Publications
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Viney W, Day S, Bruton J, et al., 2022, Personalising clinical pathways in a London breast cancer service, Sociology of Health and Illness: a journal of medical sociology, Vol: 44, Pages: 624-640, ISSN: 0141-9889
Using interview and observational data from a busy and research-intensive breast cancer service in the United Kingdom, we discuss recent developments in personalised medicine. Specifically, we show how clinical and research practices meet in clinical pathways that are reconfigured in response to changing approaches of diagnosing, monitoring, treating and understanding cancers. Clinical pathways are increasingly sensitive to changes in evidence deduced through new technologies and therapies as well as decisions based on intensive, iterative analysis of data collected across a range of platforms. We contribute to existing research by showing how the organisation of clinical pathways both maintains established clinical practices and responds to new research evidence, managing a threshold between evidence-based and experimental medicine. Finally, we invite comparisons with other forms of personalisation to understand how they depend on the ‘real time’ collection, analysis and application of data.
Elliott P, Bodinier B, Eales O, et 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.
Eales O, Ainslie KEC, Walters CE, et al., 2022, Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number
<jats:title>Abstract</jats:title><jats:p>The time-varying reproduction number (<jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub>) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub> from case data. However, these are not easily adapted to point prevalence data nor can they infer <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub> across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020 – December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats:bold><jats:italic>t</jats:italic></jats:bold></jats:sub> over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in <jats:bold><jats:italic>R</jats:italic></jats:bold><jats:sub><jats
Elliott P, Eales O, Bodinier B, et 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
Routen A, O'Mahoney L, Ayoubkhani D, et al., 2022, Understanding and tracking the impact of long COVID in the United Kingdom, NATURE MEDICINE, Vol: 28, Pages: 11-15, ISSN: 1078-8956
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Barker C, Collet K, Gbesemete D, et al., 2022, Public attitudes to a human challenge study with SARS-CoV-2: a mixed-methods study., Wellcome Open Res, Vol: 7, ISSN: 2398-502X
Background: Human challenge studies involve the deliberate exposure of healthy volunteers to an infectious micro-organism in a highly controlled and monitored way. They are used to understand infectious diseases and have contributed to the development of vaccines. In early 2020, the UK started exploring the feasibility of establishing a human challenge study with SARS-CoV-2. Given the significant public interest and the complexity of the potential risks and benefits, it is vital that public views are considered in the design and approval of any such study and that investigators and ethics boards remain accountable to the public. Methods: Mixed methods study comprising online surveys conducted with 2,441 UK adults and in-depth virtual focus groups with 57 UK adults during October 2020 to explore the public's attitudes to a human challenge study with SARS-CoV-2 taking place in the UK. Results: There was overall agreement across the surveys and focus groups that a human challenge study with SARS-CoV-2 should take place in the UK. Transparency of information, trust and the necessity to provide clear information on potential risks to study human challenge study participants were important. The perceived risks of taking part included the risk of developing long-term effects from COVID, impact on personal commitments and mental health implications of isolation. There were a number of practical realities to taking part that would influence a volunteer's ability to participate (e.g. Wi-Fi, access to exercise, outside space and work, family and pet commitments). Conclusions: The results identified practical considerations for teams designing human challenge studies. Recommendations were grouped: 1) messaging to potential study participants, 2) review of the protocol and organisation of the study, and 3) more broadly, making the study more inclusive and relevant. This study highlights the value of public consultation in research, particularly in fields attracting public intere
Elliott P, Bodinier B, Eales O, et 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
Cann A, Clarke C, Brown J, et al., 2021, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study, Publisher: Wellcome Open Research
Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.
Eales O, Page AJ, de Oliveira Martins L, et al., 2021, 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
<jats:title>Abstract</jats:title><jats:p>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. Here 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. From 9 to 27 September 2021 (round 14) and 19 October to 5 November 2021 (round 15), all lineages sequenced within REACT-1 were Delta or a Delta sub-lineage with 44 unique lineages identified. The proportion of the original Delta variant (B.1.617.2) was found to be increasing between September and November 2021, which may reflect an increasing number of sub-lineages which have yet to be identified. The proportion of B.1.617.2 was greatest in London, which was further identified as a region with an increased level of genetic diversity. The Delta sub-lineage AY.4.2 was found to be robustly increasing in proportion, with a reproduction number 15% (8%, 23%) greater than its parent and most prevalent lineage, AY.4. 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. Though no difference in the viral load based on cycle threshold (Ct) values was identified, a lower proportion of those infected with AY.4.2 had symptoms for which testing is usually recommend (loss or change of sense of taste, loss or change of sense of smell, new persistent cough, fever), compared to AY.4 (p = 0.026). The evolutionary rate of SARS-CoV-2, as measured by the mutation rate, was fou
Ward H, Flower B, Garcia PJ, et al., 2021, Global surveillance, research, and collaboration needed to improve understanding and management of long COVID, The Lancet, Vol: 398, Pages: 2057-2059, ISSN: 0140-6736
Redd R, Cooper E, Atchison C, et al., 2021, Behavioural responses to SARS-CoV-2 antibody testing in England: REACT-2 study, Wellcome Open Research, Vol: 6, Pages: 203-203
<ns5:p><ns5:bold>Background: </ns5:bold>This study assesses the behavioural responses to SARS-CoV-2 antibody test results as part of the REal-time Assessment of Community Transmission-2 (REACT-2) research programme, a large community-based surveillance study of antibody prevalence in England.</ns5:p><ns5:p> <ns5:bold>Methods:</ns5:bold> A follow-up survey was conducted six weeks after the SARS-CoV-2 antibody test. The follow-up survey included 4500 people with a positive result and 4039 with a negative result. Reported changes in behaviour were assessed using difference-in-differences models. A nested interview study was conducted with 40 people to explore how they thought through their behavioural decisions.</ns5:p><ns5:p> <ns5:bold>Results:</ns5:bold> While respondents reduced their protective behaviours over the six weeks, we did not find evidence that positive test results changed participant behaviour trajectories in relation to the number of contacts the respondents had, for leaving the house to go to work, or for leaving the house to socialise in a personal place. The qualitative findings supported these results. Most people did not think that they had changed their behaviours because of their test results, however they did allude to some changes in their attitudes and perceptions around risk, susceptibility, and potential severity of symptoms.</ns5:p><ns5:p> <ns5:bold>Conclusions: </ns5:bold>We found limited evidence that knowing your antibody status leads to behaviour change in the context of a research study. While this finding should not be generalised to widespread self-testing in other contexts, it is reassuring given the importance of large prevalence studies, and the practicalities of doing these at scale using self-testing with lateral flow immunoassay (LFIA).</ns5:p>
Chadeau-Hyam M, Eales O, Bodinier B, et 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
Chadeau-Hyam M, Eales O, Bodinier B, et 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
Elliott P, Haw D, Wang H, et al., 2021, Exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant, Science, Vol: 374, Pages: 1-11, ISSN: 0036-8075
SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.
Wilson J, Wallace H, Loftus-Keeling M, et al., 2021, Swab-yourself trial with economic monitoring and testing for infections collectively (SYSTEMATIC): Part 1. A diagnostic accuracy, and cost-effectiveness, study comparing clinician-taken versus self-taken rectal and pharyngeal samples for the diagnosis of gonorrhoea and chlamydia, Clinical Infectious Diseases, Vol: 73, Pages: e3172-e3180, ISSN: 1058-4838
BackgroundUrogenital testing misses extragenital Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). Extragenital self-sampling is frequently undertaken despite no robust RCT evidence of efficacy. We compared clinician-taken rectal and pharyngeal samples with self-taken samples for diagnostic accuracy and cost in MSM and females.MethodsProspective, convenience, sample in UK sexual health clinic. Randomised order of clinician and self-samples from pharynx and rectum, plus first catch urine (MSM) and vulvovaginal swabs (females), for NG/CT detection.ResultsOf 1793 participants (1284 females, 509 MSM), 116 had NG detected (75 urogenital site, 83 rectum, 72 pharynx); 9.4% infected females and 67.3% MSM were urogenital negative. 276 had CT detected (217 urogenital site, 249 rectum, 63 pharynx); 13.1% infected females and 71.8% MSM were urogenital negative. Sexual history did not identify those with rectal infections. Clinician-rectal and self-rectal positive percent agreements (PPA) for NG detection were 92.8% and 97.6%; clinician-rectal, and self-rectal PPA for CT detection were 95.6% and 97.2%. There was no difference in diagnostic accuracy between clinician and self-taken samples.Clinicians performed swabs quicker than participants so costs were lower. However, in asymptomatic people, non-qualified clinicians would oversee self-swabbing and these costs would be lower than clinician’s.ConclusionsThere was no difference in diagnostic accuracy of clinician compared with self-taken extragenital samples. Sexual history did not identify those with rectal infections so individuals should have extragenital clinician, or self-taken, samples. Clinician swabs cost less than self-swabs but in asymptomatic people, or doing home testing, their costs would be lower than clinician swabs.
Delisle TG, D'Souza N, Davies B, et al., 2021, PATIENT PERCEPTION OF FIT IN THE DIAGNOSTIC PATHWAY FOR COLORECTAL CANCER: A MIXED METHOD STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A166-A166, ISSN: 0017-5749
van Bergen JEAM, Hoenderboom BM, David S, et al., 2021, Where to go to in chlamydia control? From infection control towards infectious disease control, SEXUALLY TRANSMITTED INFECTIONS, Vol: 97, Pages: 501-506, ISSN: 1368-4973
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Udeh-Momoh C, Watermeyer T, Sindi S, et al., 2021, Health, lifestyle and psycho-social determinants of poor sleep quality during the Early Phase of the COVID-19 pandemic: a focus on UK older adults deemed clinically extremely vulnerable, Frontiers in Public Health, Vol: 9, Pages: 1-11, ISSN: 2296-2565
Background: Several studies have assessed the impact of COVID-19-relatedlockdownson sleep quality across global populations. However, no study to date has specifically assessed at-riskpopulations, particularly those at highest risk of complications from coronavirus infection deemed “clinically-extremely-vulnerable-(COVID-19CEV)” [as defined by Public Health England, 2020].Methods: In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio demographic factors. We examined associations between these variablesand sleep quality;and explored interactions of COVID-19CEV status with significant predictors of poor sleep,to identify potential moderating factors. Results: 37% of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19 CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19 CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep. Conclusions: Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a &ldquo
Piggin M, Johnson H, Jayacodi S, et al., 2021, Insight report: public involvement to inform the NIHR Imperial Biomedical Research Centre Reapplication 2022 to 2027, Public Involvement to inform the NIHR Imperial Biomedical Research Centre Reapplication 2022 to 2027
Piggin M, Johnson H, Shovlin C, et al., 2021, Insight report: Online public involvement session on research exploring social, genetic, and environmental determinants of health
Chadeau-Hyam M, Wang H, Eales O, et 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
Davies B, Araghi M, Moshe M, et al., 2021, Acceptability, usability and performance of lateral flow immunoassay tests for SARS-CoV-2 antibodies: REACT-2 study of self-testing in non-healthcare key workers, Open Forum Infectious Diseases, Vol: 8, ISSN: 2328-8957
Background Seroprevalence studies are essential to understand the epidemiology of SARS-CoV-2. Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests. Methods In June 2020, current and former members of the UK Police forces and Fire service performed a self-test lateral flow immunoassay (LFIA), had a nurse-performed LFIA and provided a venous blood sample for ELISA . We present the prevalence of antibodies to SARS-CoV-2; the acceptability and usability of self-test LFIAs; and determine the sensitivity and specificity of LFIAs compared to laboratory ELISA. Results In this cohort of 5189 current and former members of the Police service and 263 members of the Fire service, 7.4% (396/5,348; 95% CI, 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (6.9-11.4) in those under 40 years, 11.5% (8.8-15.0) in those of non-white ethnicity and 7.8% (7.1-8.7) in those currently working. Self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 0.77-0.83). The LFIAs had a similar performance: compared to ELISA, sensitivity was 82.1% (77.7-86.0) self-test and 76.4% (71.9-80.5) nurse-performed with specificity of 97.8% (97.3-98.2) and 98.5% (98.1-98.8) respectively. Conclusion A greater proportion of this non-healthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (5.8-6.1) following the first wave in England. The high acceptability and usability reported by participants and similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home-testing in occupational and community prevalence studies.
Papageorgiou V, Jones K, Halliday B, et al., 2021, A qualitative exploration of participant and investigator perspectives from the TRED-HF trial, ESC Heart Failure, Vol: 8, Pages: 3760-3768, ISSN: 2055-5822
Aim We explored the experiences and motivations of participants and staff who took part in the TRED-HF trial (Therapy withdrawal in REcovered Dilated cardiomyopathy). MethodsWe conducted a qualitative study, using semi-structured interviews, with participants (n=12) and the research team (n=4) from the TRED-HF trial. Interviews were carried out in 2019 and were audio-recorded and transcribed. Data were managed using NVivo and analysed using framework analysis. A patient representative provided guidance on the interpretation of findings and presentation of themes to ensure these remained meaningful, and an accurate representation, to those living with dilated cardiomyopathy.ResultsThree key themes emerged from the data: (1) perception of health; (2) experiences and relationships with healthcare services and researchers; and (3) perception of risk. Study participants held differing perceptions of their health; some did not consider themselves to have a heart condition or disagreed with the medical term ‘heart failure’. Relationships between participants, research staff and clinical management teams influenced participants’ experiences and decision-making during the trial, including following clinical advice. There were differences in participants’ perceptions of risk and their decisions to take heart failure medication after the trial was completed. Although the original TRED-HF trial did not provide the results many had hoped for, a strong motivator for taking part was the opportunity to withdraw medication in a safely monitored environment which had been previously considered by some participants before. Investigators acknowledged that the insights gained from the study can now be used to support evidence-based conversations with patients.Conclusion For people whose dilated cardiomyopathy is in remission, decisions to continue, reduce or stop their medication are influenced by perceptions of personal health, perceive risk and the important o
Elliott J, Whitaker M, Bodinier B, et 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
Eales O, Walters C, Wang H, et al., 2021, Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2
BackgroundCommunity surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administeredthroat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community.MethodsDuring round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines.ResultsWe estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportionof positive individuals detected on first swab, was found to be higher 𝑃 for those with an 0 initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in socialdistancing measures.DiscussionHome self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has hig
Redd R, Cooper E, Atchison C, et al., 2021, Behavioural responses to SARS-CoV-2 antibody testing in England: REACT-2 study, Wellcome Open Research, Vol: 6, Pages: 1-10, ISSN: 2398-502X
Background: This study assesses the behavioural responses to SARS-CoV-2 antibody test results as part of the REal-time Assessment of Community Transmission-2 (REACT-2) research programme, a large community-based surveillance study of antibody prevalence in England.Methods: A follow-up survey was conducted six weeks after the SARS-CoV-2 antibody test. The follow-up survey included 4500 people with a positive result and 4039 with a negative result. Reported changes in behaviour were assessed using difference-in-differences models. A nested interview study was conducted with 40 people to explore how they thought through their behavioural decisions.Results: While respondents reduced their protective behaviours over the six weeks, we did not find evidence that positive test results changed participant behaviour trajectories in relation to the number of contacts the respondents had, for leaving the house to go to work, or for leaving the house to socialise in a personal place. The qualitative findings supported these results. Most people did not think that they had changed their behaviours because of their test results, however they did allude to some changes in their attitudes and perceptions around risk, susceptibility, and potential severity of symptoms.Conclusions: We found limited evidence that knowing your antibody status leads to behaviour change in the context of a research study. While this finding should not be generalised to widespread self-testing in other contexts, it is reassuring given the importance of large prevalence studies, and the practicalities of doing these at scale using self-testing with lateral flow immunoassay (LFIA).
Elliott P, Haw D, Wang H, et al., 2021, REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during May to July 2021
BackgroundThe prevalence of SARS-CoV-2 infection continues to drive rates of illness andhospitalisations despite high levels of vaccination, with the proportion of cases caused by theDelta lineage increasing in many populations. As vaccination programs roll out globally andsocial distancing is relaxed, future SARS-CoV-2 trends are uncertain.MethodsWe analysed prevalence trends and their drivers using reverse transcription-polymerasechain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June2021) and round 13 (between 24 June and 12 July 2021) of the REal-time Assessment ofCommunity Transmission-1 (REACT-1) study, with swabs sent to non-overlapping randomsamples of the population ages 5 years and over in England.ResultsWe observed sustained exponential growth with an average doubling time in round 13 of 25days (lower Credible Interval of 15 days) and an increase in average prevalence from 0.15%(0.12%, 0.18%) in round 12 to 0.63% (0.57%, 0.18%) in round 13. The rapid growth acrossand within rounds appears to have been driven by complete replacement of Alpha variant byDelta, and by the high prevalence in younger less-vaccinated age groups, with a nine-foldincrease between rounds 12 and 13 among those aged 13 to 17 years. Prevalence amongthose who reported being unvaccinated was three-fold higher than those who reported beingfully vaccinated. However, in round 13, 44% of infections occurred in fully vaccinatedindividuals, reflecting imperfect vaccine effectiveness against infection despite high overalllevels of vaccination. Using self-reported vaccination status, we estimated adjusted vaccineeffectiveness against infection in round 13 of 49% (22%, 67%) among participants aged 18to 64 years, which rose to 58% (33%, 73%) when considering only strong positives (Cyclethreshold [Ct] values < 27); also, we estimated adjusted vaccine effectiveness againstsymptomatic infection of 59% (23%, 78%), with any one of three common COVID-19symptoms reported
Ward H, Atchison C, Whitaker M, et al., 2021, Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The second wave of infection in England is apparen
Papageorgiou V, Bruton J, Petretti S, et al., 2021, Impact of COVID-19 on the HIV care continuum in the United Kingdom, 11th IAS Conference on HIV Science, Publisher: IAS
Cann A, Clarke C, Brown J, et al., 2021, SARS-CoV-2 Antibody Lateral Flow Assay for antibody prevalence studies following vaccine roll out: a Diagnostic Accuracy Study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Lateral flow immunoassays (LFIAs) have the potential to deliver affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of SARS-CoV-2 vaccine.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This is a prospective diagnostic accuracy study.</jats:p><jats:sec><jats:title>Setting</jats:title><jats:p>Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Laboratory analyses were performed across Imperial College London sites and university facilities.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following SARS-CoV-2 vaccine booster, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination, and 21 day follow up. A total of 186 paired samples were collected.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>During the participants visit, capillary blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title>&
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