Imperial College London

DrLilithWhittles

Faculty of MedicineSchool of Public Health

Sir Henry Wellcome Postdoctoral Fellow
 
 
 
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Contact

 

l.whittles

 
 
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Location

 

Praed StreetSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

50 results found

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

Imai N, Hogan AB, Williams L, Cori A, Mangal TD, Winskill P, Whittles LK, Watson OJ, Knock ES, Baguelin M, Perez-Guzman PN, Gaythorpe KAM, Sonabend R, Ghani AC, Ferguson NMet al., 2021, Interpreting estimates of coronavirus disease 2019 (COVID-19) vaccine efficacy and effectiveness to inform simulation studies of vaccine impact: a systematic review, Wellcome Open Research, Vol: 6, Pages: 185-185

<ns3:p><ns3:bold>Background:</ns3:bold> The multiple efficacious vaccines authorised for emergency use worldwide represent the first preventative intervention against coronavirus disease 2019 (COVID-19) that does not rely on social distancing measures. The speed at which data are emerging and the heterogeneities in study design, target populations, and implementation make it challenging to interpret and assess the likely impact of vaccine campaigns on local epidemics. We reviewed available vaccine efficacy and effectiveness studies to generate working estimates that can be used to parameterise simulation studies of vaccine impact.</ns3:p><ns3:p> <ns3:bold>Methods:</ns3:bold> We searched MEDLINE, the World Health Organization’s Institutional Repository for Information Sharing, medRxiv, and vaccine manufacturer websites for studies that evaluated the emerging data on COVID-19 vaccine efficacy and effectiveness. Studies providing an estimate of the efficacy or effectiveness of a COVID-19 vaccine using disaggregated data against SARS-CoV-2 infection, symptomatic disease, severe disease, death, or transmission were included. We extracted information on study population, variants of concern (VOC), vaccine platform, dose schedule, study endpoints, and measures of impact. We applied an evidence synthesis approach to capture a range of plausible and consistent parameters for vaccine efficacy and effectiveness that can be used to inform and explore a variety of vaccination strategies as the COVID-19 pandemic evolves.</ns3:p><ns3:p> <ns3:bold>Results:</ns3:bold> Of the 602 articles and reports identified, 53 were included in the analysis. The availability of vaccine efficacy and effectiveness estimates varied by vaccine and were limited for VOCs. Estimates for non-primary endpoints such as effectiveness against infection and onward transmission were sparse. Synthesised estimates were relatively consistent

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

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., 2021, Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility, Scientific Reports, Vol: 11, Pages: 1-14, ISSN: 2045-2322

Background: 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 in the early phases of the COVID-19 pandemic. Methods and findings: A systematic literature review was conducted in PubMed. Reviewers extracted data from relevant, peer-reviewed studies published up to July 4th 2020 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.Conclusions: 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 e

Journal article

McCabe R, Kont M, Schmit N, Whittaker C, Lochen A, Baguelin M, Knock E, Whittles L, Lees J, Brazeau N, Walker P, Ghani A, Ferguson N, White P, Donnelly C, Hauck K, Watson Oet al., 2021, Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries, International Journal of Epidemiology, Vol: 50, Pages: 753-767, ISSN: 0300-5771

Background: The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020/21 is essential.Methods: An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff, and ventilators under different epidemic scenarios in France, Germany, and Italy across the 2020/21 winter period. The effect of implementing lockdowns triggered by different numbers of COVID-19 patients in ICU under varying levels of effectiveness is examined, using a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model.Results: Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource. Reactive lockdowns could lead to large improvements in ICU capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and sustained under a higher level of suppression. The success of such interventions also depends on baseline bed numbers and average non-COVID-19 patient occupancy.Conclusions: Reductions in capacity deficits under different scenarios must be weighed against the feasibility and drawbacks of further lockdowns. Careful, continuous decision-making by national policymakers will be required across the winter period 2020/21.

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

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

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, Publisher: Cold Spring Harbor Laboratory

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.

Working paper

Northrup GR, Qian L, Bruxvoort K, Marx FM, Whittles LK, Lewnard JAet al., 2021, Inference of Naturally Acquired Immunity Using a Self-matched Negative-Control Design, EPIDEMIOLOGY, Vol: 32, Pages: 168-178, ISSN: 1044-3983

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

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

Report

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

Report

Funk S, Abbott S, Atkins BD, Baguelin M, Baillie JK, Birrell P, Blake J, Bosse NI, Burton J, Carruthers J, Davies NG, De Angelis D, Dyson L, Edmunds WJ, Eggo RM, Ferguson NM, Gaythorpe K, Gorsich E, Guyver-Fletcher G, Hellewell J, Hill EM, Holmes A, House TA, Jewell C, Jit M, Jombart T, Joshi I, Keeling MJ, Kendall E, Knock ES, Kucharski AJ, Lythgoe KA, Meakin SR, Munday JD, Openshaw PJM, Overton CE, Pagani F, Pearson J, Perez-Guzman PN, Pellis L, Scarabel F, Semple MG, Sherratt K, Tang M, Tildesley MJ, Van Leeuwen E, Whittles LKet al., 2020, Short-term forecasts to inform the response to the Covid-19 epidemic in the UK

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Short-term forecasts of infectious disease can aid situational awareness and planning for outbreak response. Here, we report on multi-model forecasts of Covid-19 in the UK that were generated at regular intervals starting at the end of March 2020, in order to monitor expected healthcare utilisation and population impacts in real time.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We evaluated the performance of individual model forecasts generated between 24 March and 14 July 2020, using a variety of metrics including the weighted interval score as well as metrics that assess the calibration, sharpness, bias and absolute error of forecasts separately. We further combined the predictions from individual models into ensemble forecasts using a simple mean as well as a quantile regression average that aimed to maximise performance. We compared model performance to a null model of no change.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In most cases, individual models performed better than the null model, and ensembles models were well calibrated and performed comparatively to the best individual models. The quantile regression average did not noticeably outperform the mean ensemble.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Ensembles of multi-model forecasts can inform the policy response to the Covid-19 pandemic by assessing future resource needs and expected population impact of morbidity and mortality.</jats:p></jats:sec>

Journal article

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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Whittles LK, White PJ, Didelot X, 2020, Assessment of the potential of vaccination to combat antibiotic resistance in gonorrhea: a modeling analysis to determine preferred product characteristics, Clinical Infectious Diseases, Vol: 71, Pages: 1912-1919, ISSN: 1058-4838

BACKGROUND: Gonorrhea incidence is increasing rapidly in many countries, whilst antibiotic resistance is making treatment more difficult. Combined with evidence that MeNZB and Bexsero meningococcal vaccines are likely partially-protective against gonorrhea, this has renewed interest in a gonococcal vaccine, and several candidates are in development. Key questions are how protective a vaccine needs to be, how long protection needs to last, and how should it be targeted. We assessed vaccination's potential impact, and the feasibility of achieving WHO's target 90% reduction in gonorrhea incidence 2016-2030, by comparing realistic vaccination strategies under a range of scenarios of vaccine efficacy and duration of protection, and emergence of extensively-resistant gonorrhea. METHODS: We developed a stochastic transmission-dynamic model, incorporating asymptomatic and symptomatic infection and heterogeneous sexual behavior in men-who-have-sex-with-men (MSM). We used data from England, which has a comprehensive, consistent nationwide surveillance system. Using particle Markov Chain Monte Carlo methods we fitted the model to gonorrhea incidence in 2008-17, and then used Bayesian forecasting to examine an extensive range of scenarios. RESULTS: Even in the worst-case scenario of untreatable infection emerging, the WHO target is achievable if all MSM attending sexual health clinics receive a vaccine offering ≥52% protection for ≥6 years. A vaccine conferring 31% protection (as estimated for MeNZB) for 2-4 years, could reduce incidence in 2030 by 45% in the worst-case scenario, and by 75% if >70% of resistant gonorrhea remains treatable. CONCLUSIONS: Even a partially-protective vaccine, delivered through a realistic targeting strategy, could substantially reduce gonorrhea incidence, despite antibiotic resistance.

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

Lewnard JA, Whittles LK, Rick A-M, Martin JMet al., 2020, Naturally-acquired protection against upper respiratory symptoms involving group A Streptococcus in a longitudinal cohort study, Clinical Infectious Diseases, Vol: 71, Pages: e244-e254, ISSN: 1058-4838

BackgroundPharyngitis due to group A Streptococcus (GAS) represents a major cause of outpatient visits and antibiotic use in the United States. A leading vaccine candidate targets 30 of the >200 emm types of GAS. We aimed to assess natural protection conferred by GAS against respiratory symptoms.MethodsIn a 5-year study among school-aged children in Pittsburgh, Pennsylvania, pharyngeal cultures were obtained from children at 2-week intervals, and active surveillance was conducted for respiratory illnesses. We assessed protection via the relative odds of previous detection of homologous strains (defined by field-inversion gel electrophoresis banding pattern), emm types, and emm clusters at visits where GAS was detected with symptoms, versus visits where GAS was detected without symptoms. We used a cluster bootstrap of children to adjust estimates for repeated sampling.ResultsAt visits where previously-detected GAS emm types were identified, we estimated 81.8% (95%CI: 67.1-91.7%) protection against typical pharyngitis symptoms among children re-acquiring the same strain, and 94.5% (83.5-98.6%) protection among children acquiring a distinct strain. We estimated 77.1% (33.7-96.3%) protection against typical symptoms among children acquiring partially-heterologous emm types belonging to a previously-detected emm cluster. Protection was evident after both symptomatic and asymptomatic detections of GAS. We did not identify strong evidence of protection against atypical respiratory symptoms.ConclusionsWithin a 5-year longitudinal study, previous detection of GAS emm types was associated with protection against typical symptoms when homologous strains were subsequently detected. Naturally-acquired protection against partially-heterologous types suggests emm type-based vaccines may have broader strain coverage than what has been previously assumed.

Journal article

Hogan A, Winskill P, Watson O, Walker P, Whittaker C, Baguelin M, Haw D, Lochen A, Gaythorpe K, Ainslie K, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Charles G, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Donnelly C, Dorigatti I, Eales O, van Elsland S, Ferreira Do Nascimento F, Fitzjohn R, Flaxman S, Green W, Hallett T, Hamlet A, Hinsley W, Imai N, Jauneikaite E, Jeffrey B, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Ower A, Parag K, Ragonnet-Cronin M, Siveroni I, Skarp J, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walters C, Wang H, Wang Y, Whittles L, Xi X, Muhib F, Smith P, Hauck K, Ferguson N, Ghani Aet al., 2020, Report 33: Modelling the allocation and impact of a COVID-19 vaccine

Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 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 and other high-risk groups. However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.

Report

van Elsland S, Watson O, Alhaffar M, Mehchy Z, Whittaker C, Akil Z, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Charles G, Ciavarella C, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Djaafara A, Donnelly C, Dorigatti I, Eales O, van Elsland S, Nascimento F, Fitzjohn R, Flaxman S, Forna A, Fu H, Gaythorpe K, Green W, Hamlet A, Hauck K, Haw D, Hayes S, Hinsley W, Imai N, Jeffrey B, Johnson R, Jorgensen D, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Olivera Mesa D, Pons Salort M, Ragonnet-Cronin M, Siveroni I, Stopard I, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walters C, Wang H, Wang Y, Whittles L, Winskill P, Xi X, Ferguson N, Beals E, Walker P, Anonymous Authorset al., 2020, Report 31: Estimating the burden of COVID-19 in Damascus, Syria: an analysis of novel data sources to infer mortality under-ascertainment

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported substantially lower mortality rates than in Europe and the Americas. One hypothesis is that these countries have been ‘spared’, but another is that deaths have been under-ascertained (deaths that have been unreported due to any number of reasons, for instance due to limited testing capacity). However, the scale of under-ascertainment is difficult to assess with currently available data. In this analysis, we estimate the potential under-ascertainment of COVID-19 mortality in Damascus, Syria, where all-cause mortality data has been reported between 25th July and 1st August. We fit a mathematical model of COVID-19 transmission to reported COVID-19 deaths in Damascus since the beginning of the pandemic and compare the model-predicted deaths to reported excess deaths. Exploring a range of different assumptions about under-ascertainment, we estimate that only 1.25% of deaths (sensitivity range 1% - 3%) due to COVID-19 are reported in Damascus. Accounting for under-ascertainment also corroborates local reports of exceeded hospital bed capacity. To validate the epidemic dynamics inferred, we leverage community-uploaded obituary certificates as an alternative data source, which confirms extensive mortality under-ascertainment in Damascus between July and August. This level of under-ascertainment suggests that Damascus is at a much later stage in its epidemic than suggested by surveillance reports, which have repo. We estimate that 4,340 (95% CI: 3,250 - 5,540) deaths due to COVID-19 in Damascus may have been missed as of 2nd September 2020. Given that Damascus is likely to have the most robust surveillance in Syria, these findings suggest that other regions of the country could have experienced similar or worse mortality rates due to COVID-19.

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Hogan A, Jewell B, Sherrard-Smith E, Watson O, Whittaker C, Hamlet A, Smith J, Winskill P, Verity R, Baguelin M, Lees J, Whittles L, Ainslie K, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cuomo-Dannenburg G, Dighe A, Djaafara A, Donnelly C, Eaton J, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Haw D, Hayes S, Hinsley W, Imai N, Laydon D, Mangal T, Mellan T, Mishra S, Parag K, Thompson H, Unwin H, Vollmer M, Walters C, Wang H, Ferguson N, Okell L, Churcher T, Arinaminpathy N, Ghani A, Walker P, Hallett Tet al., 2020, Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: a modelling study, The Lancet Global Health, Vol: 8, Pages: e1132-e1141, ISSN: 2214-109X

Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings.Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics.Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic.Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC

Journal article

Lavezzo E, Franchin E, Ciavarella C, Cuomo-Dannenburg G, Barzon L, Del Vecchio C, Rossi L, Manganelli R, Loregian A, Navarin N, Abate D, Sciro M, Merigliano S, De Canale E, Vanuzzo MC, Besutti V, Saluzzo F, Onelia F, Pacenti M, Parisi S, Carretta G, Donato D, Flor L, Cocchio S, Masi G, Sperduti A, Cattarino L, Salvador R, Nicoletti M, Caldart F, Castelli G, Nieddu E, Labella B, Fava L, Drigo M, Gaythorpe KAM, Imperial College COVID-19 Response Team, Brazzale AR, Toppo S, Trevisan M, Baldo V, Donnelly CA, Ferguson NM, Dorigatti I, Crisanti Aet al., 2020, Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo', Nature, Vol: 584, Pages: 425-429, ISSN: 0028-0836

On the 21st of February 2020 a resident of the municipality of Vo', a small town near Padua, died of pneumonia due to SARS-CoV-2 infection1. This was the first COVID-19 death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. We collected information on the demography, clinical presentation, hospitalization, contact network and presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. On the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI) 2.1-3.3%). On the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% Confidence Interval (CI) 0.8-1.8%). Notably, 42.5% (95% CI 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (i.e. did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (p-values 0.62 and 0.74 for E and RdRp genes, respectively, Exact Wilcoxon-Mann-Whitney test). This study sheds new light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides new insights into its transmission dynamics and the efficacy of the implemented control measures.

Journal article

Sherrard-Smith E, Hogan AB, Hamlet A, Watson OJ, Whittaker C, Winskill P, Ali F, Mohammad AB, Uhomoibhi P, Maikore I, Ogbulafor N, Nikau J, Kont MD, Challenger JD, Verity R, Lambert B, Cairns M, Rao B, Baguelin M, Whittles LK, Lees JA, Bhatia S, Knock ES, Okell L, Slater HC, Ghani AC, Walker PGT, Okoko OO, Churcher TSet al., 2020, The potential public health consequences of COVID-19 on malaria in Africa., Nature Medicine, Vol: 26, Pages: 1411-1416, ISSN: 1078-8956

The burden of malaria is heavily concentrated in sub-Saharan Africa (SSA) where cases and deaths associated with COVID-19 are rising1. In response, countries are implementing societal measures aimed at curtailing transmission of SARS-CoV-22,3. Despite these measures, the COVID-19 epidemic could still result in millions of deaths as local health facilities become overwhelmed4. Advances in malaria control this century have been largely due to distribution of long-lasting insecticidal nets (LLINs)5, with many SSA countries having planned campaigns for 2020. In the present study, we use COVID-19 and malaria transmission models to estimate the impact of disruption of malaria prevention activities and other core health services under four different COVID-19 epidemic scenarios. If activities are halted, the malaria burden in 2020 could be more than double that of 2019. In Nigeria alone, reducing case management for 6 months and delaying LLIN campaigns could result in 81,000 (44,000-119,000) additional deaths. Mitigating these negative impacts is achievable, and LLIN distributions in particular should be prioritized alongside access to antimalarial treatments to prevent substantial malaria epidemics.

Journal article

Unwin HJT, Mishra S, Bradley VC, Gandy A, Mellan TA, Coupland H, Ish-Horowicz J, Vollmer MAC, Whittaker C, Filippi SL, Xi X, Monod M, Ratmann O, Hutchinson M, Valka F, Zhu H, Hawryluk I, Milton P, Ainslie KEC, Baguelin M, Boonyasiri A, Brazeau NF, Cattarino L, Cucunuba Z, Cuomo-Dannenburg G, Dorigatti I, Eales OD, Eaton JW, van Elsland SL, FitzJohn RG, Gaythorpe KAM, Green W, Hinsley W, Jeffrey B, Knock E, Laydon DJ, Lees J, Nedjati-Gilani G, Nouvellet P, Okell L, Parag KV, Siveroni I, Thompson HA, Walker P, Walters CE, Watson OJ, Whittles LK, Ghani AC, Ferguson NM, Riley S, Donnelly CA, Bhatt S, Flaxman Set al., 2020, State-level tracking of COVID-19 in the United States, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>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 modelled the US epidemic at the state-level, using publicly available death data 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 used changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on the rate of transmission of SARS-CoV-2. Nationally, we estimated 3.7% [3.4%-4.0%] of the population had been infected by 1st June 2020, with wide variation between states, and approximately 0.01% of the population was infectious. We also demonstrated that good model forecasts of deaths for the next 3 weeks with low error and good coverage of our credible intervals.</jats:p>

Working paper

Fu H, Xi X, Wang H, Boonyasiri A, Wang Y, Hinsley W, Fraser K, McCabe R, Olivera Mesa D, Skarp J, Ledda A, Dewe T, Dighe A, Winskill P, van Elsland S, Ainslie K, Baguelin M, Bhatt S, Boyd O, Brazeau N, Cattarino L, Charles G, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Donnelly C, Dorigatti I, Green W, Hamlet A, Hauck K, Haw D, Jeffrey B, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag K, Ragonnet-Cronin M, Riley S, Schmit N, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Watson O, Whittaker C, Whittles L, Imai N, Bhatia S, Ferguson Net al., 2020, Report 30: The COVID-19 epidemic trends and control measures in mainland China

Report

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, Nscimento F, Fitzjohn R, Gaythorpe K, Geidelberg L, Grassly N, Green W, Hamlet A, Hauck K, Hinsley W, Imai N, 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., 2020, Report 26: Reduction in mobility and COVID-19 transmission

In response to the COVID-19 pandemic, countries have sought to control transmission of SARS-CoV-2by restricting population movement through social distancing interventions, reducing the number ofcontacts.Mobility data represent an important proxy measure of social distancing. Here, we develop aframework to infer the relationship between mobility and the key measure of population-level diseasetransmission, the reproduction number (R). The framework is applied to 53 countries with sustainedSARS-CoV-2 transmission based on two distinct country-specific automated measures of humanmobility, Apple and Google mobility data.For both datasets, the relationship between mobility and transmission was consistent within andacross countries and explained more than 85% of the variance in the observed variation intransmissibility. We quantified country-specific mobility thresholds defined as the reduction inmobility necessary to expect a decline in new infections (R<1).While social contacts were sufficiently reduced in France, Spain and the United Kingdom to controlCOVID-19 as of the 10th of May, we find that enhanced control measures are still warranted for themajority of countries. We found encouraging early evidence of some decoupling of transmission andmobility in 10 countries, a key indicator of successful easing of social-distancing restrictions.Easing social-distancing restrictions should be considered very carefully, as small increases in contactrates are likely to risk resurgence even where COVID-19 is apparently under control. Overall, strongpopulation-wide social-distancing measures are effective to control COVID-19; however gradualeasing of restrictions must be accompanied by alternative interventions, such as efficient contacttracing, to ensure control.

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