Imperial College London

Professor Christl Donnelly CBE FMedSci FRS

Faculty of MedicineSchool of Public Health

Professor of Statistical Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3394c.donnelly Website

 
 
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Location

 

UGNorfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

400 results found

Dorigatti I, Lavezzo E, Manuto L, Ciavarella C, Pacenti M, Boldrin C, Cattai M, Saluzzo F, Franchin E, Del Vecchio C, Caldart F, Castelli G, Nicoletti M, Nieddu E, Salvadoretti E, Labella B, Fava L, Guglielmo S, Fascina M, Alvisi G, Vanuzzo MC, Zupo T, Calandrin R, Lisi V, Rossi L, Castigliuolo I, Merigliano S, Unwin HJT, Plebani M, Padoan A, Brazzale AR, Toppo S, Ferguson NM, Donnelly C, Crisanti Aet al., 2021, SARS-CoV-2 antibody dynamics, within-household transmission and the impact of contact tracing from community-wide serological testing in the Italian Municipality of Vo’, Publisher: Elsevier BV

Background: In February and Mach 2020, two mass swab testing campaigns conducted in Vo’, Italy demonstrated the extent of asymptomatic SARS-CoV-2 infection and the feasibility of epidemic suppression.Methods: We tested 86% of the Vo’ population (2,602 subjects) in May with three immuno-assays detecting antibodies against the spike (S) and nucleocapsid (N) antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November.Findings: Combining the results obtained with the three assays, we estimate a seroprevalence of 3.5% (95% Credible Interval (CrI) 2.8%-4.3%) in May. In November, all assays showed a reduction in antibody titres, though 98.8% (95% Confidence Interval (CI) 93.7%-100.0%) of sera still reacted against at least one antigen. Conversely, 18.6% (95% CI 11.0%-28.5%) showed a marked increase of antibody or viral neutralisation reactivity between May and November, linked to documented or likely re-exposures. We found significant differences in the magnitude and persistence of the antibody response by age group but not by symptom occurrence, hospitalisation, or sex. Analysis of the serostatus of 1,118 households indicated a 27.3% (95% CrI 19.2%-34.6%) probability of SARS-CoV-2 transmission among household members and that 81.8% (95% CrI 55.9%-95.2%) of transmission could be attributed to 20% of infections. Contact tracing correctly identified 44% of the infected subjects and had limited impact on the epidemic.Interpretation: We find evidence of antibody persistence up to nine months post infection. Different assays provided significantly different seroprevalence estimates, making it challenging to compare seroprevalence estimates globally. Due to the high population susceptibility and the limited impact of contact tracing, rigorous testing and improvements in contact tracing are essential to control SARS-CoV-2.Funding: Veneto Region, Med

Working paper

Christen P, D'Aeth J, Lochen A, McCabe R, Rizmie D, Schmit N, Nayagam S, Miraldo M, Aylin P, Bottle A, Perez Guzman P, Donnelly C, Ghani A, Ferguson N, White P, Hauck Ket al., 2021, The J-IDEA pandemic planner: a framework for implementing hospital provision interventions during the COVID-19 pandemic, Medical Care, Vol: 59, Pages: 371-378, ISSN: 0025-7079

Background : Planning for extreme surges in demand for hospital care of patientsrequiring urgent life-saving treatment for COVID-19, whilst retaining capacity for otheremergency conditions, is one of the most challenging tasks faced by healthcareproviders and policymakers during the pandemic. Health systems must be wellpreparedto cope with large and sudden changes in demand by implementinginterventions to ensure adequate access to care. We developed the first planning toolfor the COVID-19 pandemic to account for how hospital provision interventions (suchas cancelling elective surgery, setting up field hospitals, or hiring retired staff) will affectthe capacity of hospitals to provide life-saving care.Methods : We conducted a review of interventions implemented or considered in 12 European countries in March-April 2020, an evaluation of their impact on capacity, anda review of key parameters in the care of COVID-19 patients. This information wasused to develop a planner capable of estimating the impact of specific interventions ondoctors, nurses, beds and respiratory support equipment. We applied this to ascenario-based case study of one intervention, the set-up of field hospitals in England,under varying levels of COVID-19 patients.Results : The J-IDEA pandemic planner is a hospital planning tool that allows hospitaladministrators, policymakers and other decision-makers to calculate the amount ofcapacity in terms of beds, staff and crucial medical equipment obtained byimplementing the interventions. Flexible assumptions on baseline capacity, the numberof hospitalisations, staff-to-beds ratios, and staff absences due to COVID-19 make theplanner adaptable to multiple settings. The results of the case study show that whilefield hospitals alleviate the burden on the number of beds available, this intervention isfutile unless the deficit of critical care nurses is addressed first.Discussion : The tool supports decision-makers in delivering a fast and effectiveresponse to

Journal article

Riley S, Eales O, Haw D, Walters C, Wang H, Ainslie K, Atchison C, Fronterre C, Diggle P, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2021, REACT-1 round 10 report: Level prevalence of SARS-CoV-2 swab-positivity in England during third national lockdown in March 2021

BackgroundIn England, hospitalisations and deaths due to SARS-CoV-2 have been falling consistentlysince January 2021 during the third national lockdown of the COVID-19 pandemic. The firstsignificant relaxation of that lockdown occurred on 8 March when schools reopened.MethodsThe REal-time Assessment of Community Transmission-1 (REACT-1) study augmentsroutine surveillance data for England by measuring swab-positivity for SARS-CoV-2 in thecommunity. The current round, round 10, collected swabs from 11 to 30 March 2021 and iscompared here to round 9, in which swabs were collected from 4 to 23 February 2021.ResultsDuring round 10, we estimated an R number of 1.00 (95% confidence interval 0.81, 1.21).Between rounds 9 and 10 we estimated national prevalence has dropped by ~60% from0.49% (0.44%, 0.55%) in February to 0.20% (0.17%, 0.23%) in March. There weresubstantial falls in weighted regional prevalence: in South East from 0.36% (0.29%, 0.44%)in round 9 to 0.07% (0.04%, 0.12%) in round 10; London from 0.60% (0.48%, 0.76%) to0.16% (0.10%, 0.26%); East of England from 0.47% (0.36%, 0.60%) to 0.15% (0.10%,0.24%); East Midlands from 0.59% (0.45%, 0.77%) to 0.19% (0.13%, 0.28%); and NorthWest from 0.69% (0.54%, 0.88%) to 0.31% (0.21%, 0.45%). Areas of apparent higherprevalence remain in parts of the North West, and Yorkshire and The Humber. The highestprevalence in March was found among school-aged children 5 to 12 years at 0.41% (0.27%,0.62%), compared with the lowest in those aged 65 to 74 and 75 and over at 0.09% (0.05%,0.16%). The close approximation between prevalence of infections and deaths (suitablylagged) is diverging, suggesting that infections may have resulted in fewer hospitalisationsand deaths since the start of widespread vaccination.ConclusionWe report a sharp decline in prevalence of infections between February and March 2021.We did not observe an increase in the prevalence of SARS-CoV-2 following the reopening ofschools in England, although the decline of p

Working paper

Djaafara BA, Imai N, Hamblion E, Impouma B, Donnelly CA, Cori Aet al., 2021, A Quantitative Framework for Defining the End of an Infectious Disease Outbreak: Application to Ebola Virus Disease., Am J Epidemiol, Vol: 190, Pages: 642-651

The end-of-outbreak declaration is an important step in controlling infectious disease outbreaks. Objective estimation of the confidence level that an outbreak is over is important to reduce the risk of postdeclaration flare-ups. We developed a simulation-based model with which to quantify that confidence and tested it on simulated Ebola virus disease data. We found that these confidence estimates were most sensitive to the instantaneous reproduction number, the reporting rate, and the time between the symptom onset and death or recovery of the last detected case. For Ebola virus disease, our results suggested that the current World Health Organization criterion of 42 days since the recovery or death of the last detected case is too short and too sensitive to underreporting. Therefore, we suggest a shift to a preliminary end-of-outbreak declaration after 63 days from the symptom onset day of the last detected case. This preliminary declaration should still be followed by 90 days of enhanced surveillance to capture potential flare-ups of cases, after which the official end of the outbreak can be declared. This sequence corresponds to more than 95% confidence that an outbreak is over in most of the scenarios examined. Our framework is generic and therefore could be adapted to estimate end-of-outbreak confidence for other infectious diseases.

Journal article

Marks C, Abramovitz D, Donnelly C, Carrasco-Escobar G, Carrasco-Hernandez R, Ciccarone D, González-Izquierdo A, Martin NK, Strathdee SA, Smith DM, Bórquez Aet al., 2021, Identifying Counties at Risk of High Overdose Mortality Burden Throughout the Emerging Fentanyl Epidemic in the United States: A Predictive Statistical Modeling Study, The Lancet Public Health, ISSN: 2468-2667

Journal article

Woodroffe R, Donnelly C, Chapman K, Ham C, Moyes K, Stratton N, Cartwright Set al., 2021, Successive use of shared space by badgers and cattle: implications for Mycobacterium bovis transmission, Journal of Zoology, ISSN: 0952-8369

Managing infectious disease demands understanding pathogen transmission. In Britain, transmission of Mycobacterium bovis from badgers (Meles meles) to cattle hinders the control of bovine tuberculosis (TB), but the mechanism of such transmission is uncertain. As badgers and cattle seldom interact directly, transmission might occur in their shared environment through contact with contamination such as faeces, urine, and saliva. We used concurrent GPS-collar tracking of badgers and cattle at four sites in Cornwall, southwest Britain, to test whether each species used locations previously occupied by the other species, within the survival time of M. bovis bacteria. Although analyses of the same dataset showed that badgers avoided cattle, we found no evidence that this avoidance persisted over time: neither GPS-collared badgers or cattle avoided space which had been occupied by the other species in the preceding 36h. Defining a contact event as an animal being located <5m from space occupied by the other species within the previous 36h, we estimated that a herd of 176 cattle (mean herd size in our study areas) would contact badgers at least 6.0 times during an average 24h period. Similarly, we estimated that a social group of 3.5 badgers (mean group size in our study areas) would contact cattle at least 0.76 times during an average night. Such frequent successive use of the same shared space, within the survival time of M. bovis bacteria, could potentially facilitate M. bovis transmission via the environment.

Journal article

Donnelly R, Prots A, Donnelly C, 2021, Better educational signage could reduce disturbance of resting dolphins, PLoS One, ISSN: 1932-6203

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, 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

Riley S, Wang H, Eales O, Haw D, Walters C, Ainslie K, Atchison C, Fronterre C, Diggle P, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2021, REACT-1 round 9 final report: Continued but slowing decline of prevalence of SARS-CoV-2 during national lockdown in England in February 2021

BackgroundEngland will start to exit its third national lockdown in response to the COVID-19 pandemicon 8th March 2021, with safe effective vaccines being rolled out rapidly against abackground of emerging transmissible and immunologically novel variants of SARS-CoV-2.A subsequent increase in community prevalence of infection could delay further relaxation oflockdown if vaccine uptake and efficacy are not sufficiently high to prevent increasedpressure on healthcare services.MethodsThe PCR self-swab arm of the REal-time Assessment of Community Transmission Study(REACT-1) estimates community prevalence of SARS-CoV-2 infection in England based onrandom cross-sections of the population ages five and over. Here, we present results fromthe complete round 9 of REACT-1 comprising round 9a in which swabs were collected from4th to 12th February 2021 and round 9b from 13th to 23rd February 2021. We also comparethe results of REACT-1 round 9 to round 8, in which swabs were collected mainly from 6thJanuary to 22nd January 2021.ResultsOut of 165,456 results for round 9 overall, 689 were positive. Overall weighted prevalence ofinfection in the community in England was 0.49% (0.44%, 0.55%), representing a fall of overone third from round 8. However the rate of decline of the epidemic has slowed from 15 (13,17) days, estimated for the period from the end of round 8 to the start of round 9, to 31 daysestimated using data from round 9 alone (lower confidence limit 17 days). When comparinground 9a to 9b there were apparent falls in four regions, no apparent change in one regionand apparent rises in four regions, including London where there was a suggestion ofsub-regional heterogeneity in growth and decline. Smoothed prevalence maps suggest largecontiguous areas of growth and decline that do not align with administrative regions.Prevalence fell by 50% or more across all age groups in round 9 compared to round 8, withprevalence (round 9) ranging from 0.21% in those aged 65 and over to 0

Working paper

Ward H, Cooke G, Whitaker M, Redd R, Eales O, Brown J, Collet K, Cooper E, Daunt A, Jones K, Moshe M, Willicombe M, Day S, Atchison C, Darzi A, Donnelly C, Riley S, Ashby D, Barclay W, Elliott Pet al., 2021, REACT-2 Round 5: increasing prevalence of SARS-CoV-2 antibodies demonstrate impact of the second wave and of vaccine roll-out in England

BackgroundEngland has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering thefirst dose to the largest number of older individuals, healthcare and care home workers.MethodsA cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flowimmunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later.ResultsThe survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people.The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer.Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and alle

Working paper

Prete CA, Buss L, Dighe A, Porto VB, da Silva Candido D, Ghilardi F, Pybus OG, de Oliveira WK, Croda JHR, Sabino EC, Faria NR, Donnelly CA, Nascimento VHet al., 2021, Serial interval distribution of SARS-CoV-2 infection in Brazil., J Travel Med, Vol: 28

Journal article

Riley S, Walters C, Wang H, Eales O, Haw D, Ainslie K, Atchison C, Fronterre C, Diggle P, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2021, REACT-1 round 9 interim report: downward trend of SARS-CoV-2 in England in February 2021 but still at high prevalence

Background and Methods: England entered its third national lockdown of the COVID-19pandemic on 6th January 2021 with the aim of reducing the daily number of deaths andpressure on healthcare services. The real-time assessment of community transmission study(REACT-1) obtains throat and nose swabs from randomly selected people in England inorder to describe patterns of SARS-CoV-2 prevalence. Here, we report data from round 9aof REACT-1 for swabs collected between 4th and 13th February 2021.Results: Out of 85,473 tested-swabs, 378 were positive. Overall weighted prevalence ofinfection in the community in England was 0.51%, a fall of more than two thirds since our lastreport (round 8) in January 2021 when 1.57% of people tested positive. We estimate ahalving time of 14.6 days and a reproduction number R of 0.72, based on the difference inprevalence between the end of round 8 and the beginning of round 9. Although prevalencefell in all nine regions of England over the same period, there was greater uncertainty in thetrend for North West, North East, and Yorkshire and The Humber. Prevalence fellsubstantially across all age groups with highest prevalence among 18- to 24-year olds at0.89% (0.47%, 1.67%) and those aged 5 to12 years at 0.86% (0.60%, 1.24%). Largehousehold size, living in a deprived neighbourhood, and Asian ethnicity were all associatedwith increased prevalence. Healthcare and care home workers were more likely to testpositive compared to other workers.Conclusions: There is a strong decline in prevalence of SARS-CoV-2 in England among thegeneral population five to six weeks into lockdown, but prevalence remains high: at levelssimilar to those observed in late September 2020. Also, the number of COVID-19 cases inhospitals is higher than at the peak of the first wave in April 2020. The effects of easing ofsocial distancing when we transition out of lockdown need to be closely monitored to avoid aresurgence in infections and renewed pressure on health services.

Working paper

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

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, 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

Ward H, Atchison C, Whitaker M, Ainslie KEC, Elliott J, Okell L, Redd R, Ashby D, Donnelly C, Barclay W, Darzi A, Cooke G, Riley S, Elliott Pet al., 2021, SARS-CoV-2 antibody prevalence in England following the first peak of the pandemic., Nature Communications, Vol: 12, Pages: 1-8, ISSN: 2041-1723

England has experienced a large outbreak of SARS-CoV-2, disproportionately affecting people from disadvantaged and ethnic minority communities. It is unclear how much of this excess is due to differences in exposure associated with structural inequalities. Here we report from the REal-time Assessment of Community Transmission-2 (REACT-2) national study of over 100,000 people. After adjusting for test characteristics and re-weighting to the population, overall antibody prevalence is 6.0% (95% CI: 5.8-6.1). An estimated 3.4 million people had developed antibodies to SARS-CoV-2 by mid-July 2020. Prevalence is two- to three-fold higher among health and care workers compared with non-essential workers, and in people of Black or South Asian than white ethnicity, while age- and sex-specific infection fatality ratios are similar across ethnicities. Our results indicate that higher hospitalisation and mortality from COVID-19 in minority ethnic groups may reflect higher rates of infection rather than differential experience of disease or care.

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 SG, 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, Brazzale AR, Toppo S, Trevisan M, Baldo V, Donnelly CA, Ferguson NM, Dorigatti I, Crisanti A, Crisanti Aet al., 2021, Author Correction: Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo', Nature, Vol: 590, Pages: E11-E11, ISSN: 0028-0836

Correction to: Nature https://doi.org/10.1038/s41586-020-2488-1Published online 30 June 2020

Journal article

Franco D, Gonzalez C, Abrego LE, Carrera J-P, Diaz Y, Caicedo Y, Moreno A, Chavarria O, Gondola J, Castillo M, Valdespino E, Gaitán M, Martínez-Mandiche J, Hayer L, Gonzalez P, Lange C, Molto Y, Mojica D, Ramos R, Mastelari M, Cerezo L, Moreno L, Donnelly CA, Pascale JM, Faria NR, Lopez-Verges S, Martinez AA, Gorgas COVID19 team and Panama COVID19 Laboratory Networket al., 2021, Early transmission dynamics, spread, and genomic characterization of SARS-CoV-2 in Panama., Emerging Infectious Diseases, Vol: 27, Pages: 612-615, ISSN: 1080-6040

We report an epidemiologic analysis of 4,210 cases of infection with severe acute respiratory syndrome coronavirus 2 and genetic analysis of 313 new near-complete virus genomes in Panama during March 9-April 16, 2020. Although containment measures reduced R0 and Rt, they did not interrupt virus spread in the country.

Journal article

Riley S, Eales O, Walters C, Wang H, Ainslie K, Atchison C, Fronterre C, Diggle P, Ashby D, Donnelly C, Cooke G, Barclay W, Darzi A, Elliott P, Ward Het al., 2021, REACT-1 round 8 final report: high average prevalence with regional heterogeneity of trends in SARS-CoV-2 infection in the community in England during January 2021

In early January 2021, England entered its third national lockdown of the COVID-19 pandemic to reduce numbers of deaths and pressure on healthcare services, while rapidly rolling out vaccination to healthcare workers and those most at risk of severe disease and death. REACT-1 is a survey of SARS-CoV-2 prevalence in the community in England, based on repeated cross-sectional samples of the population. Between 6th and 22nd January 2021, out of 167,642 results, 2,282 were positive giving a weighted national prevalence of infection of 1.57% (95% CI, 1.49%, 1.66%). The R number nationally over this period was estimated at 0.98 (0.92, 1.04). Prevalence remained high throughout, but with suggestion of a decline at the end of the study period. The average national trend masked regional heterogeneity, with robustly decreasing prevalence in one region (South West) and increasing prevalence in another (East Midlands). Overall prevalence at regional level was highest in London at 2.83% (2.53%, 3.16%). Although prevalence nationally was highest in the low-risk 18 to 24 year old group at 2.44% (1.96%, 3.03%), it was also high in those over 65 years who are most at risk, at 0.93% (0.82%, 1.05%). Large household size, living in a deprived neighbourhood, and Black and Asian ethnicity were all associated with higher levels of infections compared to smaller households, less deprived neighbourhoods and other ethnicities. Healthcare and care home workers, and other key workers, were more likely to test positive compared to other workers. If sustained lower prevalence is not achieved rapidly in England, pressure on healthcare services and numbers of COVID-19 deaths will remain unacceptably high.

Working paper

Riley S, Wang H, Eales O, Walters C, Ainslie K, Atchison C, Fronterre C, Diggle P, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2021, REACT-1 round 8 interim report: SARS-CoV-2 prevalence during the initial stages of the third national lockdown in England, Publisher: Imperial College London

BackgroundHigh prevalence of SARS-CoV-2 virus in many northern hemisphere populations is causingextreme pressure on healthcare services and leading to high numbers of fatalities. Eventhough safe and effective vaccines are being deployed in many populations, the majority ofthose most at-risk of severe COVID-19 will not be protected until late spring, even incountries already at a more advanced stage of vaccine deployment.MethodsThe REal-time Assessment of Community Transmission study-1 (REACT-1) obtains throatand nose swabs from between 120,000 and 180,000 people in the community in England atapproximately monthly intervals. Round 8a of REACT-1 mainly covers a period from 6thJanuary 2021 to 15th January 2021. Swabs are tested for SARS-CoV-2 virus and patterns ofswab-positivity are described over time, space and with respect to individual characteristics.We compare swab-positivity prevalence from REACT-1 with mobility data based on the GPSlocations of individuals using the Facebook mobile phone app. We also compare resultsfrom round 8a with those from round 7 in which swabs were collected from 13th Novemberto 24th November (round 7a) and 25th November to 3rd December 2020 (round 7b).ResultsIn round 8a, we found 1,962 positives from 142,909 swabs giving a weighted prevalence of1.58% (95% CI, 1.49%, 1.68%). Using a constant growth model, we found no strongevidence for either growth or decay averaged across the period; rather, based on data froma limited number of days, prevalence may have started to rise at the end of round 8a.Facebook mobility data showed a marked decrease in activity at the end of December 2020,followed by a rise at the start of the working year in January 2021. Between round 7b andround 8a, prevalence increased in all adult age groups, more than doubling to 0.94%(0.83%, 1.07%) in those aged 65 and over. Large household size, living in a deprivedneighbourhood, and Black and Asian ethnicity were all associated with increasedprevalence. Both healthcare

Working paper

Verity R, Okell L, Dorigatti I, Winskill P, Whittaker C, Walker P, Donnelly C, Ferguson N, Ghani Aet al., 2021, COVID-19 and the difficulty of inferring epidemiological parameters from clinical data Reply, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 28-28, ISSN: 1473-3099

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

Riley S, Walters C, Wang H, Eales O, Ainslie K, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2020, REACT-1 round 7 updated report: regional heterogeneity in changes in prevalence of SARS-CoV-2 infection during the second national COVID-19 lockdown in England, REACT-1 round 7 updated report: regional heterogeneity in changes in prevalence of SARS-CoV-2 infection during the second national COVID-19 lockdown in England, London, Publisher: Imperial College London

BackgroundEngland exited a four-week second national lockdown on 2nd December 2020 initiated in response to the COVID-19 pandemic. Prior results showed that prevalence dropped during the first half of lockdown, with greater reductions in higher-prevalence northern regions.MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England, designed to monitor the spread of the epidemic and thus increase situational awareness. Round 7 of REACT-1 commenced swab-collection on 13th November 2020. A prior interim report included data from 13th to 24th November 2020 for 105,122 participants. Here, we report data for the entire round with swab results obtained up to 3rd December 2020.ResultsBetween 13th November and 3rd December (round 7) there were 1,299 positive swabs out of 168,181 giving a weighted prevalence of 0.94% (95% CI 0.87%, 1.01%) or 94 per 10,000 people infected in the community in England. This compares with a prevalence of 1.30% (1.21%, 1.39%) from 16th October to 2nd November 2020 (round 6), a decline of 28%. Prevalence during the latter half of round 7 was 0.91% (95% CI, 0.81%, 1.03%) compared with 0.96% (0.87%, 1.05%) in the first half. The national R number in round 7 was estimated at 0.96 (0.88, 1.03) with a decline in prevalence observed during the first half of this period no longer apparent during the second half at the end of lockdown. During round 7 there was a marked fall in prevalence in West Midlands, a levelling off in some regions and a rise in London. R numbers at regional level ranged from 0.60 (0.41, 0.80) in West Midlands up to 1.27 (1.04, 1.54) in London, where prevalence was highest in the east and south-east of the city. Nationally, between 13th November and 3rd December, the highest prevalence was in school-aged children especially at ages 13-17 years at 2.04% (1.69%, 2.46%), or approximately 1 in 50.ConclusionBetween the previous round and round 7 (during lockdown), there was a fall in prevalence of SARS-C

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

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

Journal article

Riley S, Eales O, Walters C, Wang H, Ainslie K, Atchison C, Fronterre C, Diggle P, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2020, REACT-1 round 7 interim report: fall in prevalence of swab-positivity in England during national lockdown, Publisher: Cold Spring Harbor Laboratory

Background The second wave of the 2020 COVID-19 pandemic in England has been characterized by high growth and prevalence in the North with lower prevalence in the South. High prevalence was first observed at younger adult ages before spreading out to school-aged children and older adults. Local tiered interventions were in place up to 5th November 2020 at which time a second national lockdown was implemented.Methods REACT-1 is a repeated cross-sectional survey of SARS-CoV-2 swab-positivity in random samples of the population of England. The current period of data collection (round 7) commenced on 13th November 2020 and we report interim results here for swabs collected up to and including 24th November 2020. Because there were two distinct periods of growth during the previous round 6, here we compare results from round 7 (mainly) with the second half of round 6, which obtained swabs between 26th October and 2nd November 2020. We report prevalence both unweighted and reweighted to be representative of the population of England. We describe trends in unweighted prevalence with daily growth rates, doubling times, reproduction numbers (R) and splines. We estimated odds ratios for swab-positivity using mutually-adjusted multivariable logistic regression models.Results We found 821 positives from 105,123 swabs giving an unweighted prevalence of 0.78% (95% CI, 0.73%, 0.84%) and a weighted prevalence of 0.96% (0.87%, 1.05%). The weighted prevalence estimate was ∼30% lower than that of 1.32% (1.20%, 1.45%) obtained in the second half of round 6. This decrease corresponds to a halving time of 37 (30, 47) days and an R number of 0.88 (0.86, 0.91). Using only data from the most recent period, we estimate an R number of 0.71 (0.54, 0.90). A spline fit to prevalence showed a rise shortly after the previous period of data collection followed by a fall coinciding with the start of lockdown. The national trends were driven mainly by reductions in higher-prevalence northern regi

Working paper

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

Parag K, Donnelly C, Jha R, Thompson Ret al., 2020, An exact method for quantifying the reliability of end-of-epidemic declarations in real time, PLoS Computational Biology, Vol: 16, ISSN: 1553-734X

We derive and validate a novel and analytic method for estimating the probability that an epidemic has been eliminated (i.e. that no future local cases will emerge) in real time. When this probability crosses 0.95 an outbreak can be declared over with 95% confidence. Our method is easy to compute, only requires knowledge of the incidence curve and the serial interval distribution, and evaluates the statistical lifetime of the outbreak of interest. Using this approach, we show how the time-varying under-reporting of infected cases will artificially inflate the inferred probability of elimination, leading to premature (false-positive) end-of-epidemic declarations. Contrastingly, we prove that incorrectly identifying imported cases as local will deceptively decrease this probability, resulting in delayed (false-negative) declarations. Failing to sustain intensive surveillance during the later phases of an epidemic can therefore substantially mislead policymakers on when it is safe to remove travel bans or relax quarantine and social distancing advisories. World Health Organisation guidelines recommend fixed (though disease-specific) waiting times for end-of-epidemic declarations that cannot accommodate these variations. Consequently, there is an unequivocal need for more active and specialised metrics for reliably identifying the conclusion of an epidemic.

Journal article

Parag KV, Cowling BJ, Donnelly CA, 2020, Deciphering early-warning signals of the elimination and resurgence potential of SARS-CoV-2 from limited data at multiple scales

<jats:title>Abstract</jats:title><jats:p>Inferring the transmission potential of an infectious disease during the low-incidence period following an epidemic wave is crucial for preparedness. In this period, necessarily scarce data hamper existing inference methods, blurring early-warning signals essential for discriminating between the likelihoods of resurgence versus elimination. Advanced insight into whether a region of interest will face elevating caseloads (requiring swift community-wide interventions) or achieve local elimination (allowing interventions to be relaxed or refocussed on controlling the importation of infections), can be the difference between decisive and ineffective policy. We propose a novel early-warning framework that formally maximises information extracted from low-incidence data to robustly infer the chances of sustained local transmission or elimination in real time, at any desired scale of investigation. Applying this framework, we decipher previously hidden disease-transmission signals from the prolonged low-incidence COVID-19 data of New Zealand, Hong Kong and Victoria state, Australia. We uncover how timely interventions averted dangerous, resurgent waves of COVID-19 and support official declarations of elimination. Across these locations, we obtain strong evidence for the effectiveness of rapid and adaptive COVID-19 responses.</jats:p>

Journal article

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

The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on healthcare systems, particularly intensive care units (ICUs), with COVID-19 patient care being a key concern of healthcare system planning for winter 2020/21. Ensuring that all patients who require intensive care, irrespective of COVID-19 status, can access it during this time is essential. This study uses an integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients to estimate the spare capacity of key ICU resources under different epidemic scenarios in France, Germany and Italy across the winter period of 2020/21. In particular, we examine the effect of implementing suppression strategies of varying effectiveness, triggered by different numbers of COVID-19 patients in ICU. The use of a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model and the consideration of multiple ICU resources that determine capacity (beds, doctors, nurses and ventilators) and the interdependencies between them, provides a detailed insight into potential capacity constraints this winter. Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource across countries. Lockdowns triggered based on ICU capacity could lead to large improvements in spare capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and implemented at a higher level of suppression. In many cases, maximum deficits are reduced to lower levels which can then be managed by expanding supply-side hospital capacity, to ensure that all patients can receive treatment. The success of such interventions also depends on baseline ICU bed numbers and average non-COVID-19 patient occupancy. We find that lockdowns of longer duration reduce the total number of days in defic

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