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

401 results found

Eales O, Page AJ, Tang S, Walters C, Wang H, Haw D, Trotter AJ, Viet TL, Foster-Nyarko E, Prosolek S, Atchison C, Ashby D, Cooke G, Barclay W, Donnelly C, O'Grady J, Volz E, The COVID-19 Genomics UK Consortium, Darzi A, Ward H, Elliott P, Riley Set al., 2021, SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples

Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.

Working paper

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, Ainslie KEC, Eales O, Walters CE, Wang H, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott Pet al., 2021, Resurgence of SARS-CoV-2: detection by community viral surveillance., Science

Surveillance of the SARS-CoV-2 epidemic has mainly relied on case reporting which is biased by health service performance, test availability and test-seeking behaviors. We report a community-wide national representative surveillance program in England involving self-administered swab results from 594,000 individuals tested for SARS-CoV-2, regardless of symptoms, from May to beginning of September 2020. The epidemic declined between May and July 2020 but then increased gradually from mid-August, accelerating into early September 2020 at the start of the second wave. When compared to cases detected through routine surveillance, we report here a longer period of decline and a younger age distribution. Representative community sampling for SARS-CoV-2 can substantially improve situational awareness and feed into the public health response even at low prevalence.

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

Riley S, Atchison C, Ashby D, Donnelly CA, Barclay W, Cooke GS, Ward H, Darzi A, Elliott Pet al., 2021, REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol, Wellcome Open Research, Vol: 5, Pages: 200-200

<ns4:p><ns4:bold>Background:</ns4:bold> England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission.</ns4:p><ns4:p> <ns4:bold>Protocol:</ns4:bold> The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community.</ns4:p><ns4:p> REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list.</ns4:p><ns4:p> REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4).</ns4:p><ns4:p> <ns4:bold>Ethics and dissemination: </ns4:bold>The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications.</ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4:bold>This study provides robust estimat

Journal article

Parag KV, Thompson RN, Donnelly CA, 2021, Are epidemic growth rates more informative than reproduction numbers?

<jats:p>Summary statistics, often derived from simplified models of epidemic spread, inform public health policy in real time. The instantaneous reproduction number, <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub>, is predominant among these statistics, measuring the average ability of an infection to multiply. However, <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub> encodes no temporal information and is sensitive to modelling assumptions. Consequently, some have proposed the epidemic growth rate, <jats:italic>r</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub>, i.e., the rate of change of the log-transformed case incidence, as a more temporally meaningful and model-agnostic policy guide. We examine this assertion, identifying if and when estimates of <jats:italic>r</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub> are more informative than those of <jats:italic>R</jats:italic><jats:sub><jats:italic>t</jats:italic></jats:sub>. We assess their relative strengths both for learning about pathogen transmission mechanisms and for guiding epidemic interventions in real time.</jats:p>

Journal article

Lovell-Read FA, Funk S, Obolski U, Donnelly C, Thompson RNet al., 2021, Interventions targeting nonsymptomatic cases can be important to prevent local outbreaks: SARS-CoV-2 as a case study, Journal of the Royal Society Interface, ISSN: 1742-5662

Dense urban areas are especially hardly hit by the Covid-19 crisis due to the limited availability of public transport, one of the most efficient means of mass mobility. In light of the Covid-19 pandemic, public transport operators are experiencing steep declines in demand and fare revenues due to the perceived risk of infection within vehicles and other facilities. The purpose of this paper is to explore the possibilities of implementing social distancing in public transport in line with epidemiological advice. Social distancing requires effective demand management to keep vehicle occupancy rates under a predefined threshold, both spatially and temporally. We review the literature of five demand management methods enabled by new information and ticketing technologies: (i) inflow control with queueing, (ii) time and space dependent pricing, (iii) capacity reservation with advance booking, (iv) slot auctioning, and (v) tradeable travel permit schemes. Thus the paper collects the relevant literature into a single point of reference, and provides interpretation from the viewpoint of practical applicability during and after the pandemic.

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

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

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

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

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

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

Journal article

Espinosa-Guerra EA, Rodríguez-Barría ER, Donnelly CA, Carrera J-Pet al., 2021, Prevalence and associated factors with mental health outcomes among interns and residents physicians during COVID-19 epidemic in Panama: a cross-sectional study

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>A new coronavirus SARS-CoV-2 was associated with a newly identified respiratory syndrome, COVID-19 in Wuhan, China, in early December 2019. SARS-CoV-2 rapidly spread across the globe resulting in 117 million cases and 2.59 million deaths by March 2021. Rapidly increased numbers of COVID-19 cases overwhelmed public health systems across the world, imposing increased working hours and workloads for health care workers. Here, we have evaluated the prevalence of health outcomes and associated factors of interns and resident physicians in Panama.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A cross-sectional study was undertaken during July 23, 2020, to August 13, 2020, to evaluate the prevalence of health outcomes and associated factors in interns and residents across Panama. Snowball sampling was used to recruit participants. Then an electronic questionnaire with scales to evaluate anxiety disorders (GAD-7), depression (PHQ-9) and post-traumatic stress (IES-R) was evaluated. In addition, socio-demographic variables, clinical history of mental disorders and COVID-19 exposure were evaluated. Independent analyses for each mental health outcome were undertaken using a logistic regression analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 517/1205 (42.9%) interns and residents were nationwide recruited. Of these 274 (53.0%) were interns and 243 (47.0%) residents. The overall prevalence of depression symptoms was 25.3%, 13.7% anxiety and 12.2% post-traumatic stress. At least, 9.3% participants reported having suicidal ideation.</jats:p><jats:p>The most parsimonious model showed females had a higher prevalence of mental health disorders, in all results and the married participants were more likely to present dep

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

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

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, JOURNAL OF TRAVEL MEDICINE, Vol: 28, ISSN: 1195-1982

Journal article

Unwin HJT, Cori A, Imai N, Gaythorpe KAM, Bhatia S, Cattarino L, Donnelly CA, Ferguson NM, Baguelin Met al., 2021, Using next generation matrices to estimate the proportion of cases that are not detected in an outbreak

<jats:p>Contact tracing, where exposed individuals are followed up to break ongoing transmission chains, is a key pillar of outbreak response for many infectious disease outbreaks, such as Ebola and SARS-CoV-2. Unfortunately, these systems are not fully effective, and cases can still go undetected as people may not know or remember all of their contacts or contacts may not be able to be traced. A large proportion of undetected cases suggests poor contact tracing and surveillance systems, which could be a potential area of improvement for a disease response. In this paper, we present a novel method for estimating the proportion of cases that are not detected during an outbreak. Our method uses next generation matrices that are parameterized by linked contact tracing and case line-lists. We use this method to investigate the proportion of undetected cases in two case studies: the SARS-CoV-2 outbreak in New Zealand during 2020 and the West African Ebola outbreak in Guinea during 2014. We estimate that only 6% of SARS-CoV-2 cases were not detected in New Zealand (95% credible interval: 1.31 – 16.7%), but over 60% of Ebola cases were not detected in Guinea (95% credible interval: 15 - 90%).</jats:p>

Journal article

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

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

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

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

Report

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