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.

Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of long-term care facilities in the VIVALDI study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused severe disease in unvaccinated long-term care facility (LTCF) residents. Initial booster vaccination following primary vaccination is known to provide strong short-term protection, but data are limited on duration of protection and the protective effect of further booster vaccinations. OBJECTIVE: To evaluate the effectiveness of third, fourth and fifth dose booster vaccination against SARS-CoV-2 related mortality amongst older residents of LTCFs. DESIGN: Prospective cohort study. SETTING: LTCFs for older people in England participating in the VIVALDI study. METHODS: Residents aged >65 years at participating LTCFs were eligible for inclusion if they had at least one polymerase chain reaction or lateral flow device result within the analysis period 1 January 2022 to 31 December 2022. We excluded individuals who had not received at least two vaccine doses before the analysis period. Cox regression was used to estimate relative hazards of SARS-CoV-2 related mortality following 1-3 booster vaccinations compared with primary vaccination, stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF size (total beds). RESULTS: A total of 13,407 residents were included. Our results indicate that third, fourth and fifth dose booster vaccination provide additional short-term protection against SARS-CoV-2 related mortality relative to primary vaccination, with consistent stabilisation beyond 112 days to 45-75% reduction in risk relative to primary vaccination. CONCLUSIONS: Successive booster vaccination doses provide additional short-term protection against SARS-CoV-2 related mortality amongst older LTCF residents. However, we did not find evidence of a longer-term reduction in risk beyond that provided by initial booster vaccination.

Inequalities in access to paid sick leave among workers in England and Wales.

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 pandemic given the relationship between presenteeism and infectious disease transmission. METHOD: This cross-sectional analysis (n = 8874) was nested within a large community cohort study based across England and Wales (Virus Watch). An online survey in February 2021 asked participants in work if they had access to paid sick leave. We used logistic regression to examine sociodemographic factors associated with lacking access to sick pay. RESULTS: Only 66% (n = 5864) of participants reported access to sick pay. South Asian workers (adjusted odds ratio [OR] 1.40, 95% confidence interval [CI] 1.06-1.83) and those from Other minority ethnic backgrounds (OR 2.93, 95% CI 1.54-5.59) were more likely to lack access to sick pay compared to White British workers. Older workers (OR range 1.72 [1.53-1.93]-5.26 [4.42-6.26]), workers in low-income households (OR 2.53, 95% CI 2.15-2.98) and those in transport, trade, and service occupations (OR range 2.03 [1.58-2.61]-5.29 [3.67-7.72]) were also more likely to lack access to sick pay compared respectively to workers aged 25-44, those in high income households and managerial occupations. DISCUSSION: Unwarranted age and ethnic 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 respiratory infections in the community, and in the context of pandemic preparation.

SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN).

BACKGROUND: Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. METHODS: A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. FINDINGS: From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13-0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. INTERPRETATION: A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. FUNDING: Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.

Occupation, work-related contact and SARS-CoV-2 anti-nucleocapsid serological status: findings from the Virus Watch prospective cohort study.

OBJECTIVES: Risk of SARS-CoV-2 infection varies across occupations; however, investigation into factors underlying differential risk is limited. We aimed to estimate the total effect of occupation on SARS-CoV-2 serological status, whether this is mediated by workplace close contact, and how exposure to poorly ventilated workplaces varied across occupations. METHODS: We used data from a subcohort (n=3775) of adults in the UK-based Virus Watch cohort study who were tested for SARS-CoV-2 anti-nucleocapsid antibodies (indicating natural infection). We used logistic decomposition to investigate the relationship between occupation, contact and seropositivity, and logistic regression to investigate exposure to poorly ventilated workplaces. RESULTS: Seropositivity was 17.1% among workers with daily close contact vs 10.0% for those with no work-related close contact. Compared with other professional occupations, healthcare, indoor trade/process/plant, leisure/personal service, and transport/mobile machine workers had elevated adjusted total odds of seropositivity (1.80 (1.03 to 3.14) - 2.46 (1.82 to 3.33)). Work-related contact accounted for a variable part of increased odds across occupations (1.04 (1.01 to 1.08) - 1.23 (1.09 to 1.40)). Occupations with raised odds of infection after accounting for work-related contact also had greater exposure to poorly ventilated workplaces. CONCLUSIONS: Work-related close contact appears to contribute to occupational variation in seropositivity. Reducing contact in workplaces is an important COVID-19 control measure.

Persistence of SARS-CoV-2 N-Antibody Response in Healthcare Workers, London, UK.

Prospective serosurveillance of severe acute respiratory syndrome coronavirus 2 in 1,069 healthcare workers in London, UK, demonstrated that nucleocapsid antibody titers were stable and sustained for <12 weeks in 312 seropositive participants. This finding was consistent across demographic and clinical variables and contrasts with reports of short-term antibody waning.

Changes in COVID-19 outbreak severity and duration in long-term care facilities following vaccine introduction, England, November 2020 to June 2021.

We describe the impact of changing epidemiology and vaccine introduction on characteristics of COVID-19 outbreaks in 330 long-term care facilities (LTCF) in England between November 2020 and June 2021. As vaccine coverage in LTCF increased and national incidence declined, the total number of outbreaks and outbreak severity decreased across the LTCF. The number of infected cases per outbreak decreased by 80.6%, while the proportion of outbreaks affecting staff only increased. Our study supports findings of vaccine effectiveness in LTCF.

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

OBJECTIVES: The importance of SARS-CoV-2 transmission via the eyes is unknown, with previous studies mainly focusing on protective eyewear in healthcare settings. This study aimed to test the hypothesis that wearing eyeglasses is associated with a lower risk of COVID-19. METHODS: Participants from the Virus Watch prospective community cohort study responded to a questionnaire on the use of eyeglasses and contact lenses. Infection was confirmed through data linkage, self-reported positive results, and, for a subgroup, monthly capillary antibody testing. Multivariable logistic regression models, controlling for age, sex, income, and occupation, were used to identify the odds of infection depending on frequency and purpose of eyeglasses or contact lenses use. RESULTS: A total of 19,166 participants responded to the questionnaire, with 13,681 (71.3%, CI 70.7-72.0) reporting they wore eyeglasses. Multivariable logistic regression model showed a 15% lower odds of infection for those who reported using eyeglasses always for general use (odds ratio [OR] 0.85, 95% 0.77-0.95, P = 0.002) compared to those who never wore eyeglasses. The protective effect was reduced for those who said wearing eyeglasses interfered with mask-wearing and was absent for contact lens wearers. CONCLUSIONS: People who wear eyeglasses have a moderate reduction in risk of COVID-19 infection, highlighting that eye protection may make a valuable contribution to the reduction of transmission in community and healthcare settings.

Symptom profiles of community cases infected by influenza, RSV, rhinovirus, seasonal coronavirus, and SARS-CoV-2 variants of concern.

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.

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).

Background: Successive severe acute respiratory syndrome coronavirus 2 (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 the effectiveness of booster vaccination against infections, hospitalizations, 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 hospitalization and death at 0-13, 14-48, 49-83, 84-111, 112-139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 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: A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06-0.63) and death (aHR, 0.50; 95% CI, 0.20-1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths. Conclusions: Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.

Bayesian reconstruction of SARS-CoV-2 transmissions highlights substantial proportion of negative serial intervals.

BACKGROUND: The serial interval is a key epidemiological measure that quantifies the time between the onset of symptoms in an infector-infectee pair. It indicates how quickly new generations of cases appear, thus informing on the speed of an epidemic. Estimating the serial interval requires to identify pairs of infectors and infectees. Yet, most studies fail to assess the direction of transmission between cases and assume that the order of infections - and thus transmissions - strictly follows the order of symptom onsets, thereby imposing serial intervals to be positive. Because of the long and highly variable incubation period of SARS-CoV-2, this may not always be true (i.e an infectee may show symptoms before their infector) and negative serial intervals may occur. This study aims to estimate the serial interval of different SARS-CoV-2 variants whilst accounting for negative serial intervals. METHODS: This analysis included 5 842 symptomatic individuals with confirmed SARS-CoV-2 infection amongst 2 579 households from September 2020 to August 2022 across England & Wales. We used a Bayesian framework to infer who infected whom by exploring all transmission trees compatible with the observed dates of symptoms, based on a wide range of incubation period and generation time distributions compatible with estimates reported in the literature. Serial intervals were derived from the reconstructed transmission pairs, stratified by variants. RESULTS: We estimated that 22% (95% credible interval (CrI) 8-32%) of serial interval values are negative across all VOC. The mean serial interval was shortest for Omicron BA5 (2.02 days, 1.26-2.84) and longest for Alpha (3.37 days, 2.52-4.04). CONCLUSIONS: This study highlights the large proportion of negative serial intervals across SARS-CoV-2 variants. Because the serial interval is widely used to estimate transmissibility and forecast cases, these results may have critical implications for epidemic control.

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.

Tracking Changes in Mobility Before and After the First SARS-CoV-2 Vaccination Using Global Positioning System Data in England and Wales (Virus Watch): Prospective Observational Community Cohort Study.

BACKGROUND: Evidence suggests that individuals may change adherence to public health policies aimed at reducing the contact, transmission, and spread of the SARS-CoV-2 virus after they receive their first SARS-CoV-2 vaccination when they are not fully vaccinated. OBJECTIVE: We aimed to estimate changes in median daily travel distance of our cohort from their registered addresses before and after receiving a SARS-CoV-2 vaccine. METHODS: 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 onward. Between September 2020 and February 2021, we invited 13,120 adult Virus Watch participants to contribute toward our tracker subcohort, which uses the GPS via a smartphone app 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 analyzed the daily travel distance of 249 vaccinated adults. From 157 days prior to vaccination until the day before vaccination, the median daily travel distance was 9.05 (IQR 8.06-10.09) km. From the day of vaccination to 105 days after vaccination, the median daily travel distance was 10.08 (IQR 8.60-12.42) km. From 157 days prior to vaccination until the vaccination date, there was a daily median decrease in mobility of 40.09 m (95% CI -50.08 to -31.10; P<.001). After vaccination, there was a median daily increase in movement of 60.60 m (95% CI 20.90-100; P<.001). Restricting the analysis to the third national lockdown (January 4, 2021, to April 5, 2021), we found a median daily movement increase of 18.30 m (95% CI -19.20 to 55.80; P=.57) in the 30 days prior to vaccination and a median daily movement increase of 9.36 m (95% CI 38.6-149.00; P=.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 data for understanding public health issues. Our various analyses produced results that ranged from no change in movement after vaccination (during the third national lock down) to an increase in movement after vaccination (considering all periods, up to 105 days after vaccination), suggesting that, among Virus Watch participants, any changes in movement distances after vaccination are small. Our findings may be attributable to public health measures in place at the time such as movement restrictions and home working that applied to the Virus Watch cohort participants during the study period.

Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes.

Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21-78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third 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.

Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England.

BACKGROUND: Long-term care facilities (LTCFs) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion of infected people among those who have survived, and duration of the antibody response to natural infection, is unknown. We determined the prevalence and stability of nucleocapsid antibodies (the standard assay for detection of previous infection) in staff and residents in LTCFs in England. METHODS: This was a prospective cohort study of residents 65 years or older and of staff 65 years or younger in 201 LTCFs in England between March 1, 2020, and May 7, 2021. Participants were linked to a unique pseudo-identifier based on their UK National Health Service identification number. Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein using the Abbott ARCHITECT i-system (Abbott, Maidenhead, UK) immunoassay. Primary endpoints were prevalence and cumulative incidence of antibody positivity, which were weighted to the LTCF population. Incidence rate of loss of antibodies (seroreversion) was estimated from Kaplan-Meier curves. FINDINGS: 9488 samples were included, 8636 (91·0%) of which could be individually linked to 1434 residents and 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 34·6% (29·6-40·0) in residents and 26·1% (23·0-29·5) in staff over 11 months. 239 (38·6%) residents and 503 women (81·3%) were included in the antibody-waning analysis, and median follow-up was 149 days (IQR 107-169). The incidence rate of seroreversion was 2·1 per 1000 person-days at risk, and median time to reversion was 242·5 days. INTERPRETATION: At least a quarter of staff and a third of surviving residents were infected with SAR-CoV-2 during the first two waves of the pandemic in England. Nucleocapsid-specific antibodies often become undetectable within the first year following infection, which is likely to lead to marked underestimation of the true proportion of people with previous infection. Given that natural infection might act to boost vaccine responses, better assays to identify natural infection should be developed. FUNDING: UK Government Department of Health and Social Care.

Duration of vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, and death in residents and staff of long-term care facilities in England (VIVALDI): a prospective cohort study.

Background: Residents and staff in long-term care facilities have been prioritised for vaccination against SARS-CoV-2, but data on potential waning of vaccine effectiveness and the effect of booster doses in this vulnerable population are scarce. We aimed to evaluate effectiveness of one, two, and three vaccine doses against infection and severe clinical outcomes in staff and residents of long-term care facilities in England over the first year following vaccine roll-out. Methods: The VIVALDI study is a prospective cohort study done in 331 long-term care facilities in England. Residents aged 65 years or older and staff aged 18 years or older were eligible for participation. Participants had routine PCR testing throughout the study period between Dec 8, 2020, and Dec 11, 2021. We retrieved all PCR results and cycle threshold values for PCR-positive samples from routine testing in long-term care facilities, and positive PCR results from clinical testing in hospitals through the UK's COVID-19 Datastore. PCR results were linked to participants using pseudo-identifiers based on individuals' unique UK National Health Service (NHS) numbers, which were also used to retrieve vaccination records from the National Immunisation Management Service, hospitalisation records from NHS England, and deaths data from the Office for National Statistics through the COVID-19 Datastore. In a Cox proportional hazards regression, we estimated vaccine effectiveness against SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death after one, two, and three vaccine doses, separately by previous SARS-CoV-2 exposure. This study is registered with the ISRCTN Registry, ISRCTN 14447421. Findings: 80 186 residents and staff of long-term care facilities had records available for the study period, of whom 15 518 eligible residents and 19 515 eligible staff were included in the analysis. For residents without evidence of previous SARS-CoV-2 exposure, vaccine effectiveness decreased from 61·7% (95% CI 35·1 to 77·4) to 22·0% (-14·9 to 47·0) against infection; from 89·0% (70·6 to 95·9) to 56·3% (30·1 to 72·6) against hospitalisation; and from 96·4% (84·3 to 99·2) to 64·4% (36·1 to 80·1) against death, when comparing 14-83 days after dose two and 84 days or more after dose two. For staff without evidence of previous exposure, vaccine effectiveness against infection decreased slightly from 57·9% (43·1 to 68·9) at 14-83 days after dose two to 42·1% (29·9 to 52·2) at 84 days or more after dose two. There were no hospitalisations or deaths among unexposed staff at 14-83 days, but seven hospitalisations (vaccine effectiveness 91·0% [95% CI 74·3 to 96·8]) and one death were observed at 84 days or more after dose two. High vaccine effectiveness was restored following a third vaccine dose, with vaccine effectiveness in unexposed residents of 72·7% (55·8 to 83·1) against infection, 90·1% (80·6 to 95·0) against hospitalisation, and 97·5% (88·1 to 99·5) against death; and vaccine effectiveness in unexposed staff of 78·2% (70·0 to 84·1) against infection and 95·8% (49·9 to 99·6) against hospitalisation. There were no COVID-19-related deaths among unexposed staff after the third vaccine dose. Interpretation: Our findings showed substantial waning of SARS-CoV-2 vaccine effectiveness against all outcomes in residents of long-term care facilities from 12 weeks after a primary course of ChAdOx1-S or mRNA vaccines. Boosters restored protection, and maximised immunity across all outcomes. These findings show the importance of boosting and the need for ongoing surveillance in this vulnerable cohort. Funding: UK Government Department of Health and Social Care.

Outcomes of SARS-CoV-2 omicron infection in residents of long-term care facilities in England (VIVALDI): a prospective, cohort study.

Background: The SARS-CoV-2 omicron variant (B.1.1.529) is highly transmissible, but disease severity appears to be reduced compared with previous variants such as alpha and delta. We investigated the risk of severe outcomes following infection in residents of long-term care facilities. Methods: We did a prospective cohort study in residents of long-term care facilities in England who were tested regularly for SARS-CoV-2 between Sept 1, 2021, and Feb 1, 2022, and who were participants of the VIVALDI study. Residents were eligible for inclusion if they had a positive PCR or lateral flow device test during the study period, which could be linked to a National Health Service (NHS) number, enabling linkage to hospital admissions and mortality datasets. PCR or lateral flow device test results were linked to national hospital admission and mortality records using the NHS-number-based pseudo-identifier. We compared the risk of hospital admission (within 14 days following a positive SARS-CoV-2 test) or death (within 28 days) in residents who had tested positive for SARS-CoV-2 in the period shortly before omicron emerged (delta-dominant) and in the omicron-dominant period, adjusting for age, sex, primary vaccine course, past infection, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset of samples. Results: 795 233 tests were done in 333 long-term care facilities, of which 159 084 (20·0%) could not be linked to a pseudo-identifier and 138 012 (17·4%) were done in residents. Eight residents had two episodes of infection (>28 days apart) and in these cases the second episode was excluded from the analysis. 2264 residents in 259 long-term care facilities (median age 84·5 years, IQR 77·9-90·0) were diagnosed with SARS-CoV-2, of whom 253 (11·2%) had a previous infection and 1468 (64·8%) had received a booster vaccination. About a third of participants were male. Risk of hospital admissions was markedly lower in the 1864 residents infected in the omicron-period (4·51%, 95% CI 3·65-5·55) than in the 400 residents infected in the pre-omicron period (10·50%, 7·87-13·94), as was risk of death (5·48% [4·52-6·64] vs 10·75% [8·09-14·22]). Adjusted hazard ratios (aHR) also indicated a reduction in hospital admissions (0·64, 95% CI 0·41-1·00; p=0·051) and mortality (aHR 0·68, 0·44-1·04; p=0·076) in the omicron versus the pre-omicron period. Findings were similar in residents with a confirmed variant. Interpretation: Observed reduced severity of the omicron variant compared with previous variants suggests that the wave of omicron infections is unlikely to lead to a major surge in severe disease in long-term care facility populations with high levels of vaccine coverage or natural immunity. Continued surveillance in this vulnerable population is important to protect residents from infection and monitor the public health effect of emerging variants. Funding: UK Department of Health and Social Care.

Deprivation and exposure to public activities during the COVID-19 pandemic in England and Wales.

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

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.