Imperial College London

Dr Daniel Laydon

Faculty of MedicineSchool of Public Health

Research Associate
 
 
 
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d.laydon

 
 
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Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

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75 results found

Penn MJJ, Laydon DJJ, Penn J, Whittaker C, Morgenstern C, Ratmann O, Mishra S, Pakkanen MSS, Donnelly CAA, Bhatt Set al., 2023, Intrinsic randomness in epidemic modelling beyond statistical uncertainty, Communications Physics, Vol: 6, ISSN: 2399-3650

Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.

Journal article

Laydon D, Cauchemez S, Hinsley W, Bhatt S, Ferguson Net al., 2023, Impact of proactive and reactive vaccination strategies for health-care workers against MERS-CoV: a mathematical modelling study, The Lancet Global Health, Vol: 11, Pages: e759-e769, ISSN: 2214-109X

BackgroundSeveral vaccine candidates are in development against MERS-CoV, which remains a major public health concern. In anticipation of available MERS-CoV vaccines, we examine strategies for their optimal deployment among health-care workers.MethodsUsing data from the 2013–14 Saudi Arabia epidemic, we use a counterfactual analysis on inferred transmission trees (who-infected-whom analysis) to assess the potential impact of vaccination campaigns targeting health-care workers, as quantified by the proportion of cases or deaths averted. We investigate the conditions under which proactive campaigns (ie vaccinating in anticipation of the next outbreak) would outperform reactive campaigns (ie vaccinating in response to an unfolding outbreak), considering vaccine efficacy, duration of vaccine protection, effectiveness of animal reservoir control measures, wait (time between vaccination and next outbreak, for proactive campaigns), reaction time (for reactive campaigns), and spatial level (hospital, regional, or national, for reactive campaigns). We also examine the relative efficiency (cases averted per thousand doses) of different strategies.FindingsThe spatial scale of reactive campaigns is crucial. Proactive campaigns outperform campaigns that vaccinate health-care workers in response to outbreaks at their hospital, unless vaccine efficacy has waned significantly. However, reactive campaigns at the regional or national levels consistently outperform proactive campaigns, regardless of vaccine efficacy. When considering the number of cases averted per vaccine dose administered, the rank order is reversed: hospital-level reactive campaigns are most efficient, followed by regional-level reactive campaigns, with national-level and proactive campaigns being least efficient. If the number of cases required to trigger reactive vaccination increases, the performance of hospital-level campaigns is greatly reduced; the impact of regional-level campaigns is variable, but tha

Journal article

Morgenstern C, Laydon D, Whittaker C, Mishra S, Haw D, Bhatt S, Ferguson Net al., 2022, The interaction of transmission intensity, mortality, and the economy: a retrospective analysis of the COVID-19 pandemic

<jats:title>Abstract</jats:title> <jats:p>The COVID-19 pandemic has caused over 6.4 million registered deaths to date, and has had a profound impact on economic activity. Here, we study the interaction of transmission, mortality, and the economy during the SARS-CoV-2 pandemic from January 2020 to December 2022 across 25 European countries. We adopt a Bayesian vector autoregressive model with both fixed and random effects. We find that increases in disease transmission intensity decreases Gross domestic product (GDP) and increases daily excess deaths, with a longer lasting impact on excess deaths in comparison to GDP, which recovers more rapidly. Broadly, our results reinforce the intuitive phenomenon that significant economic activity arises from diverse person-to-person interactions. We report on the effectiveness of non-pharmaceutical interventions (NPIs) on transmission intensity, excess deaths and changes in GDP, and resulting implications for policy makers. Our results highlight a complex cost-benefit trade off from individual NPIs. For example, banning international travel increases GDP however reduces excess deaths. We consider country random effects and their associations with excess changes in GDP and excess deaths. For example, more developed countries in Europe typically had more cautious approaches to the COVID-19 pandemic, prioritising healthcare and excess deaths over economic performance. Long term economic impairments are not fully captured by our model, as well as long term disease effects (Long Covid). Our results highlight that the impact of disease on a country is complex and multifaceted, and simple heuristic conclusions to extract the best outcome from the economy and disease burden are challenging.</jats:p>

Journal article

Mishra S, Scott JA, Laydon DJ, Zhu H, Ferguson NM, Bhatt S, Flaxman S, Gandy Aet al., 2022, Authors' reply to the discussion of 'A COVID-19 Model for Local Authorities of the United Kingdom' by Mishra et al. in Session 2 of the Royal Statistical Society's Special Topic Meeting on COVID-19 transmission: 11 June 2021, JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY, Vol: 185, Pages: S110-S111, ISSN: 0964-1998

Journal article

Mishra S, Scott JA, Laydon DJ, Zhu H, Ferguson NM, Bhatt S, Flaxman S, Gandy Aet al., 2022, A COVID-19 model for local authorities of the United Kingdom, JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY, Vol: 185, Pages: S86-S95, ISSN: 0964-1998

Journal article

Laydon DJ, Cauchemez S, Hinsley WR, Bhatt S, Ferguson NMet al., 2022, Prophylactic and reactive vaccination strategies for healthcare workers against MERS-CoV

<jats:title>Abstract</jats:title><jats:p>Several vaccines candidates are in development against Middle East respiratory syndrome–related coronavirus (MERS-CoV), which remains a major public health concern. Using individual-level data on the 2013-2014 Kingdom of Saudi Arabia epidemic, we employ counterfactual analysis on inferred transmission trees (“who-infected-whom”) to assess potential vaccine impact. We investigate the conditions under which prophylactic “proactive” campaigns would outperform “reactive” campaigns (i.e. vaccinating either before or in response to the next outbreak), focussing on healthcare workers. Spatial scale is crucial: if vaccinating healthcare workers in response to outbreaks at their hospital only, proactive campaigns perform better, unless efficacy has waned significantly. However, campaigns that react at regional or national level consistently outperform proactive campaigns. Measures targeting the animal reservoir reduce transmission linearly, albeit with wide uncertainty. Substantial reduction of MERS-CoV morbidity and mortality is possible when vaccinating healthcare workers, underlining the need for at-risk countries to stockpile vaccines when available.</jats:p>

Journal article

Christensen B, Laydon D, Chelkowski T, Jemielniak D, Vollmer M, Bhatt S, Krawczyk Ket al., 2022, Quantifying Changes in Vaccine Coverage in Mainstream Media as a Result of the COVID-19 Outbreak: Text Mining Study., JMIR Infodemiology, Vol: 2

BACKGROUND: Achieving herd immunity through vaccination depends upon the public's acceptance, which in turn relies on their understanding of its risks and benefits. The fundamental objective of public health messaging on vaccines is therefore the clear communication of often complex information and, increasingly, the countering of misinformation. The primary outlet shaping public understanding is mainstream online news media, where coverage of COVID-19 vaccines was widespread. OBJECTIVE: We used text-mining analysis on the front pages of mainstream online news to quantify the volume and sentiment polarization of vaccine coverage. METHODS: We analyzed 28 million articles from 172 major news sources across 11 countries between July 2015 and April 2021. We employed keyword-based frequency analysis to estimate the proportion of overall articles devoted to vaccines. We performed topic detection using BERTopic and named entity recognition to identify the leading subjects and actors mentioned in the context of vaccines. We used the Vader Python module to perform sentiment polarization quantification of all collated English-language articles. RESULTS: The proportion of front-page articles mentioning vaccines increased from 0.1% to 4% with the outbreak of COVID-19. The number of negatively polarized articles increased from 6698 in 2015-2019 to 28,552 in 2020-2021. However, overall vaccine coverage before the COVID-19 pandemic was slightly negatively polarized (57% negative), whereas coverage during the pandemic was positively polarized (38% negative). CONCLUSIONS: Throughout the pandemic, vaccines have risen from a marginal to a widely discussed topic on the front pages of major news outlets. Mainstream online media has been positively polarized toward vaccines, compared with mainly negative prepandemic vaccine news. However, the pandemic was accompanied by an order-of-magnitude increase in vaccine news that, due to low prepandemic frequency, may contribute to a perceived ne

Journal article

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

Mishra S, Scott JA, Laydon DJ, Flaxman S, Gandy A, Mellan TA, Unwin HJT, Vollmer M, Coupland H, Ratmann O, Monod M, Zhu HH, Cori A, Gaythorpe KAM, Whittles LK, Whittaker C, Donnelly CA, Ferguson NM, Bhatt Set al., 2021, Comparing the responses of the UK, Sweden and Denmark to COVID-19 using counterfactual modelling, SCIENTIFIC REPORTS, Vol: 11, Pages: 1-9, ISSN: 2045-2322

The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others’ policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country’s first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.

Journal article

Ohrnberger J, Segal A, Forchini G, Miraldo M, Skarp J, Nedjati-Gilani G, Laydon D, Ghani A, Ferguson N, Hauck Ket al., 2021, The impact of a COVID-19 lockdown on work productivity under good and poor compliance, European Journal of Public Health, Vol: 31, Pages: 1009-1015, ISSN: 1101-1262

BackgroundIn response to the COVID-19 pandemic, governments across the globe have imposed strict social distancing measures. Public compliance to such measures is essential for their success yet the economic consequences of compliance are unknown. This is the first study to analyse the effects of good compliance compared to poor compliance to a COVID-19 suppression strategy (i.e. lockdown) on work productivity. MethodsWe estimate the differences in work productivity comparing a scenario of good compliance with one of poor compliance to the UK government COVID-19 suppression strategy. We use projections of the impact of the UK suppression strategy on mortality and morbidity from an individual-based epidemiological model combined with an economic model representative of the labour force in Wales and England. ResultsWe find that productivity effects of good compliance significantly exceed those of poor compliance and increase with the duration of the lockdown. After three months of the lockdown, work productivity in good compliance is £398.58 million higher compared with that of poor compliance. 75% of the differences is explained by productivity effects due to morbidity and non-health reasons and 25% attributed to avoided losses due to pre-mature mortality.ConclusionGood compliance to social distancing measures exceeds positive economic effects, in addition to health benefits. This is an important finding for current economic and health policy. It highlights the importance to set clear guidelines for the public, to build trust and support for the rules and if necessary, to enforce good compliance to social distancing measures.

Journal article

Knock ES, Whittles LK, Lees JA, Perez-Guzman PN, Verity R, FitzJohn RG, Gaythorpe KAM, Imai N, Hinsley W, Okell LC, Rosello A, Kantas N, Walters CE, Bhatia S, Watson OJ, Whittaker C, Cattarino L, Boonyasiri A, Djaafara BA, Fraser K, Fu H, Wang H, Xi X, Donnelly CA, Jauneikaite E, Laydon DJ, White PJ, Ghani AC, Ferguson NM, Cori A, Baguelin Met al., 2021, Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England, Science Translational Medicine, Vol: 13, Pages: 1-12, ISSN: 1946-6234

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission.

Journal article

Krawczyk K, Chelkowski T, Laydon DJ, Mishra S, Xifara D, Gibert B, Flaxman S, Mellan T, Schwämmle V, Röttger R, Hadsund JT, Bhatt Set al., 2021, Correction: Quantifying Online News Media Coverage of the COVID-19 Pandemic: Text Mining Study and Resource., J Med Internet Res, Vol: 23

[This corrects the article DOI: 10.2196/28253.].

Journal article

Laydon D, Dorigatti I, Small R, Jackson N, Coudeville L, Ferguson Net al., 2021, Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level Phase III data, eLife, Vol: 10, ISSN: 2050-084X

Background: Sanofi-Pasteur’s CYD-TDV is the only licensed dengue vaccine. Two phase III trials showed higher efficacy in seropositive than seronegative recipients. Hospital follow-up revealed increased hospitalisation in 2-5-year-old vaccinees, where serostatus and age effects were unresolved.Methods: We fit a survival model to individual-level data from both trials, including year one of hospital follow-up. We determine efficacy by age, serostatus, serotype and severity, and examine efficacy duration and vaccine action mechanism.Results: Our modelling indicates that vaccine-induced immunity is long-lived in seropositive recipients, and therefore that vaccinating seropositives gives higher protection than two natural infections. Long-term increased hospitalisation risk outweighs short-lived immunity in seronegatives. Independently of serostatus, transient immunity increases with age, and is highest against serotype 4. Benefit is higher in seropositives, and risk enhancement is greater in seronegatives, against hospitalised disease than febrile disease.Conclusions: Our results support vaccinating seropositives only. Rapid diagnostic tests would enable viable “screen-then-vaccinate” programs. Since CYD-TDV acts as a silent infection, long-term safety of other vaccine candidates must be closely monitored.Funding: Bill and Melinda Gates Foundation, National Institute for Health Research, UK Medical Research Council, Wellcome Trust.

Journal article

Krawczyk K, Chelkowski T, Laydon DJ, Mishra S, Xifara D, Gibert B, Flaxman S, Mellan T, Schwämmle V, Röttger R, Hadsund JT, Bhatt Set al., 2021, Correction: Quantifying Online News Media Coverage of the COVID-19 Pandemic: Text Mining Study and Resource (Preprint)

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Journal article

Krawczyk K, Chelkowski T, Laydon DJ, Mishra S, Xifara D, Flaxman S, Mellan T, Schwammle V, Rottger R, Hadsund JT, Bhatt Set al., 2021, Quantifying Online News Media Coverage of the COVID-19 Pandemic: Text Mining Study and Resource, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 23, ISSN: 1438-8871

Journal article

Hogan AB, Winskill P, Watson OJ, Walker PGT, Whittaker C, Baguelin M, Brazeau NF, Charles GD, Gaythorpe KAM, Hamlet A, Knock E, Laydon DJ, Lees JA, Løchen A, Verity R, Whittles LK, Muhib F, Hauck K, Ferguson NM, Ghani ACet al., 2021, Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: a mathematical modelling analysis, Vaccine, Vol: 39, Pages: 2995-3006, ISSN: 0264-410X

The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extended a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identified optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We found that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning.

Journal article

Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DDS, Mishra S, Crispim MAE, Sales FC, Hawryluk I, McCrone JT, Hulswit RJG, Franco LAM, Ramundo MS, de Jesus JG, Andrade PS, Coletti TM, Ferreira GM, Silva CAM, Manuli ER, Pereira RHM, Peixoto PS, Kraemer MU, Gaburo N, Camilo CDC, Hoeltgebaum H, Souza WM, Rocha EC, de Souza LM, de Pinho MC, Araujo LJT, Malta FS, de Lima AB, Silva JDP, Zauli DAG, Ferreira ACDS, Schnekenberg RP, Laydon DJ, Walker PGT, Schlueter HM, dos Santos ALP, Vidal MS, Del Caro VS, Filho RMF, dos Santos HM, Aguiar RS, Proenca-Modena JLP, Nelson B, Hay JA, Monod M, Miscouridou X, Coupland H, Sonabend R, Vollmer M, Gandy A, Prete CA, Nascimento VH, Suchard MA, Bowden TA, Pond SLK, Wu C-H, Ratmann O, Ferguson NM, Dye C, Loman NJ, Lemey P, Rambaut A, Fraiji NA, Carvalho MDPSS, Pybus OG, Flaxman S, Bhatt S, Sabino ECet al., 2021, Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil, Science, Vol: 372, Pages: 815-821, ISSN: 0036-8075

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Journal article

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

Watson O, Alhaffar M, Mehchy Z, Whittaker C, Akil Z, Brazeau N, Cuomo-Dannenburg G, Hamlet A, Thompson H, Baguelin M, Fitzjohn R, Knock E, Lees J, Whittles L, Mellan T, Winskill P, COVID-19 Response Team IC, Howard N, Clapham H, Checchi F, Ferguson N, Ghani A, Walker P, Beals Eet al., 2021, Leveraging community mortality indicators to infer COVID-19 mortality and transmission dynamics in Damascus, Syria, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported considerably lower mortality rates than in Europe and the Americas. Motivated by reports of an overwhelmed health system, we estimate the likely under-ascertainment of COVID-19 mortality in Damascus, Syria. Using all-cause mortality data, we fit a mathematical model of COVID-19 transmission to reported mortality, estimating that 1.25% of COVID-19 deaths (sensitivity range 1.00% – 3.00%) have been reported as of 2 September 2020. By 2 September, we estimate that 4,380 (95% CI: 3,250 – 5,550) COVID-19 deaths in Damascus may have been missed, with 39.0% (95% CI: 32.5% – 45.0%) of the population in Damascus estimated to have been infected. Accounting for under-ascertainment corroborates reports of exceeded hospital bed capacity and is validated by community-uploaded obituary notifications, which confirm extensive unreported mortality in Damascus.

Journal article

Laydon D, Mishra S, Hinsley W, Samartsidis P, Flaxman S, Gandy A, Ferguson N, Bhatt Set al., 2021, Modelling the impact of the Tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns, BMJ Open, Vol: 11, ISSN: 2044-6055

Objective To measure the effects of the tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.Design This is a modelling study combining estimates of real-time reproduction number Rt (derived from UK case, death and serological survey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesian hierarchical model with latent factors using these quantities to account for broader national trends in addition to subnational effects from tiers.Setting The UK at lower tier local authority (LTLA) level. 310 LTLAs were included in the analysis.Primary and secondary outcome measures Reduction in real-time reproduction number Rt.Results Nationally, transmission increased between July and late September, regional differences notwithstanding. Immediately prior to the introduction of the tier system, Rt averaged 1.3 (0.9–1.6) across LTLAs, but declined to an average of 1.1 (0.86–1.42) 2 weeks later. Decline in transmission was not solely attributable to tiers. Tier 1 had negligible effects. Tiers 2 and 3, respectively, reduced transmission by 6% (5%–7%) and 23% (21%–25%). 288 LTLAs (93%) would have begun to suppress their epidemics if every LTLA had gone into tier 3 by the second national lockdown, whereas only 90 (29%) did so in reality.Conclusions The relatively small effect sizes found in this analysis demonstrate that interventions at least as stringent as tier 3 are required to suppress transmission, especially considering more transmissible variants, at least until effective vaccination is widespread or much greater population immunity has amassed.

Journal article

Laydon D, Mishra S, Bhatt S, 2021, ImperialCollegeLondon/covid19model: Impact of the Tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns

Impact of the Tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns

Software

Laydon DJ, Mishra S, Hinsley WR, Samartsidis P, Flaxman S, Gandy A, Ferguson NM, Bhatt Set al., 2021, Impact of the Tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Measure the effects of the Tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Modelling study combining estimates of the real-time reproduction number <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub> (derived from UK case, death and serological survey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesian hierarchical model with latent factors using these quantities, to account for broader national trends in addition to subnational effects from Tiers.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>The UK at Lower Tier Local Authority (LTLA) level.</jats:p></jats:sec><jats:sec><jats:title>Primary and secondary outcome measures</jats:title><jats:p>Reduction in real-time reproduction number <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub>.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Nationally, transmission increased between July and late September, regional differences notwithstanding. Immediately prior to the introduction of the tier system, <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub> averaged 1.3 (0.9 – 1.6) across LTLAs, but declined to an average of 1.1 (0.86 – 1.42) two weeks later. Decline in transmission was not solely attributable to Tiers. Tier 1 had negligible effects. Tiers 2 and 3 respectively reduced transmission by 6% (5%-7%) and 2

Journal article

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%.

Report

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

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

Dighe A, Cattarino L, Cuomo-Dannenburg G, Skarp J, Imai N, Bhatia S, Gaythorpe K, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cooper L, Coupland H, Cucunuba Perez Z, Dorigatti I, Eales O, van Elsland S, Fitzjohn R, Green W, Haw D, Hinsley W, Knock E, Laydon D, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Pons Salort M, Thompson H, Unwin H, Verity R, Vollmer M, Walters C, Watson O, Whittaker C, Whittles L, Ghani A, Donnelly C, Ferguson N, Riley Set al., 2020, Response to COVID-19 in South Korea and implications for lifting stringent interventions, BMC Medicine, Vol: 18, Pages: 1-12, ISSN: 1741-7015

Background After experiencing a sharp growth in COVID-19 cases early in the pandemic, South Korea rapidly controlled transmission while implementing less stringent national social distancing measures than countries in Europe and the US. This has led to substantial interest in their “test, trace, isolate” strategy. However, it is important to understand the epidemiological peculiarities of South Korea’s outbreak and characterise their response before attempting to emulate these measures elsewhere.MethodsWe systematically extracted numbers of suspected cases tested, PCR-confirmed cases, deaths, isolated confirmed cases, and numbers of confirmed cases with an identified epidemiological link from publicly available data. We estimated the time-varying reproduction number, Rt, using an established Bayesian framework, and reviewed the package of interventions implemented by South Korea using our extracted data, plus published literature and government sources. Results We estimated that after the initial rapid growth in cases, Rt dropped below one in early April before increasing to a maximum of 1.94 (95%CrI; 1.64-2.27) in May following outbreaks in Seoul Metropolitan Region. By mid-June Rt was back below one where it remained until the end of our study (July 13th). Despite less stringent “lockdown” measures, strong social distancing measures were implemented in high incidence areas and studies measured a considerable national decrease in movement in late-February. Testing capacity was swiftly increased, and protocols were in place to isolate suspected and confirmed cases quickly however we could not estimate the delay to isolation using our data. Accounting for just 10% of cases, individual case-based contact-tracing picked up a relatively minor proportion of total cases, with cluster investigations accounting for 66%. ConclusionsWhilst early adoption of testing and contact-tracing are likely to be important for South Korea’s successf

Journal article

Ainslie K, Walters C, Fu H, Bhatia S, Wang H, Xi X, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Cattarino L, Ciavarella C, Cucunuba Z, Cuomo-Dannenburg G, Dighe A, Dorigatti I, van Elsland S, FitzJohn R, Gaythorpe K, Ghani A, Green W, Hamlet A, Hinsley W, Imai N, Jorgensen D, Knock E, Laydon D, Nedjati-Gilani G, Okell L, Siveroni I, Thompson H, Unwin J, Verity R, Vollmer M, Walker P, Wang Y, Watson O, Whittaker C, Winskill P, Donnelly C, Ferguson N, Riley Set al., 2020, Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment, Wellcome Open Research, ISSN: 2398-502X

Background : The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. These interventions have impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic was not clear. Methods : Using daily reported cases from mainland China and Hong Kong SAR, we estimated transmissibility over time and compared it to daily within-city movement, as a proxy for economic activity. Results : Initially, within-city movement and transmission were very strongly correlated in the five mainland provinces most affected by the epidemic and Beijing. However, that correlation decreased rapidly after the initial sharp fall in transmissibility. In general, towards the end of the study period, the correlation was no longer apparent, despite substantial increases in within-city movement. A similar analysis for Hong Kong shows that intermediate levels of local activity were maintained while avoiding a large outbreak. At the very end of the study period, when China began to experience the re-introduction of a small number of cases from Europe and the United States, there is an apparent up-tick in transmission. Conclusions: Although these results do not preclude future substantial increases in incidence, they suggest that after very intense social distancing (which resulted in containment), China successfully exited its lockdown to some degree. Elsewhere, movement data are being used as proxies for economic activity to assess the impact of interventions. The results presented here illustrate how the eventual decorrelation between transmission and movement is likely a key feature of successful COVID-19 exit strategies.

Journal article

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