Household transmission of seasonal coronavirus infections: Results from the Flu Watch cohort study.

Background: In the context of the current coronavirus disease 2019 (COVID-19) pandemic, understanding household transmission of seasonal coronaviruses may inform pandemic control. We aimed to investigate what proportion of seasonal coronavirus transmission occurred within households, measure the risk of transmission in households, and describe the impact of household-related factors of risk of transmission. Methods: Using data from three winter seasons of the UK Flu Watch cohort study, we measured the proportion of symptomatic infections acquired outside and within the home, the household transmission risk and the household secondary attack risk for PCR-confirmed seasonal coronaviruses. We present transmission risk stratified by demographic features of households. Results: We estimated that the proportion of cases acquired outside the home, weighted by age and region, was 90.7% (95% CI 84.6- 94.5, n=173/195) and within the home was 9.3% (5.5-15.4, 22/195). Following a symptomatic coronavirus index case, 14.9% (9.8 - 22.1, 20/134) of households experienced symptomatic transmission to at least one other household member. Onward transmission risk ranged from 11.90% (4.84-26.36, 5/42) to 19.44% (9.21-36.49, 7/36) by strain. The overall household secondary attack risk for symptomatic cases was 8.00% (5.31-11.88, 22/275), ranging across strains from 5.10 (2.11-11.84, 5/98) to 10.14 (4.82- 20.11, 7/69). Median clinical onset serial interval was 7 days (IQR= 6-9.5). Households including older adults, 3+ children, current smokers, contacts with chronic health conditions, and those in relatively deprived areas had the highest transmission risks. Child index cases and male index cases demonstrated the highest transmission risks. Conclusion: Most seasonal coronaviruses appear to be acquired outside the household, with relatively modest risk of onward transmission within households. Transmission risk following an index case appears to vary by demographic household features, with potential overlap between those demonstrating the highest point estimates for seasonal coronavirus transmission risk and COVID-19 susceptibility and poor illness outcomes.

Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data.

Background: International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods: We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results: The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.

Between-occupation differences in work-related COVID-19 mitigation strategies over time: Analysis of the Virus Watch Cohort in England and Wales.

OBJECTIVES: COVID-19 mitigations have had a profound impact on workplaces, however, multisectoral comparisons of how work-related mitigations were applied are limited. This study aimed to investigate (i) occupational differences in the usage of key work-related mitigations over time and (ii) workers' perceptions of these mitigations. METHODS: Employed/self-employed Virus Watch study participants (N=6279) responded to a mitigation-related online survey covering the periods of December 2020-February 2022. Logistic regression was used to investigate occupation- and time-related differences in the usage of work-related mitigation methods. Participants' perceptions of mitigation methods were investigated descriptively using proportions. RESULTS: Usage of work-related mitigation methods differed between occupations and over time, likely reflecting variation in job roles, workplace environments, legislation and guidance. Healthcare workers had the highest predicted probabilities for several mitigations, including reporting frequent hand hygiene [predicted probability across all survey periods 0.61 (95% CI 0.56-0.66)] and always wearing face coverings [predicted probability range 0.71 (95% CI 0.66-0.75) - 0.80 (95% CI 0.76-0.84) across survey periods]. There were significant cross-occupational trends towards reduced mitigations during periods of less stringent national restrictions. The majority of participants across occupations (55-88%) agreed that most mitigations were reasonable and worthwhile even after the relaxation of national restrictions; agreement was lower for physical distancing (39-44%). CONCLUSIONS: While usage of work-related mitigations appeared to vary alongside stringency of national restrictions, agreement that most mitigations were reasonable and worthwhile remained substantial. Further investigation into the factors underlying between-occupational differences could assist pandemic planning and prevention of workplace COVID-19 transmission.

Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales – analysis of the Virus Watch household community cohort study [version 1, peer review: 2 approved]

Background: "Lockdowns” to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic. However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics. Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household. Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk. We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission. Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 – 1.42), APAF 6.9%);public transport (more than once per week AOR 1.82 (1.49 – 2.23), public transport APAF 12.42%);and shopping (more than once per week AOR 1.69 (1.29 – 2.21), shopping APAF 34.56%). Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities. Most participants visited shops, accounting for one-third of non-household transmission. Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective. If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.

Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.

Background: "Lockdowns" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.  However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.  Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.  Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.  We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission.  Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).  Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.  Most participants visited shops, accounting for one-third of non-household transmission.  Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.   If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.

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

BACKGROUND: Workers across different occupations vary in their risk of SARS-CoV-2 infection, 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. METHODS: Data 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). RESULTS: Increased 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. CONCLUSIONS: Occupational differences 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.

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.

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 = 1154) 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: 457/1154 (39.60 %) participants reported non-household contacts post-vaccination compared with 371/1154 (32.15 %) participants pre-vaccination. 100/1154 (8.67 %) participants reported use of non-essential shops or services post-vaccination compared with 74/1154 (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.

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.

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

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

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.

Bayesian reconstruction of household transmissions to infer the serial interval of COVID-19 by variants of concern: analysis from a prospective community cohort study (Virus Watch).

BACKGROUND: The serial interval is a key epidemiological measure that quantifies the time between an infector's and an infectee's onset of symptoms. This measure helps investigate epidemiological links between cases, and is an important parameter in transmission models used to estimate transmissibility and inform control strategies. The emergence of multiple variants of concern (VOC) during the SARS-CoV-2 pandemic has led to uncertainties about potential changes in the serial interval of COVID-19. We estimated the household serial interval of multiple VOC using data collected by the Virus Watch study. This online, prospective, community cohort study followed-up entire households in England and Wales since mid-June 2020. METHODS: This analysis included 5842 symptomatic individuals with confirmed SARS-CoV-2 infection among 2579 households from Sept 1, 2020, to Aug 10, 2022. SARS-CoV-2 variant designation was based upon national surveillance data of variant prevalence by date and geographical region. We used a Bayesian framework to infer who infected whom by exploring all transmission trees compatible with the observed dates of symptoms, given assumptions on the incubation period and generation time distributions using the R package outbreaker2. FINDINGS: We characterised the serial interval of COVID-19 by VOC. The mean serial interval was shortest for omicron BA5 (2·02 days; 95% credible interval [CrI] 1·26-2·84) and longest for alpha (3·37 days; 2·52-4·04). The mean serial interval before alpha (wild-type) was 2·29 days (95% CrI 1·39-2·94), 3·11 days (2·28-3·90) for delta, 2·72 days (2·01-3·47) for omicron BA1, and 2·67 days (1·90-3·46) for omicron BA2. We estimated that 17% (95% CrI 5-26) of serial interval values are negative across all variants. INTERPRETATION: Most methods estimating the reproduction number from incidence time series do not allow for a negative serial interval by construction. Further research is needed to extend these methods and assess biases introduced by not accounting for negative serial intervals. To our knowledge, this study is the first to use a Bayesian framework to estimate the serial interval of all major SARS-CoV-2 VOC from thousands of confirmed household cases. FUNDING: UK Medical Research Council and Wellcome Trust.

COVID-19 vaccination uptake for half a million non-EU migrants and refugees in England: a linked retrospective population-based cohort study.

BACKGROUND: COVID-19 has highlighted severe health inequities experienced by certain migrants. Despite evidence suggesting that migrants are at risk of under-immunisation, data are limited for migrants' COVID-19 vaccine uptake in England. METHODS: We did a retrospective population-based cohort study on COVID-19 vaccination uptake in England. We linked the Million Migrant cohort (which includes non-EU migrants and resettled refugees) to the national COVID-19 vaccination dataset, using a stepwise deterministic matching procedure adapted from NHS Digital, and compared migrants with the general population. For migrants who linked to at least one vaccination record, we estimate temporal trends in first dose uptake and differences in second and third dose uptake and consequent delays between Dec 8, 2020, and April 20, 2022, by age, visa type, and ethnicity. FINDINGS: Of the 465 470 migrants who linked to one or more vaccination record, 427 073 (91·8%) received a second dose and 238 721 (51·3%) received a third. Migrants (>30 years) reached 75% first-dose coverage between 1 and 2 weeks after the general population in England, with the gap widening to 6 weeks for younger migrants (16-29 years). Refugees specifically had a higher risk of a delayed second dose (odds ratio 1·75 [95 CI% 1·62-1·88]) and third dose (1·41 [1·31-1·53]). Older migrants (>65 years) were at least four times more likely to have not received their second or third dose compared with those of the same age in England. INTERPRETATION: Uptake of the first dose was slower across all age groups for migrants compared with the general population. Refugees and older migrants were more likely to have delayed uptake of COVID-19 vaccines and to not have received their second or third dose. Policymakers, researchers, and practitioners should consider how to best drive uptake of COVID-19 and other routine vaccine doses and understand and address personal and structural barriers to vaccination systems for diverse migrant populations. FUNDING: Wellcome Trust and UK Research and Innovation.

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

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.

Human mobility variations in response to restriction policies during the COVID-19 pandemic: An analysis from the Virus Watch community cohort in England, UK

Objective Since the outbreak of COVID-19, public health and social measures to contain its transmission (e.g., social distancing and lockdowns) have dramatically changed people's lives in rural and urban areas globally. To facilitate future management of the pandemic, it is important to understand how different socio-demographic groups adhere to such demands. This study aims to evaluate the influences of restriction policies on human mobility variations associated with socio-demographic groups in England, UK. Methods Using mobile phone global positioning system (GPS) trajectory data, we measured variations in human mobility across socio-demographic groups during different restriction periods from Oct 14, 2020 to Sep 15, 2021. The six restriction periods which varied in degree of mobility restriction policies, denoted as “Three-tier Restriction,” “Second National Lockdown,” “Four-tier Restriction,” “Third National Lockdown,” “Steps out of Lockdown,” and “Post-restriction,” respectively. Individual human mobility was measured with respect to the time period people stayed at home, visited places outside the home, and traveled long distances. We compared these indicators across the six restriction periods and across socio-demographic groups. Results All human mobility indicators significantly differed across the six restriction periods, and the influences of restriction policies on individual mobility behaviors are correlated with socio-demographic groups. In particular, influences relating to mobility behaviors are stronger in younger and low-income groups in the second and third national lockdowns. Conclusions This study enhances our understanding of the influences of COVID-19 pandemic restriction policies on human mobility behaviors within different social groups in England. The findings can be usefully extended to support policy-making by investigating human mobility and differences in policy effects across not only age and income groups, but also across geographical regions.

Spike-antibody responses to COVID-19 vaccination by demographic and clinical factors in a prospective community cohort study.

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

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

OBJECTIVES: Seroprevalence studies can provide a measure of SARS-CoV-2 cumulative incidence, but a better understanding of spike and nucleocapsid (anti-N) antibody dynamics following infection is needed to assess the longevity of detectability. METHODS: Adults aged ≥18 years, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary blood samples, which were tested for spike antibody and anti-N. Participants self-reported vaccination dates and past medical history. Previous polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System linkage data. The primary outcome variables were seropositivity and total anti-N and spike antibody levels after PCR-confirmed infection. RESULTS: A total of 13,802 eligible individuals provided 58,770 capillary blood samples. A total of 537 of these had a previous positive PCR-confirmed SARS-CoV-2 infection within 0-269 days of antibody sample date, among them 432 (80.45%) having a positive anti-N result. Median anti-N levels peaked between days 90 and 119 after PCR results and then began to decline. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories. CONCLUSION: Our findings suggest that anti-N has around 80% sensitivity for identifying previous COVID-19 infection, and the duration of detectability is affected by sex and age.

SARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort.

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

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

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 data from the Clinical Practice Research Datalink (CPRD) GOLD, we identified migrants using country-of-birth, visa-status or other codes indicating international migration. We linked CPRD to Office for National Statistics deprivation data and 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 4.60 (4.59-4.60) 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]). The first year of the pandemic was associated with a widening of the gap in consultation rates between migrants and non-migrants to 0.89 (95% CI 0.84-0.94) times the ratio before the pandemic. This widening in ratios 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. It was also greater in the case of telephone consultations, particularly in London. Interpretation: Migrants were less likely to use primary care than non-migrants 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 primary care is accessible and responsive to migrants' healthcare needs. Funding: This study was funded by the Medical Research Council (MC_PC 19070 and MR/V028375/1) and a Wellcome Clinical Research Career Development Fellowship (206602).

Workplace contact patterns in England during the COVID-19 pandemic: Analysis of the Virus Watch prospective cohort study.

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 across the COVID-19 pandemic in England. Methods: Data were obtained from electronic contact diaries (November 2020-November 2021) submitted by employed/self-employed prospective cohort study participants (n=4,616). We used mixed models to investigate the effects of occupation and time for: workplace attendance, number of people sharing 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, workspace sharing and close contact increased and usage of face coverings decreased during phases of less stringent restrictions. Interpretation: Major variations in workplace contact patterns and mask use likely contribute to differential COVID-19 risk. Patterns of variation by occupation and restriction phase may inform interventions for future waves of COVID-19 or other respiratory epidemics. Across occupations, increasing workplace contact and reduced face covering usage is concerning given ongoing high levels of community transmission and emergence of variants. Funding: Medical Research Council; HM Government; Wellcome Trust.