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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22281171

ABSTRACT

ObjectivesSotrovimab 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. MethodsWe performed a retrospective cohort study of individuals treated with Sotrovimab in the community and either had BA.1 or BA.2 variant classification. ResultsUsing 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). ConclusionThese results suggest that the risk of hospital admission is similar between BA.1 and BA.2 cases treated with Sotrovimab in the community.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22275827

ABSTRACT

PurposeThe 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. MethodsThe 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. ResultsThere 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. ConclusionThe 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.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-22271001

ABSTRACT

BackgroundThe 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. MethodsOmicron 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. We used multivariable logistic regression was used to control for factors associated with transmission. FindingsAnalysis 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). InterpretationOur 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. FundingStudy funded by the UK Health Security Agency.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-21267606

ABSTRACT

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases1-3. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions4,5. 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 Deltas 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. Deltas 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.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-21266540

ABSTRACT

BackgroundHousehold 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. MethodsUsing 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. ResultsA 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). ConclusionMulti-generational clusters were not highly prevalent in England during the study period, however were more common in certain populations. BOX TEXTO_ST_ABSWhat is already known on this subjectC_ST_ABSGreater risk of infection with SARS-CoV-2 in England is associated with being of non-White ethnicity, residence in an area of greater deprivation and higher population density. What is less clear is the role of household composition in the risk of COVID-19 transmission. It has been hypothesised that multi-generational housing (in which at least three different generations are resident in the same property) accounted for a substantial proportion of COVID-19 cases. We sought to test this hypothesis. What this study addsThis study provides descriptive evidence around the role of multi-generational households in the COVID-19 pandemic in England between April 2020 and March 2021. It does not support the hypothesis that this period (a period of low incidence in England), a substantial proportion of COVID-19 cases occurred in multi-generational households.

6.
Preprint in English | medRxiv | ID: ppmedrxiv-21257658

ABSTRACT

BackgroundThe 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. MethodsA 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. ResultsEffectiveness 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). ConclusionsAfter 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.

7.
Preprint in English | medRxiv | ID: ppmedrxiv-21251625

ABSTRACT

ObjectivesNosocomial transmission was an important aspect of SARS-CoV-1 and MERS-CoV outbreaks. Healthcare-associated SARS-CoV-2 infection has been reported in single and multi-site hospital-based studies in England, but not nationally. MethodsAdmission records for all hospitals in England were linked to SARS-CoV-2 national test data for the period 01/03/2020 to 31/08/2020. Case definitions were: community-onset community-acquired (CO.CA), first positive test (FPT) <14 days pre-admission, up to day 2 of admission; hospital-onset indeterminate healthcare-associated (HO.iHA), FPT on day 3-7; hospital-onset probable healthcare-associated (HO.pHA), FPT on day 8-14; hospital-onset definite healthcare-associated (HO.HA), FPT from day 15 of admission until discharge; community-onset possible healthcare-associated (CO.pHA), FPT [≤]14 days post-discharge. ResultsOne-third (34.4%, 100,859/293,204) of all laboratory-confirmed COVID-19 cases were linked to a hospital record. HO.pHA and HO.HA cases represented 5.3% (15,564/293,204) of all laboratory-confirmed cases and 15.4% (15,564/100,859) of laboratory-confirmed cases among hospital patients. CO.CA and CO.pHA cases represented 86.5% (253,582/293,204) and 5.1% (14,913/293,204) of all laboratory-confirmed cases, respectively. ConclusionsUp to 1 in 6 SARS-CoV-2 infections among hospitalised patients with COVID-19 in England during the first 6 months of the pandemic could be attributed to nosocomial transmission, but these represent less than 1% of the estimated 3 million COVID-19 cases in this period.

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