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1.
medrxiv; 2024.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2024.01.12.24301206

ABSTRACT

BackgroundBy March 2023, 54 countries, areas and territories (thereafter "CAT") reported over 2.2 million coronavirus disease 2019 (COVID-19) deaths to the World Health Organization (WHO) Regional Office for Europe (1). Here, we estimate how many lives were directly saved by vaccinating adults in the Region, from December 2020 through March 2023. MethodsWe estimated the number of lives directly saved by age-group, vaccine dose and circulating Variant of Concern (VOC) period, both regionally and nationally, using weekly data on COVID-19 mortality and COVID-19 vaccine uptake reported by 34 CAT, and vaccine effectiveness (VE) data from the literature. We calculated the percentage reduction in the number of expected and reported deaths. FindingsWe found that vaccines reduced deaths by 57% overall (CAT range: 15% to 75%), representing [~]1.4 million lives saved in those aged [≥]25 years (range: 0.7 million to 2.6 million): 96% of lives saved were aged [≥]60 years and 52% were aged [≥]80 years; first boosters saved 51%, and 67% were saved during the Omicron period. InterpretationOver nearly 2.5 years, most lives saved by COVID-19 vaccinationwere in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among these most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. FundingThis work was supported by a US Centers for Disease Control cooperative agreement (Grant number 6 NU511P000936-02-020), who had no role in data analysis or interpretation. DisclaimerThe authors affiliated with the World Health Organization (WHO) are alone responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the WHO. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince first identified in late 2019, COVID-19 has caused disproportionately high mortality rates in older adults. With the rapid development and licensing of novel COVID-19 vaccines, immunization campaigns across the WHO European Region started in late 2020 and early 2021, initially targeting the most vulnerable and exposed populations, including older adults, people with comorbidities and healthcare professionals. Several studies have estimated the number of lives saved by COVID-19 vaccination, both at national and multi-country level in the earlier stages of the pandemic. However, only one multi-country study has assessed the number of lives saved beyond the first year of the pandemic, particularly when the Omicron variant of concern (VOC) circulated, a period when vaccination coverage was high in many countries, areas and territories (CAT), but COVID-19 transmission was at its highest. Added value of this studyHere we quantified the impact of COVID-19 vaccination in adults by age-group, vaccine dose and period of circulation of VOC, across diverse settings, using real world data reported by 34 CAT in the WHO European Region for the period December 2020 to April 2023. We estimated that COVID-19 vaccination programs were associated with a 57% reduction (CAT range: 15% to 75%) in the number of deaths among the [≥]25 years old, representing over 1.5 million lives saved (range: 0.7 million to 2.6 million) in 34 European CAT during the first 2.5 years following vaccine introduction. The first booster savedthe most lives (721,122 / 1,408,967, (57%) of all lives saved). The [≥]60 years old age group accounted for 96% of the total lives saved (1,349,617 / 1,408,967) whereas the [≥]80 years old age group represented 52% of the total lives saved (728,858 / 1,408,967 lives saved) and 67% of all lives were saved during the Omicron period (942,571 / 1,408,967). Implications of all the available evidenceOur results reinforce the importance of up-to-date COVID-19 vaccination, particularly among older age-groups. Communication campaigns supporting COVID-19 vaccination should stress the value of COVID-19 vaccination in saving lives to ensure vulnerable groups are up-to-date with vaccination ahead of periods of potential increased transmission.


Subject(s)
COVID-19
2.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.07.14.23292656

ABSTRACT

Since the emergence of Omicron variant of SARS-CoV-2 in late 2021, a number of sub-lineages have arisen and circulated internationally. Little is known about the relative severity of Omicron sub-lineages BA.2.75, BA.4.6 and BQ.1. We undertook a case-control analysis to determine the clinical severity of these lineages relative to BA.5, using whole genome sequenced, PCR-confirmed infections, between 1 August 2022 to 27 November 2022, among those who presented to emergency care in England 14 days after and up to one day prior to the positive specimen. A total of 10,375 episodes were included in the analysis, of which 5,207 (50.2%) were admitted to hospital or died. Multivariable conditional regression analyses found no evidence for greater odds of hospital admission or death among those with BA.2.75 (OR= 0.96, 95% CI: 0.84 to 1.09), and BA.4.6 (OR= 1.02, 95% CI: 0.88 to 1.17) or BQ.1 (OR= 1.03, 95 % CI: 0.94 to 1.13) compared to BA.5. Future lineages may not follow the same trend and there remains a need for continued surveillance of COVID-19 variants and their clinical outcomes to inform the public health response.


Subject(s)
Death , COVID-19
4.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.21.22281171

ABSTRACT

Objectives Sotrovimab is one of several therapeutic agents that have been licensed to treat people at risk of severe outcomes following COVID-19 infection. However, there are concerns that it has reduced efficacy to treat people with the BA.2 sub-lineage of the Omicron (B.1.1.529) SARS-CoV-2 variant. We compared individuals with the BA.1 or BA.2 sub-lineage of the Omicron variant treated Sotrovimab in the community to assess their risk of hospital admission. Methods We performed a retrospective cohort study of individuals treated with Sotrovimab in the community and either had BA.1 or BA.2 variant classification. Results Using a Stratified Cox regression model it was estimated that the hazard ratios (HR) of hospital admission with a length of stay of two or more days was 1.17 for BA.2 compared to BA.1 (95% CI 0.74-1.86) and for such admissions where COVID-19 ICD-10 codes was recorded the HR was 0.98 (95% CI 0.58-1.65). Conclusion These results suggest that the risk of hospital admission is similar between BA.1 and BA.2 cases treated with Sotrovimab in the community.


Subject(s)
COVID-19
5.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.06.28.22276549

ABSTRACT

Background Over the course of the pandemic, testing policies for SARS-CoV-2 have varied considerably in England, particularly in the five months up to 1 April 2022 when free community testing ended. We described the trends and demographics of COVID-19 cases during this period. Methods COVID-19 cases reported between 15 November 2021 and 30 April 2022 were extracted and aggregated by testing pillar: Pillar 1 for those tested within the NHS, private or public health laboratories, and Pillar 2 for community testing. COVID-19 cases were described by epi-week, and stratified by test type, age, sex, index of multiple deprivation (IMD), region, and population density. Incidence rates were also calculated and stratified by IMD and region. Results Of 10,196,425 COVID-19 cases, 7.3% were reported under Pillar 1 and 92.7% under Pillar 2. From 15 November 2021 to 31 March 2022, most Pillar 2 cases were tested either by polymerase chain reaction (PCR) only or PCR with lateral flow device (LFD) (70.8%) and three in ten cases tested using LFD only. However, between 1 April and 30 April 2022 this rose to nine out of ten cases testing using LFD only. Over the whole period studied and under both pillars, the majority of cases were female (55.2%), resided in the South East (17.0%) and in the age group 30-39 years (18.6%). Trends in IMD and population density varied over the period. When stratifying by IMD the highest case numbers and incidence rates reported under Pillar 1 and NHS were in those in the most deprived quintile. This was also seen for cases reported under Pillar 2 by LFD until 11 January 2022, where a reverse in the trend occurred with the highest cases and rates in the least deprived quintile. This same pattern was observed when describing the cases by population density, with Pillar 2 LFD reported cases being highest in the most densely populated regions until 11 January, from when there was a switch to the highest cases being in the least densely populated regions. Conclusion Differences and trends were observed in reported COVID-19 cases in England, particularly those tested under Pillar 2 following the introduction of testing policy changes. To better understand the impact of these changes over the course of the COVID-19 pandemic, as well as to predict the impact of future testing policies, it would be beneficial to investigate the accessibility of testing amongst different populations. Currently, Pillar 1 COVID-19 cases are likely to be more representative of symptomatic cases requiring testing for a clinical need, as these are less impacted by variations in testing patterns compared to Pillar 2. However, a limitation of that approach is that use of Pillar 1 alone would be biased towards those more likely to be clinically unwell.


Subject(s)
COVID-19 , Sleep Deprivation
6.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.05.31.22275827

ABSTRACT

Purpose The Gamma variant of SARS-CoV-2, first detected in travellers from Brazil, was found to have high transmissibility and virulence; following this finding, this paper aims to describe the epidemiology of Gamma cases in England from its first detection on 12 February 2021 to 31 August 2021. Methods The demographic analysis of Gamma cases was stratified by travel exposure. Travel-associated cases were further analysed by countries travelled from, stratified by categories set in place by the Red (highest risk countries), Amber, Green (lowest risk countries) travel policy, which was implemented from May to October 2021. Results There were 251 confirmed Gamma cases detected in England in the study period. 35.1% were imported, 5.6% were secondary, and 29.5% were not travel associated. Early cases were predominantly travel-associated, with later cases likely obtained through community transmission. 51.0% of travel-related cases were travellers from Amber countries, and 40.2% had at least one Red country in their journey. Conclusion The Gamma variant has not seen the same expansion as other variants such as Delta, most likely due to Delta out-competing community transmission of Gamma. Findings indicate the travel policy requiring quarantine for Red and Amber list travellers may have also contributed to preventing onward transmission of Gamma.

7.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1381189.v1

ABSTRACT

Background: From 12th March 2020, individuals in England were advised to quarantine in their home if a household member tested positive for SARS-CoV-2. A mandatory isolation period of 10 days was introduced on 28th September 2020 and applied to all individuals with COVID-19. We assessed the frequency, timing, and characteristics of recovered COVID-19 cases requiring subsequent quarantine episodes due to household re-exposure. Methods In this case cohort study, all laboratory-confirmed COVID-19 cases notified in England (29th June to 28th December 2020) were analysed to identify consecutive household case(s). Multivariable logistic regression was used to determine associations between case characteristics and need to quarantine following recent infection (within 28 days of diagnosis). Results Among 1,651,550 cases resident in private dwellings and Houses of Multiple Occupancy (HMOs), 56,179 (3.4%) were succeeded by further household cases diagnosed within 11–28 days of their diagnosis. Of 1,641,412 cases arising in private homes, the likelihood of further household cases was highest for Bangladeshi (aOR = 2.20, 95% CI = 2.10–2.31) and Pakistani (aOR = 2.15, 95% CI = 2.08–2.22) individuals compared to White British, as well as among young people (17-24y vs. 25-64y; aOR = 1.19, 95% CI = 1.16–1.22), men (vs. women; aOR = 1.06, 95% CI = 1.04–1.08), London residents (vs. Yorkshire and Humber; aOR = 1.57, 95% CI = 1.52–1.63) and areas of high deprivation (IMD 1 vs. 10; aOR = 1.13, 95% CI = 1.09–1.19). Conclusions Policies requiring quarantine on re-exposure of recently recovered cases differentially impact some of the most disadvantaged populations. Quarantine exemption for individuals recently (


Subject(s)
COVID-19
8.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.02.15.22271001

ABSTRACT

Background The SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources. Methods Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. Logistic regression was used to control for factors associated with transmission. Findings Analysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16). Interpretation Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

9.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.14.21267606

ABSTRACT

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter- regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.


Subject(s)
COVID-19
10.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1159614.v1

ABSTRACT

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta’s invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.


Subject(s)
COVID-19
11.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.14.21267615

ABSTRACT

Abstract Background A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. Methods We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. Results Between 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. Conclusions Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.


Subject(s)
COVID-19
12.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.11.22.21266540

ABSTRACT

Background Household transmission has been demonstrated to be an important factor in the population-level growth of COVID-19. UK Health Security Agency (UKHSA) maintains data on positive tests for COVID-19 and the residential addresses of cases. We sought to use this information to characterise clusters of COVID-19 in multi-generational households in England. Methods Using cross-sectional design, cases of COVID-19 were assigned to clusters if they occurred in the same residential property in a 14-day rolling window. Patient demographic data were supplemented with reference to the ONS index of multiple deprivation and population density. Multi-generational households were defined as a cluster with at least three people, with one case in a person who was 0-16 years old and one case in a person who was [≥] 60 years old, with at least 16 years between two members of each age group. Results A total of 3,647,063 COVID-19 cases were reported between 01 April 2020 and 20 May 2021. Of these, 1,980,527 (54.3 %) occurred in residential clusters. Multi-generational households formed 1.5 % of clusters, with these more likely to occur in areas of higher population density and higher relative deprivation. Multi-generational clusters were more common among households of non-White ethnicity and formed larger clusters than non-multi-generational clusters (median cluster size 6, IQR 4-11 vs 3, IQR 3-4, respectively). Conclusion Multi-generational clusters were not highly prevalent in England during the study period, however were more common in certain populations.


Subject(s)
COVID-19
13.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3957121

ABSTRACT

Background: Universities in England returned to in–person teaching in September 2020, requiring a large migration of students across the country. To understand the impact this had on COVID–19 transmission, we identified and described student cases during the 2020 autumn term. Methods: Student COVID–19 cases were identified from two sources: contact tracing records identifying attendance at university prior to onset and residence in student accommodation identified from matching cases’ residential addresses against national property databases. Residential outbreaks were defined as ≥2 cases with specimen dates within 14 days residing in the same property. A matched analysis of COVID–19 rates and trends in towns/cities with and without a university campus was undertaken. Findings: We identified 53,430 student cases between 1 September and 31 December 2020, constituting 2·7% of all cases (n=1,999,180) in this time period; 39,032 reported attendance at a university during contact tracing; 19,901 resided in student accommodation premises. Cases increased rapidly following the start of term driven initially by cases in student accommodation. Over two thirds (72·2% n=14,375) of cases in student accommodation were part of a residential outbreak.Towns/cities with universities saw a threefold increase in rates amongst 18–23 year olds compared to non–university towns. Interpretation: This study suggests that the return to university teaching and associated movement of students in England was linked to large increases in SARS–CoV–2 transmission amongst this population and potentially contributing to subsequent large increases in the wider population surrounding a campus. Funding Information: No funding was received for this work. Declaration of Interests: None of the authors declare any conflicts of interest.Ethics Approval Statement: UKHSA has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information for national surveillance of communicable diseases and as such, individual patient consent is not required.


Subject(s)
COVID-19
14.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.10.22.21264701

ABSTRACT

Background This study measured the long-term health-related quality of life of non-hospitalised COVID-19 cases with PCR-confirmed SARS-CoV-2(+) infection using the recommended instrument in England (the EQ-5D). Methods Prospective cohort study of SARS-CoV-2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARS-CoV-2(-) controls. Main outcomes were loss of quality-adjusted life days (QALDs); physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. Results Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on non-prescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 15.9 (95%-CI: 12.1, 19.7) QALDs, while those reporting symptoms at month 6 lost 34.1 (29.0, 39.2) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 21% of the total COVID-19-related disease burden in England. Conclusions One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms. summary Losses of health-related quality of life in non-hospitalised COVID-19 cases increase by age and for cases with symptoms after 6 months. At a population level, at least 21% of the total COVID-19-related disease burden in England is attributable to morbidity.


Subject(s)
COVID-19 , Dyspnea
15.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.05.22.21257658

ABSTRACT

Background: The B.1.617.2 COVID-19 variant has contributed to the surge in cases in India and has now been detected across the globe, including a notable increase in cases in the UK. We estimate the effectiveness of the BNT162b2 and ChAdOx1 COVID-19 vaccines against this variant. Methods: A test negative case control design was used to estimate the effectiveness of vaccination against symptomatic disease with both variants over the period that B.1.617.2 began circulating with cases identified based on sequencing and S-gene target status. Data on all symptomatic sequenced cases of COVID-19 in England was used to estimate the proportion of cases with B.1.617.2 compared to the predominant strain (B.1.1.7) by vaccination status. Results: Effectiveness was notably lower after 1 dose of vaccine with B.1.617.2 cases 33.5% (95%CI: 20.6 to 44.3) compared to B.1.1.7 cases 51.1% (95%CI: 47.3 to 54.7) with similar results for both vaccines. With BNT162b2 2 dose effectiveness reduced from 93.4% (95%CI: 90.4 to 95.5) with B.1.1.7 to 87.9% (95%CI: 78.2 to 93.2) with B.1.617.2. With ChAdOx1 2 dose effectiveness reduced from 66.1% (95% CI: 54.0 to 75.0) with B.1.1.7 to 59.8% (95%CI: 28.9 to 77.3) with B.1.617.2. Sequenced cases detected after 1 or 2 doses of vaccination had a higher odds of infection with B.1.617.2 compared to unvaccinated cases (OR 1.40; 95%CI: 1.13-1.75). Conclusions: After 2 doses of either vaccine there were only modest differences in vaccine effectiveness with the B.1.617.2 variant. Absolute differences in vaccine effectiveness were more marked with dose 1. This would support maximising vaccine uptake with two doses among vulnerable groups.


Subject(s)
COVID-19
16.
arxiv; 2021.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2104.05560v3

ABSTRACT

Objective: To evaluate the relationship between coronavirus disease 2019 (COVID-19) diagnosis with SARS-CoV-2 variant B.1.1.7 (also known as Variant of Concern 202012/01) and the risk of hospitalisation compared to diagnosis with wildtype SARS-CoV-2 variants. Design: Retrospective cohort, analysed using stratified Cox regression. Setting: Community-based SARS-CoV-2 testing in England, individually linked with hospitalisation data. Participants: 839,278 laboratory-confirmed COVID-19 patients, of whom 36,233 had been hospitalised within 14 days, tested between 23rd November 2020 and 31st January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF). SGTF is a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test. Main outcome measures: Hospitalisation between 1 and 14 days after the first positive SARS-CoV-2 test. Results: 27,710 of 592,409 SGTF patients (4.7%) and 8,523 of 246,869 non-SGTF patients (3.5%) had been hospitalised within 1-14 days. The stratum-adjusted hazard ratio (HR) of hospitalisation was 1.52 (95% confidence interval [CI] 1.47 to 1.57) for COVID-19 patients infected with SGTF variants, compared to those infected with non-SGTF variants. The effect was modified by age (P<0.001), with HRs of 0.93-1.21 for SGTF compared to non-SGTF patients below age 20 years, 1.29 in those aged 20-29, and 1.45-1.65 in age groups 30 years or older. Conclusions: The results suggest that the risk of hospitalisation is higher for individuals infected with the B.1.1.7 variant compared to wildtype SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults above the age of 30.


Subject(s)
COVID-19
17.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3802578

ABSTRACT

Background: The emergence of VOC202012/01 in England, known as B.1.1.7 or informally as the ‘UK variant’, has coincided with rapid increases in the number of PCR-confirmed positive cases in areas where the variant has been concentrated. Methods: To assess whether infection with SARS-CoV-2 variant VOC202012/01 is associated with more severe clinical outcomes compared to wild-type infection, genomically sequenced and confirmed variant and wild-type cases were linked to routine healthcare and surveillance datasets. Two statistical analyses were conducted to compare the risk of hospital admission and death within 28 days of test between variant and wild-type cases: a case-control study and an adjusted Cox proportional hazards model. Differences in severity of disease were assessed by comparing hospital admission and mortality, including length of hospitalisation and time to death.Results: Of 63,609 genomically sequenced COVID-19 cases tested in England between October and December 2020 6,038 were variant cases. In the matched cohort analysis 2,821 variant cases were matched to 2,821 to wild-type cases. In the time to event analysis we observed a 34% increased risk in hospitalisation associated with the variant compared to wild-type cases, however, no significant difference in the risk of mortality was observed. Conclusion: We found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increase infection severity associated with this variant. Follow-up studies are needed to assess potential longer-term differences in the clinical outcomes of people infected with the VOC-202012/01 variant.


Subject(s)
COVID-19
18.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.02.22.21251534

ABSTRACT

The spatio-temporal dynamics of an outbreak provide important insights to help direct public health resources intended to control transmission. They also provide a focus for detailed epidemiological studies and allow the timing and impact of interventions to be assessed. A common approach is to aggregate case data to administrative regions. Whilst providing a good visual impression of change over space, this method masks spatial variation and assumes that disease risk is constant across space. Risk factors for COVID-19 (e.g. population density, deprivation and ethnicity) vary from place to place across England so it follows that risk will also vary spatially. Kernel density estimation compares the spatial distribution of cases relative to the underlying population, unfettered by arbitrary geographical boundaries, to produce a continuous estimate of spatially varying risk. Using test results from healthcare settings in England (Pillar 1 of the UK Government testing strategy) and freely available methods and software, we estimated the spatial and spatio-temporal risk of COVID-19 infection across England for the first six months of 2020. Widespread transmission was underway when partial lockdown measures were introduced on the 23rd March 2020 and the greatest risk erred towards large urban areas. The rapid growth phase of the outbreak coincided with multiple introductions to England from the European mainland. The spatio-temporal risk was highly labile throughout. In terms of controlling transmission, the most important practical application is the accurate identification of areas within regions that may require tailored intervention strategies. We recommend that this approach is absorbed into routine surveillance outputs in England. Further risk characterisation using widespread community testing (Pillar 2) data is needed as is the increased use of predictive spatial models at fine spatial scales.


Subject(s)
COVID-19
19.
ssrn; 2021.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3788914

ABSTRACT

Background: Care homes worldwide have suffered high rates of COVID-19, reflecting their inherent vulnerability and the institutional nature of care delivered. This study describes the impact of the pandemic in care homes across England.Method: Laboratory confirmed SARS-CoV-2 cases in England notified to PHE from 01 Jan to 25 Dec 2020 were address-matched to identify residential property classifications. Data were analysed to characterise cases and identify clusters. Associated deaths were defined as death within 60 days of diagnosis or certified as cause of death.Findings: Of 1,936,315 COVID-19 cases, 81,275 (4·2%) and 10,050 (0·52%) were identified as resident or staff in a care home, respectively, with 20,544 associated deaths identified, accounting for 31·3% of all COVID-19 deaths. Cases were identified in 69·5% of all care homes in England, with 33.1% experiencing multiple outbreaks. Multivariable analysis showed a 67% increased odds of death in care home residents ( aOR: 1·67, 95% CI: 1·63-1·72) . A total of 10,321 outbreaks were identified at these facilities, of which 8·2% identified the first case as a staff member.Interpretation: Care homes have experienced large and widespread outbreaks of COVID-19, with almost 70% affected, and just under one-third of all COVID-19 deaths occurring in this setting in-spite of early policies. A key implication of our findings is upsurges in community incidences seemingly leading to increased care homes outbreaks, thus identifying and shielding residents from key sources of infection, particularly surrounding staff, is vital to reduce the number of future outbreaks.Funding Statement: Funded by Public Health EnglandDeclaration of Interests: We declare no conflicts of interest.Ethics Approval Statement: All data were collected within statutory approvals granted to Public Health England for infectious disease surveillance and control. Information was held securely and in accordance with the Data Protection Act 2018 and Caldicott guidelines.


Subject(s)
COVID-19 , Communicable Diseases
20.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.12.30.20249034

ABSTRACT

The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.

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