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VIVALDI (ISRCTN14447421) is a government-funded longitudinal open observational cohort study of staff and residents in care homes for older people in England. The study aimed to describe epidemiology (including seroprevalence) and immune responses to COVID-19 in a subset of care homes, in the context of extremely high mortality in this setting, in the first 12-18 months of the pandemic. Data linkage to routine health data was undertaken for all staff and residents and a subset of individuals who consented to sequential blood sampling to investigate SARS-CoV-2 immunity. This paper aims to describe the samples stored within the VIVALDI biobank and associated linked data, available for use by researchers. Over 70,000 individuals from 346 care homes were included in the data linkage cohort (1 st March 2020-31 st March 2023). 4971 samples from 2264 individuals (1415 staff, 827 residents) collected between 29 th October 2020 and 10 th March 2023 are stored. Amongst these samples, there was a maximum of seven per participant however, 217 (26.2%) residents and 551 (38.9%) staff participated in one round only. Key study findings include high COVID-19 seroprevalence among surviving residents, exceeding rates in community-dwelling peers. COVID-19 vaccinations generated robust immune responses in staff and residents which waned, supporting the need for booster vaccination, particularly in response to new variants. Prior infection significantly improved vaccine-induced immune responses, however protection from infection declined following Omicron variant emergence. This is a unique cohort of pre- and post-infection samples linked to data on COVID-19 infections, vaccinations, and outcomes. The cohort spans host immune response evolution to infection and vaccination in this rarely sampled population of frail older care home residents who are especially vulnerable to infection and severe outcomes. These samples can be used to investigate biological mechanisms behind disparate infection responses in older people and make a valuable contribution to research into ageing., Competing Interests: Competing interests: LS, AC, AH, and OS report grants from the Department of Health & Social Care and the UK Health Security Agency (UKHSA) during the conduct of the study and LS is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH reports funding from the COVID Core Studies Programme and is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health and Environmental Modelling Group of the Scientific Advisory Group for Emergencies. No other competing interests were disclosed., (Copyright: © 2024 Krutikov M et al.)

Introduction: Older adults in care homes experienced some of the highest rates of mortality from SARS-CoV-2 globally and were subjected to strict and lengthy non-pharmaceutical interventions, which severely impacted their daily lives. The VIVALDI ASCOT and Ethnography Study aims to assess the impact of respiratory outbreaks on care home residents' quality of life, psychological well-being, loneliness, functional ability and use of space. This study is linked to the VIVALDI-CT, a randomised controlled trial of staff's asymptomatic testing and sickness payment support in care homes (ISRCTN13296529)., Methods and Analysis: This is a mixed-methods, longitudinal study of care home residents (65+) in Southeast England. Group 1-exposed includes residents from care homes with a recent COVID-19 or other respiratory infection outbreak. Group 2-non-exposed includes residents from care homes without a recent outbreak. The study has two components: (a) a mixed-methods longitudinal face-to-face interviews with 100 residents (n=50 from group 1 and n=50 from group 2) to assess the impact of outbreaks on residents' quality of life, psychological well-being, loneliness, functional ability and use of space at time 1 (study baseline) and time 2 (at 3-4 weeks after the first visit); (b) ethnographic observations in communal spaces of up to 10 care homes to understand how outbreaks and related restrictions to the use of space and social activities impact residents' well-being. The study will interview only care home residents who have the mental capacity to consent. Data will be compared and integrated to gain a more comprehensive understanding of the impact of outbreaks on residents' quality of life and well-being., Ethics and Dissemination: The VIVALDI ASCOT and Ethnography Study obtained ethical approval from the Health Research Authority (HRA) Social Care REC (24/IEC08/0001). Only residents with the capacity to consent will be included in the study. Findings will be published in scientific journals., Competing Interests: Competing interests: All the authors declare no financial relationships with any organisations that might have an interest in the submitted work and no other relationships or activities that could appear to have influenced the proposed work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: We have previously demonstrated that older residents of long-term care facilities (LTCF) in the UK show levels of anti-spike antibodies that are comparable to the general population following primary series and booster vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data on the humoral response to other SARS-CoV-2 proteins associated with natural infection are scarce in this vulnerable population., Methods: We measured quantitative levels of anti-nucleocapsid antibodies in blood samples taken from LTCF residents and staff after initial and repeat SARS-CoV-2 infections, between December 2020 and March 2023. Data on SARS-CoV-2 infection and vaccination were obtained through linkage to national datasets. Linear mixed effects models were used to investigate anti-nucleocapsid antibody levels, using log10 scale, in relation to time from most recent infection. This included evaluation of associations between repeat infection, staff/resident status, age, sex, Omicron infection and vaccination history and peak antibody level and slope of decline with time., Results: We analysed 405 antibody observations from 220 residents and 396 observations from 215 staff. Repeat infection was associated with 8.5-fold (95%CI 4.9-14.8-fold) higher initial (peak) median anti-nucleocapsid antibody level, with steeper subsequent slope of decline. There were no significant differences in antibody level associated with resident (vs. staff) status or age, but Omicron infection was associated with 3.6-fold (95%CI 2.4-5.4-fold) higher levels. There was stronger evidence of waning of antibody levels over time in a sensitivity analysis in which observations were censored in cases with suspected undetected repeat infection., Conclusions: We found similar levels of anti-nucleocapsid antibody in residents and staff of LTCFs. Repeat infection and infection with an Omicron strain were associated with higher peak values. There was evidence of waning of anti-nucleocapsid antibody levels over time., Competing Interests: Competing interests: LS reports grants from the Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH reports funding from the COVID Core Studies Programme and is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health and Environmental Modelling Group of the Scientific Advisory Group for Emergencies. All other authors declare no competing interests., (Copyright: © 2024 Stirrup O et al.)

Care home residents are vulnerable to severe outcomes from infections such as COVID-19 and influenza. However, measures to control outbreaks, such as care home closures to visitors and new admissions, have a detrimental impact on their quality of life. Many infections and outbreaks could be prevented but the first step is to measure them reliably. This is challenging in care homes due to the lack of data and research infrastructure. During the pandemic, the VIVALDI study measured COVID-19 infections in residents and staff by partnering with care providers and using routinely collected data. This study aims to establish sentinel surveillance and a research database to enable observational and future interventional studies in care homes. The project has been co-produced with care providers, staff, residents, relatives, and researchers. The study (October 2023 to March 2025) will explore the feasibility of establishing a network of 500-1500 care homes for older adults in England that is underpinned by a linked data platform. No data will be collected from staff. The cohort will be created by regularly extracting resident identifiers from Digital Social Care Records (DSCR), followed by pseudonymisation and linkage to routinely collected datasets. Following extensive consultation, we decided not to seek informed consent from residents for data collection, but they can 'opt out' of the study. Our goal is to be inclusive, and it is challenging to give every resident the opportunity to 'opt in' due to cognitive impairment and the requirement for consultees. The project, and all requests to use the data will be overseen by relatives, residents, staff, and care providers. The study has been approved by the Health Research Authority Confidentiality Advisory Group (23/CAG/0134&0135) and the South-West Frenchay Research Ethics Committee (23/SW/0105). It is funded by the UK Health Security Agency., Competing Interests: Competing interests: LS, AC, AH, OS, and KT report grants from the Department of Health & Social Care and the UK Health Security Agency (UKHSA) during the conduct of the study and LS was a member of the Social Care Working Group, which reported to the Scientific Advisory Group for Emergencies. GP, GC, and JH are employed by UKHSA who funded the study. AH reports funding from the COVID Core Studies Programme and was previously a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health and Environmental Modelling Group of the Scientific Advisory Group for Emergencies. All other authors declare no competing interest., (Copyright: © 2024 Krutikov M et al.)

Introduction: Care home residents have experienced significant morbidity, mortality and disruption following outbreaks of SARS-CoV-2. Regular SARS-CoV-2 testing of care home staff was introduced to reduce transmission of infection, but it is unclear whether this remains beneficial. This trial 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., Methods and Analysis: The VIVALDI-Clinical Trial is a multicentre, open-label, cluster randomised controlled, phase III/IV superiority trial in up to 280 residential and/or nursing homes in England providing care to adults aged >65 years. All regular and agency staff will be enrolled, excepting those who opt out. Homes will be randomised to the intervention arm (twice weekly asymptomatic staff testing for SARS-CoV-2) or the control arm (current national testing guidance). Staff who test positive for SARS-CoV-2 will self-isolate and receive sick pay. Care providers will be reimbursed for costs associated with employing temporary staff to backfill for absence arising directly from the trial.The trial will be delivered by a multidisciplinary research team through a series of five work packages.The primary outcome is the incidence of COVID-19-related hospital admissions in residents. Secondary outcomes include the number and duration of outbreaks and home closures. Health economic and modelling analyses will investigate the cost-effectiveness and cost consequences of the testing intervention. A process evaluation using qualitative interviews will be conducted to understand intervention roll out and identify areas for optimisation to inform future intervention scale-up, should the testing approach prove effective and cost-effective. Stakeholder engagement will be undertaken to enable the sector to plan for results and their implications and to coproduce recommendations on the use of testing for policy-makers., Ethics and Dissemination: The study has been approved by the London-Bromley Research Ethics Committee (reference number 22/LO/0846) and the Health Research Authority (22/CAG/0165). The results of the trial will be disseminated regardless of the direction of effect. The publication of the results will comply with a trial-specific publication policy and will include submission to open access journals. A lay summary of the results will also be produced to disseminate the results to participants., Trial Registration Number: ISRCTN13296529., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society.)

The chikungunya virus is an arthritogenic alphavirus. Acute infection may be followed by persistent arthralgia, often causing significant functional impairment. The 2014-2015 chikungunya fever (CHIKF) epidemic resulted in a marked increase in cases presenting to rheumatology and tropical diseases services. A combined multidisciplinary rheumatology-tropical diseases service for assessment, management, and follow-up of patients with proven CHIKF and persistent (≥ 4 weeks) arthralgia was proposed and rapidly developed at The Hospital for Tropical Diseases in London. Rapid set up of a multidisciplinary clinic in response to the epidemic was achieved. Of a total of 54 patients, 21 (38.9%) patients with CHIKF developed persistent arthralgia and were reviewed by the multidisciplinary service. A combined assessment approach enabled comprehensive multidisciplinary assessment of CHIKF, assessment of joint pathology through ultrasound, and appropriate follow-up. A combined rheumatology-tropical diseases service was successfully used to identify and assess CHIKF-associated morbidity. Future outbreaks may be approached by establishing tailored multidisciplinary clinics.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: LS reports grants from the Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AI-S and VB are employed by the Department of Health and Social Care who funded the study. AH reports funding from the COVID Core Studies Programme and is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health and Environmental Modelling Group of the Scientific Advisory Group for Emergencies. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Background: Older age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for individuals with these factors, but there is concern that immune responses might be impaired due to age-related immune dysregulation and comorbidity. We aimed to study humoral and cellular responses to COVID-19 vaccines in residents of long-term care facilities (LTCFs)., Methods: In this observational cohort study, we assessed antibody and cellular immune responses following COVID-19 vaccination in members of staff and residents at 74 LTCFs across the UK. Staff and residents were eligible for inclusion if it was possible to link them to a pseudo-identifier in the COVID-19 datastore, if they had received two vaccine doses, and if they had given a blood sample 6 days after vaccination at the earliest. There were no comorbidity exclusion criteria. Participants were stratified by age (<65 years or ≥65 years) and infection status (previous SARS-CoV-2 infection [infection-primed group] or SARS-CoV-2 naive [infection-naive group]). Anticoagulated edetic acid (EDTA) blood samples were assessed and humoral and cellular responses were quantified., Findings: Between Dec 11, 2020, and June 27, 2021, blood samples were taken from 220 people younger than 65 years (median age 51 years [IQR 39-61]; 103 [47%] had previously had a SARS-CoV-2 infection) and 268 people aged 65 years or older of LTCFs (median age 87 years [80-92]; 144 [43%] had a previous SARS-CoV-2 infection). Samples were taken a median of 82 days (IQR 72-100) after the second vaccination. Antibody responses following dual vaccination were strong and equivalent between participants younger then 65 years and those aged 65 years and older in the infection-primed group (median 125 285 Au/mL [1128 BAU/mL] for <65 year olds vs 157 979 Au/mL [1423 BAU/mL] for ≥65 year olds; p=0·47). The antibody response was reduced by 2·4-times (467 BAU/mL; p≤0·0001) in infection-naive people younger than 65 years and 8·1-times (174 BAU/mL; p≤0·0001) in infection-naive residents compared with their infection-primed counterparts. Antibody response was 2·6-times lower in infection-naive residents than in infection-naive people younger than 65 years (p=0·0006). Impaired neutralisation of delta (1.617.2) variant spike binding was also apparent in infection-naive people younger than 65 years and in those aged 65 years and older. Spike-specific T-cell responses were also significantly enhanced in the infection-primed group. Infection-naive people aged 65 years and older (203 SFU per million [IQR 89-374]) had a 52% lower T-cell response compared with infection-naive people younger than 65 years (85 SFU per million [30-206]; p≤0·0001). Post-vaccine spike-specific CD4 T-cell responses displayed single or dual production of IFN-γ and IL-2 were similar across infection status groups, whereas the infection-primed group had an extended functional profile with TNFα and CXCL10 production., Interpretation: These data reveal suboptimal post-vaccine immune responses within infection-naive residents of LTCFs, and they suggest the need for optimisation of immune protection through the use of booster vaccination., Funding: UK Government Department of Health and Social Care., Competing Interests: LS reports grants from the Department of Health and Social Care during the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

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., Competing Interests: LS, TP, AC, AH, and OS report grants from the Department of Health and Social Care during the conduct of the study and LS is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AI-S and VB are employed by the Department of Health and Social Care, which funded the study. AH reports funding from the COVID Core Studies Programme and is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health and Environmental Modelling Group of the Scientific Advisory Group for Emergencies. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

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., Competing Interests: LS and TP report grants from the Department of Health and Social Care during the conduct of the study and LS is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AI-S is employed by the Department of Health and Social Care who funded the study. AH reports funding from the Covid Core Studies Programme and is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health and Environmental Modelling Group of the Scientific Advisory Group for Emergencies. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

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.

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: UK Government Department of Health and Social Care., Competing Interests: AI-S is an employee of the UK Department of Health and Social Care, which funded the study. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health. AC reports grants from the UK Department of Health and Social Care during the conduct of the study. LS reports grants from the UK Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. All other authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

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., Methods: We 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., Funding: UK Government Department of Health and Social Care., Competing Interests: LS reports grants from the Department of Health and Social Care during the conduct of the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health. All other authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Background: Outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have occurred in long-term care facilities (LTCFs) worldwide, but the reasons why some facilities are particularly vulnerable to outbreaks are poorly understood. We aimed to identify factors associated with SARS-CoV-2 infection and outbreaks among staff and residents in LTCFs., Methods: We did a national cross-sectional survey of all LTCFs providing dementia care or care to adults aged 65 years or older in England between May 26 and June 19, 2020. The survey collected data from managers of eligible LTCFs on LTCF characteristics, staffing factors, the use of disease control measures, and the number of confirmed cases of infection among staff and residents in each LTCF. Survey responses were linked to individual-level SARS-CoV-2 RT-PCR test results obtained through the national testing programme in England between April 30 and June 13, 2020. The primary outcome was the weighted period prevalence of confirmed SARS-CoV-2 infections in residents and staff reported via the survey. Multivariable logistic regression models were fitted to identify factors associated with infection in staff and residents, an outbreak (defined as at least one case of SARS-CoV-2 infection in a resident or staff member), and a large outbreak (defined as LTCFs with more than a third of the total number of residents and staff combined testing positive, or with >20 residents and staff combined testing positive) using data from the survey and from the linked survey-test dataset., Findings: 9081 eligible wLTCFs were identified, of which 5126 (56·4%) participated in the survey, providing data on 160 033 residents and 248 594 staff members. The weighted period prevalence of infection was 10·5% (95% CI 9·9-11·1) in residents and 3·8% (3·4-4·2) in staff members. 2724 (53·1%) LTCFs reported outbreaks, and 469 (9·1%) LTCFs reported large outbreaks. The odds of SARS-CoV-2 infection in residents (adjusted odds ratio [aOR] 0·80 [95% CI 0·75-0·86], p<0·0001) and staff (0·70 [0·65-0·77], p<0·0001), and of large outbreaks (0·59 [0·38-0·93], p=0·024) were significantly lower in LTCFs that paid staff statutory sick pay compared with those that did not. Each one unit increase in the staff-to-bed ratio was associated with a reduced odds of infection in residents (0·82 [0·78-0·87], p<0·0001) and staff (0·63 [0·59-0·68], p<0·0001. The odds of infection in residents (1·30 [1·23-1·37], p<0·0001) and staff (1·20 [1·13-1·29], p<0·0001), and of outbreaks (2·56 [1·94-3·49], p<0·0001) were significantly higher in LTCFs in which staff often or always cared for both infected or uninfected residents compared with those that cohorted staff with either infected or uninfected residents. Significantly increased odds of infection in residents (1·01 [1·01-1·01], p<0·0001) and staff (1·00 [1·00-1·01], p=0·0005), and of outbreaks (1·08 [1·05-1·10], p<0·0001) were associated with each one unit increase in the number of new admissions to the LTCF relative to baseline (March 1, 2020). The odds of infection in residents (1·19 [1·12-1·26], p<0·0001) and staff (1·19 [1·10-1·29], p<0·0001), and of large outbreaks (1·65 [1·07-2·54], p=0·024) were significantly higher in LTCFs that were for profit versus those that were not for profit. Frequent employment of agency nurses or carers was associated with a significantly increased odds of infection in residents (aOR 1·65 [1·56-1·74], p<0·0001) and staff (1·85 [1·72-1·98], p<0·0001), and of outbreaks (2·33 [1·72-3·16], p<0·0001) and large outbreaks (2·42 [1·67-3·51], p<0·0001) compared with no employment of agency nurses or carers. Compared with LTCFs that did not report difficulties in isolating residents, those that did had significantly higher odds of infection in residents (1·33 [1·28-1·38], p<0·0001) and staff (1·48 [1·41-1·56], p<0·0001), and of outbreaks (1·84 [1·48-2·30], p<0·0001) and large outbreaks (1·62 [1·24-2·11], p=0·0004)., Interpretation: Half of LTCFs had no cases of SARS-CoV-2 infection in the first wave of the pandemic. Reduced transmission from staff is associated with adequate sick pay, minimal use of agency staff, an increased staff-to-bed ratio, and staff cohorting with either infected or uninfected residents. Increased transmission from residents is associated with an increased number of new admissions to the facility and poor compliance with isolation procedures., Funding: UK Government Department of Health and Social Care., (© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Global infection and mortality rates from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are disproportionately high in certain populations, including amongst older people. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit  6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months.  Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics.  Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection. Protocol registration : ISRCTN14447421 05/06/2020., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Krutikov M et al.)

Objective: To investigate the relationship between social risk factors and latent tuberculosis infection (LTBI) among individuals who are eligible for LTBI screening in the United Kingdom (UK)., Methods: This cross-sectional study used data collected in the UK Prognostic Evaluation of Diagnostic Interferon-Gamma Release Assays (IGRAs) Consortium Study which enrolled 9176 recent tuberculosis (TB) contacts and migrants at National Health Service (NHS) facilities and community settings in the UK. The study outcome was LTBI (positive IGRA test (QuantiFERON-TB Gold In-Tube or T-SPOT.TB)). The main exposures were history of smoking, history of substance misuse, homelessness, prison stay and socioeconomic deprivation., Results: 4914 (56.2%) individuals resided in the most deprived areas and 2536 (27.6%) had LTBI. In the multivariable analysis (adjusting for age, gender, place of birth, ethnicity, HIV status, BCG vaccination and recent TB contact) living in the least deprived areas compared with living in the most deprived areas was associated with reduced odds of LTBI (odds ratio (OR)=0.68, 95% CI: 0.51 to 0.90) while ever been homeless (OR=1.50, 95% CI: 1.02 to 2.21) was associated with increased odds of LTBI. Smoking, homelessness and substance misuse were not associated with LTBI., Conclusion: Social deprivation could be an important risk factor for LTBI, highlighting the social inequality in the burden of TB infection in the UK. Migrants and TB contacts who were socially deprived or homeless were at a significantly higher risk for LTBI, thus tailored intense public health interventions to these groups may help to reduce the risk of future TB disease., Trial Registration Number: ClinicalTrials.gov Registry (NCT01162265)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The risk of tuberculosis (TB) is variable among individuals with latent Mycobacterium tuberculosis infection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95% confidence interval (CI), 8.0-29.2%) among child contacts, 4.8% (95% CI, 3.0-7.7%) among adult contacts, 5.0% (95% CI, 1.6-14.5%) among migrants and 4.8% (95% CI, 1.5-14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal-external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82-0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide.

Global infection and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are disproportionately high in certain populations, including the elderly. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit  6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months.  Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics.  Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection. Protocol registration : ISRCTN14447421 05/06/2020., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Krutikov M et al.)

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.

Background: Vulnerable individuals with tuberculosis (TB) struggle to access and stay on treatment. While patient-related and social barriers to TB treatment adherence are well documented, less is known about how the organisation and delivery of TB care influences adherence behaviour., Aim: To examine the influence of TB service organisation and culture on patients' experience of starting and staying on treatment in Riga, Latvia., Methods: An intervention package to support adherence to TB treatment amongst vulnerable patients in Riga, Latvia was piloted between August 2016 and March 2017. Qualitative observations (5), interviews with staff (20) and with TB patients (10) were conducted mid-way and at the end of the intervention to understand perceptions, processes, and experiences of TB care., Results: The organisation of TB services is strongly influenced by a divide between medical and social aspects of TB care. Communication and care practices are geared towards addressing individual risk factors for non-adherence rather than the structural vulnerabilities that patients experience in accessing care. Support for vulnerable patients is limited because of standardised programmatic approaches, resource constraints and restricted job descriptions for non-medical staff., Conclusion: Providing support for vulnerable patients is challenged in this setting by the strict division between medical and social aspects of TB care, and the organisational focus on patient-related rather than systems-related barriers to access and adherence. Potential systems interventions include the introduction of multi-disciplinary approaches and teams in TB care, strengthening patient literacy at the point of treatment initiation, as well as stronger linkages with social care organisations., Competing Interests: The authors have declared that no competing interests exist.

The advent of sophisticated diagnostics has enabled the discovery of previously unknown arthropod-borne viruses like Chikungunya. This infection has become increasingly prevalent in the last 10 years across the Indian Ocean and has been brought to media attention by a recent outbreak in the Caribbean. The outbreak has been aided by a drastic rise in air travel, allowing infected individuals to transport the virus to previously unaffected regions. In addition, a recently documented viral mutation has allowed its transmission by the Aedes albopictus mosquito, therefore facilitating outbreaks in Southern Europe and the USA. The duration and extent of the arthritis seen peri- and post infection has become a topic of academic interest. Although published data are largely observational, there has been a definite increase in original research focusing on this. Symptoms can persist for years, particularly in older patients with pre-existing medical conditions. The etiology is still not fully understood, but viral persistence and immune activation within synovial fluid have been shown in mouse models. There have been no prospective clinical trials of treatment in humans; however, animal trials are in process. The mainstay of treatment remains anti-inflammatories and steroids where necessary. The clinical presentation seems to mimic common rheumatological conditions like rheumatoid arthritis; therefore recent recommendations suggest the use disease-modifying agents as a common practice for the specific syndrome. This review uses recent published data and draws on our own clinical experience to provide an overview of joint complications of Chikungunya infection., Competing Interests: No potential conflict of interest relevant to this article was reported.