Assessing the causal effect of air pollution on risk of SARS-CoV-2 infection (preprint)

IntroductionEmerging evidence suggests association of air pollution exposure with risk of SARS-CoV-2 infection, but many of these findings are limited by study design, lack of individual-level covariate data or are specific to certain subpopulations. We aim to evaluate causal effects of air pollution on risk of infection, whilst overcoming these limitations. MethodsConcentrations for black carbon(BC), particulate matter 10(PM10), particulate matter 2.5(PM2.5), nitrogen dioxide(NO2) and oxides of nitrogen(NOx) from the Department of Environment, Food and Rural Affairs (DEFRA) and Effect of Low-level Air Pollution: A Study in Europe (ELAPSE) were linked to postcodes of 53,683 Virus Watch study participants. The primary outcome was first SARS-CoV-2 infection, between 1st September 2020 and 30th April 2021. Regression analysis used modified Poisson with robust estimates, clustered by household, adjusting for individual (e.g., age, sex, ethnicity) and environmental covariates(e.g., population density, region) to estimate total and direct effects. ResultsSingle pollutant analysis showed the direct effect of higher risk of SARS-CoV-2 infection with increased exposure to PM2.5(RR1.11,95%CI 1.08;1.15), PM10(RR1.06,95%CI 1.04;1.09), NO2(RR1.04,95%CI 1.04;1.05) and NOx(RR1.02,95%CI 1.02;1.02) per 1{micro}g/m3 increment with DEFRA 2015-19 data. Sensitivity analyses altering covariates, exposure window and modelled air pollution data source produced similar estimates. Higher risk of SARS-CoV-2 per 10-5m-1 increment of BC (RR1.86, 95%CI 1.62;2.14) was observed using ELAPSE data. ConclusionLong term exposure to higher concentrations of air pollutions increases the risk of SARS-CoV-2 infection, highlighting that adverse health effects of air pollution is not only limited to non-communicable diseases.

Cohort profile: Virus Watch: Understanding community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviour (preprint)

[bullet] Virus Watch is a national community cohort study of COVID-19 in households in England and Wales, established in June 2020. The study aims to provide evidence on which public health approaches are most effective in reducing transmission, and investigate community incidence, symptoms, and transmission of COVID-19 in relation to population movement and behaviours. [bullet] 28,527 households and 58,628 participants of age (0-98 years, mean age 48), were recruited between June 2020 - July 2022 [bullet] Data collected include demographics, details on occupation, co-morbidities, medications, and infection-prevention behaviours. Households are followed up weekly with illness surveys capturing symptoms and their severity, activities in the week prior to symptom onset and any COVID-19 test results. Monthly surveys capture household finance, employment, mental health, access to healthcare, vaccination uptake, activities and contacts. Data have been linked to Hospital Episode Statistics (HES), inpatient and critical care episodes, outpatient visits, emergency care contacts, mortality, virology testing and vaccination data held by NHS Digital. [bullet] Nested within Virus Watch are a serology & PCR cohort study (n=12,877) and a vaccine evaluation study (n=19,555). [bullet] Study data are deposited in the Office of National Statistics (ONS) Secure Research Service (SRS). Survey data are available under restricted access upon request to ONS SRS.

The incidence of COVID-19-related hospitalisation in migrants in the UK: Findings from the Virus Watch prospective community cohort study (preprint)

Background: Migrants in the UK may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic. Methods: We analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran fixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and fixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed. Results: Of 30,276 adults in the analyses, 26,492 (87.5%) were UK-born and 3,784 (12.5%) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95% CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60]. Conclusions: Our findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants.

SARS-CoV-2 infections in migrants and the role of household overcrowding: A causal mediation analysis of Virus Watch data (preprint)

Background: Migrants are over-represented in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections globally; however, evidence is limited for migrants in England and Wales. Household overcrowding is a risk factor for SARS-CoV-2 infection, with migrants more likely to live in overcrowded households than UK-born individuals. We aimed to estimate the total effect of migration status on SARS-CoV-2 infection and to what extent household overcrowding mediated this effect. Methods: We included a sub-cohort of individuals from the Virus Watch prospective cohort study during the second SARS-CoV-2 wave (1st September 2020-30th April 2021) who were aged at least 18 years, self-reported the number of rooms in their household and had no evidence of SARS-CoV-2 infection pre-September 2020. We estimated total, indirect and direct effects using Buis logistic decomposition regression controlling for age, sex, ethnicity, clinical vulnerability, occupation, income and whether they lived with children. Results: In total, 23,478 individuals were included. 9.07% (187/2,062) of migrants had evidence of infection during the study period versus 6.27% (1,342/21,416) of UK-born individuals. Migrants had 22% higher odds of infection during the second wave (total effect; OR:1.22, 95%CI:1.01-1.47). Household overcrowding accounted for approximately 32% of these increased odds (indirect effect, OR:1.07, 95%CI:1.03-1.12; proportion accounted for: indirect effect[7]/total effect[22]=0.32). Conclusion: Migrants had higher odds of SARS-CoV-2 infection during the second wave compared with UK-born individuals and household overcrowding explained 32% of these increased odds. Policy interventions to reduce household overcrowding for migrants are needed as part of efforts to tackle health inequalities during the pandemic and beyond.

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

Background: Occupational 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. Methods: We 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. Findings: Vaccination 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). Interpretation: Differential 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. (preprint)

Background Respiratory 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. Methods Participants 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. Findings 19,166 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. Interpretation People 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.

Migrants' primary care utilisation before and during the COVID-19 pandemic in England: An interrupted time series (preprint)

Background: How international migrants access and use primary care in England is poorly understood. We aimed to compare primary care consultation rates between international migrants and non-migrants in England before and during the COVID-19 pandemic (2015-2020). Methods: Using linked data from the Clinical Practice Research Datalink (CPRD) GOLD and the Office for National Statistics, we identified migrants using country-of-birth, visa-status or other codes indicating international migration. We ran a controlled interrupted time series (ITS) using negative binomial regression to compare rates before and during the pandemic. Findings: In 262,644 individuals, pre-pandemic consultation rates per person-year were 4.35 (4.34-4.36) for migrants and 4.6 (4.59-4.6) for non-migrants (RR:0.94 [0.92-0.96]). Between 29 March and 26 December 2020, rates reduced to 3.54 (3.52-3.57) for migrants and 4.2 (4.17-4.23) for non-migrants (RR:0.84 [0.8-0.88]). Overall, this represents an 11% widening of the pre-pandemic difference in consultation rates between migrants and non-migrants during the first year of the pandemic (RR:0.89, 95%CI:0.84-0.94). This widening was greater for children, individuals whose first language was not English, and individuals of White British, White non-British and Black/African/Caribbean/Black British ethnicities. Interpretation: Migrants were less likely to use primary care before the pandemic and the first year of the pandemic exacerbated this difference. As GP practices retain remote and hybrid models of service delivery, they must improve services and ensure they are accessible and responsive to migrants' healthcare needs. Funding: This study was funded by the Medical Research Council (MR/V028375/1) and Wellcome Clinical Research Career Development Fellowship (206602).

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

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 (preprint)

Abstract Importance The 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. Objective To 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. Design Trial 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. Setting Prospective observational study using the Virus Watch community cohort in England and Wales. Participants People over the age of 18 years who had their booster vaccination between 16/09/2021 to 05/01/2022 without prior natural immunity. Exposures ChAdOx1 versus BNT162b2 as a primary dose, and an mRNA booster vaccine. Results Across 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 Relevance In 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 (preprint)

Introduction: Seroprevalence 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. Methods: Adults aged 18 years and older, 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. Results: A 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. Discussion: Approximately 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.

Inequalities in access to paid sick leave among workers in England and Wales (preprint)

Background It is poorly understood which workers lack access to sick pay in England and Wales. This evidence gap has been of particular interest in the context of the Covid-19 epidemic given the relationship between presenteeism and infectious disease transmission. Method This cross-sectional analysis is nested within a large community cohort study of Covid-19 epidemiology in England and Wales (Virus Watch). An online survey in February 2021 asked participants if they had access to paid sick leave. We use a fixed effect logistic regression model to examine sociodemographic factors associated with lacking access to sick pay. Results 8,874 participants in work responded to the survey item about access to sick pay. Of those, 5,864 (66%) report having access to sick pay, 2,218 (25%) report no access to sick pay and 792 (8.9%) were unsure. Workers aged 45-64 (OR 1.72) and over 65 (OR 5.26) are more likely to lack access to sick pay compared to workers aged 25-44. South Asian workers (OR 1.40) and those from Other minority ethnic backgrounds (OR 2.93) are more likely to lack access to sick pay compared to White British workers. Workers in low income households (OR 1.43-2.53) and those with working class occupations (OR 2.04-5.29) are also more likely to lack access to sick pay compared to those in high income households and managerial occupations. Discussion Unwarranted age and race inequalities in sick pay access are suggestive of labour market discrimination. Occupational differences are also cause for concern. Policymakers should consider expanding access to sick pay to mitigate transmission of Covid-19 and other endemic infectious disease epidemics in the community.

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 (preprint)

Introduction: Infections 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. Method: Trial 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. Results: Across 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. Discussion: We 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 (preprint)

Background: Workplaces 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. Methods: Data 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. Findings: Workplace 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. Interpretation: Major 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 (preprint)

Background: Workers 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 October 2021, after adjustment for potential confounding and stratification by pandemic phase. Methods: Data from 12,182 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 each occupational group based on adjusted risk ratios (aRR). Findings: Increased risk was seen in nurses (aRR=1.90 [1.40-2.40], AF=47%); doctors (1.74 [1.26-2.40], 42%); carers (2.18 [1.63-2.92], 54%); teachers (primary = 1.94 [1.44- 2.61], 48%; secondary =1.64, [1.23-2.17], 39%), and warehouse and process/plant workers (1.58 [1.20-2.09], 37%) compared to both office-based professional occupations (reported above) and all other occupations. Differential risk was apparent in the earlier phases (Feb 2020 - May 2021) and attenuated later (June - October 2021) for most groups, although teachers demonstrated persistently elevated risk. Interpretation: Occupational differentials in SARS-CoV-2 infection risk are robust to adjustment for socio-demographic, health-related, and activity-related potential confounders. Patterns of differential infection risk varied over time, and ongoing excess risk was observed in education professionals. 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 (preprint)

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.

Waning of SARS-CoV-2 antibodies targeting the Spike protein in individuals post second dose of ChAdOx1 and BNT162b2 COVID-19 vaccines and risk of breakthrough infections: analysis of the Virus Watch community cohort (preprint)

Background SARS-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. Methods We 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. Results 24049 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, p<0.001). Discussion Anti-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.

Check the Effectiveness of Face Mask and Air Quality Meter (preprint)

Following the recent emergence of COVID-19, numerous individuals have depended on delivering their homemade face covers because of supply deficiencies and to permit medical care laborers the legitimate PPE required by them in medical care. The viability of custom made face masks is a contested point as of late with a great deal of falsehood spreading, regularly with no huge logical support. The goal of this project is to create a low priced device that can obtain quantitative results and tell us how effective a homemade or surgical face mask is at removing particulates The particulate sensor that was used in the project can observe particles that are of size 1.0 μm, 2.5 μm and 10.0 μm in diameter and along with it to measure the quality of air around us using the MQ-135 air quality sensor.

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) (preprint)

Abstract Background: Some 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. Method: Participants 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. Results: We 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. Conclusions: Our 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.

Relative perceived importance of different settings for SARS-CoV2 acquisition in England and Wales: Analysis of the Virus Watch Community Cohort (preprint)

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.

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

Background: Understanding 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. Methods: Virus 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 change in sense of smell or taste) with a wider definition that also included muscle aches or chills or headache or loss of appetite. Findings: We included results from 8213 swabbed illnesses, 944 of which tested positive for COVID-19. All symptoms were more common in swab positive than swab 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. Rarer symptoms such as fever or loss or altered sense of smell or taste were often not present but were markedly more common in swab positive compared to swab negative cases. 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 one day earlier than current definition. 1.7-fold more illnesses met the broader definition than the current case definition. Interpretation: COVID-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 but with a large increase in the number of tests needed and in the number of people and contacts who do not have COVID-19 but might need to self-isolate whilst awaiting results.