Background 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. Methods 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. Findings 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).Interpretation 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...

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.

Background The effectiveness of SARS-CoV-2 vaccines in frail older adults living in Long-Term Care Facilities (LTCFs) is uncertain. We estimated protective effects of the first dose of ChAdOx1 and BNT162b2 vaccines against infection in this population. Methods Cohort study comparing vaccinated and unvaccinated LTCF residents in England, undergoing routine asymptomatic testing (8 December 2020 - 15 March 2021). We estimated the relative hazard of PCR-positive infection using Cox proportional hazards regression, adjusting for age, sex, prior infection, local SARS-CoV-2 incidence, LTCF bed capacity, and clustering by LTCF. Results Of 10,412 residents (median age 86 years) from 310 LTCFs, 9,160 were vaccinated with either ChAdOx1 (6,138; 67%) or BNT162b2 (3,022; 33%) vaccines. A total of 670,628 person days and 1,335 PCR-positive infections were included. Adjusted hazard ratios (aHRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days following the first vaccine dose to 0.44 (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 (aHR 0.32 [0.15-0.66] and BNT162b2 (aHR 0.35 [0.17, 0.71]) vaccines at 35-48 days. Mean PCR cycle threshold values were higher, implying lower infectivity, for infections 28 or more days post-vaccination compared with those prior to vaccination (31.3 vs 26.6, p<0.001). Interpretation The first dose of BNT162b2 and ChAdOx1 vaccines was associated with substantially reduced SARS-CoV-2 infection risk in LTCF residents from 4 weeks to at least 7 weeks. Funding UK Government Department of Health and Social Care.

Background SARS-CoV-2 infection represents a major challenge for long-term care facilities (LTCFs) and many residents and staff are seropositive following persistent outbreaks. We aimed to investigate the association between the SARS-CoV-2 antibody status at baseline and subsequent infection in this population. MethodsWe did a prospective cohort study of SARS-CoV-2 infection in staff (aged <65 years) and residents (aged >65 years) at 100 LTCFs in England between Oct 1, 2020, and Feb 1, 2021. Blood samples were collected between June and November, 2020, at baseline, and 2 and 4 months thereafter and tested for IgG antibodies to SARS-CoV-2 nucleocapsid and spike proteins. PCR testing for SARS-CoV-2 was done weekly in staff and monthly in residents. Cox regression was used to estimate hazard ratios (HRs) of a PCR-positive test by baseline antibody status, adjusted for age and sex, and stratified by LTCF. Findings 682 residents from 86 LCTFs and 1429 staff members from 97 LTCFs met study inclusion criteria. At baseline, IgG antibodies to nucleocapsid were detected in 226 (33%) of 682 residents and 408 (29%) of 1429 staff members. 93 (20%) of 456 residents who were antibody-negative at baseline had a PCR-positive test (infection rate 0•054 per month at risk) compared with four (2%) of 226 residents who were antibody-positive at baseline (0•007 per month at risk). 111 (11%) of 1021 staff members who were antibody-negative at baseline had PCR-positive tests (0•042 per month at risk) compared with ten (2%) of 408 staff members who were antibody-positive staff at baseline (0•009 per month at risk). The risk of PCR-positive infection was higher for residents who were antibody-negative at baseline than residents who were antibody-positive at baseline (adjusted HR [aHR] 0•15, 95% CI 0•05-0•44, p=0•0006), and the risk of a PCR-positive infection was also higher for staff who were antibody-negative at baseline compared with staff who were antibody-positive at baseline (aHR 0•39, 0•19-0•82; p=0•012). 12 of 14 reinfected participants had available data on symptoms, and 11 of these participants were symptomatic. Antibody titres to spike and nucleocapsid proteins were comparable in PCR-positive and PCR-negative cases.Interpretation The presence of IgG antibodies to nucleocapsid protein was associated with substantially reduced risk of reinfection in staff and residents for up to 10 months after primary infection.

Although results from RCTs suggested that PR reduces subsequent admissions, pooled results from the cohort studies did not, likely reflecting the heterogeneous nature of individuals included in observational research and the varying standard of PR programs.