Imperial College London

MissHayleyThompson

Faculty of MedicineSchool of Public Health

Casual - Academic Research
 
 
 
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hayley.thompson12

 
 
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VA5Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

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25 results found

Thompson H, Hogan A, Walker P, Winskill P, Zongo I, Sagara I, Tinto H, Ouedraogo J-B, Dicko A, Chandramohan D, Greenwood B, Cairns M, Ghani Aet al., 2022, Mathematical modelling of a seasonal use-case for the RTS,S/AS01 malaria vaccine, The Lancet Global Health, ISSN: 2214-109X

Background:A recent clinical trial of seasonal RTS,S/AS01E (RTS,S) vaccination showed that vaccination was non-inferior to seasonal malaria chemoprevention (SMC) in preventing clinical malaria. The combination of these two interventions provided significant additional protection against clinical and severe malaria outcomes. Impact projections of this novel approach to RTS,S vaccination in seasonal transmission settings for longer time frames and across a range of epidemiological settings are needed to inform policy recommendations. Methods:We used a mathematical model of malaria transmission to assess the potential impact of an age-based or seasonally targeted RTS,S vaccination schedule in seasonal transmission settings in both the absence and presence of SMC. Estimates of cases and deaths averted in a population of 100,000 children aged 0-5 years were calculated over a 15-year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2–10-year-olds and over two West African seasonality archetypes. Findings:Seasonally targeting RTS,S resulted in greater absolute reductions in malaria cases and deaths compared to an age-based strategy, averting between 32%-100% more clinical cases dependent on seasonality and transmission intensity. We predict that adding seasonally targeted RTS,S to SMC would reduce clinical incidence by up to an additional 36%-56% in children under five compared with SMC alone. Transmission season duration was a key determinant of intervention impact, with the advantage of adding RTS,S to SMC predicted to be smaller with shorter transmission seasons.Interpretation:RTS,S vaccination in seasonal settings could be a valuable additional tool to existing interventions, with seasonal delivery maximising impact relative to an age-based approach. Decisions surrounding deployment strategies of RTS,S in such settings will need to consider the local and regional variations in seasonality, current levels of other interventions an

Journal article

Whittaker C, Watson O, Alvarez-Moreno C, Angkasekwinai N, Boonyasiri A, Triana LC, Chanda D, Charoenpong L, Chayakulkeeree M, Cooke G, Croda J, Cucunubá ZM, Djaafara A, Estofolete CF, Grillet M-E, Faria N, Costa SF, Forero-Peña DA, Gibb DM, Gordon A, Hamers RL, Hamlet A, Irawany V, Jitmuang A, Keurueangkul N, Kimani TN, Lampo M, Levin A, Lopardo G, Mustafa R, Nayagam AS, Ngamprasertchai T, Njeri NIH, Nogueira ML, Ortiz-Prado E, Perroud Jr MW, Phillips AN, Promsin P, Qavi A, Rodger AJ, Sabino EC, Sangkaew S, Sari D, Sirijatuphat R, Sposito AC, Srisangthong P, Thompson H, Udwadia Z, Valderrama-Beltrán S, Winskill P, Ghani A, Walker P, Hallett Tet al., 2022, Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis, Clinical Infectious Diseases, Vol: 75, Pages: e224-e233, ISSN: 1058-4838

BackgroundThe public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear.MethodsUsing a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care.ResultsThe impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics.ConclusionsAdvances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Journal article

Thompson H, Mousa A, Dighe A, Fu H, Arnedo-Pena A, Barrett P, Bellido-Blasco J, Bi Q, Caputi A, Chaw L, De Maria L, Hoffmann M, Mahapure K, Hg K, Raghuram J, Singh G, Soman B, Soriano V, Valent F, Vimercati L, En Wee L, Wong J, Ghani A, Ferguson Net al., 2021, SARS-CoV-2 setting-specific transmission rates: a systematic review and meta-analysis, Clinical Infectious Diseases, Vol: 73, Pages: e754-e764, ISSN: 1058-4838

Background Understanding the drivers of SARS-CoV-2 transmission is crucial for control policies but evidence of transmission rates in different settings remains limited. MethodsWe conducted a systematic review to estimate secondary attack rates (SAR) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a Beta-Binomial model to pool SARs across studies and a Negative-binomial model to estimate Robs. ResultsHouseholds showed the highest transmission rates, with a pooled SAR of 21.1% (95%CI:17.4%-24.8%). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs. 1.2%). Estimates of SAR and Robs for asymptomatic index cases were approximately a seventh, and for pre-symptomatic two thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals under 20 years of age in the household context, which is more limited when examining all settings.ConclusionsOur results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies such as contact tracing, testing and rapid isolation of cases. There was limited data to explore transmission patterns in workplaces, schools, and care-homes, highlighting the need for further research in such settings.

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

Ragonnet-Cronin M, Boyd O, Geidelberg L, Jorgensen D, Nascimento F, Siveroni I, Johnson R, Baguelin M, Cucunuba Z, Jauneikaite E, Mishra S, Watson O, Ferguson N, Cori A, Donnelly C, Volz Eet al., 2021, Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions, Nature Communications, Vol: 12, Pages: 1-7, ISSN: 2041-1723

Unprecedented public health interventions including travel restrictions and national lockdowns have been implemented to stem the COVID-19 epidemic, but the effectiveness of non- pharmaceutical interventions is still debated. We carried out a phylogenetic analysis of more than 29,000 publicly available whole genome SARS-CoV-2 sequences from 57 locations to estimate the time that the epidemic originated in different places. These estimates were examined in relation to the dates of the most stringent interventions in each location as well as to the number of cumulative COVID-19 deaths and phylodynamic estimates of epidemic size. Here we report that the time elapsed between epidemic origin and maximum intervention is associated with different measures of epidemic severity and explains 11% of the variance in reported deaths one month after the most stringent intervention. Locations where strong non-pharmaceutical interventions were implemented earlier experienced 30 much less severe COVID-19 morbidity and mortality during the period of study.

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

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

Thompson H, Hogan A, Walker P, White M, Cunnington A, Ockenhouse C, Ghani Aet al., 2020, Modelling the roles of antibody titre and avidity in protection from Plasmodium falciparum malaria infection following RTS,S/AS01 vaccination, Vaccine, Vol: 38, Pages: 7498-7507, ISSN: 0264-410X

Anti-circumsporozoite antibody titres have been established as an essential indicator for evaluating the immunogenicity and protective capacity of the RTS,S/AS01 malaria vaccine. However, a new delayed-fractional dose regime of the vaccine was recently shown to increase vaccine efficacy, from 62.5% (95% CI 29.4–80.1%) under the original dosing schedule to 86.7% (95% CI, 66.8–94.6%) without a corresponding increase in antibody titres. Here we reanalyse the antibody data from this challenge trial to determine whether IgG avidity may help to explain efficacy better than IgG titre alone by adapting a within-host mathematical model of sporozoite inoculation. We demonstrate that a model incorporating titre and avidity provides a substantially better fit to the data than titre alone. These results also suggest that in individuals with a high antibody titre response that also show high avidity (both metrics in the top tercile of observed values) delayed-fractional vaccination provided near perfect protection upon first challenge (98.2% [95% Credible Interval 91.6–99.7%]). This finding suggests that the quality of the vaccine induced antibody response is likely to be an important determinant in the development of highly efficacious pre-erythrocytic vaccines against malaria.

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

Monod M, Blenkinsop A, Xi X, Herbert D, Bershan S, Tietze S, Bradley V, Chen Y, Coupland H, Filippi S, Ish-Horowicz J, McManus M, Mellan T, Gandy A, Hutchinson M, Unwin H, Vollmer M, Weber S, Zhu H, Bezancon A, Ferguson N, Mishra S, Flaxman S, Bhatt S, Ratmann O, Ainslie K, Baguelin M, Boonyasiri A, Boyd O, Cattarino L, Cooper L, Cucunuba Perez Z, Cuomo-Dannenburg G, Djaafara A, Dorigatti I, van Elsland S, Fitzjohn R, Gaythorpe K, Geidelberg L, Green W, Hamlet A, Jeffrey B, Knock E, Laydon D, Nedjati Gilani G, Nouvellet P, Parag K, Siveroni I, Thompson H, Verity R, Walters C, Donnelly C, Okell L, Bhatia S, Brazeau N, Eales O, Haw D, Imai N, Jauneikaite E, Lees J, Mousa A, Olivera Mesa D, Skarp J, Whittles Let al., 2020, Report 32: Targeting interventions to age groups that sustain COVID-19 transmission in the United States, Pages: 1-32

Following ini􀀂al declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementa􀀂on of non-pharmaceu􀀂cal inter-ven􀀂ons, it is s􀀂ll not known how they are impacted by changing contact pa􀀁erns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impact the loosening of interven􀀂ons such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-specific mobility trends from more than 10 million individuals and link these mechanis􀀂cally to age-specific COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age specific contact pa􀀁erns and use this rich rela􀀂onship to reconstruct accurate trans-mission dynamics. Contrary to anecdotal evidence, we find li􀀁le support for age-shi􀀃s in contact and transmission dynamics over 􀀂me. We es􀀂mate that, un􀀂l August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infec􀀂ons in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with con􀀂nued, community-wide transmission, our transmission model predicts that re-opening kindergartens and el-ementary schools could facilitate spread and lead to considerable excess COVID-19 a􀀁ributable deaths over a 90-day period. These findings indicate that targe􀀂ng interven􀀂ons to adults aged 20-49 are an important con-sidera􀀂on in hal􀀂ng resurgent epidemics, and preven􀀂ng COVID-19-a􀀁ributable deaths when kindergartens and elementary schools reopen.

Journal article

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.

Report

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

Flaxman S, Mishra S, Gandy A, Unwin HJT, Mellan TA, Coupland H, Whittaker C, Zhu H, Berah T, Eaton JW, Monod M, Perez Guzman PN, Schmit N, Cilloni L, Ainslie K, Baguelin M, Boonyasiri A, Boyd O, Cattarino L, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, van Elsland S, Fitzjohn R, Gaythorpe K, Geidelberg L, Grassly N, Green W, Hallett T, Hamlet A, Hinsley W, Jeffrey B, Knock E, Laydon D, Nedjati Gilani G, Nouvellet P, Parag K, Siveroni I, Thompson H, Verity R, Volz E, Walters C, Wang H, Watson O, Winskill P, Xi X, Walker P, Ghani AC, Donnelly CA, Riley SM, Vollmer MAC, Ferguson NM, Okell LC, Bhatt Set al., 2020, Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe, Nature, Vol: 584, Pages: 257-261, ISSN: 0028-0836

Following the emergence of a novel coronavirus1 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions such as closure of schools and national lockdowns. We study the impact of major interventions across 11 European countries for the period from the start of COVID-19 until the 4th of May 2020 when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. We use partial pooling of information between countries with both individual and shared effects on the reproduction number. Pooling allows more information to be used, helps overcome data idiosyncrasies, and enables more timely estimates. Our model relies on fixed estimates of some epidemiological parameters such as the infection fatality rate, does not include importation or subnational variation and assumes that changes in the reproduction number are an immediate response to interventions rather than gradual changes in behavior. Amidst the ongoing pandemic, we rely on death data that is incomplete, with systematic biases in reporting, and subject to future consolidation. We estimate that, for all the countries we consider, current interventions have been sufficient to drive the reproduction number Rt below 1 (probability Rt< 1.0 is 99.9%) and achieve epidemic control. We estimate that, across all 11 countries, between 12 and 15 million individuals have been infected with SARS-CoV-2 up to 4th May, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions and lockdown in particular have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.

Journal article

Bhatia S, Imai N, Cuomo-Dannenburg G, Baguelin M, Boonyasiri A, Cori A, Cucunuba Perez 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., 2020, Estimating the number of undetected COVID-19 cases among travellers from mainland China, Publisher: F1000 Research Ltd

Background: Since the start of the COVID-19 epidemic in late 2019, there have been more than 152 affected regions and countries with over 110,000 confirmed cases outside mainland China.Methods: 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.Results: 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 more than two thirds (70%, 95% CI: 54% - 80%, compared to Singapore; 75%, 95% CI: 66% - 82%, compared to multiple countries) of cases exported from mainland China have remained undetected.Conclusions: These undetected cases potentially resulted in multiple chains of human-to-human transmission outside mainland China.

Working paper

Walker PGT, Whittaker C, Watson OJ, Baguelin M, Winskill P, Hamlet A, Djafaara BA, Cucunubá Z, Olivera Mesa D, Green W, Thompson H, Nayagam S, Ainslie KEC, Bhatia S, Bhatt S, Boonyasiri A, Boyd O, Brazeau NF, Cattarino L, Cuomo-Dannenburg G, Dighe A, Donnelly CA, Dorigatti I, van Elsland SL, FitzJohn R, Fu H, Gaythorpe KAM, Geidelberg L, Grassly N, Haw D, Hayes S, Hinsley W, Imai N, Jorgensen D, Knock E, Laydon D, Mishra S, Nedjati-Gilani G, Okell LC, Unwin HJ, Verity R, Vollmer M, Walters CE, Wang H, Wang Y, Xi X, Lalloo DG, Ferguson NM, Ghani ACet al., 2020, The impact of COVID-19 and strategies for mitigation and suppression in low- and middle-income countries, Science, Vol: 369, Pages: 413-422, ISSN: 0036-8075

The ongoing COVID-19 pandemic poses a severe threat to public health worldwide. We combine data on demography, contact patterns, disease severity, and health care capacity and quality to understand its impact and inform strategies for its control. Younger populations in lower income countries may reduce overall risk but limited health system capacity coupled with closer inter-generational contact largely negates this benefit. Mitigation strategies that slow but do not interrupt transmission will still lead to COVID-19 epidemics rapidly overwhelming health systems, with substantial excess deaths in lower income countries due to the poorer health care available. Of countries that have undertaken suppression to date, lower income countries have acted earlier. However, this will need to be maintained or triggered more frequently in these settings to keep below available health capacity, with associated detrimental consequences for the wider health, well-being and economies of these countries.

Journal article

Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunubá Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NMet al., 2020, Estimates of the severity of coronavirus disease 2019: a model-based analysis., Lancet Infectious Diseases, Vol: 20, Pages: 669-677, ISSN: 1473-3099

BACKGROUND: In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. METHODS: We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. FINDINGS: Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9-19·2) and to hospital discharge to be 24·7 days (22·9-28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for cen

Journal article

Vollmer M, Mishra S, Unwin J, Gandy A, Mellan T, Bradley V, Zhu H, Coupland H, Hawryluk I, Hutchinson M, Ratmann O, Monod M, Walker P, Whittaker C, Cattarino L, Ciavarella C, Cilloni L, Ainslie K, Baguelin M, Bhatia S, Boonyasiri A, Brazeau N, Charles G, Cooper L, Cucunuba Z, Cuomo-Dannenburg G, Dighe A, Djaafara B, Eaton J, van Elsland S, FitzJohn R, Fraser K, Gaythorpe K, Green W, Hayes S, Imai N, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mousa A, Nedjati-Gilani G, Nouvellet P, Olivera D, Parag K, Pickles M, Thompson H, Verity R, Walters C, Wang H, Wang Y, Watson O, Whittles L, Xi X, Ghani A, Riley S, Okell L, Donnelly C, Ferguson N, Dorigatti I, Flaxman S, Bhatt Set al., 2020, A sub-national analysis of the rate of transmission of COVID-19 in Italy, medRxiv

Italy was the first European country to experience sustained local transmission of COVID-19. As of 1st May 2020, the Italian health authorities reported 28,238 deaths nationally. To control the epidemic, the Italian government implemented a suite of non-pharmaceutical interventions (NPIs), including school and university closures, social distancing and full lockdown involving banning of public gatherings and non essential movement. In this report, we model the effect of NPIs on transmission using data on average mobility. We estimate that the average reproduction number (a measure of transmission intensity) is currently below one for all Italian regions, and significantly so for the majority of the regions. Despite the large number of deaths, the proportion of population that has been infected by SARS-CoV-2 (the attack rate) is far from the herd immunity threshold in all Italian regions, with the highest attack rate observed in Lombardy (13.18% [10.66%-16.70%]). Italy is set to relax the currently implemented NPIs from 4th May 2020. Given the control achieved by NPIs, we consider three scenarios for the next 8 weeks: a scenario in which mobility remains the same as during the lockdown, a scenario in which mobility returns to pre-lockdown levels by 20%, and a scenario in which mobility returns to pre-lockdown levels by 40%. The scenarios explored assume that mobility is scaled evenly across all dimensions, that behaviour stays the same as before NPIs were implemented, that no pharmaceutical interventions are introduced, and it does not include transmission reduction from contact tracing, testing and the isolation of confirmed or suspected cases. New interventions, such as enhanced testing and contact tracing are going to be introduced and will likely contribute to reductions in transmission; therefore our estimates should be viewed as pessimistic projections. We find that, in the absence of additional interventions, even a 20% return to pre-lockdown mobility could le

Journal article

Ainslie KEC, Walters CE, 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 SL, FitzJohn R, Gaythorpe K, Ghani AC, Green W, Hamlet A, Hinsley W, Imai N, Jorgensen D, Knock E, Laydon D, Nedjati-Gilani G, Okell LC, Siveroni I, Thompson HA, Unwin HJT, Verity R, Vollmer M, Walker PGT, Wang Y, Watson OJ, Whittaker C, Winskill P, Donnelly CA, Ferguson NM, Riley Set al., 2020, Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment [version 1; peer review: 2 approved], Wellcome Open Res, Vol: 5, 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

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., 2020, Estimating the number of undetected COVID-19 cases among travellers from mainland China., Wellcome open research, Vol: 5, Pages: 143-143, ISSN: 2398-502X

Background: 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.Methods: 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.Results: 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.Conclusions: Our analysis shows that a large number of COVID-19 cases remain undetected across the world. These undetected cases potentially resulted in multiple chains of human-to-human transmission outside mainland China.

Journal article

Nellums LB, Thompson H, Holmes A, Castro-Sánchez E, Otter JA, Norredam M, Friedland JS, Hargreaves Set al., 2018, Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis, Lancet Infectious Diseases, Vol: 18, Pages: 796-811, ISSN: 1473-3099

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus

Journal article

Laverty AA, Thompson H, Cetateanu A, Filippidis FTet al., 2018, Macro-environmental factors and physical activity in 28 European Union countries, European Journal of Public Health, Vol: 28, Pages: 300-302, ISSN: 1101-1262

Data from the representative 2013 Eurobarometer survey were combined with macro-environmental data to assess relationships with different domains of physical activity (PA) in 28 European Union countries. Higher mean annual temperatures were the only macro-environmental factor found to be associated with levels of physical activity; an increase in the mean annual temperature by 1°C was associated with−0.94 fewer minutes of vigorous-intensity activity per week (95% CI: −1.66 to −0.23). This highlights the importance of modifiable influences (e.g. opportunities for active travel) on PA and underscores the potential of public health interventions to raise levels of physical activity.

Journal article

Whittaker C, Watson OJ, Alvarez-Moreno C, Angkasekwinai N, Boonyasiri A, Carlos Triana L, Chanda D, Charoenpong L, Chayakulkeeree M, Cooke GS, Croda J, Cucunubá ZM, Djaafara BA, Estofolete CF, Grillet ME, Faria NR, Costa SF, Forena-Pena DA, Gibb DM, Gordon AC, Hamers RL, Hamlet ATP, Irawany V, Jitmuang A, Keurueangkul N, Njoki Kimani T, Lampo M, Levin A, Lopardo G, Mustafa R, Nayagam S, Ngamprasertchai T, Hannah Njeri NAAAAI, Nogueira ML, Ortiz-Prado E, Perroud Jr MW, Phillips AN, Promsin P, Qavi A, Rodger AJ, Sabino EC, Sangkaew S, Sari D, Sirijatuphat R, Sposito AC, Srisangthong P, Thompson HA, Udwadia Z, Valderrama-Beltrán S, Winskill P, Ghani A, Walker PGT, Hallett TBet al., Understanding the Potential Role of Therapeutics in Preventing Deaths Due to COVID-19: A Modelling Analysis

Working paper

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