Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study.

The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination. The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0-6 days, 7-13 days, 14-20 days, 21-27 days, 28-34 days, 35-48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421. 10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80-91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24-0·81) at 28-34 days and 0·38 (0·19-0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15-0·66) and BNT162b2 (0·35, 0·17-0·71) vaccines at 35-48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001). Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4-7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities. UK Government Department of Health and Social Care.

Shrotri M ，Krutikov M ，Palmer T ，Giddings R ，Azmi B ，Subbarao S ，Fuller C ，Irwin-Singer A ，Davies D ，Tut G ，Lopez Bernal J ，Moss P ，Hayward A ，Copas A ，Shallcross L ... -  《-》

Effectiveness of BNT162b2 and ChAdOx1 nCoV-19 COVID-19 vaccination at preventing hospitalisations in people aged at least 80 years: a test-negative, case-control study.

On Dec 8, 2020, deployment of the first SARS-CoV-2 vaccination authorised for UK use (BNT162b2 mRNA vaccine) began, followed by an adenoviral vector vaccine ChAdOx1 nCoV-19 on Jan 4, 2021. Care home residents and staff, frontline health-care workers, and adults aged 80 years and older were vaccinated first. However, few data exist regarding the effectiveness of these vaccines in older people with many comorbidities. In this post-implementation evaluation of two COVID-19 vaccines, we aimed to determine the effectiveness of one dose in reducing COVID-19-related admissions to hospital in people of advanced age. This prospective test-negative case-control study included adults aged at least 80 years who were admitted to hospital in two NHS trusts in Bristol, UK with signs and symptoms of respiratory disease. Patients who developed symptoms before receiving their vaccine or those who received their vaccine after admission to hospital were excluded, as were those with symptoms that started more than 10 days before hospital admission. We did logistic regression analysis, controlling for time (week), sex, index of multiple deprivations, and care residency status, and sensitivity analyses matched for time and sex using a conditional logistic model adjusting for index of multiple deprivations and care residency status. This study is registered with ISRCTN, number 39557. Between Dec 18, 2020, and Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). 18 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2. The adjusted vaccine effectiveness was 71·4% (95% CI 46·5-90·6). Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19. The adjusted vaccine effectiveness was 80·4% (95% CI 36·4-94·5). When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3% (95% CI 47·0-92·5). One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years. Pfizer.

Hyams C ，Marlow R ，Maseko Z ，King J ，Ward L ，Fox K ，Heath R ，Tuner A ，Friedrich Z ，Morrison L ，Ruffino G ，Antico R ，Adegbite D ，Szasz-Benczur Z ，Garcia Gonzalez M ，Oliver J ，Danon L ，Finn A ... -  《-》

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.

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. 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. 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. 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. UK Government Department of Health and Social Care.

Shrotri M ，Krutikov M ，Nacer-Laidi H ，Azmi B ，Palmer T ，Giddings R ，Fuller C ，Irwin-Singer A ，Baynton V ，Tut G ，Moss P ，Hayward A ，Copas A ，Shallcross L ... -  《The Lancet Healthy Longevity》

Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study.

To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths. Test negative case-control study. Community testing for covid-19 in England. 156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System. Vaccination with BNT162b2 or ChAdOx1-S. Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19. Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19. Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

Lopez Bernal J ，Andrews N ，Gower C ，Robertson C ，Stowe J ，Tessier E ，Simmons R ，Cottrell S ，Roberts R ，O'Doherty M ，Brown K ，Cameron C ，Stockton D ，McMenamin J ，Ramsay M ... -  《BMJ-British Medical Journal》

Profile of humoral and cellular immune responses to single doses of BNT162b2 or ChAdOx1 nCoV-19 vaccines in residents and staff within residential care homes (VIVALDI): an observational study.

Residents of long-term care facilities (LTCFs) have been prioritised for COVID-19 vaccination because of the high COVID-19 mortality in this population. Several countries have implemented an extended interval of up to 12 weeks between the first and second vaccine doses to increase population coverage of single-dose vaccination. We aimed to assess the magnitude and quality of adaptive immune responses following a single dose of COVID-19 vaccine in LTCF residents and staff. From the LTCFs participating in the ongoing VIVALDI study (ISRCTN14447421), staff and residents who had received a first dose of COVID-19 vaccine (BNT162b2 [tozinameran] or ChAdOx1 nCoV-19), had pre-vaccination and post-vaccination blood samples (collected between Dec 11, 2020, and Feb 16, 2021), and could be linked to a pseudoidentifier in the COVID-19 Data Store were included in our cohort. Past infection with SARS-CoV-2 was defined on the basis of nucleocapsid-specific IgG antibodies being detected through a semiquantitative immunoassay, and participants who tested positive on this assay after but not before vaccination were excluded from the study. Processed blood samples were assessed for spike-specific immune responses, including spike-specific IgG antibody titres, T-cell responses to spike protein peptide mixes, and inhibition of ACE2 binding by spike protein from four variants of SARS-CoV-2 (the original strain as well as the B.1.1.7, B.1.351, and P.1 variants). Responses before and after vaccination were compared on the basis of age, previous infection status, role (staff or resident), and time since vaccination. Our cohort comprised 124 participants from 14 LTCFs: 89 (72%) staff (median age 48 years [IQR 35·5-56]) and 35 (28%) residents (87 years [77-90]). Blood samples were collected a median 40 days (IQR 25-47; range 6-52) after vaccination. 30 (24%) participants (18 [20%] staff and 12 [34%] residents) had serological evidence of previous SARS-CoV-2 infection. All participants with previous infection had high antibody titres following vaccination that were independent of age (r s=0·076, p=0·70). In participants without evidence of previous infection, titres were negatively correlated with age (r s=-0·434, p<0·0001) and were 8·2-times lower in residents than in staff. This effect appeared to result from a kinetic delay antibody generation in older infection-naive participants, with the negative age correlation disappearing only in samples taken more than 42 days post-vaccination (r s=-0·207, p=0·20; n=40), in contrast to samples taken after 0-21 days (r s=-0·774, p=0·0043; n=12) or 22-42 days (r s=-0·437, p=0·0034; n=43). Spike-specific cellular responses were similar between older and younger participants. In infection-naive participants, antibody inhibition of ACE2 binding by spike protein from the original SARS-CoV-2 strain was negatively correlated with age (r s=-0·439, p<0·0001), and was significantly lower against spike protein from the B.1.351 variant (median inhibition 31% [14-100], p=0·010) and the P.1 variant (23% [14-97], p<0·0001) than against the original strain (58% [27-100]). By contrast, a single dose of vaccine resulted in around 100% inhibition of the spike-ACE2 interaction against all variants in people with a history of infection. History of SARS-CoV-2 infection impacts the magnitude and quality of antibody response after a single dose of COVID-19 vaccine in LTCF residents. Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and should be considered for an early second dose where possible. UK Government Department of Health and Social Care.

Tut G ，Lancaster T ，Krutikov M ，Sylla P ，Bone D ，Kaur N ，Spalkova E ，Bentley C ，Amin U ，Jadir AT ，Hulme S ，Butler MS ，Ayodele M ，Bruton R ，Shrotri M ，Azmi B ，Fuller C ，Irwin-Singer A ，Hayward A ，Copas A ，Shallcross L ，Moss P ... -  《The Lancet Healthy Longevity》