Imperial College London

Dr Sabine L. van Elsland

Faculty of MedicineSchool of Public Health

External Relationships & Communications Manager
 
 
 
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Contact

 

+44 (0)20 7594 3896s.van-elsland

 
 
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Location

 

G35Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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104 results found

Christen P, van Elsland S, Saulo D, Cori A, Fitzner Jet al., 2024, Advanced analytics to inform decision making during public health emergencies, Advanced Analytics to Inform Decision Making During Public Health Emergencies, Publisher: WHO, Imperial College London

The COVID-19 pandemic has led to significant understanding of evidence-informed decision making during public health emergencies. Imperial College London and the World Health Organization (WHO) Hub for Pandemic and Epidemic Intelligence (WHO Hub) jointly organized a workshop to generate an understanding of the context and ways in which advanced analytics were used for decision making during the COVID-19 pandemic and to identify opportunities to strengthen the data-to-decisions pathways. Held on 9 – 10 May 2023 at the WHO Hub in Berlin, Germany, the workshop brought together mathematical modellers specialized in infectious disease modelling and scientists based at academic institutions, public health agencies, or Ministries of Health, and public health decision makers. The workshop was conducted in four interactive group activities. The dialogue among participants led to the identification of potential opportunities for support and actions to strengthen the use of outputs from advanced analytics for decision making. These opportunities could be actions to strengthen processes and structures, improve workflows, find consensus on ways of working together, establish a knowledge foundation for support, and jointly drive evidence-based decision-making priorities for epidemic and pandemic preparedness. Workshop participants highlighted further need to capture additional perspectives held by actors from diverse geographical areas, contexts, and roles who were not present at the workshop, and political decision makers to enrich the understanding of the different priorities for advanced analytics for decision making in different regional and local contexts. The workshop highlighted the benefit in bringing together experts from around the globe to share experience and lessons learned to identify priority activities to tackling challenges and improve the way advanced analysis is perceived and used for policy and response decision making. Overall, this workshop has contr

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Sherratt K, Carnegie AC, Kucharski A, Cori A, Pearson CAB, Jarvis CI, Overton C, Weston D, Hill EM, Knock E, Fearon E, Nightingale E, Hellewell J, Edmunds WJ, Villabona Arenas J, Prem K, Pi L, Baguelin M, Kendall M, Ferguson N, Davies N, Eggo RM, van Elsland S, Russell T, Funk S, Liu Y, Abbott Set al., 2024, Improving modelling for epidemic responses: reflections from members of the UK infectious disease modelling community on their experiences during the COVID-19 pandemic, Wellcome Open Research, Vol: 9, Pages: 12-12

<ns3:p>Background The COVID-19 pandemic both relied and placed significant burdens on the experts involved from research and public health sectors. The sustained high pressure of a pandemic on responders, such as healthcare workers, can lead to lasting psychological impacts including acute stress disorder, post-traumatic stress disorder, burnout, and moral injury, which can impact individual wellbeing and productivity. Methods As members of the infectious disease modelling community, we convened a reflective workshop to understand the professional and personal impacts of response work on our community and to propose recommendations for future epidemic responses. The attendees represented a range of career stages, institutions, and disciplines. This piece was collectively produced by those present at the session based on our collective experiences. Results Key issues we identified at the workshop were lack of institutional support, insecure contracts, unequal credit and recognition, and mental health impacts. Our recommendations include rewarding impactful work, fostering academia-public health collaboration, decreasing dependence on key individuals by developing teams, increasing transparency in decision-making, and implementing sustainable work practices. Conclusions Despite limitations in representation, this workshop provided valuable insights into the UK COVID-19 modelling experience and guidance for future public health crises. Recognising and addressing the issues highlighted is crucial, in our view, for ensuring the effectiveness of epidemic response work in the future.</ns3:p>

Journal article

Cuomo-Dannenburg G, McCain K, McCabe R, Unwin HJT, Doohan P, Nash RK, Hicks JT, Charniga K, Geismar C, Lambert B, Nikitin D, Skarp J, Wardle J, Kont M, Bhatia S, Imai N, van Elsland S, Cori A, Morgenstern Cet al., 2023, Marburg virus disease outbreaks, mathematical models, and disease parameters: a systematic review, Lancet Infectious Diseases, ISSN: 1473-3099

Recent Marburg virus disease (MVD) outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this highly lethal infectious pathogen. We conducted a systematic review (PROSPERO CRD42023393345), reported according to PRISMA guidelines, of peer-reviewed papers reporting historical outbreaks, modelling studies and epidemiological parameters focused on MVD. We searched PubMed and Web of Science until 31/03/2023. Two reviewers evaluated all titles and abstracts, with consensus-based decision-making. To ensure agreement, 31% (13/42) of studies were double-extracted and a custom-designed quality assessment questionnaire was used for risk of bias assessment. We present detailed information on 478 reported cases and 385 deaths from MVD. Analysis of historical outbreaks and seroprevalence estimates suggests the possibility of undetected MVD outbreaks, asymptomatic transmission and/or cross-reactivity with other pathogens. Only one study presented a mathematical model of MVD transmission. We estimate an unadjusted, pooled total random effect case fatality ratio for MVD of 61.9% (95% CI: 38.8-80.6%, I^2=93%). We identify important epidemiological parameters relating to transmission and natural history for which there are few estimates. This review and the accompanying database provide a comprehensive overview of MVD epidemiology, and identify key knowledge gaps, contributing crucial information for mathematical models to support future MVD epidemic responses.

Journal article

Bhatia S, Parag KV, Wardle J, Nash RK, Imai N, Elsland SLV, Lassmann B, Brownstein JS, Desai A, Herringer M, Sewalk K, Loeb SC, Ramatowski J, Cuomo-Dannenburg G, Jauneikaite E, Unwin HJT, Riley S, Ferguson N, Donnelly CA, Cori A, Nouvellet Pet al., 2023, Retrospective evaluation of real-time estimates of global COVID-19 transmission trends and mortality forecasts, PLOS ONE, Vol: 18, ISSN: 1932-6203

Journal article

Kruger M, van Elsland SL, Afungchwi GM, Bardin R, Njodzeka B, Kouya F, Nfor P, Nana P, Wharin P, Hesseling PBet al., 2022, Outcome of retinoblastoma treatment protocol in Cameroon as per SIOP-PODC recommendation for a low-income setting, PEDIATRIC BLOOD & CANCER, Vol: 69, ISSN: 1545-5009

Journal article

Ferguson N, Ghani A, Hinsley W, Volz E, on behalf of the Imperial College COVID-19 Response Teamet al., 2021, Report 50: Hospitalisation risk for Omicron cases in England

To assess differences in the risk of hospitalisation between the Omicron variant of concern (1) and the Delta variant, we analysed data from all PCR-confirmed SARS-CoV-2 cases in England with last test specimen dates between 1st and 14th December inclusive. Variant was defined using a combination of S-gene Target Failure (SGTF) and genetic data. Case data were linked by National Health service (NHS) number to the National Immunisation Management System (NIMS) database, the NHS Emergency Care (ECDS) and Secondary Use Services (SUS) hospital episode datasets. Hospital attendance was defined as any record of attendance at a hospital by a case in the 14 days following their last positive PCR test, up to and including the day of attendance. A secondary analysis examined the subset of attendances with a length of stay of one or more days. We used stratified conditional Poisson regression to predict hospitalisation status, with demographic strata defined by age, sex, ethnicity, region, specimen date, index of multiple deprivation and in some analyses, vaccination status. Predictor variables were variant (Omicron or Delta), reinfection status and vaccination status. Overall, we find evidence of a reduction in the risk of hospitalisation for Omicron relative to Delta infections, averaging over all cases in the study period. The extent of reduction is sensitive to the inclusion criteria used for cases and hospitalisation, being in the range 20-25% when using any attendance at hospital as the endpoint, and 40-45% when using hospitalisation lasting 1 day or longer or hospitalisations with the ECDS discharge field recorded as “admitted” as the endpoint (Table 1). These reductions must be balanced against the larger risk of infection with Omicron, due to the reduction in protection provided by both vaccination and natural infection. A previous infection reduces the

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Ferguson N, Ghani A, Cori A, Hogan A, Hinsley W, Volz Eet al., 2021, Report 49: Growth, population distribution and immune escape of Omicron in England

To estimate the growth of the Omicron variant of concern (1) and its immune escape (2–9) characteristics, we analysed data from all PCR-confirmed SARS-CoV-2 cases in England excluding those with a history of recent international travel. We undertook separate analyses according to two case definitions. For the first definition, we included all cases with a definitive negative S-gene Target Failure (SGTF) result and specimen dates between 29/11/2021 and 11/12/2021 inclusive. For the second definition, we included cases with a positive genotype result and specimen date between 23/11/2021 and 11/12/2021 inclusive. We chose a later start date for the SGTF definition to ensure greater specificity of SGTF for Omicron.We used logistic and Poisson regression to identify factors associated with testing positive for Omicron compared to non-Omicron (mostly Delta) cases. We explored the following predictors: day, region, symptomatic status, sex, ethnicity, age band and vaccination status. Our results suggest rapid growth of the frequency of the Omicron variant relative to Delta, with the exponential growth rate of its frequency estimated to be 0.34/day (95% CI: 0.33-0.35) [2.0 day doubling time] over the study period from both SGTF and genotype data. The distribution of Omicron by age, region and ethnicity currently differs markedly from Delta, with 18–29-year-olds, residents in the London region, and those of African ethnicity having significantly higher rates of infection with Omicron relative to Delta.Hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta.To estimate the impact of Omicron on vaccine effectiveness (VE) for symptomatic infection we used conditional Poisson regression to estimate the hazard ratio of being an Omicron case (using SGTF definition) compared with Delta, restricting our analysis to symptomatic cases and matching by da

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Hogan A, Wu SL, Doohan P, Watson OJ, Winskill P, Charles G, Riley EM, Khoury D, Ferguson N, Ghani Aet al., 2021, Report 48: The value of vaccine booster doses to mitigate the global impact of the Omicron SARS-CoV-2 variant

Vaccines have played a central role in mitigating severe disease and death from COVID-19 in the past 12 months. However, efficacy wanes over time and this loss of protection will be compounded by the emergence of the Omicron variant. By fitting an immunological model to population-level vaccine effectiveness data, we estimate that neutralizing antibody titres for Omicron are reduced by 4.5-fold (95% CrI 3.1–7.1) compared to the Delta variant. This is predicted to result in a drop in vaccine efficacy against severe disease (hospitalisation) from 96.5% (95% CrI 96.1%–96.8%) against Delta to 80.1% (95% CrI 76.3%–83.2%) against Omicron for the Pfizer-BioNTech booster by 60 days post boost if NAT decay at the same rate following boosting as following the primary course, and from 97.6% (95% CrI 97.4%-97.9%) against Delta to 85.9% (95% CrI 83.1%-88.3%) against Omicron if NAT decay at half the rate observed after the primary course. Integrating this immunological model within a model of SARS-CoV-2 transmission, we show that booster doses will be critical to mitigate the impact of future Omicron waves in countries with high levels of circulating virus. They will also be needed in “zero-COVID” countries where there is little prior infection-induced immunity in order to open up safely. Where dose supply is limited, targeting boosters to the highest risk groups to ensure continued high protection in the face of waning immunity is of greater benefit than giving these doses as primary vaccination to younger age-groups. In all scenarios it is likely that health systems will be stretched. It may be essential, therefore, to maintain and/or reintroduce NPIs to mitigate the worst impacts of the Omicron variant as it replaces the Delta variant. Ultimately, Omicron variant-specific vaccines are likely to be required.

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Bhatia S, Imai N, Cuomo-Dannenburg G, Baguelin M, Boonyasiri A, Cori A, Cucunubá Z, Dorigatti I, FitzJohn R, Fu H, Gaythorpe K, Ghani A, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Okell L, Riley S, Thompson H, van Elsland S, Volz E, Wang H, Wang Y, Whittaker C, Xi X, Donnelly CA, Ferguson NMet al., 2021, Estimating the number of undetected COVID-19 cases among travellers from mainland China, Wellcome Open Research, Vol: 5, Pages: 143-143

<ns4:p><ns4:bold>Background:</ns4:bold> As of August 2021, every region of the world has been affected by the COVID-19 pandemic, with more than 196,000,000 cases worldwide.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>We analysed COVID-19 cases among travellers from mainland China to different regions and countries, comparing the region- and country-specific rates of detected and confirmed cases per flight volume to estimate the relative sensitivity of surveillance in different regions and countries.</ns4:p><ns4:p> <ns4:bold>Results: </ns4:bold>Although travel restrictions from Wuhan City and other cities across China may have reduced the absolute number of travellers to and from China, we estimated that up to 70% (95% CI: 54% - 80%) of imported cases could remain undetected relative to the sensitivity of surveillance in Singapore. The percentage of undetected imported cases rises to 75% (95% CI 66% - 82%) when comparing to the surveillance sensitivity in multiple countries.</ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4:bold>Our analysis shows that a large number of COVID-19 cases remain undetected across the world.<ns4:bold> </ns4:bold>These undetected cases potentially resulted in multiple chains of human-to-human transmission outside mainland China.</ns4:p>

Journal article

Bhatia S, Wardle J, Nash R, Nouvellet P, Cori Aet al., 2021, Report 47: A generic method and software to estimate the transmission advantage of pathogen variants in real-time : SARS-CoV-2 as a case-study

Recent months have demonstrated that emerging variants may set back the global COVID-19 response.The ability to rapidly assess the threat of new variants in real-time is critical for timely optimisation ofcontrol strategies.We extend the EpiEstim R package, designed to estimate the time-varying reproduction number (Rt),to estimate in real-time the e ective transmission advantage of a new variant compared to a referencevariant. Our method can combine information across multiple locations and over time and was validatedusing an extensive simulation study, designed to mimic a variety of real-time epidemic contexts.We estimate that the SARS-CoV-2 Alpha variant is 1.46 (95% Credible Interval 1.44-1.47) and 1.29,(95% CrI 1.29-1.30) times more transmissible than the wild type, using data from England and Francerespectively. We further estimate that Beta and Gamma combined are 1.25 (95% CrI 1.24-1.27) timesmore transmissible than the wildtype (France data). All results are in line with previous estimates fromliterature, but could have been obtained earlier and more easily with our o -the-shelf open-source tool.Our tool can be used as an important rst step towards quantifying the threat of new variants inreal-time. Given the popularity of EpiEstim, this extension will likely be used widely to monitor theco-circulation and/or emergence of multiple variants of infectious pathogens.

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Brizzi A, Whittaker C, Servo LMS, Hawryluk I, Prete Jr CA, de Souza WM, Aguiar RS, Araujo LJT, Bastos LS, Blenkinsop A, Buss LF, Candido D, Castro MC, Costa SF, Croda J, de Souza Santos A, Dye C, Flaxman S, Fonseca PLC, Geddes VEV, Gutierrez B, Lemey P, Levin AS, Mellan T, Bonfim DM, Miscouridou X, Mishra S, Monod M, Moreira FRR, Nelson B, Pereira RHM, Ranzani O, Schnekenberg RP, Semenova E, Sonnabend R, Souza RP, Xi X, Sabino EC, Faria NR, Bhatt S, Ratmann Oet al., 2021, Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals

The SARS‐CoV‐2 Gamma variant spread rapidly across Brazil, causing substantial infection and death wa ves. We use individual‐level patient records following hospitalisation with suspected or confirmed COVID‐19 to document the extensive shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time pe riods. We show that extensive fluctuations in COVID‐19 in‐hospital fatality rates also existed prior to Gamma’s detection, and were largely transient after Gamma’s detection, subsiding with hospital d emand. Using a Bayesian fatality rate model, we find that the geo‐graphic and temporal fluctuations in Brazil’s COVID‐19 in‐hospital fatality rates are primarily associated with geo‐graphic inequities and shortages in healthcare c apacity. We project that approximately half of Brazil’s COVID‐19 deaths in hospitals could have been avoided without pre‐pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly trans‐missible and deadly pathogens such as SARS‐CoV‐2, especially in low‐ and middle‐income countries.

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Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, Hinsley WR, Laydon DJ, Dabrera G, O'Toole Á, Amato R, Ragonnet-Cronin M, Harrison I, Jackson B, Ariani CV, Boyd O, Loman NJ, McCrone JT, Gonçalves S, Jorgensen D, Myers R, Hill V, Jackson DK, Gaythorpe K, Groves N, Sillitoe J, Kwiatkowski DP, COVID-19 Genomics UK COG-UK consortium, Flaxman S, Ratmann O, Bhatt S, Hopkins S, Gandy A, Rambaut A, Ferguson NMet al., 2021, Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England, Nature, Vol: 593, Pages: 266-269, ISSN: 0028-0836

The SARS-CoV-2 lineage B.1.1.7, designated a Variant of Concern 202012/01 (VOC) by Public Health England1, originated in the UK in late Summer to early Autumn 20202. Whole genome SARS-CoV-2 sequence data collected from community-based diagnostic testing shows an unprecedentedly rapid expansion of the B.1.1.7 lineage during Autumn 2020, suggesting a selective advantage. We find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Time-varying reproduction numbers for the VOC and cocirculating lineages were estimated using SGTF and genomic data. The best supported models did not indicate a substantial difference in VOC transmissibility among different age groups. There is a consensus among all analyses that the VOC has a substantial transmission advantage with a 50% to 100% higher reproduction number.

Journal article

Olivera Mesa D, Hogan A, Watson O, Charles G, Hauck K, Ghani A, Winskill Pet al., 2021, Report 43: Quantifying the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic

Vaccine hesitancy – a delay in acceptance or refusal of vaccines despite availability 1 – has the potential to threaten the successful roll-out of SARS-CoV-2 vaccines globally 2 . Here, we evaluate the potential impact of vaccine hesitancy on the control of the pandemic and the relaxation of non-pharmaceutical interventions (NPIs) by combining an epidemiological model of SARS-CoV-2 transmission 3 with data on vaccine hesitancy from population surveys. Our findings suggest that the mortality over a 2-year period could be up to 8 times higher in countries with high vaccine hesitancy compared to an ideal vaccination uptake if NPIs are relaxed. Alternatively, high vaccine hesitancy could prolong the need for NPIs to remain in place. Addressing vaccine hesitancy with behavioural interventions is therefore an important priority in the control of the COVID-19 pandemic.

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van Elsland S, Imai N, on behalf of the Imperial College COVID-19 Response Team, 2021, Imperial College COVID-19 Response Team 2020-2021 Report, Publisher: Imperial College London

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Nouvellet P, Bhatia S, Cori A, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, Eales O, van Elsland S, NASCIMENTO F, Fitzjohn R, Gaythorpe K, Geidelberg L, green W, Hamlet A, Hauck K, Hinsley W, Imai N, Jeffrey, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Nedjati Gilani G, Parag K, Pons Salort M, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Watson O, Whittaker C, Whittles L, Xi X, Ferguson N, Donnelly Cet al., 2021, Reduction in mobility and COVID-19 transmission, Nature Communications, Vol: 12, ISSN: 2041-1723

In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts.Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world.Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation.In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

Journal article

Fu H, Wang H, Xi X, Boonyasiri A, Wang Y, Hinsley W, Fraser KJ, McCabe R, Olivera Mesa D, Skarp J, Ledda A, Dewé T, Dighe A, Winskill P, van Elsland SL, Ainslie KEC, Baguelin M, Bhatt S, Boyd O, Brazeau NF, Cattarino L, Charles G, Coupland H, Cucunubá ZM, Cuomo-Dannenburg G, Donnelly CA, Dorigatti I, Eales OD, Fitzjohn RG, Flaxman S, Gaythorpe KAM, Ghani AC, Green WD, Hamlet A, Hauck K, Haw DJ, Jeffrey B, Laydon DJ, Lees JA, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag KV, Ragonnet-Cronin M, Riley S, Schmit N, Thompson HA, Unwin HJT, Verity R, Vollmer MAC, Volz E, Walker PGT, Walters CE, Waston OJ, Whittaker C, Whittles LK, Imai N, Bhatia S, Ferguson NMet al., 2021, A database for the epidemic trends and control measures during the first wave of COVID-19 in mainland China, International Journal of Infectious Diseases, Vol: 102, Pages: 463-471, ISSN: 1201-9712

Objectives: This data collation effort aims to provide a comprehensive database to describe the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19)across main provinces in China. Methods: From mid-January to March 2020, we extracted publicly available data on the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted a descriptive analysis of the epidemics in the six most-affected provinces. Results: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends were different across provinces. Compared to Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as local transmission of COVID-19 declined, switching the focus of measures to testing and quarantine of inbound travellers could help to sustain the control of the epidemic. Conclusions: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database with these indicators and information on control measures provides useful source for exploring further research and policy planning for response to the COVID-19 epidemic.

Journal article

Knock E, Whittles L, Lees J, Perez Guzman P, Verity R, Fitzjohn R, Gaythorpe K, Imai N, Hinsley W, Okell L, Rosello A, Kantas N, Walters C, Bhatia S, Watson O, Whittaker C, Cattarino L, Boonyasiri A, Djaafara A, Fraser K, Fu H, Wang H, Xi X, Donnelly C, Jauneikaite E, Laydon D, White P, Ghani A, Ferguson N, Cori A, Baguelin Met al., 2020, Report 41: The 2020 SARS-CoV-2 epidemic in England: key epidemiological drivers and impact of interventions

England has been severely affected by COVID-19. We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional 2020 surveillance data. Only national lockdown brought the reproduction number below 1 consistently; introduced one week earlier in the first wave it could have reduced mortality by 23,300 deaths on average. The mean infection fatality ratio was initially ~1.3% across all regions except London and halved following clinical care improvements. The infection fatality ratio was two-fold lower throughout in London, even when adjusting for demographics. The infection fatality ratio in care homes was 2.5-times that in the elderly in the community. Population-level infection-induced immunity in England is still far from herd immunity, with regional mean cumulative attack rates ranging between 4.4% and 15.8%.

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D'Aeth J, Ghosal S, Grimm F, Haw D, Koca E, Lau K, Moret S, Rizmie D, Deeny S, Perez Guzman P, Ferguson N, Hauck K, Smith P, Wiesemann W, Forchini G, Miraldo Met al., 2020, Report 40: Optimal scheduling rules for elective care to minimize years of life lost during the SARS-CoV-2 pandemic: an application to England

SummaryCountries have deployed a wide range of policies to prioritize patients to hospital care to address unprecedent surges in demand during the course of the pandemic. Those policies included postponing planned hospital care for non-emergency cases and rationing critical care.We develop a model to optimally schedule elective hospitalizations and allocate hospital general and critical care beds to planned and emergency patients in England during the pandemic. We apply the model to NHS England data and show that optimized scheduling leads to lower years of life lost and costs than policies that reflect those implemented in England during the pandemic. Overall across all disease areas the model enables an extra 50,750 - 5,891,608 years of life gained when compared to standard policies, depending on the scenarios. Especially large gains in years of life are seen for neoplasms, diseases of the digestive system, and injuries & poisoning.

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Unwin H, Mishra S, Bradley V, Gandy A, Mellan T, Coupland H, Ish-Horowicz J, Vollmer M, Whittaker C, Filippi S, Xi X, Monod M, Ratmann O, Hutchinson M, Valka F, Zhu H, Hawryluk I, Milton P, Ainslie K, Baguelin M, Boonyasiri A, Brazeau N, Cattarino L, Cucunuba Z, Cuomo-Dannenburg G, Dorigatti I, Eales O, Eaton J, van Elsland S, Fitzjohn R, Gaythorpe K, Green W, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Siveroni I, Thompson H, Walker P, Walters C, Watson O, Whittles L, Ghani A, Ferguson N, Riley S, Donnelly C, Bhatt S, Flaxman Set al., 2020, State-level tracking of COVID-19 in the United States, Nature Communications, Vol: 11, Pages: 1-9, ISSN: 2041-1723

As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available deathdata within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on therate of transmission of SARS-CoV-2. We estimate thatRtwas only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.

Journal article

Watson O, Abdelmagid N, Ahmed A, Ahmed Abd Elhameed AE, Whittaker C, Brazeau N, Hamlet A, Walker P, Hay J, Ghani A, Checchi F, Dahab Met al., 2020, Report 39: Characterising COVID-19 epidemic dynamics and mortality under-ascertainment in Khartoum, Sudan

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Grassly NC, Pons-Salort M, Parker EPK, White PJ, Ferguson NM, Imperial College COVID-19 Response Teamet al., 2020, Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study, Lancet Infectious Diseases, Vol: 20, Pages: 1381-1389, ISSN: 1473-3099

BACKGROUND: WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports. FINDINGS: If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval [UI] 32-55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16-40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timelines

Journal article

Thompson H, Imai N, Dighe A, Ainslie K, Baguelin M, Bhatia S, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Z, Cuomo-Dannenburg G, Djaafara B, Dorigatti I, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Hallett T, Hamlet A, Haw D, Hayes S, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Mousa A, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Wang Y, Watson O, Whittaker C, Whittles L, Winskill P, Xi X, Donnelly C, Ferguson Net al., 2020, SARS-CoV-2 infection prevalence on repatriation flights from Wuhan City, China, Journal of Travel Medicine, Vol: 27, Pages: 1-3, ISSN: 1195-1982

We estimated SARS-CoV-2 infection prevalence in cohorts of repatriated citizens from Wuhan to be 0.44% (95% CI: 0.19%–1.03%). Although not representative of the wider population we believe these estimates are helpful in providing a conservative estimate of infection prevalence in Wuhan City, China, in the absence of large-scale population testing early in the epidemic.

Journal article

Thompson H, Mousa A, Dighe A, Fu H, Arnedo-Pena A, Barrett P, Bellido-Blasco J, Bi Q, Caputi A, Chaw L, De Maria L, Hoffmann M, Mahapure K, Ng K, Raghuram J, Singh G, Soman B, Soriano V, Valent F, Vimercati L, En Wee L, Wong J, Ghani A, Ferguson Net al., 2020, Report 38: SARS-CoV-2 setting-specific transmission rates: a systematic review and meta-analysis

Since the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly across the world. Understanding the drivers of SARS-CoV-2 transmission is crucial for disease control policies but evidence of transmission rates in different settings remains limited. We conducted a systematic review to estimate the secondary attack rate (SAR) and observed reproduction number (Robs) in different settings and to explore differences by age, symptom status, duration of exposure and household size. A total of 97 studies were identified, 45 of which met inclusion criteria for meta-analysis. Households showed the highest transmission rates, with pooled SAR and Robs estimates of 21.1% (95% CI: 17.4%-24.8%) and 0.96 (95% CI: 0.67-1.32), respectively. Household SAR estimates were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of 5 days or less. Attack rates related to familiar and prolonged close contacts, such as social events with family and friends were higher than those related to low-risk casual contacts, such as strangers (SAR of 5.9%, 95% CI: 3.8%-8.1% vs. 1.2%, 95% CI: 0.3%-2.1%). Estimates of SAR for asymptomatic index cases were approximately two thirds of those for symptomatic index (3.5% vs. 12.8%, p<0.001). We find moderate evidence for less transmission both from and to individuals under 20 years of age in the household context, but this difference is less evident when examining all settings. Prolonged contact in households and in settings with familiar close contacts increases the potential for transmission of SARS-CoV-2. Additionally, the differences observed in transmissibility by symptom status of index cases and the potential for age-dependent effects has important implications for outbreak control strategies such as contact tracing, testing and rapid isolation of cases. There was limited data to allow exploration of transmission patterns in workplaces, schools, and care-homes, hig

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Gaythorpe K, Bhatia S, Mangal T, Unwin H, Imai N, Cuomo-Dannenburg G, Walters C, Jauneikaite E, Bayley H, Kont M, Mousa A, Whittles L, Riley S, Ferguson Net al., 2020, Report 37: Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility

SARS-CoV-2 infections have been reported in all age groups including infants, children, and adolescents. However, the role of children in the COVID-19 pandemic is still uncertain. This systematic review of early studies synthesises evidence on the susceptibility of children to SARS-CoV-2 infection, the severity and clinical outcomes in children with SARS-CoV-2 infection, and the transmissibility of SARS-CoV-2 by children. A systematic literature review was conducted in PubMed. Reviewers extracted data from relevant, peer-reviewed studies published during the first wave of the SARS-CoV-2 outbreak using a standardised form and assessed quality using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. For studies included in the meta-analysis, we used a random effects model to calculate pooled estimates of the proportion of children considered asymptomatic or in a severe or critical state. We identified 2,775 potential studies of which 128 studies met our inclusion criteria; data were extracted from 99, which were then quality assessed. Finally, 29 studies were considered for the meta-analysis that included information of symptoms and/or severity, these were further assessed based on patient recruitment. Our pooled estimate of the proportion of test positive children who were asymptomatic was 21.1% (95% CI: 14.0 - 28.1%), based on 13 included studies, and the proportion of children with severe or critical symptoms was 3.8% (95% CI: 1.5 - 6.0%), based on 14 included studies. We did not identify any studies designed to assess transmissibility in children and found that susceptibility to infection in children was highly variable across studies.Children’s susceptibility to infection and onward transmissibility relative to adults is still unclear and varied widely between studies. However, it is evident that most children experience clinically mild disease or remain asymptomatically infected. More comprehensive contact-tracing studie

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McCabe R, Kont M, Schmit N, Whittaker C, Lochen A, Baguelin M, Knock E, Whittles L, Lees J, Walker P, Ghani A, Ferguson N, White P, Donnelly C, Hauck K, Watson Oet al., 2020, Report 36: Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries

The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on healthcare systems, particularly intensive care units (ICUs), with COVID-19 patient care being a key concern of healthcare system planning for winter 2020/21. Ensuring that all patients who require intensive care, irrespective of COVID-19 status, can access it during this time is essential. This study uses an integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients to estimate the spare capacity of key ICU resources under different epidemic scenarios in France, Germany and Italy across the winter period of 2020/21. In particular, we examine the effect of implementing suppression strategies of varying effectiveness, triggered by different numbers of COVID-19 patients in ICU. The use of a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model and the consideration of multiple ICU resources that determine capacity (beds, doctors, nurses and ventilators) and the interdependencies between them, provides a detailed insight into potential capacity constraints this winter. 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 across countries. Lockdowns triggered based on ICU capacity could lead to large improvements in spare capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and implemented at a higher level of suppression. In many cases, maximum deficits are reduced to lower levels which can then be managed by expanding supply-side hospital capacity, to ensure that all patients can receive treatment. The success of such interventions also depends on baseline ICU bed numbers and average non-COVID-19 patient occupancy. We find that lockdowns of longer duration reduce the total number of days in defic

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Haw D, Forchini G, Christen P, Bajaj S, Hogan A, Winskill P, Miraldo M, White P, Ghani A, Ferguson N, Smith P, Hauck Ket al., 2020, Report 35: How can we keep schools and universities open? Differentiating closures by economic sector to optimize social and economic activity while containing SARS-CoV-2 transmission

There is a trade-off between the education sector and other economic sectors in the control of SARS-Cov-2 transmission. Here we integrate a dynamic model of SARS-CoV-2 transmission with a 63-sector economic model reflecting sectoral heterogeneity in transmission and economic interdependence between sectors. We identify COVID-19 control strategies which optimize economic production while keeping schools and universities operational and constraining infections such that emergency hospital capacity is not exceeded. The model estimates an economic gain of between £163bn and £205bn for the United Kingdom compared to a blanket lockdown of non-essential activity over six months, depending on hospital capacity. Sectors identified as potential priorities for closure are contact-intensive and/or less economically productive.

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Brazeau N, Verity R, Jenks S, Fu H, Whittaker C, Winskill P, Dorigatti I, Walker P, Riley S, Schnekenberg RP, Heltgebaum H, Mellan T, Mishra S, Unwin H, Watson O, Cucunuba Perez Z, Baguelin M, Whittles L, Bhatt S, Ghani A, Ferguson N, Okell Let al., 2020, Report 34: COVID-19 infection fatality ratio: estimates from seroprevalence

The infection fatality ratio (IFR) is a key statistic for estimating the burden of coronavirus disease 2019 (COVID-19) and has been continuously debated throughout the current pandemic. Previous estimates have relied on data early in the epidemic, or have not fully accounted for uncertainty in serological test characteristics and delays from onset of infection to seroconversion, death, and antibody waning. After screening 175 studies, we identified 10 representative antibody surveys to obtain updated estimates of the IFR using a modelling framework that addresses the limitations listed above. We inferred serological test specificity from regional variation within serosurveys, which is critical for correctly estimating the cumulative proportion infected when seroprevalence is still low. We find that age-specific IFRs follow an approximately log-linear pattern, with the risk of death doubling approximately every eight years of age. Using these age-specific estimates, we estimate the overall IFR in a typical low-income country, with a population structure skewed towards younger individuals, to be 0.23% (0.14-0.42 95% prediction interval range). In contrast, in a typical high income country, with a greater concentration of elderly individuals, we estimate the overall IFR to be 1.15% (0.78-1.79 95% prediction interval range). We show that accounting for seroreversion, the waning of antibodies leading to a negative serological result, can slightly reduce the IFR among serosurveys conducted several months after the first wave of the outbreak, such as Italy. In contrast, uncertainty in test false positive rates combined with low seroprevalence in some surveys can reconcile apparently low crude fatality ratios with the IFR in other countries. Unbiased estimates of the IFR continue to be critical to policymakers to inform key response decisions. It will be important to continue to monitor the IFR as new treatments are introduced. The code for reproducing these results are av

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