Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. Methods With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021. Results Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41–2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48–1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74–1.95; P = .45). Conclusions The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.


Further information on OpenSAFELY
All data were linked, stored and analysed securely within the OpenSAFELY platform https://opensafely.org/. The dataset analysed within OpenSAFELY is based on 24 million people currently registered with GP surgeries using TPP SystmOne software. Data include pseudonymized data such as coded diagnoses, medications and physiological parameters. No free text data are included. All code is shared openly for review and re-use under MIT open license (https://github.com/opensafely/SGTF-CFR-research). Detailed pseudonymised patient data is potentially re-identifiable and therefore not shared. We rapidly delivered the OpenSAFELY data analysis platform without prior funding to deliver timely analyses on urgent research questions in the context of the global Covid-19 health emergency: now that the platform is established we are developing a formal process for external users to request access in collaboration with NHS England; details of this process will be published shortly on OpenSAFELY.org.

Information governance and ethics
NHS England is the data controller; TPP is the data processor; and the key researchers on OpenSAFELY are acting on behalf of NHS England. This implementation of OpenSAFELY is hosted within the TPP environment which is accredited to the ISO 27001 information security standard and is NHS IG Toolkit compliant; 1,2 patient data has been pseudonymised for analysis and linkage using industry standard cryptographic hashing techniques; all pseudonymised datasets transmitted for linkage onto OpenSAFELY are encrypted; access to the platform is via a virtual private network (VPN) connection, restricted to a small group of researchers; the researchers hold contracts with NHS England and only access the platform to initiate database queries and statistical models; all database activity is logged; only aggregate statistical outputs leave the platform environment following best practice for anonymisation of results such as statistical disclosure control for low cell counts. 3 The OpenSAFELY research platform adheres to the obligations of the UK General Data Protection Regulation (GDPR) and the Data Protection Act 2018. In March 2020, the Secretary of State for Health and Social Care used powers under the UK Health Service (Control of Patient Information) Regulations 2002 (COPI) to require organisations to process confidential patient information for the purposes of protecting public health, providing healthcare services to the public and monitoring and managing the COVID-19 outbreak and incidents of exposure; this sets aside the requirement for patient consent. 4 Taken together, these provide the legal bases to link patient datasets on the OpenSAFELY platform. GP practices, from which the primary care data are obtained, are required to share relevant health information to support the public health response to the pandemic, and have been informed of the OpenSAFELY analytics platform.
Pillar 1 is tests in hospital (patients and health care workers). Only some of the labs used for testing in England use the 3 channel PCR for which a "failure to detect the Spike-gene target" is indicative of the VOC, therefore not all positive tests have known SGTF status. The data come from Public Health England's (PHE) Second Generation Surveillance System.
General Practitioner (GP) data GP data are drawn from patients who are registered at a practice that runs the TPP SystmOne (https://www.tpp-uk.com/products/systmone). This is approximately 40% of GPs in England. Each patient encounter with a GP is coded using CTV3 codes, which fully aligns with SNOMED-CT which describe the reason for the encounter, and these codes are used to define the health history of each individual. 6 Prescribed medications are also stored in the health record. Demographic data such as age and ethnicity are collected by GPs, as are some behavioural data like whether an individual smokes.
Hospital admission Secondary Uses Statistics (SUS) data used to define hospital admission and ICU admission. Data are collected on hospital admissions with ICD-10 codes for conditions, and procedural codes for treatment. Whether the patient is admitted to intensive care during their hospital admission is also included. (https://digital.nhs.uk/services/secondary-uses-service-sus)

Mortality date
The date of death plus codes for the cause of death are from the Office for National Statistics. We only use date of death in this study.

Vaccination date
The date, dose number, vaccine manufacturer and batch are entered into their health record. We only use the date of administration of the first dose in this study.

Index of multiple deprivation (IMD)
We use the England IMD which is matched to individuals at the postcode level.

Urban/Rural classification
We use 5 categories of Urban/Rural classifications which are matched to individuals at the postcode level. Table S1. Data sources used in this analysis.

Definition of comorbidities
A patient is identified as having a comorbidity if their health record includes codes indicative of each of the conditions (Table S2).