Imperial College London

Prof Marc Chadeau-Hyam

Faculty of MedicineSchool of Public Health

Professor of Computational Epidemiology and Biostatistics
 
 
 
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Contact

 

+44 (0)20 7594 1637m.chadeau

 
 
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Location

 

VC7Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

166 results found

Eales O, de Oliveira Martins L, Page AJ, Wang H, Bodinier B, Tang D, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly CA, Chadeau-Hyam Met al., 2022, Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England, Nature Communications, Vol: 13

<jats:title>Abstract</jats:title><jats:p>The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England’s Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the ‘new normal’.</jats:p>

Journal article

Chadeau-Hyam M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby J, Whitaker M, Elliott J, Haw D, Walters CE, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott Pet al., 2022, Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys, The Lancet Regional Health - Europe, Vol: 21, Pages: 100462-100462, ISSN: 2666-7762

Journal article

Maitre L, Guimbaud J-B, Warembourg C, Guil-Oumrait N, Petrone PM, Chadeau M, Vrijheid M, Gonzalez J, Basagana Xet al., 2022, State-of-the-art methods for exposure-health studies: results from the exposome data challenge event, Environment International, ISSN: 0160-4120

The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P>100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother-child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and env

Journal article

Eales O, de Oliveira Martins L, Page A, Wang H, Bodinier B, Tang D, Haw D, Jonnerby LJA, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly C, Chadeau Met al., 2022, Dynamics and scale of the SARS-CoV-2 variant Omicron epidemic in England, Nature Communications, ISSN: 2041-1723

Journal article

Elliott P, Eales O, Bodinier B, Tang D, Wang H, Jonnerby LJA, Haw D, Elliott J, Whitaker M, Walters C, Atchison C, Diggle P, Page A, Trotter A, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke G, Chadeau M, Donnelly Cet al., 2022, Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England, Nature Communications, ISSN: 2041-1723

Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n=102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R=0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.

Journal article

Said S, Pazoki R, Karhunen V, Vosa U, Ligthart S, Bodinier B, Koskeridis F, Welsh P, Alizadeh BZ, Chasman DI, Sattar N, Chadeau-Hyam M, Evangelou E, Jarvelin M-R, Elliott P, Tzoulaki I, Dehghan Aet al., 2022, Genetic analysis of over half a million people characterises C-reactive protein loci (vol 13, 2198, 2022), Nature Communications, Vol: 13, Pages: 1-1, ISSN: 2041-1723

Journal article

Eales O, Wang H, Bodinier B, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Chadeau M, Donnelly C, Elliott Pet al., 2022, SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2, BMC Infectious Diseases, ISSN: 1471-2334

Background: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September - 27 September 2021) and 15 (19 October - 5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month.Results: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI, 8%-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England.Conclusions: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.

Journal article

Elliott P, Eales O, Steyn N, Tang D, Bodinier B, Wang H, Elliott J, Whitaker M, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Donnelly CA, Chadeau-Hyam Met al., 2022, Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England., Science, Vol: 376

Rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to record-breaking incidence rates around the world. The Real-time Assessment of Community Transmission-1 (REACT-1) study has tracked SARS-CoV-2 infection in England using reverse transcription polymerase chain reaction (RT-PCR) results from self-administered throat and nose swabs from randomly selected participants aged 5 years and older approximately monthly from May 2020 to March 2022. Weighted prevalence in March 2022 was the highest recorded in REACT-1 at 6.37% (N = 109,181), with the Omicron BA.2 variant largely replacing the BA.1 variant. Prevalence was increasing overall, with the greatest increase in those aged 65 to 74 years and 75 years and older. This was associated with increased hospitalizations and deaths, but at much lower levels than in previous waves against a backdrop of high levels of vaccination.

Journal article

Chadeau M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby LJA, Whitaker M, Elliott J, Haw D, Walters C, Atchison C, Diggle P, Page A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly C, Elliott Pet al., 2022, Cross-sectional community surveys to monitor the Omicron SARS-CoV-2 epidemic in England during February 2022, The Lancet Regional Health Europe, ISSN: 2666-7762

Background: The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).Findings: We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76–3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0–0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1,047, 64.8% (62.4–67.2) were BA.1; N=568, 35.2% (32.8–37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34–0.41). The highest proportion of BA.2 among positives was found in London. Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.Funding Department of Health and Social Care, England.

Journal article

Gruzieva O, Jeong A, Yu Z, de Bont J, Pinho M, Eze I, Kress S, Wheelock C, Peters A, Vlaanderen J, de Hoogh K, Scalbert A, Chadeau M, Vermeulen R, Gehring U, Probst-Hensch N, Melen Eet al., 2022, Air pollution, metabolites and respiratory health across the life-course, European Respiratory Review, ISSN: 0905-9180

Previous studies have explored relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and associated mechanisms have not been reviewed from a life-course perspective. Here we provide a narrative review summarizing recent evidence on the associations of metabolic profiles with both air pollution exposure and lung function in both children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analyzing air pollution-related metabolic profiles, and 16 analyzing lung function-related metabolic profiles. A wide range of metabolites were identified being associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general populationand respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many suffer from small sample size, cross-sectional designs, preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools forhealthy living in urbAN Settings (EXPANSE) project aims at addressing some of these shortcomings by combining biospecimens from large European cohorts, and harmonized air pollution exposure and exposome data.

Journal article

Chadeau M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Elliott J, Walters C, Jonnerby LJA, Atchison C, Diggle P, Page A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly C, Elliott Pet al., 2022, Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study, EClinicalMedicine, Vol: 48, Pages: 1-14, ISSN: 2589-5370

Background: Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years. Methods: SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N= 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses. Findings: Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted odds ratio of 0.36 (0.25, 0.53). Interpretation: Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.

Journal article

Tayal U, 2022, Exposure to elevated nitrogen dioxide concentrations and cardiac remodelling in patients with dilated cardiomyopathy, Journal of Cardiac Failure, Vol: 28, Pages: 924-934, ISSN: 1071-9164

Rationale: Empirical evidence suggests a strong link between exposure to air pollution and heart failure incidence, hospitalisations and mortality, but the biological basis of this remains unclear. Objective: To determine the relationship between differential air pollution levels and changes in cardiac structure and function in patients with dilated cardiomyopathy. Methods and Results: We undertook a prospective longitudinal observational cohort study of patients in England with dilated cardiomyopathy (enrollment 2009-2015; n=716, 66% male, 85% Caucasian) and conducted cross sectional analysis at the time of study enrollment. Annual average air pollution exposure estimates for nitrogen dioxide (NO2) and particulate matter with diameter ≤ 2.5µm (PM2.5) at enrolment were assigned to each residential postcode (on average 12 households). The relationship between air pollution and cardiac morphology was assessed using linear regression modelling. Greater ambient exposure to NO2 was associated with higher indexed left ventricular mass (4.3 g/m2 increase per interquartile range (IQR) increase in NO2, 95% CI 1.9 to 7.0 g/m2) and lower left ventricular ejection fraction (-1.5% decrease per IQR increase in NO2, 95% CI -2.7 to -0.2%), independent of age, sex, socio-economic status and clinical covariates. The associations were robust to adjustment for smoking status and geographical clustering by postcode area. The effect of air pollution on left ventricular mass was greatest in women. These effects were specific to NO2 exposure. Conclusion: Exposure to air pollution is associated with raised left ventricular mass and lower left ventricular ejection fraction, with the strongest effect in women. Whilst epidemiological associations between air pollution and heart failure have been established and supported by pre-clinical studies, our findings provide novel empirical evidence of cardiac remodelling and exposure to air pollution with important clinical and public health

Journal article

Whitaker M, Elliott J, Bodinier B, Barclay W, Ward H, Cooke G, Donnelly CA, Chadeau-Hyam M, Elliott Pet al., 2022, Variant-specific symptoms of COVID-19 among 1,542,510 people in England

<jats:title>Abstract</jats:title><jats:p>Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important.</jats:p>

Journal article

Petrovic D, Bodinier B, Dagnino S, Whitaker M, Karimi M, Campanella G, Haugdahl Nøst T, Polidoro S, Palli D, Krogh V, Tumino R, Sacerdote C, Panico S, Lund E, Dugue PA, Giles G, Severi G, Southey M, Vineis P, Stringhini S, Bochud M, Sandanger T, Vermeulen R, Guida F, Chadeau Met al., 2022, Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking, European Journal of Epidemiology, Vol: 37, Pages: 629-640, ISSN: 0393-2990

Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case–control studies, using (LASSO)-penalised regression. We accounted for the effects of smoking using known smoking-related CpGs, and through conditional-independence network. We identified 29 CpGs (8 smoking-related, 21 smoking-unrelated) associated with lung cancer. Models additionally adjusted for Comprehensive Smoking Index-(CSI) selected 1 smoking-related and 49 smoking-unrelated CpGs. Selected CpGs yielded excellent discriminatory performances, outperforming information provided by CSI only. Of the 8 selected smoking-related CpGs, two captured lung cancer-relevant effects of smoking that were missed by CSI. Further, the 50 CpGs identified in the CSI-adjusted model complementarily explained lung cancer risk. These markers may provide further insight into lung cancer carcinogenesis and help improving early identification of high-risk patients.

Journal article

Woelfe T, Linkohr B, Waterboer T, Thorand B, Seissler J, Chadeau M, Peters Aet al., 2022, Health impact of seven herpesviruses on (pre)diabetes incidence and HbA1c – results from the KORA cohort, Diabetologia, Vol: 65, Pages: 1328-1338, ISSN: 0012-186X

Introduction: T2D prevalence is increasing worldwide and previous studies suggested that itis higher in individuals seropositive for herpesviruses. This study examines the prospectiveassociation of herpesviruses with (pre)diabetes to evaluate their potential role in diabetesaetiology.Methods: Two follow–up examinations of the German population–based KORA cohort (F4and FF4) were used to identify participants with normal glucose tolerance at baseline at riskfor seven–year (pre)diabetes incidence (n=1257). All participants had repeated oral glucosetolerance tests and antibody measurements for herpes simplex virus (HSV) 1 & 2, varicella–zoster virus, Epstein–Barr virus, cytomegalovirus (CMV), and human herpesvirus 6 & 7.Regression models were used to evaluate the association linking serostatus with(pre)diabetes incidence and HbA1c.Results: HSV–2 and CMV were associated with (pre)diabetes incidence after adjustment forsex, age, BMI, education, smoking, physical activity, parental diabetes, hypertension, lipidlevels, insulin resistance, and fasting glucose. Seropositivity of both viruses was also cross–sectionally associated with higher HbA1c at baseline, with the association of HSV–2 beingindependent of confounders, including prevalence of (pre)diabetes itself. Whileseropositivity for multiple herpesviruses was associated with a higher incidence of(pre)diabetes, this association was not independent of confounders.Conclusion: The novel associations of HSV–2 and CMV serostatus with (pre)diabetesincidence indicate that these herpesviruses may contribute to the development of impairedglucose metabolism. Our results highlight the link between viruses and (pre)diabetes and theneed for more research evaluating viral prevention strategies.

Journal article

Jarvelin M-R, 2022, DNA methylation signature of chronic low-gradeinflammation and its role in cardio-respiratorydiseases, Nature Communications, Vol: 13, ISSN: 2041-1723

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Journal article

Said S, Karhunen V, vosa U, ligthart S, Bodinier B, Koskeridis F, welsh P, Alizadeh B, Daniel C, sattar N, Chadeau M, evalgelou E, Jarvelin M-R, Elliott P, Tzoulaki I, Dehghan Aet al., 2022, Genetic analysis of over half a million people characterises C-reactive protein loci, Nature Communications, Vol: 13, ISSN: 2041-1723

Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10−6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.

Journal article

Whitaker M, Elliott J, Chadeau M, Riley S, Darzi A, Cooke G, Ward H, Elliott Pet al., 2022, Persistent COVID-19 symptoms in a community study of 606,434 people in England, Nature Communications, Vol: 13, ISSN: 2041-1723

Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3–5 of the REACT-2 study (n=508,707; September 2020 – February 2021), a representative community survey of adults in England, and replication data from round 6 (n=97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3–5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3–5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.

Journal article

Chadeau-Hyam M, Wang H, Eales O, Haw D, Bodinier B, Whitaker M, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Donnelly CA, Elliott Pet al., 2022, SARS-CoV-2 infection and vaccine effectiveness in England (REACT-1): a series of cross-sectional random community surveys, The Lancet Respiratory Medicine, Vol: 10, Pages: 355-366, ISSN: 2213-2600

SummaryBackground England has experienced a third wave of the COVID-19 epidemic since the end of May, 2021, coincidingwith the rapid spread of the delta (B.1.617.2) variant, despite high levels of vaccination among adults. Vaccinationrates (single dose) in England are lower among children aged 16–17 years and 12–15 years, whose vaccination inEngland commenced in August and September, 2021, respectively. We aimed to analyse the underlying dynamicsdriving patterns in SARS-CoV-2 prevalence during September, 2021, in England.Methods The REal-time Assessment of Community Transmission-1 (REACT-1) study, which commenced datacollection in May, 2020, involves a series of random cross-sectional surveys in the general population of Englandaged 5 years and older. Using RT-PCR swab positivity data from 100 527 participants with valid throat and noseswabs in round 14 of REACT-1 (Sept 9–27, 2021), we estimated community-based prevalence of SARS-CoV-2 andvaccine effectiveness against infection by combining round 14 data with data from round 13 (June 24 to July 12, 2021;n=172 862).Findings During September, 2021, we estimated a mean RT-PCR positivity rate of 0·83% (95% CrI 0·76–0·89), with areproduction number (R) overall of 1·03 (95% CrI 0·94–1·14). Among the 475 (62·2%) of 764 sequenced positiveswabs, all were of the delta variant; 22 (4·63%; 95% CI 3·07–6·91) included the Tyr145His mutation in the spikeprotein associated with the AY.4 sublineage, and there was one Glu484Lys mutation. Age, region, key worker status,and household size jointly contributed to the risk of swab positivity. The highest weighted prevalence was observedamong children aged 5–12 years, at 2·32% (95% CrI 1·96–2·73) and those aged 13–17 years, at 2·55% (2·11–3·08).The SARS-CoV-2 epidemic grew in those aged 5–11 years, with an R of 1&m

Journal article

Chadeau-Hyam M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby J, Whitaker M, Elliott J, Haw D, Walters C, Atchison C, Diggle P, Page A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly C, Elliott Pet al., 2022, The Omicron SARS-CoV-2 epidemic in England during February 2022

Background The third wave of COVID-19 in England peaked in January 2022 resulting fromthe rapid transmission of the Omicron variant. However, rates of hospitalisations and deathswere substantially lower than in the first and second wavesMethods In the REal-time Assessment of Community Transmission-1 (REACT-1) study weobtained data from a random sample of 94,950 participants with valid throat and nose swabresults by RT-PCR during round 18 (8 February to 1 March 2022).Findings We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credibleinterval [CrI] 2.76–3.00), with a within-round reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) andadults aged 18 to 54 years, we observed a level or increasing weighted prevalence amongthose aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,195 positive sampleswith sublineages determined, only one (0.1% [0.0–0.5]) corresponded to AY.39 Deltasublineage and the remainder were Omicron: N=390, 32.7% (30.0–35.4) were BA.1; N=473,39.6% (36.8–42.5) were BA.1.1; and N=331, 27.7% (25.2–30.4) were BA.2. We estimated anR additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36–0.43). The highest proportionof BA.2 among positives was found in London.Interpretation In February 2022, infection prevalence in England remained high with levelor increasing rates of infection in older people and an uptick in hospitalisations. Ongoingsurveillance of both survey and hospitalisations data is required.Funding Department of Health and Social Care, England.

Working paper

Elliott P, Bodinier B, Eales O, Wang H, Haw D, Elliott J, Whitaker M, Jonnerby J, Tang D, Walters CE, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Chadeau-Hyam M, Donnelly CAet al., 2022, Rapid increase in Omicron infections in England during December 2021: REACT-1 study., Science, Vol: 375, Pages: eabn8347-eabn8347, ISSN: 0036-8075

The unprecedented rise in SARS-CoV-2 infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed prevalence of SARS-CoV-2 and its dynamics in England from end November to mid-December 2021 among almost 100,000 participants from the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, and an increasing proportion of infections due to Omicron. We observed large falls in swab positivity among mostly vaccinated older children (12-17 years) compared with unvaccinated younger children (5-11 years), and in adults who received a third (booster) vaccine dose vs. two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.

Journal article

Ronkainen J, Nedelec R, Atehortua A, Balkhiyarova Z, Cascarano A, Vien ND, Elhakeem A, van Enckevort E, Soares AG, Haakma S, Halonen M, Heil KF, Heiskala A, Hyde E, Jacquemin B, Keikkala E, Kerckhoffs J, Klavus A, Kopinska JA, Lepeule J, Marazzi F, Motoc I, Naatanen M, Ribbenstedt A, Rundblad A, Savolainen O, Simonetti V, Eadie NDT, Tzala E, Ulrich A, Wright T, Zarei I, d'Amico E, Belotti F, Brunius C, Castleton C, Charles M-A, Gaillard R, Hanhineva K, Hoek G, Holven KB, Jaddoe VWV, Kaakinen MA, Kajantie E, Kavousi M, Lakka T, Matthews J, Mortari AP, Vaarasmaki M, Voortman T, Webster C, Zins M, Atella V, Bulgheroni M, Chadeau-Hyam M, Conti G, Evans J, Felix JF, Heude B, Jarvelin M-R, Kolehmainen M, Landberg R, Lekadir K, Parusso S, Prokopenko I, de Rooij SR, Roseboom T, Swertz M, Timpson N, Ulven SM, Vermeulen R, Juola T, Sebert Set al., 2022, LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases, ENVIRONMENTAL EPIDEMIOLOGY, Vol: 6

Journal article

Elliott P, Eales O, Bodinier B, Tang D, Wang H, Jonnerby J, Haw D, Elliott J, Whitaker M, Walters C, Atchison C, Diggle P, Page A, Trotter A, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke G, Chadeau-Hyam M, Donnelly Cet al., 2022, Post-peak dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022

Background: Rapid transmission of the SARS-CoV-2 Omicron variant has led to the highestever recorded case incidence levels in many countries around the world.Methods: The REal-time Assessment of Community Transmission-1 (REACT-1) study hasbeen characterising the transmission of the SARS-CoV-2 virus using RT-PCR test results fromself-administered throat and nose swabs from randomly-selected participants in England atages 5 years and over, approximately monthly since May 2020. Round 17 data were collectedbetween 5 and 20 January 2022 and provide data on the temporal, socio-demographic andgeographical spread of the virus, viral loads and viral genome sequence data for positiveswabs.Results: From 102,174 valid tests in round 17, weighted prevalence of swab positivity was4.41% (95% credible interval [CrI], 4.25% to 4.56%), which is over three-fold higher than inDecember 2021 in England. Of 3,028 sequenced positive swabs, 2,393 lineages weredetermined and 2,374 (99.2%) were Omicron including 19 (0.80% of all Omicron lineages)cases of BA.2 sub-lineage and one BA.3 (0.04% of all Omicron) detected on 17 January 2022,and only 19 (0.79%) were Delta. The growth of the BA.2 Omicron sub-lineage against BA.1and its sub-lineage BA.1.1 indicated a daily growth rate advantage of 0.14 (95% CrI, 0.03,0.28) for BA.2, which corresponds to an additive R advantage of 0.46 (95% CrI, 0.10, 0.92).Within round 17, prevalence was decreasing overall (R=0.95, 95% CrI, 0.93, 0.97) butincreasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). Those 75 years andolder had a swab-positivity prevalence of 2.46% (95% CI, 2.16%, 2.80%) reflecting a highlevel of infection among a highly vulnerable group. Among the 3,613 swab-positiveindividuals reporting whether or not they had had previous infection, 2,334 (64.6%)reported previous confirmed COVID-19. Of these, 64.4% reported a positive test from 1 to30 days before their swab date. Risks of infection were increased among essential/keyworkers

Working paper

Elliott P, Bodinier B, Eales O, Wang H, Haw D, Elliott J, Whitaker M, Jonnerby J, Tang D, Walters C, Atchison C, Diggle P, Page A, Trotter A, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke G, Chadeau-Hyam M, Donnelly Cet al., 2021, Rapid increase in Omicron infections in England during December 2021: REACT-1 study

Background: The highest-ever recorded numbers of daily severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in England has been observed during December 2021 and have coincided with a rapid rise in the highly transmissible Omicron variant despite high levels of vaccination in the population. Although additional COVID-19 measures have beenintroduced in England and internationally to contain the epidemic, there remains uncertainty about the spread and severity of Omicron infections among the general population.Methods: The REal-time Assessment of Community Transmission–1 (REACT-1) study has been monitoring the prevalence of SARS-CoV-2 infection in England since May 2020.REACT-1 obtains self-administered throat and nose swabs from a random sample of the population of England at ages 5 years and over. Swabs are tested for SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) and samples testing positive are sent for viral genome sequencing. To date 16 rounds have been completed, each including~100,000 or more participants with data collected over a period of 2 to 3 weeks per month.Socio-demographic, lifestyle and clinical information (including previous history of COVID-19 and symptoms prior to swabbing) is collected by online or telephone questionnaire. Here we report results from round 14 (9-27 September 2021), round 15 (19 October - 05 November2021) and round 16 (23 November - 14 December 2021) for a total of 297,728 participants with a valid RT-PCR test result, of whom 259,225 (87.1%) consented for linkage to their NHS records including detailed information on vaccination (vaccination status, date). We usedthese data to estimate community prevalence and trends by age and region, to evaluate vaccine effectiveness against infection in children ages 12 to 17 years, and effect of a third (booster) dose in adults, and to monitor the emergence of the Omicron variant in England.Results: We observed a high overall prevalen

Working paper

Chadeau M, Wang H, Eales O, Haw D, Bodinier B, Whitaker M, Walters C, Ainslie K, Atchison C, Fronterre C, Diggle P, Page A, Trotter A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Donnelly C, Elliott Pet al., 2021, Randomised community surveys of SARS-CoV-2 infection and vaccine effectiveness in England: REACT-1 study., The Lancet Respiratory Medicine, ISSN: 2213-2600

Background: England experienced a third wave of the COVID-19 epidemic from end May 2021 coinciding with the rapid spread of Delta variant despite high levels of vaccination among adults. Vaccination rates (single-dose) are lower among children aged 16-17 and 12-15 years whose vaccination in England commenced in August and September respectively. Methods: The REACT-1 study involves a series of random cross-sectional surveys in the general population of England aged 5 years and over. Using RT-PCR swab-positivity data from (N=100,527) participants with valid swabs in round 14 (9 to 27 September 2021), we estimated community-based prevalence of SARS-CoV-2 and vaccine effectiveness against infection by combining data with round 13 (24 June to 12 July 2021, N=172,862).Findings: During September 2021 we estimated a mean RT-PCR positivity rate of 0.83% (0.76%, 0.89%) with a reproduction number R overall of 1.03 (0.94, 1.14). Among the 475 sequenced positive swabs, all were Delta variant; 22 (4.63%) included the Y145H mutation in the spike protein associated with the AY.4 sub-lineage, and there was one E484K mutation. Age, region, key worker status, and household size jointly contributed to the risk of swab-positivity. The highest weighted prevalence was observed among children aged 5-12 years at 2.32% (1.96%, 2.73%) and 13-17 years at 2.55% (2.11%, 3.08%). The epidemic grew in those aged 5-11 years with R of 1.42, but decreased in those aged 18-54. At ages 18-64 years, the adjusted vaccine effectiveness against infection was 62.8% (49.3%, 72.7%) after two doses compared to unvaccinated people, for all vaccines combined, and 44.8% (22.5%, 60.7%) and 71.3% (56.6%, 81.0%) for AstraZeneca and Pfizer-BioNTech, respectively. At ages >18 years, weighted prevalence of swab-positivity was 0.35% (0.31%, 0.40%) if second dose was <3 months before their swab but 0.55% (0.50%, 0.61%) for those who received their second dose 3-6 months prior, compared to 1.76% (1.60%, 1.95%) among

Journal article

Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Walters C, Jonnerby J, Atchison C, Diggle P, Page A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly C, Elliott Pet al., 2021, REACT-1 round 15 final report: Increased breakthrough SARS-CoV-2 infections among adults who had received two doses of vaccine, but booster doses and first doses in children are providing important protection

Background: It has been nearly a year since the first vaccinations against SARS-CoV-2were delivered in England. The third wave of COVID-19 in England began in May 2021 asthe Delta variant began to outcompete and largely replace other strains. The REal-timeAssessment of Community Transmission-1 (REACT-1) series of community surveys forSARS-CoV-2 infection has provided insights into transmission dynamics since May 2020.Round 15 of the REACT-1 study was carried out from 19 October to 5 November 2021.Methods: We estimated prevalence of SARS-CoV2 infection and used multiple logisticregression to analyse associations between SARS-CoV-2 infection in England anddemographic and other risk factors, based on RT-PCR results from self-administered throatand nose swabs in over 100,000 participants. We estimated (single-dose) vaccineeffectiveness among children aged 12 to 17 years, and among adults comparedswab-positivity in people who had received a third (booster) dose with those who hadreceived two vaccine doses. We used splines to analyse time trends in swab-positivity.Results: During mid-October to early-November 2021, weighted prevalence was 1.57%(1.48%, 1.66%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14).Weighted prevalence increased between rounds 14 and 15 across most age groups(including older ages, 65 years and over) and regions, with average reproduction numberacross rounds of R=1.09 (1.08, 1.11). During round 15, there was a fall in prevalence from amaximum around 20-21 October, with an R of 0.76 (0.70, 0.83), reflecting falls in prevalenceat ages 17 years and below and 18 to 54 years. School-aged children had the highestweighted prevalence of infection: 4.95% (4.39%, 5.58%) in those aged 5 to 12 years and5.21% (4.61%, 5.87%) in those aged 13 to 17 years. In multiple logistic regression, age, sex,key worker status and presence of one or more children in the home were associated withswab positivity. There was evidence of heterogeneity between rounds in

Working paper

Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Walters C, Atchison C, Diggle P, Page A, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly C, Elliott Pet al., 2021, REACT-1 round 15 interim report: Exponential rise in prevalence of SARS-CoV-2 infection in England from end September 2021 followed by dip during October 2021

Background: The third wave of COVID-19 in England coincided with the rapid spread of theDelta variant of SARS-CoV-2 from the end of May 2021. Case incidence data from thenational testing programme (Pillar 2) in England may be affected by changes in testingbehaviour and other biases. Community surveys may provide important contextualinformation to inform policy and the public health response.Methods: We estimated patterns of community prevalence of SARS-CoV-2 infection inEngland using RT-PCR swab-positivity, demographic and other risk factor data from round15 (interim) of the REal-time Assessment of Community Transmission-1 (REACT-1) study(round 15a, carried out from 19 to 29 October 2021). We compared these findings with thosefrom round 14 (9 to 27 September 2021).Results: During mid- to late-October 2021 (round 15a) weighted prevalence was 1.72%(1.61%, 1.84%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). Theoverall reproduction number (R) from round 14 to round 15a was 1.12 (1.11, 1.14) withincreases in prevalence over this period (September to October) across age groups andregions except Yorkshire and The Humber. However, within round 15a (mid- to late-October)there was evidence of a fall in prevalence with R of 0.76 (0.65, 0.88). The highest weightedprevalence was observed among children aged 5 to 12 years at 5.85% (5.10%, 6.70%) and13 to 17 years at 5.75% (5.02%, 6.57%). At regional level, there was an almost four-foldincrease in weighted prevalence in South West from round 14 at 0.59% (0.43%,0.80%) toround 15a at 2.18% (1.84%, 2.58%), with highest smoothed prevalence at subregional levelalso found in South West in round 15a. Age, sex, key worker status, and presence ofchildren in the home jointly contributed to the risk of swab-positivity. Among the 126sequenced positive swabs obtained up until 23 October, all were Delta variant; 13 (10.3%)were identified as the AY.4.2 sub-lineage.Discussion: We observed the highest overall prevalence of swab-p

Working paper

Chadeau-Hyam M, Wang H, Eales O, Haw D, Bodinier B, Whitaker M, Walters C, Ainslie K, Atchison C, Fronterre C, Diggle P, Page A, Trotter A, COG-UK TCGUKC, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Donnelly C, Elliott Pet al., 2021, REACT-1 study round 14: High and increasing prevalence of SARS-CoV-2 infection among school-aged children during September 2021 and vaccine effectiveness against infection in England

Background: England experienced a third wave of the COVID-19 epidemic from end May2021 coinciding with the rapid spread of Delta variant. Since then, the population eligible forvaccination against COVID-19 has been extended to include all 12-15-year-olds, and abooster programme has been initiated among adults aged 50 years and over, health careand care home workers, and immunocompromised people. Meanwhile, schoolchildren havereturned to school often with few COVID-19-related precautions in place.Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study,throat and nose swabs were sent to non-overlapping random samples of the populationaged 5 years and over in England. We analysed prevalence of SARS-CoV-2 using reversetranscription-polymerase chain reaction (RT-PCR) swab-positivity data from REACT-1 round14 (between 9 and 27 September 2021). We combined results for round 14 with round 13(between 24 June and 12 July 2021) and estimated vaccine effectiveness and prevalence ofswab-positivity among double-vaccinated individuals. Unlike all previous rounds, in round 14,we switched from dry swabs transported by courier on a cold chain to wet swabs usingsaline. Also, at random, 50% of swabs (not chilled until they reached the depot) weretransported by courier and 50% were sent through the priority COVID-19 postal service.Results: We observed stable or rising prevalence (with an R of 1.03 (0.94, 1.14) overall)during round 14 with a weighted prevalence of 0.83% (0.76%, 0.89%). The highest weightedprevalence was found in children aged 5 to 12 years at 2.32% (1.96%, 2.73%) and 13 to 17years at 2.55% (2.11%, 3.08%). All positive virus samples analysed correspond to the Deltavariant or sub-lineages of Delta with one instance of the E484K escape mutation detected.The epidemic was growing in those aged 17 years and under with an R of 1.18 (1.03, 1.34),but decreasing in those aged 18 to 54 years with an R of 0.81 (0.68, 0.97). For allparticipants and all vaccin

Working paper

Misra N, Bastien P, Bourokba N, Chadeau-Hyam M, Cavusoglu Net al., 2021, Metabolomics, a tool to construe skin phenotype, Publisher: ELSEVIER SCIENCE INC, Pages: S162-S162, ISSN: 0022-202X

Conference paper

Elliott J, Whitaker M, Bodinier B, Eales O, Riley S, Ward H, Cooke G, Darzi A, Chadeau M, Elliott Pet al., 2021, Predictive symptoms for COVID-19 in the community: REACT-1 study of over one million people, PLoS Medicine, Vol: 18, Pages: 1-14, ISSN: 1549-1277

Background:Rapid detection, isolation and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and whether predictive symptoms differ between B.1.1.7 (Alpha) lineage (predominating as of April 2021in the USA, UK and elsewhere) and wild type.Methods and Findings:We obtained throat and nose swabs with valid SARS-CoV-2 polymerase chain reaction (PCR) test results from 1,147,370 volunteers aged 5 years and above (6,450 positives) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least one symptom identified seven symptoms as jointly and positively predictive of PCR positivity in rounds 2–7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss and muscle aches. The resulting model (rounds 2–7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same seven symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. Main

Journal article

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