VIVALDI Publications

The VIVALDI research team publish extensively across a wide range of academic journals. Below you will find details of their papers.

Anti-nucleocapsid antibody levels following initial and repeat SARS-CoV-2 infections in a cohort of long-term care facility residents in England (VIVALDI)

This study focused on older adults living in long-term care facilities in the UK and their response to COVID-19 vaccination and natural infection. We found that after vaccination, levels of antibodies against one part of the virus were similar to those seen in the general population. However, there was limited data on response to other parts of the virus after natural infection. We collected blood samples from residents and staff between December 2020 and March 2023 and measured their levels of antibodies against a different part of the virus. We found that those who had been infected more than once had higher levels of these antibodies, especially if they were infected with the Omicron variant. Additionally, we observed that these antibody levels decreased over time. Overall, our study suggests that residents and staff in long-term care facilities have similar antibody levels, but repeat infections and infection with certain variants can lead to higher antibody levels, with evidence of a decline over time.

Built Environment and SARS-CoV-2 Transmission in Long-Term Care Facilities: Cross-Sectional Survey and Data Linkage

This study aimed to understand how the design and features of long-term care facilities (LTCFs) in England might be connected to the introduction and spread of COVID-19 infection. We looked at factors, like the structure of the buildings, air quality, and how outbreaks occurred. The study involved 134 LTCFs caring for adults aged 65 and older, looking at data from over 13,000 residents and 17,000 staff members. The findings showed that the likelihood of outbreaks in LTCFs was mainly linked to the level of infection in the surrounding community. However, certain features of the LTCF environment, such as the number of floors and bedrooms, the type of building, air quality, funding model, crowding, and bedroom temperature, were associated with different aspects of infection transmission.

VIVALDI Cohort Profile: Using linked, routinely collected data and longitudinal blood sampling to characterise COVID-19 infections, vaccinations, and related outcomes in care home staff and residents in England

 

COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023

The COVID-19 pandemic had a severe impact on care homes, but since the initial wave protection against infection has been built up by vaccination and accumulating prior exposures. This study aimed to evaluate the overall impact of COVID-19 on mortality rates of older care home residents and to investigate how the infection fatality ratio for SARS-CoV-2 infections has changed over time in this population, considering the period from October 2020 to March 2023. The occurrence of COVID-19-related deaths peaked in the first quarters of 2021 and 2022 coinciding, respectively, with the emergence of the Alpha and Omicron variants. The proportion of all deaths that were associated with SARS-CoV-2 infection declined substantially over the study period, but the infection fatality ratio stabilized at a non-negligible level of around 7% in 2022.

Shaping care home COVID-19 testing policy: a protocol for a pragmatic cluster randomised controlled trial of asymptomatic testing compared with standard care in care home staff (VIVALDI-CT)

Regular COVID-19 testing was important at the start of the pandemic, but now most people are vaccinated their chance of getting seriously unwell is much lower, although protection against infection can reduce over time. COVID-19 testing also has negative consequences. It is uncomfortable, expensive, it takes time, and care home staff who test positive cannot work so they lose money. Staff sickness can also affect how care is delivered to care home residents. These negative consequences of testing are not usually measured and so they are not very visible to policymakers.  There is also no evidence on whether regular testing is beneficial to residents and whether it is cost-effective. This paper sets out the protocol for this trial which aims to investigate whether use of regular asymptomatic staff testing, alongside funding to reimburse sick pay for those who test positive and meet costs of employing agency staff, is a feasible and effective strategy to reduce COVID-19 impact in care homes.

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

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

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.

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).

In this study we investigated how effective booster COVID-19 vaccine doses were against infection, hospitalisation and death among care home staff and residents. We looked at PCR and LFD results from 14175 residents and 19973 staff that were taken between December 12 2021 and March 31 2022 and linked these results to routine data on vaccination, hospitalisation, and deaths and compared effectiveness of 2 against 3 vaccine doses. We found that vaccines protected against infection for the first 3 months after the third vaccine dose in residents and staff but there did not seem to be protection against infection after that. However the third vaccine dose were protective against COVID-19 associated hospitalisation for more than 3 months amongst residents. People who had had a previous infection with COVID-19 as well as vaccination had a greater level of protection than those who had only been vaccinated.

Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naïve residents of long-term care facilities: an observational cohort study

In this study we measured immune responses (antibody and cellular) following dual COVID-19 vaccination in 202 staff members and 286 residents of care homes. We observed that both staff and residents that have evidence or prior infection show evidence of strong antibody responses following dual vaccination.  However, in infection naïve donors the antibody immune response to vaccination was 2.4-fold reduced in staff members and 8.1-fold reduced in residents. By looking at cellular immune responses, we observed 52% lower responses in infection naïve residents compared to staff members, and that those with prior infection have cells that have an extended functional profile compared to infection naïve vaccine recipients. Taking all of these into consideration, the data reveals that there is a suboptimal post vaccine immune response within infection naive elderly residents of care homes. This indicates that there is need for further optimization of immune protection using a booster vaccine.

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

This paper examines the effectiveness of one, two, and three vaccine doses against PCR-confirmed SARS-CoV2 infection and against hospitalisation and death related to COVID-19 between December 2020 and December 2021 in residents and staff from more than 330 VIVALDI care homes. We examine vaccine effects separately for residents and staff, and for those with and without evidence of previous infection, using a time-varying Cox regression approach. Our results demonstrate high effectiveness of two doses, irrespective of vaccine type, for 3 months after receiving the second dose; however, protection appears to decline substantially over time. The significant waning of protection against more severe outcomes in residents is especially notable as this has not been observed for other population groups, and is not observed for staff within our study. Reassuringly, however, a third booster dose restores very high levels of protection against all outcomes across all groups, including for staff and those previously infected, illustrating the benefit to everyone of receiving three vaccine doses. These data are unique for the size of the study population, the number of care homes involved, and the length of follow-up spanning 12 months following rollout of vaccines in the care home setting, and covering the successive periods of wild-type virus, and Alpha and Delta variant dominance in England. We were not able to include outcomes related to the Omicron variant or any detailed immunological analysis in this paper, however these important questions are covered in other VIVALDI papers.

Robust SARS-CoV-2-specific and heterologous immune responses after natural infection in elderly residents of Long-Term Care Facilities

This study aimed to determine virus-specific and general inflammatory and immune response profiles in both staff and residents in care home setting over a 4-month period. We took 3 serial blood samples from residents and staff members pre vaccine roll out. We looked at serological response to the original and variants of concerns. We also measured the memory cellular response to SARS-CoV-2 in prior infected donors. The study found an elevated levels of antibodies in residents who survived the infection. The antibody responses was comparable and stable to SARS-CoV-2 variants of concern in staff and residents. SARS-CoV-2-specific cellular responses are comparable between staff and residents.

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

The aim was to investigate antibody responses to the second dose of COVID-19 vaccination in care home residents and how these changed over time. VIVALDI report on 1317 samples from 402 residents (median age 86 years) and 632 staff (median age 50 years). It was found that residents had strong and durable responses to vaccines that were comparable to the antibody levels that have been described in the general population. This is reassuring as frail care home residents have been the worst affected by the pandemic; these findings suggest that they have good immune responses to vaccination.

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

The aim was to describe and compare the severity of Delta with Omicron infection in frail older care home residents. In this study researchers compared at the proportion of care home residents who were admitted to hospital or that died after being infected with COVID-19 in the period before and after the arrival of the Omicron variant. They included data from over 1600 residents with confirmed COVID-19 infection and found that people infected with the virus after 13 December 2021 (when Omicron was dominant) were 50% less likely to be admitted to hospital after infection than those infected before 12 December 2021 (when Delta was dominant) and were less likely to die following infection. This is very reassuring as it suggests that although Omicron is more transmissible than Delta, the infections that it causes are not as severe as Delta in care home residents, most of whom have received booster vaccination before they became infected.

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

This study used results of 9488 SARS-CoV-2 nucleocapsid antibody tests from staff and residents in 201 care homes in England that were taken between June 2020 and April 2021. Nucleocapsid antibodies are commonly used to detect past COVID-19 infection as they are not generated in response to vaccination. Over one quarter of staff and one third of residents had evidence of having survived infection over the first two pandemic waves which is higher than has been seen in the general community-dwelling population.  This high proportion of people with natural immunity who have stronger antibody responses to vaccination may affect vaccine effectiveness as over time these numbers will drop. The study also found that nucleocapsid antibodies became undetectable eight months from initial infection in around half of participants, suggesting that more durable and reliable tests for past infection are needed.

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

This study looked at how the frequency and severity of care home COVID-19 outbreaks changed between November 2020 and June 2021, as vaccinations were introduced and new disease variants began to circulate.  We studied 330 care homes taking part in the VIVALDI study and found that as the number of staff and residents vaccinated increased over time, there were fewer COVID-19 outbreaks.  In addition, we found that outbreaks which were still occurring became less severe over time - with fewer COVID-19 deaths and fewer people infected in each outbreak – and that by June 2021 outbreaks were more likely to consist purely of staff infections.  The study supports the effectiveness of vaccinations for care home staff and residents and has implications for future COVID-19 testing within this setting. 

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.

This study aimed to assess the magnitude of protection of a single dose of COVID-19 vaccine in care home residents and staff given the extended interval between vaccines doses that was adopted on the UK. Blood samples were collected from residents and staff before and after their received their first dose of vaccine. Immune response to the virus protein spike was measured for 4 variants of concern. We found out that after a single dose, residents that are infection naïve make lower antibody response and are much slower at generating an antibody response to vaccine, it takes >21 days for them to catch up to the younger staff members. However, residents make comparable cellular immune responses to younger staff members after single vaccine dose. Those with prior infection status show strong immune response to variants of concern.

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

This analysis looked at the effectiveness of a single vaccine dose (Pfizer or Oxford/AstraZeneca) against infection with SARS-CoV-2, using routine PCR test results for 10,412 residents (aged 65+ years) from 310 care homes across England. We observed vaccine effectiveness to be 56% between four and five weeks after vaccination, and 62% between five to seven weeks, with similar timing and level of protection for both vaccine types. Additionally, we found that people with prior infection were already well protected irrespective of vaccination status; and average Cycle Threshold (Ct) values of PCR-positive tests were higher from 28 days after vaccination compared to before vaccination (31.3 vs 26.6) - suggesting lower viral load, and therefore potentially reduced transmissibility, due to vaccination.

Incidence of SARS-CoV-2 infection according to baseline antibody status in staff and residents of 100 long-term care facilities (VIVALDI study): a prospective cohort study

In this study, VIVALDI researchers looked at rates of COVID-19 infections based on results from PCR testing between October 2020 and February 2021 among more than 2,000 care home residents and staff. They compared those who had evidence of a previous infection up to 10 months earlier, as determined by antibody testing, with those who had not been previously infected. They found that residents with a previous infection were 85% less likely to be infected during this four-month period than residents who had never been infected, while staff with past infection were 60% less likely than staff who had not had the infection before.

Spread of a Variant SARS-CoV-2 in Long-Term Care Facilities in England

The study, published as a letter in the New England Journal of Medicine, described the initial spread of the alpha or Kent (B.1.1.7) SARS-CoV-2 variant in care homes between October and December 2020. Researchers looked at positive PCR tests processed at the Milton Keynes Lighthouse laboratory as part of Pillar 2 surveillance testing of care home staff and residents and found that, among the samples they had access to, the proportion of infections caused by the new variant rose from 12% in the week beginning 23 November to 60% of positive cases just two weeks later, in the week beginning 7 December. In the South East of England, where the variant was most dominant, the proportion increased from 55% to 80% over the same period. In London, where the variant spread fastest, the proportion increased from 20% to 66%. This suggests that the new variant spread as rapidly through care homes as in the general population.

Factors associated with SARS-CoV-2 infection and outbreaks in long-term care facilities in England: a national cross-sectional survey.

To identify the risk factors for SARS-CoV-2 infection and outbreaks in care homes, researchers conducted a cross-sectional survey of 5126 care homes in England that provide care to people older than 65 years between May 26 and June 19 2020. They found that half of care homes had not experienced any cases in the first pandemic wave. Lower transmission from staff was found in care homes who paid adequate sick pay, used low numbers of agency staff, had higher numbers of staff per resident, and implemented staff cohorting with either infected or uninfected residents. Risk factors for transmission of SARS-CoV-2 from residents were higher number of admissions of residents to the care homes and low compliance with isolation precautions.

Study Protocol: Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI)

Impact of coronavirus in care homes in England: 26 May to 19 June 2020

This report was published following the first COVID-19 pandemic wave and outlines results of a cross-sectional survey conducted in collaboration with the Office for National Statistics (ONS) in 5126 care homes in England that provide care to people older than 65 years. Results showed