A case-crossover study of the effect of vaccination on SARS-CoV-2 transmission relevant behaviours during a period of national lockdown in England and Wales

BackgroundStudies of COVID-19 vaccine effectiveness show increases in COVID-19 cases within 14 days of a first dose, potentially reflecting post-vaccination behaviour changes associated with SARS-CoV-2 transmission before vaccine protection. However, direct evidence for a relationship between vaccination and behaviour is lacking. We aimed to examine the association between vaccination status and self-reported non-household contacts and non-essential activities during a national lockdown in England and Wales. MethodsParticipants (n=1,154) who had received the first dose of a COVID-19 vaccine reported non-household contacts and non-essential activities from February to March 2021 in monthly surveys during a national lockdown in England and Wales. We used a case-crossover study design and conditional logistic regression to examine the association between vaccination status (pre-vaccination vs. 14 days post-vaccination) and self-reported contacts and activities within individuals. Stratified subgroup analyses examined potential effect heterogeneity by sociodemographic characteristics such as sex, household income or age group. Results457/1,154 (39.60%) participants reported non-household contacts post-vaccination compared with 371/1,154 (32.15%) participants pre-vaccination. 100/1,154 (8.67%) participants reported use of non-essential shops or services post-vaccination compared with 74/1,154 (6.41%) participants pre-vaccination. Post-vaccination status was associated with increased odds of reporting non-household contacts (OR 1.65, 95% CI 1.31-2.06, p<0.001) and use of non-essential shops or services (OR 1.50, 95% CI 1.03-2.17, p=0.032). This effect varied between men and women and different age groups. ConclusionParticipants had higher odds of reporting non-household contacts and use of non-essential shops or services within 14 days of their first COVID-19 vaccine compared to pre-vaccination. Public health emphasis on maintaining protective behaviours during this post-vaccination time period when individuals have yet to develop full protection from vaccination could reduce risk of SARS-CoV-2 infection.

Occupation, Worker Vulnerability, and COVID-19 Vaccination Uptake: Analysis of the Virus Watch prospective cohort study

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.

Glasses and risk of COVID-19 transmission - analysis of the Virus Watch Community Cohort study.

BackgroundRespiratory viruses, including SARS-CoV-2, can infect the eyes or pass into the nose via the nasolacrimal duct. The importance of transmission via the eyes is unknown but might plausibly be reduced in those who wear glasses. Previous studies have mainly focussed on protective eyewear in healthcare settings. MethodsParticipants from the Virus Watch prospective community cohort study in England and Wales responded to a questionnaire on the use of glasses and contact lenses. This included frequency of use, purpose, and likelihood of wearing a mask with glasses. Infection was confirmed through data linkage with Second Generation Surveillance System (Pillar 1 and Pillar 2), weekly questionnaires to self-report positive polymerase chain reaction or lateral flow results, and, for a subgroup, monthly capillary blood testing for antibodies (nucleocapsid and spike). A multivariable logistic regression model, controlling for age, sex, income and occupation, was used to identify odds of infection depending on the frequency and purpose of using glasses or contact lenses. Findings19,166 Virus Watch participants responded to the questionnaire, with 13,681 (71.3%, CI 70.7-72.0) reporting they wore glasses. A multivariable logistic regression model showed a 15% lower odds of infection for those who reported using glasses always for general use (OR 0.85, 95% 0.77-0.95, p = 0.002) compared to those who never wore glasses. The protective effect was reduced in those who said that wearing glasses interfered with mask wearing. No protective effect was seen for contact lens wearers. InterpretationPeople who wear glasses have a moderate reduction in risk of COVID-19 infection highlighting the importance of the eye as a route of infection. Eye protection may make a valuable contribution to the reduction of transmission in community and healthcare settings. 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 Cares 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]. Funding from the HSE Protect study, GOSH Childrens Charity and the Great Ormond Street Hospital BRC supported the involvement of CO in the project. Research in contextO_ST_ABSEvidence before the studyC_ST_ABSDespite the risk of SARS-CoV-2 transmission via the eyes, very few countries have advocated eye protection to reduce transmission amongst the public and, except when providing close care for those known or suspected to be infected, is variable and based on case-by-case assessment of exposure risk. The mechanism, but not the extent, of the transmission route through the eyes is well described in the literature, with several studies reporting detection of SARS-CoV-2 RNA in the tear film, conjunctiva and conjunctival sac. There have been a small number of hospital based observational studies suggesting that eye protection may help prevent COVID-19 infection. A literature search was carried out on 23rd February 2022 across Medline and Embase using the search terms eyewear, glasses, SARS-CoV-2, COVID-19, SARS, transmission and infectivity, providing 105 manuscripts. Of these, only eight investigated the risk of infection associated with eye protection, all in hospital settings or followed a cohort of healthcare workers. Among the studies was a systematic review that identified 5 observational studies from 898 articles that were screened. The cohort study with the largest sample size, 345 healthcare professionals, demonstrated a relative risk of 10.25 (95% CI 1.28-82.39; P = 0.009) for infection when not using eye protection. No studies of the potential protective effect of glasses wearing, for visual correction, in community settings were identified. Added value of this studyThe Virus Watch study is a prospective community household study across England and Wales. 19,166 participants responded to the monthly questionnaire on glasses and contact lens use, assessing reported frequency, the purpose of use and how likely they were to wear a mask with glasses. Infections were identified in data linked to the Second Generation Surveillance System (Pillar 1 and Pillar 2 testing), weekly surveys seeking self-reports of polymerase chain reaction or lateral flow device results and, in a subset of 11,701, self-collected capillary blood testing for antibodies (nucleocapsid and spike - nucleocapsid antibodies were taken as evidence of prior infection as these are unaffected by vaccination). Our multivariable logistic regression model, controlling for age, sex, household income and occupation, demonstrated 15% lower odds of infection for those who reported always using glasses for general use compared to those who never wear glasses. The protective effect was not observed in those who strongly agreed with the statement, I am less likely to wear a face covering when I have my glasses on because my glasses steam up. Counterfactual analysis of contact lenses did not suggest a protective effect regardless of frequency of use. Implications of all the available evidenceThe findings of this study demonstrate a moderate reduction in risk of SARS-CoV-2 infection in those who always wear glasses compared to never. Unlike other studies, our results are representative of a community setting, adjust for potential confounders and provide a counterfactual analysis with contact lenses. This extends the current evidence to community settings and validates proposed biological mechanisms of eye protection reducing the risk of SARS-CoV-2 transmission.

Anti-spike antibody trajectories in individuals previously immunised with BNT162b2 or ChAdOx1 following a BNT162b2 booster dose

The two most commonly-used 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 (aged [≥]18 years) participating in Virus Watch, a prospective community cohort study in England and Wales. 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 September 1, 2021 and stratified the results by second dose vaccine type (ChAdOx1 or BNT162b2), age, sex and clinical vulnerability. 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). Our findings suggest that peak anti-S levels are higher post-booster than post-second dose, but that 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.

Comparative effectiveness of different primary vaccination courses on mRNA based booster vaccines against SARs-COV-2 infections: A time-varying cohort analysis using trial emulation in the Virus Watch community cohort

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 individuals 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.

Nucleocapsid and spike antibody responses post virologically confirmed SARS-CoV-2 infection: An observational analysis in the Virus Watch community cohort

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 manufacturers 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 Cares 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].

Comparative effectiveness of ChAdOx1 versus BNT162b2 vaccines against SARS-CoV-2 infections in England and Wales: A cohort analysis using trial emulation in the Virus Watch community data

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.

Workplace Contact Patterns in England during the COVID-19 Pandemic: Analysis of the Virus Watch prospective cohort study

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.

Differential Risk of SARS-CoV-2 Infection by Occupation: Evidence from the Virus Watch prospective cohort study in England and Wales

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.

Relative contribution of leaving home for work or education, transport, shopping and other activities on risk of acquiring COVID-19 infection outside the household in the second wave of the pandemic in England and Wales

BackgroundWith the potential for and emergence of new COVID-19 variants, such as the reportedly more infectious Omicron, and their potential to escape the existing vaccines, understanding the relative importance of which non-household activities increase risk of acquisition of COVID-19 infection is vital to inform mitigation strategies. MethodsWithin an adult subset of the Virus Watch community cohort study, we sought to identify which non-household activities increased risk of acquisition of COVID-19 infection and which accounted for the greatest proportion of non-household acquired COVID-19 infections during the second wave of the pandemic. Among participants who were undertaking antibody tests and self-reporting PCR and lateral flow tests taken through the national testing programme, we identified those who were thought to be infected outside the household during the second wave of the pandemic. We used exposure data on attending work, using public or shared transport, using shops and other non-household activities taken from monthly surveys during the second wave of the pandemic. We used multivariable logistic regression models to assess the relative independent contribution of these exposures on risk of acquiring infection outside the household. We calculated Adjusted Population Attributable Fractions (APAF - the proportion of non-household transmission in the cohort thought to be attributable to each exposure) based on odds ratios and frequency of exposure in cases. ResultsBased on analysis of 10475 adult participants including 874 infections acquired outside the household, infection was independently associated with: leaving home for work (AOR 1.20 (1.02 - 1.42) p=0.0307, APAF 6.9%); public transport use (AOR for use more than once per week 1.82 (1.49 - 2.23) p<0.0001, APAF for public transport 12.42%); and shopping (AOR for shopping more than once per week 1.69 (1.29 - 2.21) P=0.0003, APAF for shopping 34.56%). Other non-household activities such as use of hospitality and leisure venues were rare due to restrictions and there were no significant associations with infection risk. ConclusionsA high proportion of the second wave of the pandemic was spent under conditions where people were being advised to work from home where possible, and to minimize exposure to shops, and a wide range of other businesses were subject to severe restrictions. Vaccines were being rolled out to high-risk groups. During this time, going to work was an important risk factor for infection but public transport use likely accounted for a lot of this risk. Only a minority of the cohort left home for work or used public or shared transport. By contrast, the majority of participants visited shops and this activity accounted for about one-third of non-household transmission.

Changes in mobility pre and post first SARS-CoV-2 vaccination: findings from a prospective community cohort study including GPS movement tracking in England and Wales (Virus Watch)

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 participants 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 <0.001) per day. After the removal of outlier data, and between the vaccination date and 99 days after vaccination, there was a median daily increase in movement of 45.0m (95%CI: 25m, 65m, p-value = <0.001). Restricting the analysis to the 3rd national lockdown (4th of January 2021 to the 5th of April 2021), we found a median daily movement increase of 9m (95%CI: -25m, 45m, p = 0.57) in the 30 days prior to vaccination and the vaccination date, and a median daily movement increase of 10m (95%CI: -60m, 94m, p-value = 0.69) in the 30 days after vaccination. 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.

Household overcrowding and risk of SARS-CoV-2: analysis of the Virus Watch prospective community cohort study in England and Wales

BackgroundHousehold overcrowding is associated with increased risk of infectious diseases across contexts and countries. Limited data exist linking household overcrowding and risk of COVID-19. We used data collected from the Virus Watch cohort to examine the association between overcrowded households and SARS-CoV-2. MethodsThe Virus Watch study is a household community cohort of acute respiratory infections in England & Wales that began recruitment in June 2020. We calculated the persons per room for each household and classified accommodation as overcrowded when the number of rooms{square}was fewer than the number of people. We considered two primary outcomes - PCR-confirmed positive SARS-CoV-2 antigen tests and laboratory confirmed SARS-CoV-2 antibodies (Roche Elecsys anti-N total immunoglobulin assay). We used mixed effects logistic regression models that accounted for household structure to estimate the association between household overcrowding and SARS-CoV-2 infection. ResultsThe proportion of participants with a positive SARS-CoV-2 PCR result was highest in the overcrowded group (6.6%; 73/1,102) and lowest in the under-occupied group (2.9%; 682/23,219). In a mixed effects logistic regression model that included age, sex, ethnicity, household income and geographical region, we found strong evidence of an increased odds of having a positive PCR SARS-CoV-2 antigen result (Odds Ratio 3.72; 95% CI: 1.92, 7.13; p-value < 0.001) and increased odds of having a positive SARS-CoV-2 antibody result in individuals living in overcrowded houses (2.96; 95% CI: 1.13, 7.74; p-value =0.027) compared to people living in under-occupied houses. The proportion of variation at the household level was 9.91% and 9.97% in the PCR and antibody models respectively. DiscussionPublic health interventions to prevent and stop the spread of SARS-CoV-2 should consider the much greater risk of infection for people living in overcrowded households and pay greater attention to reducing household transmission. There is an urgent need to better recognise housing as a leading determinant of health in the context of a pandemic and beyond.

Occupation, Work-Related Contact, and SARS-CoV-2 Anti-Nucleocapsid Serological Status: Findings from the Virus Watch prospective cohort study

BackgroundWorkers differ in their risk of acquiring SARS-CoV-2 infection according to their occupation; however, few studies have been able to control for multiple confounders or investigate the work-related factors that drive differences in occupational risk. Using data from the Virus Watch community cohort study in England and Wales, we set out to estimate the total effect of occupation on SARS-CoV-2 serological status, whether this is mediated by frequency of close contact within the workplace, and how exposure to poorly ventilated workplaces varied across occupations. MethodsWe used data from a sub-cohort (n =3761) of adults ([≥]18) tested for SARS-CoV-2 anti-nucleocapsid antibodies between 01 February-28 April 2021 and responded to a questionnaire about work during the pandemic. Anti-nucleocapsid antibodies were used as a proxy of prior natural infection with COVID-19. We used logistic decomposition to estimate the total and direct effect of occupation and indirect effect of workplace contact frequency on odds of seropositivity, adjusting for age, sex, household income and region. We investigated the relationship between occupation and exposure to poorly-ventilated workplace environments using ordinal logistic regression. ResultsSeropositivity was 16.0% (113/707) amongst workers with daily close contact, compared to 12.9% (120/933) for those with intermediate-frequency contact and 9.6% (203/2121) for those with no work-related close contact. Healthcare (OR= 2.14, 95% CI 1.47,3.12), indoor trade, process and plant (2.09, 1.31,3.33), leisure and personal service (1.96, 1.004,3.84), and transport and mobile machine (2.17, 1.12,4.18) workers had elevated total odds of SARS-CoV-2 seropositivity compared to other professional and associate occupations. Frequency of workplace contact accounted for a variable part of the increased odds in different occupational groups (OR range 1.04 [1.0004,1.07] - 1.22 [1.07, 1.38]). Healthcare workers and indoor trades and process plant workers continued to have raised odds of infection after accounting for work-related contact, and also had had greater odds of frequent exposure to poorly-ventilated workplaces (respectively 2.15 [1.66, 2.79] and (1.51, [1.12, 2.04]). DiscussionMarked variations in occupational odds of seropositivity remain after accounting for age, sex, region, and household income. Close contact in the workplace appears to contribute substantially to this variation. Reducing frequency of workplace contact is a critical part of COVID-19 control measures.

Symptom profiles and accuracy of clinical definitions for COVID-19 in the community. Results of the Virus Watch community cohort.

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.

Spike-antibody responses following first and second doses of ChAdOx1 and BNT162b2 vaccines by age, gender, and clinical factors - a prospective community cohort study (Virus Watch)

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 UKs 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 Roches 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. Results8,517 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 13,232 samples (8,115 following ChAdOx1, 5,008 following BNT162b2). Seropositivity to Spike was 96.42% (95%CI 96, 96.79) at 28-34 days following a single dose, reaching 99.08% (97.8, 99.62) at 7-14 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 of 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 (25.9 vs 42.3 U/ml, p<0.0001), those with a chronic condition (33.0 vs 41.2 U/ml, p<0.0001), diabetes (22.32 vs 36.01 U/ml, p<0.0001), cardiovascular disease (32.1 vs 36.7 U/ml, p=0.0002), or history of cancer (30.1 vs 35.7 U/ml, p=0.0001), particularly those with haematological rather than solid organ cancer (7.48 vs 31.68 U/ml, p<0.0001), and those currently on immunosuppressive therapy (21.7 vs 35.6 U/ml, p<0.0001). Following a second dose, high S-antibody titres ([≥]250U/ml) were observed for nearly all individuals. InterpretationA single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. However, observed disparities in antibody levels after the first dose by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures such as social distancing, for partially vaccinated adults, particularly those who are older and more clinically vulnerable.

Deprivation and Exposure to Public Activities during the COVID-19 Pandemic in England and Wales

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.

Trends, patterns and psychological influences on COVID-19 vaccination intention: findings from a large prospective community cohort study in England and Wales (Virus Watch)

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.