Search

Background The Omicron B.1.1.529 variant increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in doubly vaccinated individuals, particularly in the Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1) recipients. To tackle infections, the UK’s booster vaccination programmes used messenger ribonucleic acid (mRNA) vaccines irrespective of an individual’s primary course vaccine type, and prioritized the clinically vulnerable. These mRNA vaccines included the Pfizer–BioNTech COVID-19 vaccine (BNT162b2) the Moderna COVID-19 vaccine (mRNA-1273). There is limited understanding of the effectiveness of different primary vaccination courses on mRNA booster vaccines against SARs-COV-2 infections and how time-varying confounders affect these evaluations. Methods Trial emulation was applied to a prospective community observational cohort in England and Wales to reduce time-varying confounding-by-indication driven by prioritizing vaccination based upon age, vulnerability and exposure. Trial emulation was conducted by meta-analysing eight adult cohort results whose booster vaccinations were staggered between 16 September 2021 and 05 January 2022 and followed until 23 January 2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end of study was modelled using Cox proportional hazard models and adjusted for age, sex, minority ethnic status, clinically vulnerability and deprivation. Results A total of 19 159 participants were analysed, with 11 709 ChAdOx1 primary courses and 7450 BNT162b2 primary courses. Median age, clinical vulnerability status and infection rates fluctuate through time. In mRNA-boosted adults, 7.4% (n = 863) of boosted adults with a ChAdOx1 primary course experienced a SARS-CoV-2 infection compared with 7.7% (n = 571) of those who had BNT162b2 as a primary course. The pooled adjusted hazard ratio (aHR) was 1.01 with a 95% confidence interval (CI) of: 0.90 to 1.13. Conclusion After an mRNA booster dose, we found no difference in protection comparing those with a primary course of BNT162b2 with those with a ChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection.

Purpose We aimed to understand which non-household activities increased infection odds and contributed greatest to SARS-CoV-2 infections following the lifting of public health restrictions in England and Wales. Procedures We undertook multivariable logistic regressions assessing the contribution to infections of activities reported by adult Virus Watch Community Cohort Study participants. We calculated adjusted weighted population attributable fractions (aPAF) estimating which activity contributed greatest to infections. Findings Among 11 413 participants (493 infections), infection was associated with: leaving home for work (aOR 1.35 (1.11–1.64), aPAF 17%), public transport (aOR 1.27 (1.04–1.57), aPAF 12%), shopping once (aOR 1.83 (1.36–2.45)) vs. more than three times a week, indoor leisure (aOR 1.24 (1.02–1.51), aPAF 10%) and indoor hospitality (aOR 1.21 (0.98–1.48), aPAF 7%). We found no association for outdoor hospitality (1.14 (0.94–1.39), aPAF 5%) or outdoor leisure (1.14 (0.82–1.59), aPAF 1%). Conclusion Essential activities (work and public transport) carried the greatest risk and were the dominant contributors to infections. Non-essential indoor activities (hospitality and leisure) increased risk but contributed less. Outdoor activities carried no statistical risk and contributed to fewer infections. As countries aim to ‘live with COVID’, mitigating transmission in essential and indoor venues becomes increasingly relevant.

BackgroundDifferential exposure to public activities may contribute to stark deprivation-related inequalities in SARS-CoV-2 infection and outcomes but has not been directly investigated. We set out to investigate whether participants in Virus Watch—a large community cohort study based in England and Wales—reported differential exposure to public activities and non-household contacts during the autumn–winter phase of the COVID-19 pandemic according to postcode-level socioeconomic deprivation.MethodsParticipants (n=20 120–25 228 across surveys) reported their daily activities during 3 weekly periods in late November 2020, late December 2020 and mid-February 2021. Deprivation was quantified based on participants’ residential postcode using English or Welsh Index of Multiple Deprivation quintiles. We used Poisson mixed-effect models with robust standard errors to estimate the relationship between deprivation and risk of exposure to public activities during each survey period.ResultsRelative to participants in the least deprived areas, participants in the most deprived areas exhibited elevated risk of exposure to vehicle sharing (adjusted risk ratio (aRR) range across time points: 1.73–8.52), public transport (aRR: 3.13–5.73), work or education outside of the household (aRR: 1.09–1.21), essential shops (aRR: 1.09–1.13) and non-household contacts (aRR: 1.15–1.19) across multiple survey periods.ConclusionDifferential exposure to essential public activities—such as attending workplaces and visiting essential shops—is likely to contribute to inequalities in infection risk and outcomes. Public health interventions to reduce exposure during essential activities and financial and practical support to enable low-paid workers to stay at home during periods of intense transmission may reduce COVID-related inequalities.

Vaccination constitutes the best long-term solution against Coronavirus Disease-2019; however, vaccine-derived immunity may not protect all groups equally, and the durability of protective antibodies may be short. We evaluate Spike-antibody responses following BNT162b2 or ChAdOx1-S vaccination amongst SARS-CoV2-naive adults across England and Wales enrolled in a prospective cohort study (Virus Watch). Here we show BNT162b2 recipients achieved higher peak antibody levels after two doses; however, both groups experience substantial antibody waning over time. In 8356 individuals submitting a sample ≥28 days after Dose 2, we observe significantly reduced Spike-antibody levels following two doses amongst individuals reporting conditions and therapies that cause immunosuppression. After adjusting for these, several common chronic conditions also appear to attenuate the antibody response. These findings suggest the need to continue prioritising vulnerable groups, who have been vaccinated earliest and have the most attenuated antibody responses, for future boosters.

A range of studies globally demonstrate that the effectiveness of SARS-CoV-2 vaccines wane over time, but the total effect of anti-S antibody levels on risk of SARS-CoV-2 infection and whether this varies by vaccine type is not well understood. Here we show that anti-S levels peak three to four weeks following the second dose of vaccine and the geometric mean of the samples is nine fold higher for BNT162b2 than ChAdOx1. Increasing anti-S levels are associated with a reduced risk of SARS-CoV-2 infection (Hazard Ratio 0.85; 95%CIs: 0.79-0.92). We do not find evidence that this antibody relationship with risk of infection varies by second dose vaccine type (BNT162b2 vs. ChAdOx1). In keeping with our anti-S antibody data, we find that people vaccinated with ChAdOx1 had 1.64 times the odds (95% confidence interval 1.45-1.85) of a breakthrough infection compared to BNT162b2. We anticipate our findings to be useful in the estimation of the protective effect of anti-S levels on risk of infection due to Delta. Our findings provide evidence about the relationship between antibody levels and protection for different vaccines and will support decisions on optimising the timing of booster vaccinations and identifying individuals who should be prioritised for booster vaccination, including those who are older, clinically extremely vulnerable, or received ChAdOx1 as their primary course. Our finding that risk of infection by anti-S level does not interact with vaccine type, but that individuals vaccinated with ChAdOx1 were at higher risk of infection, provides additional support for the use of using anti-S levels for estimating vaccine efficacy.

Background: The two most common SARS-CoV-2 vaccines in the UK, BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca), employ different immunogenic mechanisms. Compared to BNT162b2, two-dose immunisation with ChAdOx1 induces substantially lower peak anti-spike antibody (anti-S) levels and is associated with a higher risk of breakthrough infections. To provide preliminary indication of how a third booster BNT162b2 dose impacts anti-S levels, we performed a cross-sectional analysis using capillary blood samples from vaccinated adults participating in Virus Watch, a prospective community cohort study in England and Wales. Methods: Blood samples were analysed using Roche Elecsys Anti-SARS-CoV-2 S immunoassay. We analysed anti-S levels by week since the third dose for vaccines administered on or after 1 September 2021 and stratified the results by second-dose vaccine type (ChAdOx1 or BNT162b2), age, sex and clinical vulnerability. Results: Anti-S levels peaked at two weeks post-booster for BNT162b2 (22,185 U/mL; 95%CI: 21,406-22,990) and ChAdOx1 second-dose recipients (19,203 U/mL; 95%CI: 18,094-20,377). These were higher than the corresponding peak antibody levels post-second dose for BNT162b2 (12,386 U/mL; 95%CI: 9,801-15,653, week 2) and ChAdOx1 (1,192 U/mL; 95%CI: 818-1735, week 3). No differences emerged by second dose vaccine type, age, sex or clinical vulnerability. Anti-S levels declined post-booster for BNT162b2 (half-life=44 days) and ChAdOx1 second dose recipients (half-life=40 days). These rates of decline were steeper than those post-second dose for BNT162b2 (half-life=54 days) and ChAdOx1 (half-life=80 days). Conclusions: Our findings suggest that peak anti-S levels are higher post-booster than post-second dose, but levels are projected to be similar after six months for BNT162b2 recipients. Higher peak anti-S levels post-booster may partially explain the increased effectiveness of booster vaccination compared to two-dose vaccination against symptomatic infection with the Omicron variant. Faster waning trajectories post-third dose may have implications for the timing of future booster campaigns or four-dose vaccination regimens for the clinically vulnerable.

BackgroundOccupational disparities in COVID-19 vaccine uptake can impact the effectiveness of vaccination programmes and introduce particular risk for vulnerable workers and those with high workplace exposure. This study aimed to investigate COVID-19 vaccine uptake by occupation, including for vulnerable groups and by occupational exposure status.MethodsWe used data from employed or self-employed adults who provided occupational information as part of the Virus Watch prospective cohort study (n=19,595) and linked this to study-obtained information about vulnerability-relevant characteristics (age, medical conditions, obesity status) and work-related COVID-19 exposure based on the Job Exposure Matrix. Participant vaccination status for the first, second, and third dose of any COVID-19 vaccine was obtained based on linkage to national records and study records. We calculated proportions and Sison-Glaz multinomial 95% confidence intervals for vaccine uptake by occupation overall, by vulnerability-relevant characteristics, and by job exposure.FindingsVaccination uptake across occupations ranged from 89-96% for the first dose, 87-94% for the second dose, and 75-86% for the third dose, with transport, trade, service and sales workers persistently demonstrating the lowest uptake. Vulnerable workers tended to demonstrate fewer between-occupational differences in uptake than non-vulnerable workers, although clinically vulnerable transport workers (76%-89% across doses) had lower uptake than several other occupational groups (maximum across doses 86-96%). Workers with low SARS-CoV-2 exposure risk had higher vaccine uptake (86%-96% across doses) than those with elevated or high risk (81-94% across doses).InterpretationDifferential vaccination uptake by occupation, particularly amongst vulnerable and highly-exposed workers, is likely to worsen occupational and related socioeconomic inequalities in infection outcomes. Further investigation into occupational and non-occupational factors influencing differential uptake is required to inform relevant interventions for future COVID-19 booster rollouts and similar vaccination programmes.

ImportanceThe Omicron (B.1.1.529) variant has increased SARs-CoV-2 infections in double vaccinated individuals globally, particularly in ChAdOx1 recipients. To tackle rising infections, the UK accelerated booster vaccination programmes used mRNA vaccines irrespective of an individual’s primary course vaccine type with booster doses rolled out according to clinical priority. There is limited understanding of the effectiveness of different primary vaccination courses on mRNA based booster vaccines against SARs-COV-2 infections and how time-varying confounders can impact the evaluations comparing different vaccines as primary courses for mRNA boosters.ObjectiveTo evaluate the comparative effectiveness of ChAdOx1 versus BNT162b2 as primary doses against SARs-CoV-2 in booster vaccine recipients whilst accounting for time-varying confounders.DesignTrial emulation was used to reduce time-varying confounding-by-indication driven by prioritising booster vaccines based upon age, vulnerability and exposure status e.g. healthcare worker. Trial emulation was conducted by meta-analysing eight cohort results whose booster vaccinations were staggered between 16/09/2021 to 05/01/2022 and followed until 23/01/2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end-of-study was modelled using Cox proportional hazards models for each cohort and adjusted for age, sex, minority ethnic status, clinically vulnerability, and deprivation.SettingProspective observational study using the Virus Watch community cohort in England and Wales.ParticipantsPeople over the age of 18 years who had their booster vaccination between 16/09/2021 to 05/01/2022 without prior natural immunity.ExposuresChAdOx1 versus BNT162b2 as a primary dose, and an mRNA booster vaccine.ResultsAcross eight cohorts, 19,692 mRNA vaccine boosted participants were analysed with 12,036 ChAdOx1 and 7,656 BNT162b2 primary courses with a median follow-up time of 73 days (IQR:54-90). Median age, clinical vulnerability status and infection rates fluctuate through time. 7.2% (n=864) of boosted adults with ChAdOx1 primary course experienced a SARS-CoV-2 infection compared to 7.6% (n=582) of those with BNT162b2 primary course during follow-up. The pooled adjusted hazard ratio was 0.99 [95%CI:0.88-1.11], demonstrating no difference between the incidence of SARs-CoV-2 infections based upon the primary vaccine course.Conclusion and RelevanceIn mRNA boosted individuals, we found no difference in protection comparing those with a primary course of BNT162b2 to those with aChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection.

IntroductionSeroprevalence studies can provide a measure of cumulative incidence of SARS-CoV-2 infection, but a better understanding of antibody dynamics following infection is needed to assess longevity of detectability. Infection is characterised by detection of spike (anti-S) and nucleocapsid (anti-N) antibodies, whereas vaccination only stimulates anti-S. Consequently, in the context of a highly vaccinated population, presence of anti-N can be used as a marker of previous infection but waning over time may limit its use.MethodsAdults aged ≥18 years old, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary blood samples which were tested for anti-S and anti-N. Participants self-reported vaccination dates and past medical history. Prior polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System (SGSS) linkage data. Primary outcome variables were seropositivity (antibodies at or above the manufacturer’s cut-off for positivity) and total anti-N and anti-S levels after PCR confirmed infection. Outcomes were analysed by days since infection, self-reported demographic and clinical factors.ResultsA total of 13,802 eligible individuals, median age 63, provided 58,770 capillary blood samples. 537 of these had a prior positive PCR confirmed SARS-CoV-2 infection 0-269 days before the antibody sample date. 432 out of the 537 (80.44%) were anti-N positive and detection remained stable through-out follow-up. Median anti-N levels peaked between days 90 and 119 post PCR results and then began to decline. Logistic regression models, both univariable and multivariable, only showed higher odds of positive anti-N result between 0-269 days for 35-49 year olds, compared to 18-34 year olds. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories.DiscussionApproximately 4 in 5 participants with prior PCR-confirmed infection were anti-N positive, and this remained stable through follow-up for at least 269 days. However, median antibody levels began to decline from about 120 days post-infection. This suggests that anti-N have around 80% sensitivity for identifying previous COVID-19 infection and that this sensitivity is maintained through 269 days of follow up.FundingThe research costs for the study have been supported by the MRC Grant Ref: MC_PC 19070 awarded to UCL on 30 March 2020 and MRC Grant Ref: MR/V028375/1 awarded on 17 August 2020. The study also received $15,000 of Facebook advertising credit to support a pilot social media recruitment campaign on 18th August 2020. The study also received funding from the UK Government Department of Health and Social Care’s Vaccine Evaluation Programme to provide monthly Thriva antibody tests to adult participants. This study was supported by the Wellcome Trust through a Wellcome Clinical Research Career Development Fellowship to RA [206602].

IntroductionInfections of SARS-CoV-2 in vaccinated individuals have been increasing globally. Understanding the associations between vaccine type and a post-vaccination infection could help prevent further COVID-19 waves. In this paper, we use trial emulation to understand the impact of a phased introduction of the vaccine in the UK driven by vulnerability and exposure status. We estimate the comparative effectiveness of COVID-19 vaccines (ChAdOx1 versus BNT162b2) against post-vaccination infections of SARS-CoV-2 in a community setting in England and Wales.MethodTrial emulation was conducted by pooling results from six cohorts whose recruitment was staggered between 1st January 2021 and 31st March 2021 and followed until 12th November 2021. Eligibility for each trial was based upon age (18+ at the time of vaccination), without prior signs of infection or an infection within the first 14 days of the first dose. Time from vaccination of ChAdOx1 or BNT162b2 until SARS-CoV-2 infection (positive polymerase chain reaction or lateral flow test after 14 of the vaccination) was modelled using Cox proportional hazards model for each cohort and adjusted for age at vaccination, gender, minority ethnic status, clinically vulnerable status and index of multiple deprivation quintile. For those without SARS-CoV-2 infection during the study period, follow-up was until loss-of-follow-up or end of study (12th November 2021). Pooled hazard ratios were generated using random-effects meta-analysis.ResultsAcross six cohorts, there were a total of 21,283 participants who were eligible and vaccinated with either ChAdOx1 (n = 13,813) or BNT162b2 (n = 7,470) with a median follow-up time of 266 days (IQR: 235 - 282). By November 12th 2021, 750 (5.4%) adults who had ChAdOx1 as their vaccine experienced a SARS-CoV-2 infection, compared to 296 (4.0%) who had BNT162b2. We found that people who received ChAdOx1 vaccinations had 10.54 per 1000 people higher cumulative incidence for SARS-CoV-2 infection compared to BNT162b2 for infections during a maximum of 315 days of follow-up. When adjusted for age at vaccination, sex, minority ethnic status, index of multiple deprivation, and clinical vulnerability status, we found a pooled adjusted hazard ratio of 1.35 [HR: 1.35, 95%CI: 1.15 - 1.58], demonstrating a 35% increase in SARS-CoV-2 infections in people who received ChAdOx1 compared to BNT162b2.DiscussionWe found evidence of greater effectiveness of receiving BNT162b2 compared to ChAdOx1 vaccines against SARS-CoV-2 infection in England and Wales during a time period when Delta became the most prevalent variant of concern. Our findings demonstrate the importance of booster (third) doses to maintain protection and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.

BackgroundWorkplaces are an important potential source of SARS-CoV-2 exposure; however, investigation into workplace contact patterns is lacking. This study aimed to investigate how workplace attendance and features of contact varied between occupations and over time during the COVID-19 pandemic in England.MethodsData were obtained from electronic contact diaries submitted between November 2020 and November 2021 by employed/self-employed prospective cohort study participants (n=4,616). We used mixed models to investigate the main effects and potential interactions between occupation and time for: workplace attendance, number of people in shared workspace, time spent sharing workspace, number of close contacts, and usage of face coverings.FindingsWorkplace attendance and contact patterns varied across occupations and time. The predicted probability of intense space sharing during the day was highest for healthcare (78% [95% CI: 75-81%]) and education workers (64% [59%-69%]), who also had the highest probabilities for larger numbers of close contacts (36% [32%-40%] and 38% [33%-43%] respectively). Education workers also demonstrated relatively low predicted probability (51% [44%-57%]) of wearing a face covering during close contact. Across all occupational groups, levels of workspace sharing and close contact were higher and usage of face coverings at work lower in later phases of the pandemic compared to earlier phases.InterpretationMajor variations in patterns of workplace contact and mask use are likely to contribute to differential COVID-19 risk. Across occupations, increasing workplace contact and reduced usage of face coverings presents an area of concern given ongoing high levels of community transmission and emergence of variants.

BackgroundWorkers differ in their risk of SARS-CoV-2 infection according to their occupation, but the direct contribution of occupation to this relationship is unclear. This study aimed to investigate how infection risk differed across occupational groups in England and Wales up to April 2022, after adjustment for potential confounding and stratification by pandemic phase.MethodsData from 15,190 employed/self-employed participants in the Virus Watch prospective cohort study were used to generate risk ratios for virologically- or serologically-confirmed SARS-CoV-2 infection using robust Poisson regression, adjusting for socio-demographic and health-related factors and non-work public activities. We calculated attributable fractions (AF) amongst the exposed for belonging to each occupational group based on adjusted risk ratios (aRR).FindingsIncreased risk was seen in nurses (aRR=1.44, 1.25-1.65; AF=30%, 20-39%), doctors (aRR=1.33, 1.08-1.65; AF=25%, 7-39%), carers (1.45, 1.19-1.76; AF=31%, 16-43%), primary school teachers (aRR=1.67, 1.42-1.96; AF=40%, 30-49%), secondary school teachers (aRR=1.48, 1.26-1.72; AF=32%, 21-42%), and teaching support occupations (aRR=1.42, 1.23-1.64; AF=29%, 18-39%) compared to office-based professional occupations. Differential risk was apparent in the earlier phases (Feb 2020 - May 2021) and attenuated later (June - October 2021) for most groups, although teachers and teaching support workers demonstrated persistently elevated risk across waves.InterpretationOccupational differentials in SARS-CoV-2 infection risk vary over time and are robust to adjustment for socio-demographic, health-related, and non-workplace activity-related potential confounders. Direct investigation into workplace factors underlying elevated risk and how these change over time is needed to inform occupational health interventions.

BackgroundSARS-CoV-2 vaccines stimulate production of antibodies targeting the spike protein (anti-S). The level of antibodies following vaccination and trajectories of waning may differ between vaccines influencing the level of protection, how soon protection is reduced and, consequently the optimum timing of booster doses.MethodsWe measured SARS-CoV-2 anti-S titre in the context of seronegativity for SARS-CoV-2 anti-Nucleocapsid (anti-N), in samples collected between 1st July and 24th October 2021 in a subset of adults in the Virus Watch community cohort. We compared anti-S levels after BNT162b2 (BioNTech/Pfizer) or ChAdOx1 (AstraZeneca/Oxford) vaccination using time since second dose of vaccination, age, sex and clinical vulnerability to investigate antibody waning. To investigate the use of anti-S levels as a correlate of protection against SARS-CoV-2 infection, we undertook a survival analysis (Kaplan-Meier and Cox) with individuals entering 21 days after their second dose of vaccine, or first antibody test after 1st July (whichever was latest) and exiting with the outcome of SARS-Cov-2 infection or at the end of follow up 24th October 2021. We also undertook a negative test design case-control analysis of infections occurring after the second vaccine dose (breakthrough infections) to determine whether the type of vaccine affected the risk of becoming infected.Results24049 samples from 8858 individuals (5549 who received a second dose of ChAdOx1 and 3205 BNT162b2) who remained anti-N negative were included in the analysis of anti-S waning over time. Three weeks after the second dose of vaccine BNT162b2 mean anti-S levels were 9039 (95%CI: 7946-10905) U/ml and ChadOx1 were 1025 (95%CI: 917-1146) U/ml. For both vaccines, waning anti-S levels followed a log linear decline from three weeks after the second dose of vaccination. At 20 weeks after the second dose of vaccine, the mean anti-S levels were 1521 (95%CI: 1432-1616) U/ml for BNT162b2 and 342 (95%CI: 322-365) U/ml for ChadOx1. We identified 197 breakthrough infections and found a reduced risk of infection post second dose of vaccine for individuals with anti-S levels greater than or equal to 500 U/ml compared to those with levels under 500 U/ml (HR 0.62; 95%CIs:0.44-0.87; p=0.007). Time to reach an anti-S threshold of 500 U/ml was estimated at 96 days for ChAdOx1 and 257 days for BNT162b2. We found an increased risk of a breakthrough infection for those who received the ChAdOx1 compared to those who received BNT162b2 (OR: 1.43, 95% CIs:1.18-1.73, pDiscussionAnti-S levels are substantially higher following the second dose of BNT162b2 compared to ChAdOx1. There is a log linear waning in levels for both vaccines following the second dose. Anti-S levels are an important correlate of protection as demonstrated by those with anti-S levels < 500U/ml following vaccination being at significantly greater risk of subsequent infection. Since anti-S levels are substantially lower in ChAdOx1 than in BNT162b2 and both decline at similar rates we would expect waning immunity to occur earlier in ChAdOx1 compared to BNT162b2. Our results showing an increased risk of breakthrough infections for those who were vaccinated with ChAdOx1 compared to BNT162b2 are in line with this hypothesis. Consistent with our data, national analyses of vaccine effectiveness also suggest that waning of immunity for infection and, to a lesser extent for severe disease, is seen earlier in ChAdOx1 than in BNT162b2. Our data demonstrate the importance of booster doses to maintain protection in the elderly and clinically vulnerable and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.

Background Vaccination intention is vital to the success of any vaccination programme, alongside vaccine availability and access. Public intention to take a COVID-19 vaccine if offered is high in the UK, but evidence of disparities between ethnic, social and age groups has led to concern. Methods Online survey of prospective household community cohort study participants across England and Wales (Virus Watch). Vaccination intention was measured by individual participant responses to ‘Would you accept a COVID-19 vaccine if offered?’, collected in December 2020 and February 2021. Responses to a 13-item questionnaire collected in January 2021 were analysed using factor analysis to investigate psychological influences on vaccination intention. Results Survey response rate was 56% (20,785/36,998) in December 2020 and 53% (20,590/38,727) in February 2021, with 14880 adults reporting across both time points. Of participants reporting across both timepoints, 13,411 (90%) answered ‘Yes’ and 1,469 (10%) responded ‘No’ or ‘Unsure’ in December 2020. Of those answering ‘No’ or ‘Unsure’ in December 2020, 1,266 (86%) subsequently answered ‘Yes’ or ‘Already had a COVID-19 vaccine’ in February 2021. Vaccination intention increased across all ethnic groups and levels of social deprivation. Age was most strongly associated with vaccination intention, with 16–24-year-olds more likely to respond “Unsure” or “No” versus “Yes” than 65-74-year-olds in December 2020 (OR: 4.63, 95%CI: 3.42, 6.27 & OR 7.17 95%CI: 4.26, 12.07 respectively) and February 2021 (OR: 27.92 95%CI: 13.79, 56.51 & OR 17.16 95%CI: 4.12, 71.55). The association between ethnicity and vaccination intention has weakened, but not disappeared, over time. Both vaccine- and illness-related psychological factors were shown to influence vaccination intention. Conclusions Four in five adults (86%) who were reluctant or intending to refuse a COVID-19 vaccine in December 2020 had changed their mind in February 2021 and planned to accept, or had already accepted, a vaccine.

BackgroundSome evidence suggests that individuals may change adherence to public health policies aimed at reducing contact, transmission and spread of the SARS-CoV-2 virus after they receive their first SARS-CoV-2 vaccination. In this study, we aim to estimate the rate of change in average daily travel distance from a participant’s registered address before and after SARS-CoV-2 vaccination.MethodParticipants were recruited into Virus Watch starting in June 2020. Weekly surveys were sent out to participants and vaccination status was collected from January 2021 onwards. Between September 2020 and February 2021, we invited 13,120 adult Virus Watch participants to contribute towards our tracker sub-cohort which uses the Global Positioning System (GPS) to collect data on movement. We used segmented linear regression to estimate the median daily travel distance before and after the first self-reported SARS-CoV-2 vaccine dose.ResultsWe analysed the daily travel distance of 228 vaccinated adults. Between 157 days prior to vaccination until the day before vaccination, the median daily travel distance travelled was 8.9km (IQR: 3.50km, 24.17km). Between the day of vaccination and 100 days after vaccination, the median daily travel distance travelled was 10.30km (IQR: 4.11, 27.53km). Between 157 days prior to vaccination and the vaccination date, there was a daily median decrease in mobility of 40m (95%CI: −51m, −31m, p-value ConclusionsOur study demonstrates the feasibility of collecting high volume geolocation data as part of research projects, and the utility of these for understanding public health issues. Our results are consistent with both an increase and decrease in movement after vaccination and suggest that, amongst Virus Watch participants, any changes in movement distances post-vaccination are small.

We aimed to assess the relative importance of different settings for SARS-CoV2 transmission in a large community cohort. We demonstrate the importance of home, work and education as venues for transmission. In children, education was most important and in older adults essential shopping was of high importance. Our findings support public health messaging about infection control at home, advice on working from home and restrictions in different venues.

Using data from 4678 children participating in VirusWatch, a household cohort study, we estimated the prevalence of persistent symptoms lasting ≥4 weeks as 1.7%, and 4.6% in children with a history of SARS-CoV-2 infection. Persistent symptom prevalence was higher in girls, teenagers and children with long-term conditions.

IntroductionThe Coronavirus (COVID-19) Pandemic has caused significant global mortality and impacted lives around the world. Virus Watch aims to provide evidence on which public health approaches are most likely to be effective in reducing transmission and impact of the virus, and will investigate community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviours.Methods and analysisVirus Watch is a household community cohort study of acute respiratory infections in England & Wales and will run from June 2020 to August 2021. The study aims to recruit 50,000 people, including 12,500 from minority ethnic backgrounds, for an online survey cohort and monthly antibody testing using home finger prick kits. Nested within this larger study will be a sub-cohort of 10,000 individuals, including 3,000 people from minority ethnic backgrounds. This cohort of 10,000 people will have full blood serology taken between October 2020 and January 2021 and repeat serology between May 2021 and August 2021. Participants will also post self-administered nasal swabs for PCR assays of SARS-CoV-2 and will follow one of three different PCR testing schedules based upon symptoms.Ethics and disseminationThis study has been approved by the Hampstead NHS Health Research Authority Ethics Committee. Ethics approval number – 20/HRA/2320. We are monitoring participant queries and using these to refine methodology where necessary, and are providing summaries and policy briefings of our preliminary findings to inform public health action by working through our partnerships with our study advisory group, Public Health England, NHS and Government Scientific Advisory panels.Strengths and limitations of this studyVirus Watch is a large national household community cohort study of the occurrence and risk factors for COVID-19 infection that aims to recruit 50,000 people, including 12,500 from minority ethnic backgrounds.Virus Watch is designed to estimate incidence of PCR confirmed COVID-19 in those with respiratory and non-respiratory presentations and the incidence of hospitalisation among PCR confirmed COVID-19 cases.Virus Watch will measure effectiveness and impact of recommended COVID-19 control measures including testing, isolation, social distancing, respiratory and hand hygiene measures on risk of respiratory infection.Only households with a lead householder able to speak English were able to take part in the study up until March 2021.Only households of up to six people were eligible for inclusion and they were also required to have access to an internet connection. These restrictions will limit the generalisability to large or multigenerational households, and those without access to the internet.

BackgroundUnderstanding the symptomatology and accuracy of clinical case definitions for COVID-19 in the community is important for the initiation of Test, Trace and Isolate (TTI) and may, in future, be important for early prescription of antivirals.MethodsVirus Watch is a large community cohort with prospective daily recording of a wide range of symptoms and self-reporting of swab results (mainly undertaken through the UK TTI system). We compared frequency, severity, timing, and duration of symptoms in test positive and test negative cases. We compared the test performance of the current UK case definition used by TTI (any one of: new continuous cough, high temperature, or loss of or altered sense of smell or taste) with a wider definition that also included muscle aches, chills, headache, or loss of appetite.FindingsWe included results from 8213 swabbed illnesses, 944 of which tested positive for SARS-CoV-2. All symptoms were more common in test positive than test negative illnesses and symptoms were also more severe and of longer duration. Common symptoms such as cough, headache, fatigue, muscle aches, and loss of appetite occurred early in the course of illness but were also very common in test-negative illnesses. In contrast, high temperature and loss of or altered sense of smell or taste were less frequently identified in swab positive illnesses but were markedly more common than in swab negative illnesses. The current UK definition had a sensitivity and specificity of 81% and 47% respectively for symptomatic COVID-19 compared to 93% and 26% for the broader definition. On average, cases met the broader case definition 0.3 days earlier than the current definition. 1.7-fold more illnesses met the broader definition than the current case definition.InterpretationCOVID-19 is difficult to distinguish from other respiratory infections and common ailments on the basis of symptoms. Broadening the list of symptoms used to encourage engagement with TTI could moderately increase the number of infections identified and shorten delays to isolation, but with a large increase in the number of tests needed and the number of unwell individuals and contacts who are advised to self-isolate whilst awaiting results, and subsequently test negative for SARS-CoV-2.

IntroductionIncreased transmissibility of B.1.17 variant of concern (VOC) in the UK may explain its rapid emergence and global spread. We analysed data from putative household infector - infectee pairs in the Virus Watch Community cohort study to assess the serial interval of COVID-19 and whether this was affected by emergence of the B.1.17 variant.MethodsThe Virus Watch study is an online, prospective, community cohort study following up entire households in England and Wales during the COVID-19 pandemic. Putative household infector-infectee pairs were identified where more than one person in the household had a positive swab matched to an illness episode. Data on whether individual infections were caused by the B.1.1.7 variant were not available. We therefore developed a classification system based on the percentage of cases estimated to be due to B.1.17 in national surveillance data for different English regions and study weeks.ResultsOut of 24,887 illnesses reported, 915 tested positive for SARS-CoV-2 and 186 likely infector-infectee pairs in 186 households amongst 372 individuals were identified. The mean COVID-19 serial interval was 3.18 (95%CI: 2.55 - 3.81) days. There was no significant difference (p=0.267) between the mean serial interval for Variants of Concern (VOC) hotspots (mean = 3.64 days, (95%CI: 2.55 – 4.73)) days and non-VOC hotspots, (mean = 2.72 days, (95%CI: 1.48 – 3.96)).ConclusionsOur estimates of the average serial interval of COVID-19 are broadly similar to estimates from previous studies and we find no evidence that B.1.1.7 is associated with a change in serial intervals. Alternative explanations such as increased viral load, longer period of viral shedding or improved receptor binding may instead explain the increased transmissibility and rapid spread and should undergo further investigation.

BackgroundVaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the UK’s extended dosing interval, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose.MethodsAdults aged ≥18 years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike (≥0.8 U/ml), as per Roche’s Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors.Results8,837 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 17,160 samples (10,508 following ChAdOx1, 6,547 following BNT162b2). Seropositivity to Spike was 96.79% (95% CI 96.42, 97.12) from 28 days following a single dose, reaching 99.34% (98.91, 99.60) from 14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence for lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men compared with women (26.50 vs 44.01 U/ml, pInterpretationA single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. Observed disparities in antibody levels by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures for partially vaccinated adults, particularly those who are older and more clinically vulnerable; and high antibody levels across all groups following a second dose demonstrate the importance of complete vaccination. However, the relationship between Spike-antibody levels and protection against COVID-19, and thus the clinical significance of observed disparities, is not yet clear.

BackgroundDifferential exposure to public activities and non-household contacts may contribute to stark deprivation-related inequalities in SARS-CoV-2 infection and outcomes, but has not been directly investigated. We set out to investigate whether participants in Virus Watch – a large community cohort study based in England and Wales – reported different levels of exposure to public activities and non-household contacts during the Autumn-Winter phase of the COVID-19 pandemic according to postcode-level socioeconomic deprivation.MethodsParticipants (n=20120-25228 across surveys) reported their daily activities during three weekly periods in late November 2020, late December 2020, and mid-February 2021. Deprivation was quantified based on participants’ postcode of residence using English or Welsh Indices of Multiple Deprivation quintiles. We used Poisson mixed effect models with robust standard errors to estimate the relationship between deprivation and risk of exposure to public activities during each survey period.ResultsRelative to participants in the least deprived areas, participants in the most deprived areas persistently exhibited elevated risk of exposure to vehicle sharing (aRR range across time points 1.73-8.52), public transport (aRR 3.13-5.73), work or education outside of the household (aRR 1.09-1.21), essential shops (aRR 1.09-1.13) and non-household contacts (aRR 1.15-1.19) across multiple survey periods.ConclusionDifferential exposure to essential public activities in deprived communities is likely to contribute to inequalities in infection risk and outcomes during the COVID-19 pandemic. Public health interventions to reduce exposure during essential activities and financial and practical support to enable low-paid workers to stay at home during periods of intense transmission may reduce COVID-related inequalities.

ObjectivesTo assess trends in intention to accept a COVID-19 vaccine between 1 December 2020 and 25 February 2021, explore associations between socio-demographic factors and vaccination intention and investigate how COVID-19 vaccine- and illness-related attitudes, beliefs and emotions influence vaccination intention.DesignProspective household community cohort study of COVID-19 infection (Virus Watch).SettinOnline survey of Virus Watch study participants in the community across England and Wales.ParticipantsIndividuals could enrol in Virus Watch if all household members agreed to participate and at least one household member had access to the internet, an email address, and could read English. All Virus Watch participants aged 16 years and over who responded to questions relating to COVID-19 vaccine intention in questionnaires between December 2020 and February 2021 were included in this analysis.Main outcome measuresVaccination intention was measured by individual participant responses to ‘Would you accept a COVID-19 vaccine if offered?’, collected between 1-14 December 2020 and 17-25 February 2021. Possible responses were ‘Yes’, ‘No’ and ‘Unsure’ (December 2020 &February 2021) and ‘Already had a COVID-19 vaccine’ (February 2021 only). Responses to a 13-item questionnaire collected between 4-11 January 2021 were analysed using factor analysis to investigate psychological influences (attitudes, beliefs and emotions) on vaccination intention.ResultsSurvey response rate was 56% (20,792/36,998) in December 2020 and 52% (20,284/38,727) in February 2021, with 14,713 adults reporting across both time points. Of participants reporting across both timepoints, 13,281 (90%) answered ‘Yes’ and 1,432 (10%) responded ‘No’ or ‘Unsure’ in December 2020. Of those answering ‘No’ or ‘Unsure’ in December 2020, 1,233 (86%) went on to answer ‘Yes’ or ‘Already had a COVID-19 vaccine’ in February 2021. The magnitude of this shift was consistent across all ethnic groups measured and all levels of social deprivation. Age was most strongly associated with vaccination intention, with 16–24-year-olds more likely to respond “No” or “Unsure” than those aged 75+ in December 2020 (RR: 4.32, 95% CI: 2.40-7.78 &2.93 95% CI: 2.19-3.92, respectively) and February 2021 (RR: 5.30 95% CI: 1.39-20.20 &20.21 95%CI: 7.19-56.78). The association between ethnicity and vaccination intention has weakened, but not disappeared, over time. Both vaccine- and illness-related psychological factors were shown to influence vaccination intention.ConclusionsOver four in five adults (86%) who were reluctant or intending to refuse a COVID-19 vaccine in December 2020 had changed their mind in February 2021 and planned on accepting, or had already accepted, a vaccine.

Background/Aim: We have a limited understanding of the broader determinants of health of international migrants and how these change over time since migration to the United Kingdom (UK). To address this knowledge gap, we aim to conduct a prospective cohort study with data acquisition via a smartphone application (app). In this pilot study, we aim to 1) determine the feasibility of the use of an app for data collection in international migrants, 2) optimise app engagement by quantifying the impact of specific design features on the completion rates of survey questionnaires and on study retention, 3) gather preliminary profile health status data, to begin to examine how risk factors for health are distributed among migrants. Methods: We will recruit 275 participants through a social media campaign and through third sector organisations that work with or support migrants in the UK. Following consent and registration, data will be collected via surveys. To optimise app engagement and study retention, we will quantify the impact of specific design features (i.e. the frequency of survey requests, the time of day for app notifications, the frequency of notifications, and the wording of notifications) via micro-randomised process evaluations. The primary outcome for this study is survey completion rates with numerator as the number of surveys completed and denominator as the total number of available surveys. Secondary outcomes are study retention rates and ratings of interest after app usage. Ethics and dissemination: We have obtained approval to use consented patient identifiable data from the University College London Ethics Committee. Improving engagement with the app and gathering preliminary health profile data will help us identify accessibility and usability issues and other barriers to app and study engagement prior to moving to a larger study.

Introduction Non-valvular cardiac aspergillosis is a rare infection of the pericardium, myocardium or endocardium and is associated with a high mortality. There is a paucity of reports of non-valvular cardiac aspergillosis in critically ill and solid organ transplant (SOT) patients. The majority of cases have been reported in haemato-oncology patients, some of whom have undergone a bone marrow transplant. Objectives We describe four cases affected by non-valvular cardiac aspergillosis in the intensive care setting including a systematic review of this extremely rare infection which is associated with high mortality. Results All four-patients died but presented with varying clinical, radiological and microbiological evidence of the disease. Three patients presented following complications after solid organ transplantation, two in the context of acute liver failure and emergency liver transplant and one several years after a double lung transplant. The last patient presented with necrotising gall stone pancreatitis, multi-organ failure and subsequently a prolonged intensive care unit (ICU) stay. On review of the literature, January 1955 to July 2019, 45 cases were identified, with different risk factors, clinical and radiological manifestations, treatment regimen and outcome. Conclusion Antemortem diagnosis of cardiac aspergillosis is difficult and rare, with no cases reporting positive blood culture results. Galactomannan serology has poor sensitivity in solid organ transplant patients, further reduced by prophylactic antimicrobial treatment, which is common in the ICU setting especially post-transplant patients. Due to the scarcity of cases, treatment is extrapolated from invasive aspergillosis management, with emphasis on early treatment with combination therapy.

The authors report an extremely rare case of Klebsiella pneumoniae pyomyositis of the left thigh in a patient with type II diabetes mellitus on renal replacement therapy (haemodialysis), with untreated hepatitis C. This patient presented via the dialysis unit with fevers, rigors and a swollen left thigh and knee. Initial differential diagnoses included deep vein thrombosis with systemic inflammatory response syndrome, septic arthritis and crystal arthropathy-all of which were subsequently excluded. Although missed on ultrasound duplex scan, lower limb magnetic resonance imaging (MRI) revealed communicating abscesses in the anterior and medial compartments of the left thigh, with associated inflammation of the muscle. Blood cultures on admission and cultures from direct aspiration of the abscesses grew Klebsiella pneumoniae. The abscesses were managed with a computed tomography-guided drain and combination antibiotic therapy.

The Baveno VI guidelines propose that cirrhotic patients with a liver stiffness measurement (LSM)20kPa and a platelet count150,000/μl can avoid screening endoscopy as their combination is highly specific for excluding clinically significant varices. The aim of the study was to validate these criteria.Transient elastography data was collected from two institutions from 2006-2015. Inclusion criteria were a LSM ⩾10kPa and an upper gastrointestinal endoscopy within 12months, with a diagnosis of compensated chronic liver disease. Exclusion criteria were porto-mesenteric-splenic vein thrombosis and non-cirrhotic portal hypertension. Varices were graded as low risk (grade2) or high risk (grade ⩾2).The study included 310 patients (169 (55%) hepatitis C, and 275 (89%) Child-Pugh A). Varices were present in 23% cases, with 5% prevalence of high risk varices. Overall 102/310 (33%) met the Baveno VI criteria. Within this group 11% had varices and 2% had high risk varices, representing 2/15 (13%) of all high risk varices. The Baveno VI criteria gave a sensitivity 0.87, specificity 0.34, positive predictive value 0.06, negative predictive value 0.98, positive likelihood ratio 1.31 and negative likelihood ratio 0.39. The AUROC for LSM and platelet count combined was 0.746.The Baveno VI criteria performed well correctly identifying 98% of patients who could safely avoid endoscopy.This study examines the effectives of a recent set of guidelines published by the Baveno VI conference, which states that patients with chronic liver disease and a low liver stiffness (20kPa) and high platelet count (150) are at low risk of having varices and do not need a screening endoscopy. Varices are a complication of cirrhosis, confer a risk of serious bleeding, and can be diagnosed and treated by endoscopy. Our study reviewed the clinical records of patients who have had liver stiffness scans and endoscopy over a 9-year period at two hospitals. The results show that only about 2% of patients who meet the Baveno VI criteria will be miss-classified as not having varices.

To investigate the etiology and management of a poorly understood complication of transjugular intrahepatic portosystemic shunt; "endotipsitis".A MEDLINE database search was carried out, reviewing all papers with specific words in the title or abstract, and excluding appropriately. Of 283 papers that were reviewed, 22 papers reporting 53 cases in total were included in the analyses.No predominant etiology for endotipsitis was identified, but gram-positive organisms were more common among early-onset infections (P0.01). A higher mortality rate was associated with Staphylococcus aureus and Candida spp infections (P0.01). There was no trend in choice of antibiotic based on the microorganisms isolated and treatment varied from the guidelines of other vegetative prosthetic infections. In endotipsitis "high risk" organisms have been identified, emphasizing the importance of ensuring optimal antimicrobial therapy and adjunctive management strategies.Higher mortality rate was associated with Staphylococcus aureus and Candida spp infections. A prospective multicenter trial is needed before specific treatment can be recommended.

A 97-year-old woman presented with 4-day history of vesicular rash, initially at the feet but then spread up to the thighs bilaterally, abdomen and trunk. The initial differentials included bullous pemphigus and cellulitis by the emergency department. She was then managed as bullous pemphigus by the acute medical team and started on high-dose steroids, with no other differentials considered. When her care was taken over by the general medical team, varicella zoster virus (VZV) infection was suspected. After confirmation by the dermatology team regarding the clinical diagnosis and the positive VZV DNA swabs, she was started on acyclovir.

SUMMARYWhere very young children come into contact with water containing schistosome cercariae, infections occur and schistosomiasis can be found. In high transmission environments, where mothers daily bathe their children with environmentally drawn water, many infants and preschool-aged children have schistosomiasis. This ‘new’ burden, inclusive of co-infections with Schistosoma haematobium and Schistosoma mansoni, is being formally explored as infected children are not presently targeted to receive praziquantel (PZQ) within current preventive chemotherapy campaigns. Thus an important PZQ treatment gap exists whereby infected children might wait up to 4–5 years before receiving first treatment in school. International treatment guidelines, set within national treatment platforms, are presently being modified to provide earlier access to medication(s). Although detailed pharmacokinetic studies are needed, to facilitate pragmatic dosing in the field, an extended ‘dose pole’ has been devised and epidemiological monitoring has shown that administration of PZQ (40 mg/kg), in either crushed tablet or liquid suspension, is both safe and effective in this younger age-class; drug efficacy, however, against S. mansoni appears to diminish after repeated rounds of treatment. Thus use of PZQ should be combined with appropriate health education/water hygiene improvements for both child and mother to bring forth a more enduring solution.