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BackgroundSuccessive 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 effectiveness of booster vaccination against infections, hospitalisations and deaths among LTCF residents and staff in England. MethodsWe 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 hospitalisation and death at 0-13, 14-48, 49-83 and 84 days after dose 3 of SARS-CoV-2 vaccination compared to 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. Results14175 residents and 19973 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-83 days after first booster, but no protection was apparent after 84 days. Additional protection following booster vaccination waned, but was still present at 84+ days for COVID-associated hospitalisation (aHR: 0.47, 0.24-0.89) and death (aHR: 0.37, 0.21-0.62). Most residents (64.4%) had received primary course of AstraZeneca, but this did not impact on pre- or post-booster risks. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalisations and no deaths. ConclusionsBooster vaccination provides sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 3 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial. SummaryThe COVID-19 pandemic has severely impacted residents in long-term care facilities (LTCFs). Booster vaccination provides sustained moderate protection against severe outcomes, but no protection against infection was apparent from around 3 months onwards. Ongoing surveillance in LTCFs is crucial.
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Structured summaryO_ST_ABSBackgroundC_ST_ABSWhole genome sequencing (WGS) for managing healthcare associated infections (HCAIs) has developed considerably through experiences with SARS-CoV-2. We interviewed various healthcare professionals (HCPs) with direct experience of using WGS in hospitals (within the COG-UK Hospital Onset COVID-19 Infection (HOCI) study) to explore its acceptability and future use. MethodAn exploratory, cross-sectional, qualitative design employed semi-structured interviews with 39 diverse HCPs between December 2020 and June 2021. Participants were recruited from five sites within the larger clinical study of a novel genome sequencing reporting tool for SARS-CoV-2 (the HOCI study). All had experience, in their diverse roles, of using sequencing data to manage nosocomial SARS-CoV-2 infection. Deductive and inductive thematic analysis identified themes exploring aspects of the acceptability of sequencing. FindingsThe analysis highlighted the overall acceptability of rapid WGS for infectious disease using SARS-CoV-2 as a case study. Diverse professionals were largely very positive about its future use and believed that it could become a valuable and routine tool for managing HCAIs. We identified three key themes 1) Proof of concept achieved; 2) Novel insights and implications; and 3) Challenges and demands. ConclusionOur qualitative analysis, drawn from five diverse hospitals, shows the broad acceptability of rapid sequencing and its potential. Participants believed it could and should become an everyday technology capable of being embedded within typical hospital processes and systems. However, its future integration into existing healthcare systems will not be without challenges (e.g., resource, multi-level change) warranting further mixed methods research.
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BackgroundLong-term care facilities (LTCF) have been prioritised for vaccination, but data on potential waning of vaccine effectiveness (VE) and the impact of booster doses in this vulnerable population remains scarce. MethodsWe included residents and staff from 331 LTCFs enrolled in VIVALDI (ISRCTN 14447421), who underwent routine PCR testing between Dec 8, 2020 - Dec 11, 2021 in a Cox proportional hazards regression, estimating VE against SARS-CoV2 infection, COVID-19-related hospitalisation, and COVID-19-related death after 1-3 vaccine doses, stratifying by previous SARS-CoV2 exposure. ResultsFor 15,518 older residents, VE declined from 50{middle dot}7% (15{middle dot}5, 71{middle dot}3) to 17{middle dot}2% ([~]23{middle dot}9, 44{middle dot}6) against infection; from 85{middle dot}4% (60{middle dot}7, 94{middle dot}.6) to 54{middle dot}3% (26{middle dot}2, 71{middle dot}7) against hospitalisation; and from 94{middle dot}4% (76{middle dot}4, 98{middle dot}7) to 62{middle dot}8% (32{middle dot}9, 79{middle dot}4) against death, when comparing 2-12 weeks and [≥]12 weeks after two doses. For 19,515 staff, VE against infection declined slightly from 50{middle dot}3% (32{middle dot}7, 63{middle dot}3) to 42{middle dot}1% 29{middle dot}5, 52{middle dot}4). High VE was restored following a third dose, with VE of 71{middle dot}6% (53{middle dot}5, 82{middle dot}7) and 78{middle dot}3% (70{middle dot}1, 84{middle dot}3) against infection and 89{middle dot}9% (80{middle dot}0, 94{middle dot}6) and 95{middle dot}8% (50{middle dot}4, 99{middle dot}6) against hospitalisation, for residents and staff respectively; and 97{middle dot}5% (88{middle dot}1, 99{middle dot}5) against death for residents. InterpretationSubstantial waning of VE is observed against all outcomes in residents from 12 weeks after a primary course of AstraZeneca or mRNA vaccines. Boosters restore protection, and maximise immunity across all outcomes. These findings demonstrate the importance of boosting and the need for ongoing surveillance of VE in this vulnerable cohort. FundingUK Government Department of Health and Social Care. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched MEDLINE and medRxiv for studies reporting vaccine effectiveness (VE) over time after two or three doses against SARS-CoV2 infection, COVID-19-related hospitalisation, or COVID-19-related death amongst staff or residents of long-term care facilities (LTCFs), that were published between Jan 1, 2020, and December 21, 2021. We used variations of the search terms "COVID-19" OR "SARS-CoV-2" AND "vaccine effectiveness" OR "vaccine efficacy" AND "care homes" OR "long term care facilities". We identified 8 articles reporting two-dose data from LTCFs, including 1 peer-reviewed paper from Israel, 1 preprint from Denmark, 1 preprint from Norway, 1 peer-reviewed paper from France, two peer-reviewed papers from Spain, 1 peer-reviewed paper from the USA, and 1 preprint from England; however none of these studies examined waning of protection over time after two doses. Five studies (mRNA vaccines 3-4 weeks interval) reported short-term two-dose VE of 49-71% in residents, and 82-90% in staff. Two-dose VE was reported to be 75-88% against hospitalisation, 87-97% against death, and 86% against either outcome. An English study of residents (Pfizer or AstraZeneca, 8-12 week interval) reported 73% VE against infection and noted VE waning from 7 weeks after the first dose, but did not examine waning after the second dose. All of these studies were set prior to emergence of the Delta variant and did not examine waning of immunity due to short lengths of follow-up after Dose 2. Only one study (USA) compared Pfizer/Moderna two-dose VE against infection in LTCF residents before (67{middle dot}5% [60{middle dot}1-73{middle dot}5%]) and during (53{middle dot}1% [49{middle dot}1-56{middle dot}7%]) Delta variant predominance; however, authors could not access vaccination dates therefore did not account for any waning of immunity over time; they also did not examine any severe clinical outcomes. We identified only one correspondence piece from Israel (Pfizer 3-4 week interval) describing the benefit of a third booster dose in LTCFs; it reported relative rate reductions of 71% for infection and 80%, for hospitalisation in the period after booster roll-out. However, individual-level VE estimates by time since vaccination were not reported, and adjustment for prior infection was not undertaken. Overall, there was a paucity of data on non-mRNA vaccines, waning of immunity over time after two doses, and VE following a third (booster) dose in LTCF populations, which we address in this study. Added value of this studyWe report findings from a prospective cohort study that includes 15,518 residents and 19,515 staff from 331 LTCFs across England, who underwent routine PCR testing 2-3 times per month, looking at SARS-CoV2 vaccine effectiveness over 12 months (Dec 8, 2020-Dec 11, 2021), which is the longest duration of follow-up of any study within this vulnerable cohort. We evaluated the effectiveness of first, second, and booster vaccine doses of AstraZeneca, Pfizer, and Moderna against infection, hospitalisation, and death over the 12 months when the Alpha and Delta variants were dominant. Our findings affirm that complete vaccination with two doses of AstraZeneca or mRNA vaccines offers moderate protection against infection, and high protection against severe clinical outcomes, however this protection declines over time, particularly for residents. A third booster dose of an mRNA vaccine restores, and indeed maximises, VE to 71{middle dot}6% (53{middle dot}5, 82{middle dot}7) and 78{middle dot}3% (70{middle dot}1, 84{middle dot}3) against infection, and 89{middle dot}9% (80{middle dot}0, 94{middle dot}6) and 95{middle dot}8% (50{middle dot}4, 99{middle dot}6) against hospitalisation, for residents and staff respectively, and to 97{middle dot}5% (88{middle dot}1, 99{middle dot}5) against death for residents, with similar protection offered after the third dose irrespective of primary course type. This is the first study to examine and describe waning of immunity over a one-year period, as well as vaccine effectiveness of a booster dose, in a large cohort of LTCF staff and residents. Implications of all the available evidenceTaken together, our findings indicate high short-term immunity against SARS-CoV2 infection and very high immunity against severe clinical outcomes of COVID-19 for LTCF residents and staff following vaccination. However substantial waning in vaccine-derived immunity is seen beyond 3 months, irrespective of vaccine type, suggesting the need for regular boosting to maintain protection in this vulnerable cohort. Although this analysis took place in the pre-Omicron period, these trends of waning immunity over time are likely to be generalisable across variants, carrying important implications for long-term vaccination policy in LTCFs. Ongoing surveillance in this vulnerable cohort remains crucial, in order to describe further changes in vaccine-induced immunity, particularly in the context of new variants.
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BackgroundGeneral population studies have shown strong humoral response following SARS-CoV-2 vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations such as Long-Term Care Facility (LTCF) residents but published data are scarce. MethodsVIVALDI is a prospective cohort study in England which links serial blood sampling in LTCF staff and residents to routine healthcare records. We measured quantitative titres of SARS-CoV-2 anti-spike antibodies in residents and staff following second vaccination dose with ChAdOx1 nCov-19 (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech). We investigated differences in peak antibody levels and rates of decline using linear mixed effects models. ResultsWe report on 1317 samples from 402 residents (median age 86 years, IQR 78-91) and 632 staff (50 years, 37-58), [≤]280 days from second vaccination dose. Peak antibody titres were 7.9-fold higher after Pfizer-BioNTech vaccine compared to Oxford-AstraZeneca (95%CI 3.6-17.0; P<0.01) but rate of decline was increased, and titres were similar at 6 months. Prior infection was associated with higher peak antibody levels in both Pfizer-BioNTech (2.8-fold, 1.9-4.1; P<0.01) and Oxford-AstraZeneca (4.8-fold, 3.2-7.1; P<0.01) recipients and slower rates of antibody decline. Increasing age was associated with a modest reduction in peak antibody levels for Oxford-AstraZeneca recipients. ConclusionsDouble-dose vaccination elicits robust and stable antibody responses in older LTCF residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.
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BackgroundRecently there has been a rapid, global increase in SARS-CoV-2 infections associated with the Omicron variant (B.1.1.529). Although severity of Omicron cases may be reduced, the scale of infection suggests hospital admissions and deaths may be substantial. Definitive conclusions about disease severity require evidence from populations with the greatest risk of severe outcomes, such as residents of Long-Term Care Facilities (LTCFs). MethodsWe used a cohort study to compare the risk of hospital admission or death in LTCF residents in England who had tested positive for SARS-CoV-2 in the period shortly before Omicron emerged (Delta dominant) and the Omicron-dominant period, adjusting for age, sex, vaccine type, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset. ResultsRisk of hospital admission was markedly lower in 1241 residents infected in the Omicron-period (4.01% hospitalised, 95% CI: 2.87-5.59) compared to 398 residents infected in the pre-Omicron period (10.8% hospitalised, 95% CI: 8.13-14.29, adjusted Hazard Ratio 0.50, 95% CI: 0.29-0.87, p=0.014); findings were similar in residents with confirmed variant. No residents with previous infection were hospitalised in either period. Mortality was lower in the Omicron versus the pre-Omicron period, (p<0.0001). ConclusionsRisk of severe outcomes in LTCF residents with the SARS-CoV-2 Omicron variant was substantially lower than that seen for previous variants. This suggests the current wave of Omicron infections is unlikely to lead to a major surge in severe disease in LTCF populations with high levels of vaccine coverage and/or natural immunity. Trial Registration NumberISRCTN 14447421
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BackgroundLong Term Care Facilities (LTCF) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion infected amongst survivors 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 prior infection - in staff and residents from 201 LTCFs. MethodsProspective cohort study of residents aged >65 years and staff of LTCFs in England (11 June 2020-7 May 2021). Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein. Prevalence and cumulative incidence of antibody-positivity were weighted to the LTCF population. Cumulative incidence of sero-reversion was estimated from Kaplan-Meier curves. Results9488 samples were included, 8636 (91%) of which could be individually-linked to 1434 residents or 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 35% (95% CI: 30-40%) in residents and 26% (95% CI: 23-30%) in staff over 11 months. The incidence rate of loss of antibodies (sero-reversion) was 2{middle dot}1 per 1000 person-days at risk, and median time to reversion was around 8 months. InterpretationAt least one-quarter of staff and one-third of surviving residents were infected during the first two pandemic waves. 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 those with prior infection. Since natural infection may act to boost vaccine responses, better assays to identify natural infection should be developed. FundingUK Government Department of Health and Social Care. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA search was conducted of Ovid MEDLINE and MedRxiv on 21 July 2021 to identify studies conducted in long term care facilities (LTCF) that described seroprevalence using the terms "COVID-19" or "SARS-CoV-2" and "nursing home" or "care home" or "residential" or "long term care facility" and "antibody" or "serology" without date or language restrictions. One meta-analysis was identified, published before the introduction of vaccination, that included 2 studies with a sample size of 291 which estimated seroprevalence as 59% in LTCF residents. There were 28 seroprevalence surveys of naturally-acquired SARS-CoV-2 antibodies in LTCFs; 16 were conducted in response to outbreaks and 12 conducted in care homes without known outbreaks. 16 studies included more than 1 LTCF and all were conducted in Autumn 2020 after the first wave of infection but prior to subsequent peaks. Seroprevalence studies conducted following a LTCF outbreak were biased towards positivity as the included population was known to have been previously infected. In the 12 studies that were conducted outside of known outbreaks, seroprevalence varied significantly according to local prevalence of infection. The largest of these was a cross-sectional study conducted in 9,000 residents and 10,000 staff from 362 LTCFs in Madrid, which estimated seroprevalence in staff as 31{middle dot}5% and 55{middle dot}4% in residents. However, as this study was performed in one city, it may not be generalisable to the whole of Spain and sequential sampling was not performed. Of the 28 studies, 9 undertook longitudinal sampling for a maximum of four months although three of these reported from the same cohort of LTCFs in London. None of the studies reported on antibody waning amongst the whole resident population. Added value of this studyWe estimated the proportion of care home staff and residents with evidence of SARS-CoV-2 natural infection using data from over 3,000 staff and 1,500 residents in 201 geographically dispersed LTCFs in England. Population selection was independent of outbreak history and the sample is therefore more reflective of the population who reside and work in LTCFs. Our estimates of the proportion of residents with prior natural infection are substantially higher than estimates based on population-wide PCR testing, due to limited testing coverage at the start of the pandemic. 1361 individuals had at least one positive antibody test and participants were followed for up to 11 months, which allowed modelling of the time to loss of antibody in over 600 individuals in whom the date of primary infection could be reliably estimated. This is the longest reported serological follow up in a population of LTCF residents, a group who are known to be most at risk of severe outcomes following infection with SARS-CoV-2 and provides important evidence on the duration that nucleocapsid antibodies remained detectable over the first and second waves of the pandemic. Implications of all available researchA substantial proportion of the LTCF population will have some level of natural immunity to infection as a result of past infection. Immunological studies have highlighted greater antibody responses to vaccination in seropositive individuals, so vaccine efficacy in this population may be affected by this large pool of individuals who have survived past infection. In addition, although the presence of nucleocapsid-specific antibodies is generally considered as the standard marker for prior infection, we find that antibody waning is such that up to 50% of people will lose detectable antibody responses within eight months. Individual prior natural infection history is critical to assess the impact of factors such as vaccine response or protection against re-infection. These findings may have implications for duration of immunity following natural infection and indicate that alternative assays for prior infection should be developed.
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Long term care facilities (LTCF) provide residential and/or nursing care support for frail and elderly people and many have suffered from a high prevalence of SARS-CoV-2 infection. Although mortality rates have been high in LTCF residents there is little information regarding the features of SARS-CoV-2-specific immunity after infection in this setting or how this may influence immunity to other infections. We studied humoral and cellular immunity against SARS-CoV-2 in 152 LTCF staff and 124 residents over a prospective 4-month period shortly after the first wave of infection and related viral serostatus to heterologous immunity to other respiratory viruses and systemic inflammatory markers. LTCF residents developed high levels of antibodies against spike protein and RBD domain which were stable over 4 months of follow up. Nucleocapsid-specific responses were also elevated in elderly donors but showed waning across all populations. Antibodies showed stable and equivalent levels of functional inhibition against spike-ACE2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or RSV. SARS-CoV-2-specific cellular responses were equivalent across the life course but virus-specific populations showed elevated levels of activation in older donors. LTCF residents who are survivors of SARS-CoV-2 infection thus show robust and stable immunity which does not impact responses to other seasonal viruses. These findings augur well for relative protection of LTCF residents to re-infection. Furthermore, they underlie the potent influence of previous infection on the immune response to Covid-19 vaccine which may prove to be an important determinant of future vaccine strategy. One sentence summeryCare home residents show waning of nucleocapsid specific antibodies and enhanced expression of activation markers on SARS-CoV-2 specific cells
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BackgroundThe 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. MethodsCohort 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. ResultsOf 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{middle dot}44 (0{middle dot}24, 0{middle dot}81) at 28-34 days and 0{middle dot}38 (0{middle dot}19, 0{middle dot}77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (aHR 0{middle dot}32 [0{middle dot}15-0{middle dot}66] and BNT162b2 (aHR 0{middle dot}35 [0{middle dot}17, 0{middle dot}71]) vaccines at 35-48 days. Mean PCR cycle threshold values were higher, implying lower infectivity, for infections [≥]28 days post-vaccination compared with those prior to vaccination (31{middle dot}3 vs 26{middle dot}6, p<0{middle dot}001). InterpretationThe 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. FundingUK Government Department of Health and Social Care. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe conducted a systematic search for studies which evaluated SARS-CoV-2 vaccine effectiveness in residents of long-term care facilities (LTCFs) published between 01/01/2020 and 11/03/2021. We used variations of search terms for "COVID-19" AND "vaccine effectiveness" OR "vaccine efficacy" AND "care homes" OR "long term care facilities" OR "older people" on Ovid MEDLINE and MedRxiv. We identified one pre-print article regarding LTCFs in Denmark, which reported that a single dose of BNT162b was ineffective against SARS-CoV-2 infection in residents, however, participants received the second vaccine dose 24 days following the first dose on average, which is likely to be too soon to capture the protective effects of a single vaccine dose. Additionally, we identified two pre-print reports of studies evaluating vaccine effectiveness against symptomatic infection and hospitalisation amongst older adults in the community. The first of these found 81% vaccine effectiveness against COVID-19-related hospitalisation at 28-34 days following a single dose of BNT162b or ChAdOx1 in [≥]80-year-olds. The second of these found vaccine effectiveness against symptomatic infection of 60% at 28-34 days and 73% at 35+ days following a single dose of ChAdOx1 in [≥]70-year-olds. No studies were identified that focused on the effectiveness of a single vaccine dose against infection amongst LTCF residents at more than 4 weeks post-vaccination, a particularly important question in the context of the UK policy decision to extend the dose interval beyond 3 weeks. Added value of this studyWe conducted a prospective cohort study of 10,412 residents aged [≥]65 years, from 310 LTCFs across England, to investigate the protective effect of the first dose of the ChAdOx1 and BNT162b vaccines against SARS-CoV-2 infection in frail older adults. We retrieved results from routine monthly PCR testing, as well as outbreak and clinical testing for SARS-CoV-2, thereby capturing data on asymptomatic as well as symptomatic infections, which we linked to vaccination records. We estimated vaccine effectiveness to be 56% (19-76%) at 28-34 days, and 62% (23-81%) at 35-48 days following a single dose of ChAdOx1 or BNT162. Our findings suggest that the risk of SARS-CoV-2 infection is substantially reduced from 28 days following the first dose of either vaccine and that this effect is maintained for at least 7 weeks, with similar protection offered by both vaccine types. We also found that PCR cycle threshold (Ct) values, which are negatively associated with the ability to isolate virus, were significantly higher in infections occurring at [≥] 28days post vaccination compared to those occurring in the unvaccinated period, suggesting that vaccination may reduce onward transmission of SARS-CoV-2 in breakthrough infections. To the best of our knowledge, our findings constitute the first real-world evidence on vaccine effectiveness against infection for ChAdOx1, in any age group. We can also infer that both vaccines are effective against the B.1.1.7 variant, because our analysis period coincided with the rapid emergence of B.1.1.7 in England during the second wave of the pandemic. Implications of all the available evidenceOur findings add to the growing body of evidence on the protective effect of the BNT162b vaccines in residents of LTCFs and demonstrate the effectiveness of ChAdOx1 in this vulnerable population. Evaluating single-dose vaccine efficacy has become increasingly important in light of extended dosing intervals that have been implemented in order to maximise vaccine coverage across high-risk groups. Further work is required to evaluate the effectiveness of the first vaccine dose after 8-12 weeks, as well as following the second dose, and to evaluate the long-term impact of vaccination on SARS-CoV-2 infection, transmission and mortality in LTCFs. This will inform policy decisions regarding the ongoing need for disease control measures in LTCF such as visitor restrictions, which continue to have a detrimental impact on the wellbeing of residents, their relatives, and staff. Supplementary material attached.
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BackgroundOutbreaks of SARS-CoV-2 have occurred worldwide in Long Term Care Facilities (LTCFs), but the reasons why some facilities are particularly vulnerable to infection are poorly understood. We aimed to identify risk factors for SARS-CoV-2 infection and outbreaks in LTCFs. MethodsCross-sectional survey of all LTCFs providing dementia care or care to adults >65 years in England with linkage to SARS-CoV-2 test results. Exposures included: LTCF characteristics, staffing factors, and use of disease control measures. Main outcomes included risk factors for infection and outbreaks, estimated using multivariable logistic regression, and survey and test-based weighted estimates of SARS-CoV-2 prevalence. Findings5126/9081 (56%) LTCFs participated in the survey, with 160,033 residents and 248,594 staff. The weighted period prevalence of infection in residents and staff respectively was 10.5% (95% CI: 9.9-11.1%) and 3.8% (95%: 3.4-4.2%) and 2724 LTCFs (53.1%) had [≥]1 infection. Odds of infection and/or outbreaks were reduced in LTCFs that paid sickness pay, cohorted staff, did not employ agency staff and had higher staff to resident ratios. Higher odds of infection and outbreaks were identified in facilities with more admissions, lower cleaning frequency, poor compliance with isolation and "for profit" status. InterpretationHalf of LTCFs had no cases suggesting they remain vulnerable to outbreaks. Reducing transmission from staff requires adequate sick pay, minimal use of temporary staff, improved staffing ratios and staff cohorting. Transmission from residents is associated with the number of admissions to the facility and poor compliance with isolation. FundingUK Government Department of Health & Social Care Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCOVID-19 outbreaks have occurred worldwide in long-term care facilities (LTCFs), which provide care to elderly and vulnerable residents, and are associated with high mortality. The reasons why LTCFs are particularly vulnerable to COVID-19 are poorly understood. Most studies of risk factors for COVID-19 to date have been limited by scale, and poor quality administrative, demographic and infection control data. We conducted a systematic search on 27 July 2020 in MEDLINE Ovid, WHO COVID-19 database and in MedRxiv to identify studies reporting risk factors for COVID-19 infection or outbreaks in LTCFs, with no date or language restrictions. We used the search terms "COVID-19", "SARS-CoV-2", "coronavirus" and "care home", "nursing home", "long term care facilit" and excluded studies that did not investigate LTCF-level risk factors. 14 studies met our inclusion criteria comprising 11 cross-sectional studies and 3 surveys. The largest cross-sectional study was conducted in 9395 specialised nursing facilities across 30 states in USA; the largest survey was conducted in 124 LTCFs in Haute-Garrone region of France. Risk of bias was high across all studies, and results could not be pooled due to heterogeneity between studies. Main risk factors for infection and/or outbreaks related to the size of the facility, lower ratios of staff to residents, urban location, higher occupancy, and the community prevalence of infection. Only one study collected data on the use of disease control measures during the pandemic, and no studies provided data on risk factors such as the use of temporary staff, or the impact of staff working across multiple locations. Added value of this studyWe conducted a national telephone survey with managers of all LTCFs in England which provided dementia care or care to residents aged > 65 years to collect data on the number of staff and residents in each facility, confirmed SARS-CoV-2 infections, characteristics of the facility e.g.size, staffing (use of temporary staff, staffing ratios, sickness pay) and disease control measures such as cohorting and isolation. We identified risk factors for infection in residents and staff, outbreaks (defined as [≥]1 case per LTCF) and large outbreaks using logistic regression. We also estimated the proportion of staff and residents who had been infected with SARS-CoV-2. Responses were obtained from 5126 of out 9081 (56%) of eligible LTCFs. To our knowledge, this is the largest and most detailed survey of risk factors for SARS-CoV-2 infection and outbreaks that has been conducted in LTCFs. Implications of all the available evidenceAlmost half of LTCFs surveyed in this study did not report any cases of infection, and remain vulnerable to infection and outbreaks, highlighting the need for effective control measures. Reducing transmission from staff requires adequate sick pay, minimal use of temporary staff, improved staffing ratios and staff cohorting. Transmission from residents is associated with the number of admissions to the facility and poor compliance with control measures such as isolation.
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BackgroundDiagnostic testing forms a major part of the UKs response to the current COVID-19 pandemic with tests offered to people with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. MethodsIn this analysis of the Bug Watch prospective community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests and four second wave scenarios and then compared to current national capacity. ResultsThe baseline incidence of cough or fever in the UK is expected to rise rapidly from 154,554 (95%CI 103,083 - 231,725) cases per day in August 2020 to 250,708 (95%CI 181,095 - 347,080) in September, peaking at 444,660 (95%CI 353,084 - 559,988) in December. If 80% of baseline cough or fever cases request tests, average daily UK testing demand would exceed current capacity for five consecutive months (October 2020 to February 2021), with a peak demand of 147,240 (95%CI 73,978 - 239,502) tests per day above capacity in December 2020. ConclusionsOur results show that current national COVID-19 testing capacity is likely to be exceeded by demand due to baseline cough and fever alone. This study highlights that the UKs response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is immediately scaled up to meet this high predicted demand.
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BackgroundEpidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic. MethodsCohort study of 179 UK care homes with 9,339 residents and 11,604 staff.We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality, and estimate attributable mortality. Results2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff respectively. 121/179 (67.6%) care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection. 217/607 residents with confirmed infection died (case-fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was two-fold higher in care homes with outbreaks versus those without (adjusted HR 2.2 [1.8; 2.6]). ConclusionsFindings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.
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BackgroundUp to 80% of active SARS-CoV-2 infections are proposed to be asymptomatic based on cross-sectional studies. However, accurate estimates of the asymptomatic proportion require systematic detection and follow-up to differentiate between truly asymptomatic and pre-symptomatic cases. We conducted a rapid review and meta-analysis of current evidence regarding the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections based on methodologically-appropriate studies in community settings. MethodsWe searched Medline and EMBASE for peer-reviewed articles, and BioRxiv and MedRxiv for pre-prints published prior to 05/05/2020. We included studies based in community settings that involved systematic PCR testing on participants and follow-up symptom monitoring regardless of symptom status. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold values and/or duration of viral shedding by symptom status. We computed estimates of the asymptomatic proportion and 95% confidence intervals for each study and overall using random effect meta-analysis. FindingsWe screened 270 studies and included 6. The pooled estimate for the asymptomatic proportion of SARS-CoV-2 infections was 11% (95% CI 4%-18%). Estimates of baseline viral load appeared to be similar for asymptomatic and symptomatic cases based on available data in three studies, though detailed reporting of cycle threshold values and natural history of viral shedding by symptom status was limited. InterpretationThe asymptomatic proportion of SARS-CoV-2 infections is relatively low when estimated from methodologically-appropriate studies. Further investigation into the degree and duration of infectiousness for asymptomatic infections is warranted. FundingMedical Research Council
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BackgroundThe medical, health service, societal and economic impact of the COVID-19 emergency has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom (to date at least) have underlying conditions. Models have not incorporated information on high risk conditions or their longer term background (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence rates and differing mortality impacts. MethodsUsing population based linked primary and secondary care electronic health records in England (HDR UK - CALIBER), we report the prevalence of underlying conditions defined by UK Public Health England COVID-19 guidelines (16 March 2020) in 3,862,012 individuals aged [≥]30 years from 1997-2017. We used previously validated phenotypes, openly available (https://caliberresearch.org/portal), for each condition using ICD-10 diagnosis, Read, procedure and medication codes. We estimated the 1-year mortality in each condition, and developed simple models of excess COVID-19-related deaths assuming relative risk (RR) of the impact of the emergency (compared to background mortality) of 1.2, 1.5 and 2.0. Findings20.0% of the population are at risk according to current PHE guidelines, of which; 13.7% were age>70 years and 6.3% aged [≤]70 years with [≥]1 underlying condition (cardiovascular disease (2.3%), diabetes (2.2%), steroid therapy (1.9%), severe obesity (0.9%), chronic kidney disease (0.6%) and chronic obstructive pulmonary disease, COPD (0.5%). Multimorbidity (co-occurrence of [≥]2 conditions in an individual) was common (10.1%). The 1-year mortality in the at-risk population was 4.46%, and age and underlying conditions combine to influence background risk, varying markedly across conditions (5.9% in age>70 years, 8.6% for COPD and 13.1% in those with [≥]3 or more conditions). In a suppression scenario (at SARS CoV2 rates of 0.001% of the UK population), there would be minimal excess deaths (3 and 7 excess deaths at relative risk, RR, 1.5 and 2.0 respectively). At SARS CoV2 rates of 10% of the UK population (mitigation) the model estimates the numbers of excess deaths as: 13791, 34479 and 68957 (at RR 1.2, 1.5 and 2.0 respectively). At SARS CoV2 rates of 80% in the UK population ("do-nothing"), the model estimates the number of excess deaths as 110332, 275,830 and 551,659 (at RR 1.2, 1.5 and 2.0) respectively. InterpretationWe provide the public, researchers and policy makers a simple model to estimate the excess mortality over 1 year from COVID-19, based on underlying conditions at different ages. If the relative mortality impact of COVID-19 were to be about 20% (similar magnitude as the established winter vs summer mortality excess), then the excess deaths would be 0 when 1 in 100 000 (suppression), 13791 when 1 in 10 (mitigation) and 110332 when 8 in 10 are infected ("do nothing") scenario. However, the relative impact of COVID-19 is unknown. If the emergency were to double the mortality risk, then we estimate 7, 68957 and 551,659 excess deaths in the same scenarios. These results may inform the need for more stringent suppression measures as well as efforts to target those at highest risk for a range of preventive interventions.