - 9,904) in Wales over this period, significantly fewer than the number of deaths reported. This means that there were 8,983 (95% CI 5,971 - 10,785) total excess non-COVID-19 deaths in England. For every 100 COVID-19 deaths during the period from 29th February to 5th June 2020 there were 19 (95% CI 13 – 24) cumulative excess non-COVID-19 deaths. The proportion of cumulative excess non-COVID-19 deaths of all reported deaths during this period was 4.4% (95% CI 3.2% - 5.7%) in England, with small regional variations. Excess deaths were highest in the South East at 2,213 (95% CI 327 - 4,047) and in London at 1,937 (95% CI 896 - 3,010), respectively. There is no evidence of

Published
2020
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25. Clinical Characteristics and Predictors of Outcomes of Hospitalized Patients With Coronavirus Disease 2019 in a Multiethnic London National Health Service Trust: A Retrospective Cohort Study.

Author

Perez-Guzman, Pablo N, Daunt, Anna, Mukherjee, Sujit, Crook, Peter, Forlano, Roberta, Kont, Mara D, Løchen, Alessandra, Vollmer, Michaela, Middleton, Paul, Judge, Rebekah, Harlow, Christopher, Soubieres, Anet, Cooke, Graham, White, Peter J, Hallett, Timothy B, Aylin, Paul, Ferguson, Neil, Hauck, Katharina, Thursz, Mark R, and Nayagam, Shevanthi

Subjects
ALBUMINS, COVID-19, HOSPITAL patients, CONFIDENCE intervals, RETROSPECTIVE studies, REGRESSION analysis, GUTTMAN scale, TREATMENT effectiveness, NATIONAL health services, KIDNEY diseases, COMPARATIVE studies, SYMPTOMS, SURVIVAL analysis (Biometry), DESCRIPTIVE statistics, ETHNIC groups, ODDS ratio, THROMBOCYTOPENIA, LONGITUDINAL method, HYPOXEMIA, LEUKOCYTE disorders
Abstract

Background Emerging evidence suggests ethnic minorities are disproportionately affected by coronavirus disease 2019 (COVID-19). Detailed clinical analyses of multicultural hospitalized patient cohorts remain largely undescribed. Methods We performed regression, survival, and cumulative competing risk analyses to evaluate factors associated with mortality in patients admitted for COVID-19 in 3 large London hospitals between 25 February and 5 April, censored as of 1 May 2020. Results Of 614 patients (median age, 69 [interquartile range, 25] years) and 62% male), 381 (62%) were discharged alive, 178 (29%) died, and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (adjusted odds ratio [aOR], 4.25 [95% confidence interval {CI}, 2.36–7.64]), leukocytosis (aOR, 2.35 [95% CI, 1.35–4.11]), thrombocytopenia (aOR [1.01, 95% CI, 1.00–1.01], increase per 109 decrease), severe renal impairment (aOR, 5.14 [95% CI, 2.65–9.97]), and low albumin (aOR, 1.06 [95% CI, 1.02–1.09], increase per gram decrease) were associated with death. Forty percent (n = 244) were from black, Asian, and other minority ethnic (BAME) groups, 38% (n = 235) were white, and ethnicity was unknown for 22% (n = 135). BAME patients were younger and had fewer comorbidities. Although the unadjusted odds of death did not differ by ethnicity, when adjusting for age, sex, and comorbidities, black patients were at higher odds of death compared to whites (aOR, 1.69 [95% CI, 1.00–2.86]). This association was stronger when further adjusting for admission severity (aOR, 1.85 [95% CI, 1.06–3.24]). Conclusions BAME patients were overrepresented in our cohort; when accounting for demographic and clinical profile of admission, black patients were at increased odds of death. Further research is needed into biologic drivers of differences in COVID-19 outcomes by ethnicity. [ABSTRACT FROM AUTHOR]

Published
2021
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