Barriers in accessing healthcare during the COVID-19 pandemic: analysis of the Virus Watch community cohort study (preprint)

Background: Differential barriers to accessing healthcare contribute to inequitable health outcomes. This study aims to describe the characteristics of individuals who experienced barriers, and what those barriers were, during the COVID-19 pandemic. Methods: We analysed data from Virus Watch: an online survey-based community study of households in England and Wales. The primary outcome was reported difficulty accessing healthcare in the previous year. Results: Minority ethnic participants reported difficulty accessing healthcare more than White British participants (41.6% vs 37%), while for migrants this was at broadly similar levels to non-migrants. Those living in the most deprived areas reported difficulty more than those living in the least deprived quintile (45.5% vs. 35.5%). The most frequently reported barrier was cancellation/disruption of services due to the COVID-19 pandemic (72.0%) followed by problems with digital or telephone access (21.8%). Ethnic minority participants, migrants, and those from deprived areas more commonly described 'insufficient flexibility of appointments' and 'not enough time to explain complex needs' as barriers. Conclusions: Minority ethnic individuals and those living in deprived areas were more likely to experience barriers to healthcare during the COVID-19 pandemic, and it is essential they are addressed as services seek to manage backlogs of care.

Adherence to mask wearing and social distancing following vaccination and use of lateral flow testing during the COVID-19 pandemic in England and Wales: Results from a cross-sectional study nested within the prospective Virus Watch household community cohort study (preprint)

Background Personal protective behaviours (PPBs) played a crucial role in limiting the spread of infection during the COVID-19 pandemic, yet adherence to these behaviours varied at population level. Understanding the factors influencing adherence to protective behaviours is important, as PPBs will be a critical part of the response in future pandemics. Using behavioural science, we investigated the influences on adherence to PPBs, focusing on face mask wearing, social distancing, and lateral flow testing (LFT). Methods Two online surveys, the first gathering data on mask wearing and social distancing, and the second on lateral flow testing, were conducted in July and August 2021 with a sample from England and Wales (N = 20,488 (survey 1) and N = 26,613 (survey 2)). The survey questions were designed based on the Capability, Opportunity, Motivation (COM-B) model of Behavior. Multivariate models were used to examine associations between identified influences and adoption of these protective behaviours. Results Most respondents reported wearing a face mask in public indoor places (88.5%) and maintaining a 1+ metre distance (86.8%) all or most of the time. After two doses of COVID-19 vaccine, social distancing decreased with 48.3% reporting meeting friends or family and 38.3% visiting indoor places more frequently. Motivation, Opportunity and Capability factors were significantly associated with increased odds of wearing a face covering and social distancing. Among individuals who indicated using an LFT (comprising 68% of the total sample), 50.4% reported engaging in routine testing. For those who had never used an LFT, the predominant reason cited was a perceived lack of necessity for testing (55.3%). Statistically significant associations were found between routine testing and accurate interpretation of test results across all LFT belief-based statements (p < 0.05). Conclusions Findings indicated high levels of adherence to face masks, social distancing, and lateral flow testing, even amid reduced restrictions and high vaccination rates. Utilising a behavioural science framework, factors related to capability, opportunity, and motivation were found to significantly influence the use of these protective behaviours. Our recommendations can inform public health intervention design and guide the selection of implementation strategies for public health emergencies preparedness.

Long-Term Outcomes of SARS-CoV-2 Variants and Other Respiratory Infections: Evidence from the Virus Watch Prospective Cohort in England (preprint)

BackgroundGiven the considerable prevalence of long-term sequelae following SARS-CoV-2 infection, understanding pathogen-related factors that influence long-term outcomes is warranted. We aimed to compare the likelihood of long-term symptoms for SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals. MethodData were from 5,630 individuals participating in Virus Watch, a prospective community cohort study of SARS-CoV-2 epidemiology in England. We used logistic regression to compare the predicted probability of developing long-term symptoms (>2 months duration) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status. ResultsPredicted probability of long-term sequelae was greater following SARS-CoV-2 infection during the Wild Type (adjusted predicted probability (PP) 0.28, 95% confidence interval (CI) =0.14-0.43), Alpha (PP= 0.28, 95% CI =0.14-0.42), Delta (PP= 0.34, 95% CI=0.25-0.43) and Omicron BA.1 periods (PP= 0.27, 95% CI =0.22-0.33) compared to later Omicron sub-variants (PP range from 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, estimates for long-term symptoms following both infection types substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00,0.02 to 0.03, 95% CI 0.01-0.06) across all variant periods. ConclusionsBetween-variant differences influenced the likelihood of post-infection sequelae for SARS-CoV-2, with lower predicted probabilities for recent Omicron sub-variants similar to those for other contemporaneous ARIs. Both SARS-CoV-2 and other ARIs were associated with long-term symptom development, and further aetiological investigation including between-pathogen comparison is recommended.

Examining the association of live virus neutralisation activity of capillary microsamples and risk of SARS-CoV-2 infections: a nested case control study within the Virus Watch community cohort (preprint)

Due to the proliferation of new SARS-CoV-2 variants, most COVID-19 cases are now caused by post-vaccine infections and a substantial proportion are reinfections. While prior research on correlates of protection has focused on the role of anti-spike antibodies, the results of the corresponding antibody assays may not accurately predict the risk of infection with new SARS-CoV-2 variants. In this study, we investigated the association between live virus neutralising antibody activity and SARS-CoV-2 infection risk using self-administered capillary microsample blood tests from VirusWatch participants. The study was conducted during the transition between the dominance of the B.1.617.2 (Delta) and B.1.1.529 (Omicron BA.1) SARS-CoV-2 variants, enabling us to investigate the association between variant-specific virus inhibition and subsequent infections within each dominance period. Greater inhibition of Omicron BA.1 live virus was associated with a reduction in infection risk during both the Delta and Omicron BA.1 dominance periods. Delta virus inhibition was associated with infection risk reduction during the Delta dominance period, but we found no association between Delta inhibition and protection against infection during the Omicron BA.1 dominance period. Our results are consistent with earlier findings and suggest that variant-specific serosurveillance of immunity and protection against SARS-CoV-2 infection at the population level could inform public health policy in near-real time using inexpensive and accessible home-based testing.

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.

Synthesis and new evidence from the PROTECT UK National Core Study: Determining occupational risks of SARS-CoV-2 infection and COVID-19 mortality (preprint)

Introduction: The PROTECT National Core Study was funded by the UK Health and Safety Executive (HSE) to investigate routes of transmission for SARS-CoV-2 and variation between settings. Methods: A workshop was organised in Oct 2022.We brought together evidence from five published epidemiological studies that compared risks of SARS-CoV-2 infection or COVID-19 mortality by occupation or sector funded by PROTECT relating to three non-overlapping data sets, plus additional unpublished analyses relating to the Omicron period. We extracted descriptive study level data and model results. We investigated risk across four pandemic waves using forest plots for key occupational groups by time-period. Results: Results were largely consistent across different studies with different expected biases. Healthcare and social care sectors saw elevated risks of SARS-CoV-2 infection and COVID-19 mortality early in the pandemic, but thereafter this declined and varied by specific occupational subgroup. The education sector saw sustained elevated risks of infection after the initial lockdown period with little evidence of elevated mortality. Conclusions: Increased in risk of infection and mortality were consistently observed for occupations in high risk sectors particularly during the early stage of the pandemic. The education sector showed a different pattern compared to the other high risk sectors, as relative risk of infections remained high in the later phased of the pandemic, although no increased in COVID-19 mortality (compared to low-risk occupations) was observed in this sector in any point during the pandemic.

Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of Long-Term Care Facilities in the VIVALDI study (preprint)

We evaluated the effectiveness of 1-3 booster vaccinations against SARS-CoV-2 related mortality among a cohort of 13407 older residents of long-term care facilities (LTCFs) participating in the VIVALDI study in England in 2022. Cox regression was used to estimate relative hazards of SARS-CoV-2 related death following booster vaccination relative to 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF capacity. Each booster provided additional short-term protection relative to primary vaccination, with consistent pattern of waning to 45-75% reduction in risk beyond 112 days.

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.

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.

Symptom profiles of community cases infected by Influenza, RSV, rhinovirus, seasonal coronavirus, and SARS-CoV-2 variants of concern (preprint)

Respiratory viruses that were suppressed through previous lockdowns during the COVID-19 pandemic have recently started to co-circulate with SARS-CoV-2. Understanding the clinical characteristics and symptomatology of different respiratory viral infections can help address the challenges related to the identification of cases and the understanding of SARS-CoV-2 variants' evolutionary patterns. Flu Watch (2006-2011) and Virus Watch (2020-2022) are household community cohort studies monitoring the epidemiology of influenza, respiratory syncytial virus, rhinovirus, seasonal coronavirus, and SARS-CoV-2, in England and Wales. This study describes and compares the proportion of symptoms reported during illnesses infected by common respiratory viruses. The SARS-CoV-2 symptom profile increasingly resembles that of other respiratory viruses as new strains emerge. Increased cough, sore throat, runny nose, and sneezing are associated with the emergence of the Omicron strains. As SARS-CoV-2 becomes endemic, monitoring the evolution of its symptomatology associated with new variants will be critical for clinical surveillance.

Exploring the relationship between job characteristics and infection: Application of a COVID-19 Job Exposure Matrix to SARS-CoV-2 infection data in the United Kingdom (preprint)

ObjectivesTo assess whether workplace exposures as estimated via a COVID-19 Job Exposure Matrix (JEM) are associated with SARS-CoV-2. MethodsData on 244,470 participants were available from the ONS Coronavirus Infection Survey (CIS) and 16,801 participants from the Virus Watch Cohort, restricted to workers aged 20 to 64. Analysis used logistic regression models with SARS-CoV-2 as the dependent variable for eight individual JEM domains (number of workers, nature of contacts, contact via surfaces, indoor or outdoor location, ability to social distance, use of face covering, job insecurity, migrant workers) with adjustment for age, sex, ethnicity, Index of Multiple Deprivation (IMD), region, household size, urban vs rural area, and health conditions. Analyses were repeated for three time periods (i) February 2020 (Virus Watch)/April 2020 (CIS) to May 2021), (ii)June 2021 to November 2021, (iii) December 2021 to January 2022. ResultsOverall, higher risk classifications for the first six domains tended to be associated with an increased risk of infection, with little evidence of a relationship for domains relating to proportion of workers with job insecurity or migrant workers. By time there was a clear exposure-response relationship for these domains in the first period only. Results were largely consistent across the two cohorts. ConclusionsAn exposure-response relationship exists in the early phase of the COVID-19 pandemic for number of contacts, nature of contacts, contacts via surfaces, indoor or outdoor location, ability to social distance and use of face coverings. These associations appear to have diminished over time.

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 (preprint)

ABSTRACT Background Studies 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. Methods Participants (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. Results 457/1,154 (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. Conclusion Participants 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.

Clinical effectiveness of SARS-CoV-2 booster vaccine against Omicron infection in residents and staff of Long-Term Care Facilities: a prospective cohort study (VIVALDI) (preprint)

Background Successive SARS-CoV-2 variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated effectiveness of booster vaccination against infections, hospitalisations and deaths among LTCF residents and staff in England. Methods We included residents and staff of LTCFs within the VIVALDI study ( ISRCTN 14447421 ) who underwent routine, asymptomatic testing (December 12 2021-March 31 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalisation and death at 0-13, 14-48, 49-83 and 84 days after dose 3 of SARS-CoV-2 vaccination compared to 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity and local SARS-CoV-2 incidence. Results 14175 residents and 19973 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-83 days after first booster, but no protection was apparent after 84 days. Additional protection following booster vaccination waned, but was still present at 84+ days for COVID-associated hospitalisation (aHR: 0.47, 0.24-0.89) and death (aHR: 0.37, 0.21-0.62). Most residents (64.4%) had received primary course of AstraZeneca, but this did not impact on pre- or post-booster risks. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalisations and no deaths. Conclusions Booster vaccination provides sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 3 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial. Summary The COVID-19 pandemic has severely impacted residents in long-term care facilities (LTCFs). Booster vaccination provides sustained moderate protection against severe outcomes, but no protection against infection was apparent from around 3 months onwards. Ongoing surveillance in LTCFs is crucial.

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.

Strong peak immunogenicity but rapid antibody waning following third vaccine dose in elderly residents of care homes (preprint)

Third dose COVID-19 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable elderly people who exhibit suboptimal responses after primary series vaccination. We studied spike-specific immune responses in 341 staff and residents in long-term care facilities (LTCF) who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third dose vaccination strongly increased antibody responses with preferential enhancement in older people and was required to elicit neutralisation of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titres fell 21-78% within 100 days post vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a 3rd vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.

Duration of vaccine effectiveness against SARS-CoV2 infection, hospitalisation, and death in residents and staff of Long-Term Care Facilities (VIVALDI): a prospective cohort study, England, Dec 2020-Dec 2021 (preprint)

Background Long-term care facilities (LTCF) have been prioritised for vaccination, but data on potential waning of vaccine effectiveness (VE) and the impact of booster doses in this vulnerable population remains scarce. Methods We included residents and staff from 331 LTCFs enrolled in VIVALDI (ISRCTN 14447421), who underwent routine PCR testing between Dec 8, 2020 - Dec 11, 2021 in a Cox proportional hazards regression, estimating VE against SARS-CoV2 infection, COVID-19-related hospitalisation, and COVID-19-related death after 1-3 vaccine doses, stratifying by previous SARS-CoV2 exposure. Results For 15,518 older residents, VE declined from 50.7% (15.5, 71.3) to 17.2% (-23.9, 44.6) against infection; from 85.4% (60.7, 94.6) to 54.3% (26.2, 71.7) against hospitalisation; and from 94.4% (76.4, 98.7) to 62.8% (32.9, 79.4) against death, when comparing 2-12 weeks and [≥]12 weeks after two doses. For 19,515 staff, VE against infection declined slightly from 50.3% (32.7, 63.3) to 42.1% 29.5, 52.4). High VE was restored following a third dose, with VE of 71.6% (53.5, 82.7) and 78.3% (70.1, 84.3) against infection and 89.9% (80.0, 94.6) and 95.8% (50.4, 99.6) against hospitalisation, for residents and staff respectively; and 97.5% (88.1, 99.5) against death for residents. Interpretation Substantial waning of VE is observed against all outcomes in residents from 12 weeks after a primary course of AstraZeneca or mRNA vaccines. Boosters restore protection, and maximise immunity across all outcomes. These findings demonstrate the importance of boosting and the need for ongoing surveillance of VE in this vulnerable cohort. Funding UK Government Department of Health and Social Care.

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.

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.

SARS-CoV-2 anti-spike antibody levels following second dose of ChAdOx1 nCov-19 or BNT162b2 in residents of long-term care facilities in England (VIVALDI) (preprint)

Background General population studies have shown strong humoral response following SARS-CoV-2 vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations such as Long-Term Care Facility (LTCF) residents but published data are scarce. Methods VIVALDI is a prospective cohort study in England which links serial blood sampling in LTCF staff and residents to routine healthcare records. We measured quantitative titres of SARS-CoV-2 anti-spike antibodies in residents and staff following second vaccination dose with ChAdOx1 nCov-19 (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech). We investigated differences in peak antibody levels and rates of decline using linear mixed effects models. Results We report on 1317 samples from 402 residents (median age 86 years, IQR 78-91) and 632 staff (50 years, 37-58), ≤280 days from second vaccination dose. Peak antibody titres were 7.9-fold higher after Pfizer-BioNTech vaccine compared to Oxford-AstraZeneca (95%CI 3.6-17.0; P <0.01) but rate of decline was increased, and titres were similar at 6 months. Prior infection was associated with higher peak antibody levels in both Pfizer-BioNTech (2.8-fold, 1.9-4.1; P <0.01) and Oxford-AstraZeneca (4.8-fold, 3.2-7.1; P <0.01) recipients and slower rates of antibody decline. Increasing age was associated with a modest reduction in peak antibody levels for Oxford-AstraZeneca recipients. Conclusions Double-dose vaccination elicits robust and stable antibody responses in older LTCF residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.