Approved Projects

This page lists the projects that form part of our first wave of pilot users for OpenSAFELY.

All projects are reviewed by NHS England to ensure they support relevant research and planning activities in response to the COVID-19 emergency; have a favourable ethical opinion (for research) or appropriate sensor sponsorship (for service evaluation or audit); and all users have signed up to the OpenSAFELY principles.

In this wave, pilot users need to have substantial computational data science skills, and strong experience of working with primary care electronic health record data.

The pilot users have also written the summaries of their project below. Their emails are shared if you would like to contact them to understand more about their project.

An onboarding process flowchart is described here.

Project #84: Fit notes in primary care post-COVID
  • Type: Research
  • Topic areas: Post-COVID health impacts [e.g. long COVID]

Fit notes (sometimes called “sick notes”) are issued by GPs in the UK where a person needs to demonstrate to their employer that they are unable to work for health reasons for more than 7 days. Given the large number of patients living after being diagnosed with COVID-19, it is important to know the degree to which recovering from COVID affects people’s ability to work. Coding of fit notes by GPs should provide a window on the scale of the continuing public health and economic burden for those recovering from COVID-19. This in turn can assist policy makers in prioritising resources for COVID recovery services.

In parallel with this, measuring the diagnoses that are associated with fit note coding would provide important insights into the types of conditions that are causing substantial continued problems for people recovering from COVID-19. This could provide important information for the continued care of these patients.

This study examines to what extent (rate and duration) fit notes are given to patients with COVID (identified through three routes—those testing positive for SARS-CoV-2, those with a probably diagnostic code in primary care, and those hospitalised with a diagnostic code for COVID) and compare against general populations from 2019 and 2020, as well as an active comparator (patients hospitalised with pneumonia in 2019 for comparison with hospitalised COVID patients). It also evaluates what diagnoses are commonly coded alongside the recording of a fit note. The study also analyses what type of patients get a fit note, according to demographic, clinical, and organisational factors.


  • Study leads: Alex Walker
  • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
Project #83: Long-term kidney outcomes after SARS-CoV-2 infection
  • Type: Research
  • Topic areas: Post-COVID health impacts [e.g. long COVID]

Around a third of people admitted to hospital with COVID-19 develop kidney damage (known as acute kidney injury or AKI). While AKI is often recoverable, it can sometimes lead to worsening of long-term kidney function and in some cases, permanent kidney failure requiring long-term dialysis or a kidney transplant. The complications caused by long-term kidney damage exert considerable stress on the NHS and it is important that we know what to expect to be able to ensure that services are planned with sufficient capacity to cope. For example, growing numbers of people requiring dialysis will require investment in the workforce and infrastructure. Our research plans to investigate what happens to long-term kidney function after COVID-19 using electronically coded GP records combined with hospital records from England.

Our study will include adults without kidney failure to begin with (i.e. those not on dialysis or a kidney transplant). We will compare people with and without COVID-19 for differences in the rates of the following kidney outcomes:

  1. New kidney failure,
  2. 50% or more reduction in kidney function from before,
  3. Further AKI.

We will be able to determine whether outcomes vary based on the severity of COVID-19, based on time (e.g. during peaks, after widespread use of effective anti-COVID-19 drugs), and based on levels of vaccination. We will account for factors such as age, sex, ethnicity, socioeconomic deprivation, smoking, BMI, and pre-existing medical problems such as diabetes.

As kidney failure is relatively rare at the general population level, very large studies are needed to be able to investigate whether or not a group is at increased risk compared to other groups. Because of the size of the population in OpenSAFELY, we will be uniquely placed to be able to detect differences in this outcome due to COVID-19.


  • Study leads: Viyaasan Mahalingasivam
  • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
Project #82: Spatiotemporal risk of infection of care homes during the first wave of the COVID-19 pandemic in the UK
  • Type: Research (Retired)
  • Topic areas: COVID transmission/prevalence/non-pharmaceutical prevention

Care home residents have restricted mixing with the general population but staff provide a route of infection introduction from the surrounding community. The aim of this analysis was to investigate the timing of first evidence of introduction of COVID-19 to care homes across England, to understand care home characteristics associated with earlier introduction and the relationship between risk of introduction and the surrounding local epidemic.

A rolling analysis over time was planned with the primary outcome being occurrence of a covid-related event (test positive, clinical diagnosis, admission or death) among residents of a care home within the next 14 days from the current time step. Explanatory factors for 14-day risk considered were care home size, whether residential/nursing, proportion of residents with dementia, deprivation index and rural/urban classification of the home’s postcode, and daily incidence of probable COVID-19 infections within the local population of the home’s Middle Super Output Area (MSOA).

The analysis was ultimately retired due to complications with identifying individuals residing in the same household and defining whether or not each household was a care home or private home.


  • Study leads: Emily Nightingale
  • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
Project #81: Analysis of the relative severity of the SARS-CoV-2 Delta variant compared to the Alpha variant
  • Type: Research (Retired)
  • Topic areas: COVID transmission/prevalence/non-pharmaceutical prevention

The SARS-CoV-2 Delta variant first emerged in India in late 2020. The Delta variant became the dominant circulating form of SARS-CoV-2 in the UK by summer 2021.

This study considered the feasibility of an analysis to estimate the relative severity of the SARS-CoV-2 Delta variant compared to the previously circulating forms of the virus.


  • Study leads: daniel.grintroz.eggo
  • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
Project #80: Analysis of the relative severity of the SARS-CoV-2 Alpha variant compared to wild type virus

The SARS-CoV-2 Alpha variant was first identified in Kent, UK in autumn 2020. The variant was more transmissible than the prevalent wild type virus and quickly became the dominant circulating form of the virus.

This study aimed to estimate the relative severity of the SARS-CoV-2 Alpha variant compared to the previously circulating wild type virus.

The study population was defined by all people testing positive for SARS-CoV-2 in the window 16th November 2020 to 11th January 2021, with data available on the gene marker that can differentiate between the two virus types (SGTF).

The exposure of interest was infection with the Alpha variant. The outcomes of interest were hospital admission, admission to the intensive care unit (ICU), and all-cause mortality.

The key finding of this research is that infection with the Alpha variant is associated with a 70% increased risk of all-cause death compared to wild type virus.


  • Study leads: daniel.grintroz.eggo
  • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
Project #79: Viral competition and non-specific immunity between COVID-19 and non-COVID-19 respiratory diseases
  • Type: Research (Retired)
  • Topic areas: COVID transmission/prevalence/non-pharmaceutical prevention

There is some thought that viruses that cause respiratory illness may compete with one another so that only one can become established in the host at a time. Further, it may be possible that respiratory illnesses other than COVID-19 may induce some immune protection against COVID-19.

This study aimed to estimate the impact of non-COVID-19 respiratory infections on the incidence of COVID-19 infection and its severity among the general population.

The exposure of interest was infection with non-COVID-19 respiratory infections. The outcomes of interest were infection with COVID-19 and the resulting outcome of COVID-19 infection.


  • Study leads: Daniel GrintRoz Eggo
  • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
Project #78: Long-term kidney outcomes after COVID-19

Around a third of people admitted to hospital with COVID-19 develop kidney damage (known as acute kidney injury or AKI). While AKI is often recoverable, it can sometimes lead to worsening of long-term kidney function and in some cases, permanent kidney failure requiring long-term dialysis or a kidney transplant. The complications caused by long-term kidney damage exert considerable stress on the NHS and it is important that we know what to expect to be able to ensure that services are planned with sufficient capacity to cope. For example, growing numbers of people requiring dialysis will require investment in the workforce and infrastructure. We plan to investigate what happens to long-term kidney function after COVID-19 using electronically coded GP records combined with hospital records routinely-collected from day-to-day patient care inEngland.

Our study will include adults without kidney failure to begin with (i.e. those not on dialysis or a kidney transplant). We will compare people with and without COVID-19 for differences in the rates of the following kidney outcomes:

  1. Newly-diagnosed kidney failure,
  2. 50% or more reduction in kidney function from before,
  3. Further AKI.

We will be able to determine whether outcomes vary based on the severity of COVID-19, based on time (e.g. during peaks, after widespread use of effective anti-COVID-19 drugs such as steroids), and based on levels of vaccination. We will account for factors such as age, sex, ethnicity, socioeconomic deprivation, smoking, BMI, and pre-existing medical problems such as diabetes.

As kidney failure is relatively rare in the general population, very large studies are needed to be able to investigate whether or not a group is at increased risk compared to other groups. Because of the size of the population in OpenSAFELY, we will be uniquely placed to be able to detect differences in this outcome due to COVID-19.


Project #77: Investigating the impact of COVID-19 on childhood immunisations - prototyping a dashboard

    The pandemic put pressure on routine healthcare services such as family practices, who are usually responsible for giving a range of childhood vaccines, up to the age when children start school. We set out to investigate the impact of the pandemic on childhood immunisations, for example to explore whether they were more likely to be given later or missed altogether. We aimed to produce a prototype of a dashboard which would show, nationally and at local levels, the impacts of the pandemic on childhood immunisation rates and any “catch-up” action which may be required.


    • Study leads: Helen Curtis
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #76: Serious outcomes after COVID hospitalisation

    Patients with COVID-19 are thought to be at higher risk of cardiometabolic and pulmonary complications, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in survivors of severe COVID-19.

    Working on behalf of NHS England, we used linked primary care records, death certificate and hospital data from the OpenSAFELY platform. We constructed three cohorts: patients discharged following hospitalisation with COVID-19, patients discharged following hospitalisation with pneumonia in 2019, and a frequency-matched cohort from the general population in 2019. We studied eight cardiometabolic and pulmonary outcomes. Absolute rates were measured in each cohort and Cox regression models were fitted to estimate age/sex adjusted hazard ratios comparing outcome rates between discharged COVID-19 patients and the two comparator cohorts.

    Cardiometabolic and pulmonary adverse outcomes were markedly raised following hospitalisation for COVID-19 compared to the general population. However, the excess risks were more comparable to those seen following hospitalisation with pneumonia. Identifying patients at particularly high risk of outcomes would inform targeted preventive measures.


    • Study leads: John Tazare
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #75: TPP Representativeness
    • Type: Research (Ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    OpenSAFELY provides a secure software interface allowing a federated analysis of pseudonymised primary care patient records from England in near real-time within the EMIS and TPP highly secure data environments. To date OpenSafely have published more than X papers focussing on delivering vital and urgent results related to the global COVID-19 emergency. The robustness of the evidence they contribute depends on the continued representativeness of data to the background population.

    With the approval of NHS England we set out to investigate the representativeness of TPP data by comparing it to ONS estimates. Proportions of age, sex, imd, ethnicity and causes of death per total study population were calculated and compared to the corresponding ONS data. The five leading causes of death occurring between the 1st January 2020 and the 31st December 2020 were compared to deaths registered in England and Wales during the same period.

    Despite regional variations TPP is largely representative of the general population of England in terms of IMD, age, sex, ethnicity and causes of death. The proportion of the five leading causes of death is broadly similar to those reported by ONS. TPP data made available via OpenSAFELY-TPP is broadly representative of the English population.


    • Study leads: Colm Andrews
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #74: Investigating the effect of SGLT2is on COVID-19 outcomes
    • Type: Research (Ongoing)
    • Topic areas: Risk from COVID (short term) [e.g. hospitalisation/death]

    This study is investigating the use of sodium glucose cotransporter 2 inhibitors (SGLT2is) on the risk of COVID-19 outcomes in the general population.


    • Study leads: John Tazare
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #73: Exploring quality and completeness of ethnicity recording in TPP, EMIS and linked data sources
    • Type: Audit (Postponed)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    To describe quality annd completeness of ethnicity recording in TPP, EMIS linked data sources and validate against 2021 Census ethnicity from ONS.


    • Study leads: Rohini MathurBrian Mackenna
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #72: Post COVID Type 1 Diabetes
    • Type: Research (Retired)
    • Topic areas: Post-COVID health impacts [e.g. long COVID]

    This study aimed to look at whether COVID-19 increases the risk of incident type 1 diabetes in children and adults.


    • Study leads: Rohini MathurKevin Wing
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #71: OpenPROMPT
    • Type: Research (Onoging)
    • Topic areas: Long COVID

    We want to understand the impacts of long COVID on the quality-of-life of people who have developed this condition. For many health conditions, researchers ask people to fill in standardised surveys which measure quality-of-life, which help them understand how much the condition is affecting people. These kinds of measures are used in planning the resources for health systems, because they allow a standard way of comparing different health conditions, and, if people fill them in repeatedly, tracking changes in wellbeing over time.

    These quality-of-life measurements are not currently available for people with long COVID who did not need to be hospitalised during their COVID-19 episode. Our study aims to collect these measurements, by using a smartphone app linked to a patient’s GP records. We will ask people to voluntarily participate in the study and use the app, and if they do so to give their consent for filling the questionnaires and for linkage to their health records.

    These results will tell us if long COVID has different quality-of-life impacts among different age groups, ethnicities, geographic regions, or because of any underlying health conditions.

    We will convert the results into standardised measurements that are used in the NHS to assess the impact of illnesses. This means they will be useful for working out how much the effects of long COVID cost the health service, and how we should prioritise interventions such as booster vaccines to avoid more people getting long COVID.

    Together with other researchers studying long COVID we will provide results to support long-term care. At all stages we will work with people affected by long COVID to ensure their input is central to designing the study plans and interpreting the outputs.


    • Study leads: Emily HerrettRoz Eggo
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #70: Lone households and mental health outcomes
    • Type: Research (Ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Loneliness and living alone have been linked with poor mental and physical health. Evidence suggests that the COVID pandemic exacerbated feelings of loneliness, social isolation and connectivity, due to national lockdowns, social distancing rules and shielding. There is also evidence that the pandemic increased psychological distress including feelings of anxiety and depression, and perhaps particularly for those living alone.

    This study will use a large cohort of adults to see how diagnoses of mental health conditions changed before and during the COVID pandemic, and how this differed among people living alone and not living alone.


    • Study leads: Emily Herrett
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #69: Monitoring safety and adverse events in coronavirus vaccine trials
    • Type: Research
    • Topic areas: COVID-19 vaccine safety

    To provide background rates of adverse events in populations similar to those recruited in COVID-19 vaccine trials. This helps to contextualise safety outcomes in vaccine trials.


    • Study leads: William Hulme
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #68: COVID-19 outcome time series
    • Type: Research
    • Topic areas: COVID-19 outcomes overview

    To describe the occurrence and timings of key COVID-19 related clinical outcomes, such as positive tests, hospital admissions, and death.


    • Study leads: William Hulme
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #67: Assessing effectiveness of 3rd / booster COVID-19 vaccine doses in England
    • Type: Research
    • Topic areas: COVID vaccine effectiveness/safety

    The national COVID-19 vaccination effort in the United Kingdom continued in September 2021 with third doses administered to the most vulnerable, and with eligibility extended to the entire adult population by the end of the year.

    This study will assess effectiveness of a third dose of COVID-19 vaccine compared with a complete 2-dose vaccination course.


    • Study leads: William Hulme
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #66: Changes in PINCER indicators throughout the COVID-19 pandemic
    • Type: Research
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    PINCER is a pharmacist-led information technology intervention that aims to reduce the risk of patient harm due to medication errors as captured by 13 indicators of hazardous prescribing or delayed medication monitoring. The COVID-19 pandemic has been shown to have caused significant disruption to healthcare services. This study examines the rate of hazardous prescribing or delayed monitoring as indicated by each individual PINCER indicator between September 2019 and September 2021 to assess the impact of the pandemic.


    • Study leads: Louis FisherLisa Hopcroft
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #65: Describing trends and variation in HbA1c levels during COVID-19 in 24 million patients' primary care records using OpenSAFELY
    • Type: Research
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    The HbA1c test, used to measure blood glucose level, is a key primary care service that has been disrupted by the COVID-19 pandemic. Getting an accurate read of blood glucose level is necessary to make new diabetes diagnoses and detect increased risks of complications for existing diabetics. Furthermore, diabetes has been linked to greater COVID-19 severity and mortality, making regular monitoring and management of blood glucose levels more crucial.

    This study aims to describe the impact of service disruption on HbA1c test results across 23.8 million patients' records in England. It presents cohort-based observational analyses to examine metrics such as the number of HbA1c tests recorded, percentage of abnormal results, and mean of test values between January 2019 and June 2021, focusing on breakdowns by healthcare inequalities, which include age group, sex, ethnicity, region, IMD, diabetes, learning disability, and mental health conditions.


    • Study leads: Robin Park
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #64: Short-term safety of COVID-19 vaccines in England 2020/21 - acute venous thromboembolic events
    • Type: Research
    • Topic areas: COVID-19 vaccine safety (venous thromboembolic events)

    Safe and effective vaccination is vital for the public health response to the COVID-19 pandemic. The COVID-19 pandemic prompted rapid vaccine development and roll-out. Each vaccine demonstrated a reassuring safety profile in large clinical trials before licensing for use. However, post-licensing vaccine safety surveillance remains important for vaccine safety and public confidence. On March 11 2021, the Danish authorities temporarily paused delivery of COVID-19 vaccination while investigating a report of a fatal blood clot in a person who had received the AstraZeneca COVID-19 adenovirus vector vaccine. A new syndrome of thrombosis with thrombocytopaenia has been described, prompting further investigation of venous thromboembolism events following vaccination.

    This study aims to investigate the associations of each of Pfizer BioNTech and AstraZeneca COVID-19 vaccines with any venous thromboembolism (VTE) in England. The study will also look at the specific outcomes of pulmonary embolism and cerebral venous thrombosis.

    Primary analysis will use a self-controlled case series (SCCS) design, a case-only design which compares incidence of events within the same individual across different time periods. A separate analysis will be conducted for each vaccine brand. Vaccination status will be obtained from the primary care record. We will use primary care and hospital admission records to define episodes of venous thromboembolism.

    A secondary objective is to investigate the extent to which self-controlled case series (SCCS) and cohort study designs differ in their estimations of any associations of COVID-19 vaccination with venous thromboembolic events, to aid interpretation of findings from other observational vaccine safety studies. A secondary analysis will use a cohort study design with both historical and concurrent comparator groups. A cohort study design can be a useful complement to investigate the robustness of findings from SCCS analysis in safety studies, since they have a different profile of biases. We will use this analysis to explore the effect of study design on estimates of vaccine safety.

    This study is a partnership between the OpenSAFELY collaboration, the NIHR Health Protection Research Unit (HPRU) in Vaccines and Immunisation (a partnership between the London School of Hygiene and the UK Health Security Agency), the NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, and the Medicines and Healthcare products Regulatory Agency (MHRA).


    • Study leads: Helen McDonald
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #63: Short-term safety of COVID-19 vaccines in England 2020/21 - neurological events
    • Type: Research
    • Topic areas: COVID-19 vaccine safety (neurological events)

    Safe and effective vaccination is vital for the public health response to the COVID-19 pandemic. The COVID-19 pandemic prompted rapid vaccine development and roll-out. Each vaccine demonstrated a reassuring safety profile in large clinical trials before licensing for use. However, post-licensing vaccine safety surveillance remains important for vaccine safety and public confidence. This study aims to investigate for any association of COVID-19 vaccination with each of Guillain-Barré syndrome, transverse myelitis and Bell’s palsy.

    Primary analysis will use a self-controlled case series (SCCS) design, a case-only design which compares incidence of events within the same individual across different time periods. A separate analysis will be conducted for each combination of vaccine brand and outcome. Vaccination status will be obtained from the primary care record. We will use primary care and hospital admission records to define episodes of Guillain-Barré syndrome, transverse myelitis and Bell’s palsy, and will additionally use emergency care attendance data to enhance ascertainment of Bell’s palsy.

    We also plan to follow with a secondary analysis using a cohort study design with both historical and concurrent comparator groups. A cohort study design can be a useful complement to investigate the robustness of findings from SCCS analysis in safety studies, since they have a different profile of biases. We will use this analysis to explore the effect of study design on estimates of vaccine safety.

    This study is a partnership between the OpenSAFELY collaboration, the NIHR Health Protection Research Unit (HPRU) in Vaccines and Immunisation (a partnership between the London School of Hygiene and the UK Health Security Agency),the NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, and the Medicines and Healthcare products Regulatory Agency (MHRA).


    • Study leads: Helen McDonald
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #62: Comparing effectiveness of the Pfizer-BioNTech vaccine with the Oxford-AstraZeneca vaccine in Health and Social Care workers in England

    Many studies have been conducted that estimate the effect of COVID-19 vaccines in reducing infection or disease compared with unvaccinated people. However, there have been no randomised controlled trials that have made direct head-to-head comparisons. Such comparisons are difficult in observational data without the rollout of both vaccines across the same population at the same time. The concurrent rollout of the Pfizer-BioNTech vaccine and the Oxford-AstraZeneca vaccine in health and social care workers in England provides a rare opportunity to do this.

    We compared effectiveness in around ⅓ million health and social care workers in England, vaccinated between 4 January and 28 February 2021, and followed up for 20 weeks. Primary outcomes were recorded SARS-CoV-2 infection, COVID-19-related accident and emergency attendance, and COVID-19-related hospital admission.

    We found very little difference in between the vaccines on the studied outcomes. Whilst some material differences in the protective effect may exist, both are extremely effective for reducing COVID-19 disease and there were too few events to reliably detect such differences up to 20 weeks after vaccination.


    • Study leads: William Hulme
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #61: Estimating COVID-19 vaccine effectiveness in early recipients of the vaccine under the UK national vaccination programme
    • Type: Research
    • Topic areas: COVID vaccine effectiveness/safety

    The COVID-19 vaccines were developed and rigorously evaluated in randomized trials within a year of the first reports of COVID-19 in Wuhan, China. However, many questions about vaccine effectiveness were not answered by randomized trials, for example protection for sick or elderly people, or against severe outcomes such as hospitalisation. The UK started its general population COVID-19 vaccination programme in early December 2020, prioritising vaccination in the most vulnerable people, in particular elderly people, who were not well-represented in trials.

    We assessed vaccine effectiveness amongst >2.6 million people aged over 70 in England, using linked routine clinical data from the OpenSAFELY TPP database. We looked at the vaccine’s ability to reduce infection, hospitalisation, and death compared with those who were not vaccinated. We studied both the Pfizer-BioNTech and the Oxford-AstraZeneca vaccines.

    We found that the vaccines were highly effective. However, we also found evidence of biases in these estimates. For example, the estimated protective effect of vaccination was very high in the first two weeks after vaccination, yet we know from trials that immunity does not develop until after the first week.

    We discuss the challenges of estimated vaccine effectiveness in observational data, using our study as an exemplar.


    • Study leads: William Hulme
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #60: Describing the rates of COVID-19 vaccine breakthrough in fully vaccinated individuals in England

    The vaccination programme for COVID-19 in the UK started on 8th December 2020. As with any vaccine, despite being vaccinated, COVID-19 vaccine breakthrough is likely and a small number of people will still fall ill, be hospitalised, or die from COVID-19.

    As of 30th June 2021, a total of 10,782,870 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 43 days (IQR: 23-64). From within this population, the total number of COVID-19 vaccine breakthrough cases was 17,030 (0.2%). The majority of COVID-19 vaccine breakthrough cases were mild with relatively few fully vaccinated individuals being hospitalised or dying as a result. However, some concerning differences in rates of breakthrough cases were identified in several clinical groups; comorbidities with the highest rates of breakthrough COVID-19 included renal replacement therapy, organ transplant, haematological malignancy, and immunocompromised

    The continued increase in numbers of positive SARS-CoV-2 tests in England are concerning and, as numbers of fully vaccinated individuals increases and follow-up time lengthens, so too will the number of COVID-19 breakthrough cases.

    To help inform roll-out of the third and booster dose vaccination, and to support the redesignation of dialysis patients into the 3rd dose group, with eligibility for subsequent vaccination, this analysis was rerun in November 2021 (with the previous CKD group split out into categories). As expected, there had been a rise in all rates (calculated per 1000 person-years);

    • Positive SARS-CoV-2 test from 12.33 (12.14-12.51) to 99.44 (99.31-99.57)
    • COVID related hospitalisation from 0.70 (0.65-0.74) to 2.31 (2.29-2.34)
    • COVID related death from 0.12 (0.1-0.14) to 0.64 (0.63-0.66)

    Despite these increases, reassuringly, breakthrough cases remain relatively mild; 312, 530 Positive SARS-CoV-2 tests vs 3840 COVID-19 related deaths (with the majority (80%) of deaths occurring in those over 70 years of age).


    • Study leads: Millie Green
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #59: Care homes excess mortality
    • Type: Research
    • Topic areas: Excess mortality in Care Homes

    This project was initiated to quantify care home mortality on the care home level as so called excess mortality. After initial feasibility work, this was paused due to the lack of a time-updated household identifier.


    • Study leads: Anna Schultze
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #58: Carehomes Short Data Report

    This short data report compared different strategies for identifying care home residents in electronic health records in England. Historically, GPs do not enter whether or not a person is living in a care home in their medical record. There is also no central registry of care home residents. Therefore, when we want to study people in care homes using electronic health records from GP surgeries, we need to rely on other methods to identify these people.

    In this report we compared using medical codes, an address linkage, and household information to identify care home residents. We describe how these methods are implemented in OpenSAFELY, and compared the overlap between them.


    • Study leads: Anna Schultze
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #57: OpenSAFELY NHS Service Restoration Observatory: describing trends and variation in key measures of general practice clinical activity.
    • Type: Research
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    The COVID-19 pandemic has had a significant impact on the delivery of care within the NHS. We have developed the OpenSAFELY Service Restoration Observatory to describe this impact on primary care activity and monitor the restoration of service. We developed 11 key measures of primary care activity indicative of overall activity and describe the trend in activity of these measures throughout the COVID-19 pandemic. A substantial drop in activity was observed in all measures during the COVID-19 pandemic. By April 2021, seven of the measures had recovered to within 15% of pre-pandemic levels. The remaining measures show a sustained drop in activity ranging from a 16.8% reduction in asthma reviews to a 39.7% reduction in cardiovascular disease risk assessment. Changes in activity during the pandemic varied in key demographic subgroups, with the rate of activity relative to the population rate increasing in all measures in those with a recorded learning disability. Other population subgroups showed decreases in activity relative to the population rate.


    Project #56: Mortality among Care Home Residents in England

    This study aimed to quantify the mortality risk among care home residents compared to residents of private homes during the first and second wave of the pandemic. We used a technique called standardisation to account for age differences between care home residents and residents of private homes, and described how the mortality risk changed between February 2019 and March 2021.

    We found that care home residents had an approximately 10-fold higher risk of death compared to residents of private homes prior to the first pandemic wave; this increased to an approximately 17 times higher risk during the first wave. Despite absolute increases in the risk of death during the second wave, the relative mortality risk for care home residents remained stable at approximately 10-fold higher compared to residents of private homes.

    These analyses were largely descriptive, and as such we cannot say why there was a spike in the risk of death for care home residents during the first but not the second wave. Plausible explanations include improved protections in care homes such as testing and better use of personal protective equipment (PPE), pre-existing immunity from the first wave among residents and staff, or an element of mortality displacement. The peak of the second wave occurred prior to the point where the UK vaccination program is anticipated to have an effect. This study quantifies the impact of the pandemic on care home residents in England, and suggests a number of important questions for future research to ensure that this vulnerable population is protected for the next pandemic.


    • Study leads: Anna Schultze
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #55: Potentially inappropriate prescribing of DOACs to patients with a mechanical heart valve throughout the COVID-19 pandemic

    National guidance was issued during the COVID-19 pandemic to switch patients on warfarin to direct oral anticoagulants (DOACs) where appropriate as these require less frequent blood testing. DOACs are not recommended for patients with mechanical heart valves. We conducted a retrospective cohort study of DOAC prescribing in people with a record of a mechanical heart valve between September 2019 and May 2021, and describe the characteristics of this population. We identified 15,457 individuals with a mechanical heart valve recorded in their records, of whom 1058 (6.8%) had been prescribed a DOAC during the study period. 767 individuals with a record of a mechanical heart valve were currently prescribed a DOAC as of May 31st 2021.


    • Study leads: Louis Fisher
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #54: Association between living with children and outcomes from COVID-19: an update of an OpenSAFELY cohort study in England
    • Type: Audit / Research
    • Topic areas: Risk from COVID (short term) [e.g. hospitalisation/death]

    COVID-19 disease in children and young people is typically mild or asymptomatic, however the role of children and young people in transmission of SARs-CoV-2 remains unclear. At the start of the COVID-19 pandemic, schools were shut, on the premise that children may be vectors of COVID-19, as they are for other respiratory diseases, such as seasonal influenza. Evidence on the absolute impacts of educational settings being closed on community transmission is mixed; quantifying the impact is challenging, as closures have been implemented alongside other public health measures, infection control measures vary across educational settings and school opening may be associated with other behavioural changes. The negative impacts of school closures on the educational, developmental and mental health of children is undisputed.

    In our previous analysis we showed during the first wave of the UK pandemic, when schools were largely closed, for adults 65 years and under living with children there was no evidence of a markedly increased risk of SARS-CoV-2 infection or severe COVID-19 outcomes. However, during wave 2 (1st September to 19th December 2020) when schools were largely open, there was evidence of increased risk of infection and hospitalisation with COVID-19, although the risk of death from COVID-19 was not increased in either wave.

    In this analysis, we examine the risk of SARS-CoV-2 infection and outcomes from COVID-19 associated with living with children compared to those without during 2021, and the impact that adult vaccination had on that risk.


    • Study leads: Harriet ForbesLaurie Tomlinson
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #53: Short report for JCVI

    This was an early look at work which was later written up for publication (see Risks of COVID-19 hospital admission and death for people with learning disabilities - a cohort study.)

    Two cohorts were assembled, reflecting the two first waves of COVID-19 experienced in the UK, comprising males and females aged up to 105 years: (1) wave 1, from 1st March 2020 until 31st August 2020; (2) wave 2, 1st September 2020 until 31st December 2020 (for admissions) or 8th February 2021 (for deaths). The main outcomes were COVID-19 related death and COVID-19 related hospitalisation. Various risk factors were included, with particular focus on whether or not the person was on the learning disability register.

    Generally, age was the strongest factor associated with both outcomes, but much stronger for COVID-19 death than mortality. Various comorbidities were associated with increased absolute risks, aligning with the earlier work on risk factors (Nature, 2020). Learning disabilities was noted as being associated with increased risks (leading to subsequent publication focused on that question).


    • Study leads: Elizabeth Williamson
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #52: Risks of COVID-19 hospital admission and death for people with learning disabilities - a cohort study.

    This study aimed to assess the association between learning disability and risk of hospitalisation and mortality from COVID-19 in England among adults and children.

    Two cohorts were assembled, reflecting the two first waves of COVID-19 experienced in the UK, comprising males and females aged up to 105 years: (1) wave 1, from 1st March 2020 until 31st August 2020; (2) wave 2, 1st September 2020 until 31st December 2020 (for admissions) or 8th February 2021 (for deaths). The main exposure group was people included on a general practice learning disability register (LDR), with a subgroup of people classified as having profound or severe learning disability. We also identified patients with Down syndrome and cerebral palsy. The main outcomes were COVID-19 related death and COVID-19 related hospitalisation. Non-COVID-19 related death was also explored.

    In wave 1, of 14,301,415 included individuals aged 16 and over, 90,095 (0.63%) were identified as being on the LDR. 30,173 COVID-related hospital admissions, 13,919 COVID-19 related deaths and 69,803 non-COVID deaths occurred; of which 538 (1.8%), 221 (1.6%) and 596 (0.85%) were among individuals on the LDR, respectively. Wave 1 hazard ratios for individuals on the LDR, adjusted for age, sex, ethnicity and geographical location, were 5.3 (95% confidence interval (CI) 4.9, 5.8) for COVID-19 related hospital admissions and 8.2 (95% CI: 7.1, 9.4) for COVID-19 related death. Wave 2 produced similar estimates.

    Associations were stronger among those classed as severe-profound and among those in residential care. Down syndrome and cerebral palsy were associated with increased hazard of both events in both waves; Down syndrome to a much greater extent. Hazards of non-COVID-19 related death followed similar patterns with weaker associations.

    People with learning disabilities have markedly increased risks of hospitalisation and mortality from COVID-19. This raised risk is over and above that seen for non-COVID causes of death. Ensuring prompt access to Covid-19 testing and health care and consideration of prioritisation for COVID-19 vaccination and other targeted preventive measures are warranted.


    • Study leads: Elizabeth Williamson
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #51: Predicting risk of COVID-19 mortality: comparison of methods
    • Type: Risk from COVID (short term) [e.g. hospitalisation/death]
    • Topic areas: Research

    Obtaining accurate estimates of risk is challenging in the context of changing levels of circulating infection, which standard risk prediction models commonly ignore.

    We adopt a landmarking approach for risk prediction to dynamically incorporate time- and region-dependent information on infection prevalence. We compare this approach with more commonly used Cox models that do not take infection prevalence into account, in terms of discriminaton and calibration. We also compare simpler models to more richly specified ones.

    The target population was adults registered at a general practice in England in March 2020. The outcome was 28-day COVID-19-related-death. Predictors included demographic characteristics and comorbidities. Three proxies of local infection prevalence were used: model-based estimates; rate of COVID-19-related attendances in emergency care; and rate of suspected COVID-19 cases in primary care.

    Prediction models were developed on 11,972,947 individuals, of whom 7,999 experienced COVID-19-related-death. All models discriminated well between individuals who did and did not experience COVID-19 mortality, including simple models adjusting only for basic demographics and number of comorbidities: C-statistics 0.92-0.94. However, absolute risk estimates were substantially miscalibrated when infection prevalence was not explicitly modelled.

    Our study suggests that models that ignore the infection prevalence provide poorly calibrated estimates of absolute risk; models that include time-varying measures of the infection prevalence can provide more accurate estimates. Simple models based only on number of comorbidities and basic demographics performed almost as well as more complex risk prediction models, both within models including infection prevalence and models that ignore this, suggesting that policies targeting population level reduction of COVID-19 mortality risk may not need to distinguish between all comorbidities in detail.


    • Study leads: Elizabeth Williamson
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #50: Trends and clinical characteristics of COVID-19 vaccine recipients

    The COVID-19 vaccination programme was launched in England on 8th December 2020. Limited information was available on vaccination coverage in detailed demographic and clinical subgroups.

    We deployed a data monitoring framework using publicly auditable methods and a secure, in-situ processing model, using linked but pseudonymised patient-level NHS data on 57.9 million patients. We describe vaccine coverage and time trends across a range of subgroups of Joint Committee on Vaccination and Immunisation (JCVI) priority cohorts.

    Our study highlights lower vaccination coverage among certain key groups: ethnic minorities, those living in areas of higher deprivation, and individuals living with severe mental illness or learning disabilities; where targeted activity may be needed to ensure equitable protection against COVID-19.


    • Study leads: Helen Curtis
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #49: Association between household composition and severe COVID-19 outcomes in older people by ethnicity: an observational cohort study using the OpenSAFELY platform
    • Type: Research (Ongoing)
    • Topic areas: Risk from COVID (short term) [e.g. hospitalisation/death]

    Ethnic differences in the risk of severe COVID-19 may be linked to ethnic differences in household composition. In this study our aim was to assess whether household composition (= the number of age-based generations in a household) was associated with risk of severe COVID-19 for older individuals (people aged 67 or older) after taking account of other risk factors for severe COVID-19, and whether this association differed by ethnicity.

    We created a cohort that included all people over the age of 67 in OpenSAFELY, and analysed whether the number of younger generations that the 67+ year old lived with was associated with their risk of being hospitalised or dying from COVID-19. We performed separate analyses for wave 1 (01/02/2020-31/08/2020) and wave 2 (01/09/2020-31/01/2021) in the UK, and analysed the effect of the following living arrangements: 67+ year old living alone, 67+ year old living with other 67+ year olds, 67+ year old living with people from 1 younger generation, 67+ year old living with people from 2 younger generations, 67+ year olds living with people from 3 younger generations (with distinct younger generations defined as 0-18, 18-29, 30-66). For all analyses, we assessed whether observed effects were different by ethnic group (defined as White, Black, South Asian, Mixed and Other).

    Initial results showed that in Wave 1 there was no association between household composition and severe COVID-19 for any ethnicity, but that in wave 2 living with increasing numbers of younger generations was associated with an increased risk of severe COVID-19 for White and for South Asian people. We also found that older South Asian people are over-represented within multi-generational household in the most deprived settings, and older people in these settings have a particularly high risk of severe COVID-19.


    • Study leads: Kevin WingRoz Eggo
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #48: Recording of "COVID-19 vaccine declined" among vaccination priority groups

    All patients in England within vaccine priority groups were offered a COVID-19 vaccine by mid-April 2021. Clinical record systems contain codes to denote when such an offer has been declined by a patient (although these can in some cases be entered for a variety of other reasons including vaccination delay, or other administrative issues). We set out to describe the patterns of usage of codes for COVID-19 vaccines being declined.

    We identified all patients in key vaccine priority groups: aged over 50, or over 16 and at increased risk from COVID-19 (Clinically Extremely Vulnerable [CEV] or otherwise “at risk”). We describe the proportion of patients recorded as declining a COVID-19 vaccination for each priority group, and by other clinical and demographic factors; whether patients recorded as “declined” subsequently went on to receive a vaccination; and the distribution of code usage across GP practices.

    We found that clinical codes indicative of COVID-19 vaccinations being declined are widely used in English general practice. Of 24.5 million patients in priority groups as of May 25th 2021, 89.2% had received a vaccine, 8.8% had neither a vaccination nor a decline recorded, and 2.7% had a decline code recorded. Of patients with a recorded decline, 18.9% were subsequently vaccinated.

    Declines were substantially more commonly recorded among Black and South Asian patients, and patients from more deprived areas. There is a need for more detailed survey and/or qualitative research with patients and clinicians to determine the most common reasons for these recorded declines.


    • Study leads: Helen Curtis
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #47: OpenSAFELY NHS Service Restoration Observatory 1: describing trends and variation in primary care clinical activity for 23.3 million patients in England during the first wave of COVID-19

    The COVID-19 pandemic has disrupted healthcare activity. The NHS stopped non-urgent work in March 2020, later recommending services be restored to near-normal levels before winter where possible.

    We aimed to describe the volume and variation of coded clinical activity in general practice across the whole population in OpenSAFELY-TPP between January 2019-September 2020, taking respiratory disease and laboratory procedures as examples.

    We found that activity recorded in general practice declined during the pandemic, but largely recovered by September 2020. There was a large drop in coded activity for laboratory tests, with broad recovery to pre-pandemic levels by September. One exception was International Normalised Ratio test, with a smaller reduction. The pattern of recording for respiratory symptoms was less affected, following an expected seasonal pattern and classified as “no change”. Respiratory infections exhibited a sustained drop not returning to pre-pandemic levels by September. Asthma reviews experienced a small drop but recovered, while COPD reviews remained below baseline.

    In conclusion: We delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVID-19 pandemic led to a substantial change in healthcare activity.


    • Study leads: Helen Curtis
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #46: OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic

    From the beginning of the COVID-19 pandemic, the NHS recommended putting measures in place to reduce face-to-face contact with patients where possible to reduce the risk of transmission. This included guidance to consider switching warfarin patients to a direct acting oral anticoagulant (DOAC) where suitable. This aimed to reduce the number of times patients had to attend for blood tests. However, it was not known how widespread this practice was, whether it resulted in potentially dangerous co-administration of both drugs in some patients, or whether those patients who remained on warfarin were tested frequently and maintained good clotting results.

    We identified patients who were taking warfarin prior to the pandemic and the factors associated with being switched to DOACs.

    This is the first widespread study on the impact of the NHS England guidance. We showed that a substantial number of patients in general practice in England had their anticoagulant switched from warfarin to a DOAC. We also showed that there was a small number of patients who potentially received both warfarin and a DOAC. There did not appear to be a widespread reduction in INR control during the pandemic.

    This study highlights that national prescribing guidance can be implemented in primary care in England, both on a large scale and at a fast pace when necessary to improve patient care. It also highlights the importance of good clinical governance processes when switching medications, in order to reduce the risk of co-prescribing of both agents.


    • Study leads: Helen Curtis
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #45: Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: cohort study in OpenSAFELY using linked primary care, secondary care and death registration data
    • Type: Research
    • Topic areas: Post-COVID health impacts [e.g. long COVID]

    There is concern about medium to long-term effects of COVID-19. The aim of this study was to investigate whether people have a higher risk of hospital admission and death after being discharged from hospital following illness with COVID-19.

    We used anonymised electronic health records from English hospitals to identify people who had been admitted to hospital with COVID-19 and then later discharged. We also gathered further details about these individuals from linked GP records. We then looked at whether these patients were re-admitted to hospital later, or died (using national death registration data). For comparison, we also used data from before the pandemic and looked at hospitalisations and deaths in people who had previously been in hospital with influenza, and in people who had not been in hospital at all.

    24,673 people who had been discharged from hospital following illness with COVID-19 were identified. These individuals had higher risks of returning to hospital and dying compared with people who had never been in hospital. They also had higher risks of dying than people who had been in hospital with influenza prior to the pandemic, but similar risks of being readmitted to hospital.

    We concluded that the higher risks for rehospitalisation and death in people discharged after a COVID-19 hospital admission compared with the general population might create a substantial extra burden on healthcare.


    • Study leads: Krishnan Bhaskaran
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #44: Pre-Covid: Anti-coags

    (1) It was reported that people with severe COVID-19 are at risk of blood clots. Warfarin is a commonly used blood thinning treatment. A previous study suggested that it might increase the risk of severe COVID-19 related outcomes due to the process of how it produces an effect in the human body to prevent blood clots, which is different from its alternative treatment (direct oral anticoagulants, DOACs). However, little is known about the impact of routine use of warfarin on COVID-19 related blood clots.

    Therefore, we studied a large number of people with atrial fibrillation (a medical condition of an irregular heart rhythm that can lead to blood clots in the heart) who were prescribed warfarin or DOACs as part of normal clinical care and followed them up to compare the effects of warfarin on several COVID-19 related outcomes with DOACs.

    Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease, compared with DOACs. This study provides reassurance about the safety of warfarin use among patients with atrial fibrillation in the context of the COVID-19 pandemic.

    (2) Early studies showed that blood thinning treatment (anticoagulants) reduce the risk of thrombotic events amongst those infected. However, current evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is unclear.

    Therefore, we studied a large number of people with atrial fibrillation (a medical condition of an irregular heart rhythm that can lead to blood clots in the heart) who had a low risk of stroke. Among this study cohort, the decision of prescribing OAC would typically be borderline. We followed them up to compare the effects of those who prescribed oral anticoagulants on several COVID-19 related outcomes with those who did not .

    In conclusion, this study shows that people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users. This might be explained by the potential effect of OACs in preventing severe COVID-19 outcomes or more cautious behaviours leading to reduced infection risk.


    • Study leads: Angel Wong
    • Organisation: NHS England (in collaboration with University of Oxford and LSHTM)
    Project #43: Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death.

    COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

    GP data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. Self-reported ethnicity as captured on the GP record was used, grouped into five main categories (White, South Asian, Black, other, and mixed) and 16 subcategories.

    Our findings show that minority ethnic groups have higher risks of COVID-19-related hospitalisation, ICU admission, and death even after accounting for other medical conditions individuals may be suffering from; in particular, the risks of COVID-19-related hospitalisation and death in wave 2 were increased for South Asian groups and reduced in all other ethnic minority groups relative to the White group.

    The causes of the worse outcomes for minority ethnic groups is likely to involve many factors and require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination.


    • Study leads: Rohini Mathur
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #42: HIV infection and COVID-19 related death.

    This study aimed to investigate whether people with HIV had different risks of dying from COVID-19 compared with people without HIV.

    We used anonymised electronic health records from GP practices and information from national death registrations to compare COVID-19 death rates between people who had a record of HIV in the GP record and people with no record of HIV. We also took account of other factors, like age and other illnesses, that might affect risk of COVID-19 death.

    Over 17 million people were included, and 27 480 had a record of HIV. People living with HIV had higher risk of COVID-19 death than those without HIV after taking account of other factors and this was particularly pronounced in people of black ethnicity.

    We concluded that people with HIV in the UK seem to be at increased risk of dying from COVID-19. Targeted policies should be considered to address this raised risk as the pandemic response evolves.


    • Study leads: Krishnan Bhaskaran
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #41: Factors associated with deaths due to COVID-19 versus other causes.

    The aim of this study was to answer the question: to what extent is a person’s risk of dying from COVID-19 governed by their broader risk of death, based on their age, medical history, and other characteristics?

    We used anonymised routinely collected GP records data from over 17 million people and information on deaths and causes of death from national death registrations. We looked at all deaths after February 2020 and analysed how individual characteristics like age, ethnicity, and medical history were linked to both COVID and non-COVID deaths.

    We found that a person’s individual characteristics broadly affected their risk of COVID-19 death and non-COVID deaths in similar ways. But there were exceptions, most notably ethnicity: non-white groups had higher risks of dying from COVID-19 death, despite generally lower risks of dying from non-COVID causes.

    We concluded that COVID-19 largely multiplies existing risks faced by patients, with some notable exceptions. Identifying the unique factors contributing to the higher COVID-19 mortality risk among non-white groups is a priority to inform efforts to reduce deaths from COVID-19.


    • Study leads: Krishnan Bhaskaran
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #40: Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19.

    In the early pandemic, there have been concerns that non-steroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen, naproxen, diclofenac, etc.) may increase the risk of COVID-19 related death, but the evidence for this was lacking. This study investigated the routine use of NSAIDs and risk of COVID-19 related death using data from patients in a database covering 40% of the population of England.

    In the first study we identified people with an NSAID prescription in the last 3 years from the general population. We compared the risk of COVID-19 related death among these people with those who were not prescribed NSAIDs.

    In the second study we identified people with rheumatoid arthritis/osteoarthritis and divided them into two groups: those who were prescribed NSAIDs and those who were not prescribed NSAIDS. We compared the risk of COVID-19 related death between these two groups.

    In both studies we found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. We concluded that becoming infected by COVID-19 should not influence decisions about the routine prescribing of NSAIDs.


    • Study leads: Angel Wong
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #39: Effect of pre-exposure use of hydroxychloroquine on COVID-19 death in patients with rheumatoid arthritis or systemic lupus erythematosus.

    This is the first study, to our knowledge, to investigate the ongoing routine use of hydroxychloroquine and risk of COVID-19 mortality in a general population. In this study, which uses a database that includes around 40% of the population of England, we investigated whether routine use of hydroxychloroquine before the COVID-19 outbreak (ie, pre-exposure) prevented COVID-19 death.

    We found no evidence to support a substantial benefit of hydroxychloroquine in preventing COVID-19 death. At the same time, we have shown no evidence of harm. The absence of clear harms or benefits would therefore support ongoing clinical trials using hydroxychloroquine.


    • Study leads: Christopher Rentsch
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #38: Inhaled corticosteroids and risk of COVID-19 death.

    This study aimed to evaluate how regular use of a type of drug used to treat respiratory diseases, inhaled corticosteroids (ICS), might have influenced the risk of dying from COVID-19 during the first wave of the pandemic. We studied two groups of people - those with asthma, and those with chronic obstructive pulmonary disease (COPD) - and compared their risk of death from COVID-19. We used a number of techniques to try and account for the fact that people who receive treatments such as ICS are different from those who do not.

    We found that:

    • For people with COPD, those who were prescribed ICS were at higher risk of dying from COVID-19 compared to those not receiving ICS treatments.
    • For people with asthma, those receiving high-dose (but not low-dose) ICS were at higher risk of dying compared to those individuals receiving a non-steroid based reliever inhaler (called salbutamol).

    However, our study results also suggest that the higher risk of death in individuals taking ICS might not be fully related to the use of the ICS medication, and might also be related to other factors, for example, people using ICS typically have more severe lung disease, which might explain the reason why they have a higher risk of COVID-19 related death.

    We therefore concluded that our study provided no convincing evidence that use of ICS was associated with an increased risk of dying from COVID-19 during the first wave of the pandemic, which should be seen as reassuring for people with these respiratory diseases who rely on ICS to manage their respiratory symptoms.


    • Study leads: Anna Schultze
    • Organisation: NHS England (in collaboration with University of Oxford and London School of Hygiene and Tropical Medicine)
    Project #37: Factors associated with COVID-19 related death.

    We used the newly created OpenSAFELY platform to examine factors associated with COVID-19-related death. General practice records of 17,278,392 adults were linked to 10,926 COVID-19-related deaths. A range of factors, including demographic characteristics and comorbidities were explored to determine their relationship with COVID-19 related death.

    COVID-19-related death was associated with: being male; greater age and deprivation; diabetes; severe asthma; and various other medical conditions. Compared with people of white ethnicity, Black and South Asian people were at higher risk, even after adjustment for other factors.

    We measured a range of factors associated with COVID-19-related death in one of the largest studies of COVID-19 on this topic at this point in time, very early in the pandemic.


    Project #36: Impact of the Covid-19 pandemic on anticoagulation for atrial fibrillation.
    • Type: Audit (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Atrial fibrillation is a heart condition characterised by an irregular heartbeat. Patients with atrial fibrillation have an increased risk of stroke and NICE recommends they are treated with drugs that reduce that risk of stroke (blood thinners or anticoagulants). Warfarin used to be the drug of choice but new anticoagulants that are safer and more convenient to take have been preferred for the past years. This is because warfarin requires adjusting the dose on a regular basis based on blood tests, which are a burden for patients and doctors. For safety reasons, during the COVID-19 pandemic, doctors were encouraged to switch patients from warfarin to the new anticoagulants. However, it is uncertain how many patients were actually switched to the new anticoagulants over time and which proportion of patients are currently prescribed the new anticoagulants as per NICE guidelines. Therefore, this study aims to assess the impact of the pandemic on compliance with NICE guidelines regarding anticoagulation for atrial fibrillation.


    Project #35: Impact of the Covid-19 pandemic on prevention of cardiovascular disease.
    • Type: Audit (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Cardiovascular disease is the main cause of death in England, accounting for one in four deaths. Risk factors for cardiovascular disease include non-modifiable factors (e.g., age, sex, family history, ethnic background) and modifiable risk factors (e.g., smoking, raised blood pressure and cholesterol). Assessing risk of cardiovascular disease and treating risk factors is very important to prevent heart attacks and strokes. However, the COVID-19 pandemic caused substantial disruption to usual care in GP practices, particularly during lockdowns. It is possible that many patients with risk factors for cardiovascular disease have missed opportunities for GPs to assess their risk and take the necessary steps, including prescribing drugs, to reduce that risk. Therefore, the aim of this study is to investigate the impact of the COVID-19 pandemic on assessment and treatment of cardiovascular risk factors, particularly raised blood pressure and cholesterol.


    Project #34: Deaths at home during Covid-19 and implications for patients and services.
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    The Covid-19 pandemic has seen a huge shift in where patients are dying, in addition to increased mortality overall. While the majority of patients who died from Covid-19 did so in hospitals or care homes, between March 2020 and July 2021 a third more people than usual died at home, largely from causes other than Covid-19. At the same time, services for people at the end of life were severely disrupted, with many services shifting to remote working as far as possible. This impacted how much support patients and families received to care for people in their own homes.

    This study will use data from GP and hospital records, and data on registered deaths to:

    • Understand what services were provided to patients who died over the course of the pandemic, compared with pre-pandemic, and how did service use vary between sub-groups of patients? This will include considering place and cause of death, demographic, social and clinical factors.
    • Develop measures of quality of end of life care from the data, taking account of the quality of the data available. We will use published standards on quality of care, for example, guidance from NICE, to identify potential measures of quality which could be identified from the data.
    • Develop questions for future research, once we have identified which measures of quality of care are feasible to assess from the data.

    The shift in place of death during the pandemic, and the exacerbation of existing health inequalities and pressures on health and care services, make this an even more important policy area to address now.


    Project #33: Post-operative outcomes and resource use in cancer surgery patients with perioperative SARS-CoV2.
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Patients who need surgery for cancer must balance the risks of undergoing and not undergoing surgery. The decision to undergo surgery is complicated by other existing conditions and diseases that the patient has. For example, there is some evidence that patients with an indication of SARS-CoV-2 infection might be at greater risk of death shortly after surgery, compared with patients who did not have an indication of infection. This increased risk might persist up to 7 weeks after surgery, in some cases.

    In light of the increased risk of death, NHS England and NHS Improvement issued guidance to delay non-urgent, non-emergency operations for three months. The findings of research studies around that time varied in their support of such delays. For example, one global study suggested that non-emergency surgeries should be delayed for more than 4 weeks, while another study suggested the increase in the risk of death related to a SARS-CoV-2 infection was very low and might not outweigh the risks of delaying. The conflicting evidence makes it difficult for hospitals to safely plan surgeries, especially because it is not clear why there is such a wide range of advice given.

    Our study attempts to review the relationship between surgery timing and cancer patient outcomes after surgery in light of the NHS England and NHS Improvement guidance. In addition to patient outcomes - e.g. death and post-operative complications - we will study the effect of surgery timing and patients' SARS-CoV-2 status on outcomes related to hospital planning (e.g. patients' length of stay in hospital and readmissions after discharge).


    • Study leads: Ciarán McInerney
    • Organisation: University of Leeds and NIHR Yorkshire and Humber Patient and Safety Translational Research Centre
    Project #32: The emergence of Omicron in England.
    • Type: Research (ongoing)
    • Topic areas: COVID transmission/prevalence/non-pharmaceutical prevention; Risk from COVID (short term) [e.g. hospitalisation/death]; COVID vaccine effectiveness/safety

    We will describe the incidence of SARS-CoV-2 Omicron infections in England in comparison to Delta infections. Should Omicron become established in England, we will compare the risk of re-infection, hospitalisation and death between the Omicron and Delta variants.

    These data will be vital to understand the impact that the emergence of Omicron will have on the course of the pandemic in England and around the world.


    • Study leads: Daniel Grint
    • Organisation: London School of Hygiene and Tropical Medicine
    Project #31: Risk factors and prediction models for Long COVID.
    • Type: Research (Approved subject to obtaining favourable HRA application)
    • Topic areas: Post-COVID health impacts [e.g. long COVID]

    Reports of people developing long-lasting post COVID symptoms are rising, with a latest estimate of 1.1 million people living in private households in the UK (1.7% of the population), according to the Office of National Statistics. However, little is known about which groups of individuals with a history of COVID-19 are more likely to have symptoms over a long period (e.g. more than 12 weeks). Recent research showed that not all patients who self-report long COVID have been diagnosed clinically or referred to recovery services by their doctors.

    This is a population based cohort study from the electronic health records using the OpenSAFELY platform. In this study, we aim to identify risk factors associated with long COVID diagnosis in the primary care records. We will investigate the following questions:

    • What are the risk factors associated with long COVID diagnosis?
    • What are the differences between risk factors for acute COVID and long COVID?
    • Can we predict or discriminate between these two types of COVID?
    • How the clinical coding of long COVID diagnosis impacts on the above analyses?

    The identified risk factors will help increase the awareness of long COVID, improve the diagnosis coverage and subsequently improve the access/referral to recovery services and inform a risk prediction model to identify and prioritise care, education and rehabilitation for patients at risk of long COVID.


    • Study leads: Yinghui Wei
    • Organisation: University of Plymouth / University of Bristol
    Project #30: Pathology Comparators Short Report.
    • Type: Audit (ongoing)
    • Topic areas: Risk from COVID (short term) [e.g. hospitalisation/death]; Post-COVID health impacts [e.g. long COVID]; Other/indirect impacts of COVID on health/healthcare

    In this study we will investigate how blood test results can be interpreted in OpenSAFELY. Blood test results give us important information about someone’s health. However, for some tests, the values can be reported as “less than” or “more than” a threshold, typically for values outside the accurate range that the machine can detect. Therefore a test result may appear as “<10”, and for some tests this type of result is very common. However, when conducting research, researchers may wish to group patients together and if the comparators (< and >) are not taken into account we may group the values incorrectly, e.g. the “<10” above would be taken as “10” and incorrectly grouped with values “>=10”. Here we will identify which tests involve comparators most often, and which values they are typically associated with. For example, if a certain test often has values “>5.5” then when creating groups researchers might need to use 5.5 as their highest value. The findings of this audit will be useful in various context, for example (a) assessing patients' severity of preexisting disease, which may impact their risk from COVID, (b) assessing the impact on patients' health after contracting COVID or (c) assessing indirect impacts of COVID on healthcare provision (e.g. whether people with diabetes generally experienced worsening disease during the pandemic).


    • Study leads: Helen Curtis
    • Organisation: University of Oxford
    Project #29: Monitoring Attendance INvestigations Referrals and OUTcomEs related to Cancer in the NHS through the COVID-19 era (MAINROUTE).
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Health care and the way we consult doctors has changed as a result of the COVID-19 pandemic and lockdown. Many more appointments with doctors (GPs) have been over the telephone instead of in person. Many routine appointments, blood tests, cancer screening and non-urgent treatment have been cancelled in both GP practices and in hospitals. Urgent cancer referrals reduced dramatically.

    However, it is unlikely that patients have stopped having symptoms. It is more likely that people have been avoiding going to the doctors or to the hospital. This may be because they do not want to bother doctors or nurses at this time of higher workload, or they are not sure that GPs are available to deal with non-COVID problems or they are worried about catching the virus. This could mean that there may be a build-up of medical problems in the community. Delays in the diagnosis or treatment of conditions such as cancer may cause longer-term health problems for some groups of patients. As social distancing rules are relaxed, and life starts to return to normal, doctors will need to ‘catch-up’ on clinical care for a wide range of conditions.

    This study will track changes in the number of people visiting their GP for symptoms of cancer, the number of tests done, numbers of hospital appointments and longer-term outcomes focussing on cancer. We will present the data so that GP and hospital staff will be able to see which disease areas or groups of patients that will be most in need.


    Project #28: Androgen deprivation therapy (ADT) for prostate cancer and COVID-19
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Androgen deprivation therapy (ADT) for prostate cancer is used to shrink the cancer before or after the surgery or radiotherapy. ADT is also used to manage advanced cancers that cannot be cured with surgery and radiotherapy. Patients receive injections monthly or every three months long-term. In this research we are seeking to investigate if and how this was affected during the pandemic. There is evidence that the pandemic affected access to healthcare, especially when face-to-face appointments were required for the provision of services. We will access primary care and hospital (SUS) data to assess the impact on ADT delivery.

    In this study we will extract and analyse data on the prescribing of injectable forms of ADT for prostate cancer between pre-pandemic (2015-2019) and pandemic years (2020-2021) to investigate any potential effect of the COVID-19 on the delivery of ADT for prostate cancer. This information may help to identify where services require more support as well as assist government and policymakers plan for future lockdowns and pandemics.

    We will also analyse by age, ethnicity, deprivation, region of the country and care-home residency to identify possible patient groups with difficulties in accessing medication. Prostate cancer, comparatively, is one of the cancers more strongly affected by demographic, socioeconomic and ethnic inequalities.


    Project #27: The effect of COVID-19 on pancreatic cancer diagnosis and care.
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Pancreatic cancer is relatively rare (10,000 new cases per year) and a difficult cancer to diagnose early. Due to the difficulty in early diagnosis it has a high mortality rate, with 90% of people dying within a year from diagnosis.

    It is therefore possible that the COVID-19 pandemic has resulted in delayed diagnoses and worse outcomes in pancreatic cancer care.

    In this service evaluation we will investigate if there was any detrimental effect of COVID-19 on pancreatic cancer including stage at diagnosis (are people diagnosed at more advanced stages), and the mechanisms that lead to diagnosis and healthcare provided.

    This information may help to identify where services require more support as well as assist government and policymakers plan for future lockdowns and pandemics.


    Project #26: Uptake of 'NHS @home' interventions during COVID-19.
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    The use of [email protected] interventions as a means of patients better self-managing health and care at home has been a key part of NHS England’s response to the indirect impact of the COVID-19 pandemic. This analysis aims to establish the breadth and depth of coverage - geographically and among the target populations. This will not be used in performance management, but rather as an initial assessment of uptake and usage of the services to inform modelling and help shape future analysis requirements.


    • Study leads: Andy Weaver
    • Organisation: NHS England and NHS Improvement
    Project #25: Representativeness of TPP data.
    • Type: Audit (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    The OpenSAFELY framework allows analysis of the full pseudonymised patient primary care records for 57 million people registered at a general practice in England. This comprises 24m patients from practices that use TPP and 33m patients from practices that use EMIS. Use of the TPP and EMIS systems is known to be geographically clustered, however little is currently known about the extent to which the separate populations within these systems is representative of the population at large.

    OpenSAFELY has been, and continues to be, used to support research that delivered urgent results related to the global COVID-19 emergency.

    Assessing sample representativeness is a critical component of health research and provides context for researchers to understand the validity / applicability of their research. Understanding differences in geographic spread, sex, age, IMD and ethnicity distributions between TPP patients and non-TPP patients is important for the interpretation of COVID-19 research analysis and generalization to the background population.

    In order to understand the representativeness of TPP data we will compare broad demographic data to ONS estimates for England for Index of Multiple Deprivation (IMD); age and sex and population per MSOA / STP. We will also compare ethnic breakdowns of TPP to the 2011 ONS Census and compare the 5 most common underlying causes of death in England in 2020 ONS to the equivalent in TPP.


    • Study leads: Colm Andrews
    • Organisation: University of Oxford
    Project #24: Incidence of mental illness following coronavirus infection in the community.
    • Type: Post-COVID health impacts [e.g. long COVID]

    Mental health conditions such as anxiety and depression have become more prevalent throughout the population during the coronavirus COVID-19 pandemic, but the existing evidence as to whether people infected with SARS-CoV-2 are at greater risk is mixed. This study will therefore examine rates of common mental disorders, serious mental illness and mental health behaviours (such as self-harm) in people aged 16 years or over infected with SARS-CoV-2, for up to a year after the first testing positive for the virus. Rates of these conditions will be compared with those in several non-infected control groups (people who tested negative for SARS-CoV-2, and people diagnosed with influenza before and during the pandemic) to ascertain the extent to which risk is elevated after SARS-CoV-2 infection. The findings of this study may identify groups of the population particularly at risk of mental health conditions following infection, and inform public health policies and service provision around mental health.


    Project #23: Risk of severe COVID-19 outcomes associated with atopic eczema and dupilumab.
    • Type: Research (ongoing)
    • Topic areas: Risk from COVID (short term) [e.g. hospitalisation/death]

    In a recent study we found that people with conditions that are related to problems with the immune system, such as Cohn’s disease, psoriasis, and arthritis, and people taking treatments affecting the immune system might be at an increased risk of severe COVID-19 infection. Atopic eczema, a common skin condition presenting with itching and rash, is also thought to be related to problems with the immune system, and some individuals with more severe eczema are treated with dupilumab, a drug that affects the immune system. In this study we aim to explore whether people with eczema and people with eczema who take dupilumab are at an increased risk of severe COVID-19 infection. Clinicians and public health experts need to know this, in order to develop strategies to prevent severe COVID-19 in people with atopic eczema.


    • Study leads: Julian Matthewman
    • Organisation: London School of Hygiene and Tropical Medicine
    Project #22: Investigating the effectiveness of the COVID-19 vaccination programme in the UK.
    • Type: Research (ongoing)
    • Topic areas: COVID vaccine effectiveness/safety

    All adults in the UK are eligible to receive coronavirus (COVID-19) vaccines to protect them against COVID-19. The vaccines currently available are given in two doses. Most people who have had a 2nd dose received it 8 to 12 weeks after their 1st dose. Although clinical trials have shown that the vaccines are safe and effective at protecting against COVID-19, there are still many questions that need to be answered in order to understand longer term effects of vaccination and keep people protected against COVID-19. Our work aims to understand the long-term effects by answering questions such as:

    • Which groups are choosing not to get their COVID-19 vaccines?
    • Does the protection given by the vaccines against COVID-19 infection, hospitalization and death reduce over time?
    • Does the time between the 1st and 2nd doses affect the efficacy of the vaccines against COVID-19 infection, hospitalization and death?
    • What is the effect of additional (more than 2) doses of the vaccine?

    Project #21: Direct Oral Anticoagulant (DOAC) prescribing during COVID-19.
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    During COVID-19, GPs have been encouraged to switch patients from Warfarin to alternative anticoagulants called Direct Oral Anticoagulants (DOACs) as they require less frequent monitoring and avoid additional visits to the GP practice. DOACs do however require renal function tests to ensure the correct dose is prescribed to avoid harm in patients. This evaluation wants to identify the proportion of patients who are at risk of harm whilst prescribed the incorrect dose of DOAC.


    Project #20: Ethnic disparities in COVID19 outcomes in London: evaluation of COVID19 vaccination programme.
    • Type: Service evaluation (ongoing)
    • Topic areas: COVID vaccine eligibility/coverage; Other/indirect impacts of COVID on health/healthcare

    This study will explore the impact of COVID-19 on those of ethnic minority backgrounds in London throughout the pandemic and determine whether the vaccination programme has made a difference in ethnic disparities in health outcomes. We will also look at potential mechanisms through which COVID-19 has an adverse effect on people of minority ethnic backgrounds, these include whether there is a greater impact from certain health conditions, living environments, certain health behaviours such as vaccination uptake.


    • Study leads: Jennifer Yip
    • Organisation: Department of Health and Social Care (originally application made by Public Health England)
    Project #19: How has the COVID-19 pandemic impacted the need for targeted weight management interventions amongst adults in the UK? An evaluation of pandemic-associated changes in BMI and metabolic parameters.
    • Type: Service evaluation (ongoing)
    • Topic areas: Other/indirect impacts of COVID on health/healthcare

    Lockdowns, stay at home orders and social distancing guidelines have had an impact on the lifestyles of people living in the UK. Studies have shown a reduction in physical activity during the pandemic, using a variety of data sources such as smartphone apps, recording from implantable cardiac devices and surveys. Some international surveys have reported that lifestyle changes during the pandemic have resulted in weight gain and increased Body Mass Index (BMI) (a measure of if you are a healthy weight for your height). In the UK people joining the NHS Diabetes Prevention Program, a targeted intervention for people at high risk of diabetes, in the year following the pandemic were on average heavier than those who joined the programme in the years before the pandemic. But there is a lack of data on how the weight (and consequently BMI) of the general population of adults living in the UK has changed since the onset of the pandemic.

    Even prior to the pandemic, obesity was common in the UK. The 2019 Health Survey for England demonstrated that 64% of adults were overweight or obese. Obesity has long been known to be a risk factor for the development of a range of conditions such as diabetes, heart disease and stroke. This can be through the effect of obesity on established markers of metabolic risk such as: Blood Pressure (BP), Blood Cholesterol and Lipids Profiles (Lipid Profile), and blood sugar levels measured by Haemoglobin A1c (HbA1c). Furthermore, obesity, and conditions linked to obesity such as diabetes, have been shown to increase the risk of hospitalisation and/or death from COVID-19.

    In response to these challenges the NHS has invested in a range of interventions to support weight loss. Such as the NHS England Digital Weight Management Programme (DWMP), which is currently available to help overweight and obese people living with diabetes and/or hypertension manage their weight. This analysis will look at how the number of people meeting the eligibility criteria for the DWMP has changed since the onset of the pandemic through assessing BMI changes in these groups. We will also describe, amongst all adults living in the UK, how BMI and metabolic markers have changed since the onset of the pandemic, in order to assess the need for weight loss interventions in the overall population.

    We will further investigate whether some groups of people have, since the onset of the pandemic, experienced more weight gain (and resultant increase in BMI) and/or worsening of their metabolic markers than others. These groups will be identified based on personal characteristics (such as age, sex, ethnicity, deprivation and/or region of residence) and whether they have another co-existent medical condition, such as asthma or chronic kidney disease. This will demonstrate specific population groups that may most benefit from targeted weight loss interventions. We will specifically look at co-existing medical conditions that have been deemed common and important by the NHS Qualify Outcome Framework (QOF) - a tool that is used to assess the quality of care provided by GPs.

    The findings of this study will help inform NHS England health care policy around the extent of need for specific weight loss interventions and which specific groups are at greatest need of these interventions. Furthermore, we hope the findings of the analysis will inform future focussed research.


    • Study leads: Miriam Samuel
    • Organisation: Queen Mary's University London
    Project #18
    • Type: Audit (ongoing)

    We need to know to what extent the actual treatment of people with ongoing symptoms of COVID-19 matches published NICE guidance. This corresponds to carrying out an audit. If differences are found, NICE could use the information either to improve the presentation of guidelines or improve its implementation work.

    This study uses OpenSAFELY data to compare summarised information from GP records against NICE’s guidelines for long-term effects of COVID-19.


    • Study leads: Robert Willans, 
    • Organisation: NICE
    Project #17
    • Type: Research (ongoing)

    Since the outbreak of COVID-19 in the UK, primary care has changed quite dramatically, with many general practices restricting physical consultations and instead providing phone and video consultations. This has affected the monitoring and management of a range of long-term conditions and is of particular importance in people with diabetes who would ordinarily have their diabetes and associated comorbidities frequently monitored through diabetic reviews at their GP practice and at diabetes clinics within the NHS. It is not yet understood what impact the change in access to services has had on these patients in terms of their diabetes control, cardiovascular risk factors, diabetes-related complications, and mortality.

    In previous work, we sought to compare the frequency of primary care interactions, services, monitoring, prescribing, and diagnoses before and after the start of the pandemic, with a view to quantifying the level of unmet need in this patient group and highlighting the anticipated backlog that primary care services would face as restrictions were gradually eased. In this proposed phase of the project, we aim to examine rates of hospitalisation, ICU admissions, diabetes-related complications and associated adverse events by combining data from primary and secondary care, and to investigate specific causes of mortality in people with diabetes.


    • Study leads: Matthew Carr
    • Organisation: University of Manchester
    Project #16
    • Type: Research and service evaluation (ongoing)

    The Covid-19 pandemic has resulted in major changes in how and whether patients can consult their General Practitioner. This has an impact on how their common infections (such as sore throat or bladder) are being diagnosed and treated. The number of telephone or web appointments has increased and there are concerns, in addition to patients not consulting their GP, that more antibiotics may be given inappropriately as it is difficult to diagnose remotely.

    Prior to Covid-19, improvements in antibiotic prescribing in primary care (also known as antibiotic stewardship) were a major priority for the NHS. This was related to increased rates of infections in which antibiotics no longer work (known as antibiotic resistance), often related to overuse of antibiotics.

    This project will provide up-to-date information to antibiotic stewardship activities in primary care.

    Specific aims are to evaluate

    • the impact of Covid-19 on the primary care treatment pathways for common infections
    • the effects on antibiotic prescribing
    • the effects of prior antibiotic exposure (types and extent) on severity of outcomes in Covid-19 infections (including during and after hospital admission)

    Project #15
    • Type: Service evaluation (ongoing)

    We will investigate how the prescribing of groups of medicines used to treat the mental health of residents of care homes has changed over the COVID-19 period. Residents have been more socially isolated given restrictions on visits from family and friends and trips outside the care home setting. There have also been high rates of death in care homes due to COVID-19, which may have affected the mental health of surviving residents and staff.

    Given rates of depression, anxiety and stress are considered to have increased in the general UK population over the COVID-19 pandemic, we are interested in looking at how the prescribing of anti-psychotic and anti-depressant medicines to residents in care homes has changed over the COVID-19 pandemic and relative to the general population.


    • Study leads: Greg Eydmann
    • Organisation: NHS England & NHS Improvement
    Project #14
    • Type: Service evaluation (ongoing)

    The NHS Cancer Programme is working to identify more people with prostate cancer as part of the pandemic recovery. To aid that work, we would like to know:

    • What was the impact of the pandemic on the number of patients who received prostate-specific antigen (PSA) tests?
    • If there was an impact on PSA test undertaken, which patients did this affect (by patient characteristic, geography, symptoms at presentation)?
    • Was the change in the quantity of PSA tests undertaken followed by a corresponding drop in the number of patients receiving onwards tests and treatment for prostate cancer?

    Project #13
    • Type: Research and service evaluation (ongoing)

    We want to understand how many people are diagnosed with Long COVID in general practice, who is diagnosed with Long COVID, and how long after getting COVID-19 people are diagnosed with Long COVID. We will also find out how this changes over time; and how different comorbidities and other factors impact the above.


    • Study leads: Emma Mi
    • Organisation: NHS England and NHS Improvement
    Project #12
    • Type: Research (ongoing)

    COVID-19 infection may increase the chances of certain conditions, including strokes and heart attacks. We will study people alive on 1 January 2020 with a record in OpenSAFELY to investigate whether this is the case. Specifically, we will compare the number of people with COVID-19 infection who also have a record of one of these conditions against the number of people without COVID-19 infection who also have a record of one of these conditions. This will allow us to estimate how much COVID-19 infection increases the risk of these conditions. Our work may inform whether people with COVID-19 infection should be offered preventative treatments to protect against these conditions.


    Project #11
    • Type: Service evaluation (ongoing)

    We will assess the impact of COVID-19 on antidepressant prescribing; one of five medicine classes identified in the PHE Review which NHSE/I are prioritising and leading on. As described by the OpenSafely paper in the Lancet, addressing the effect that the pandemic has had on mental health is important and we will use primary care data to measure and mitigate the indirect health impacts of COVID-19 on the NHS.

    We will investigate whether potential barriers to accessing mental health services over the course of the pandemic have led to specific (or a change in) indications driving the already increasing trend in antidepressant prescribing by observing:

    • the rate of new initiations of antidepressants
    • the discontinuation of antidepressants

    We will investigate the the impact of COVID-19 on dependency forming medication use by age, gender, Index of Multiple Deprivation (IMD), ethnicity, region (and other system level geographical cuts)


    Project #10
    • Type: Service Evaluation (withdrawn)

    Concern raised by the national clinical director of cardiovascular disease (CVD) about inequalities in the prevalence of CVD. The purpose for requesting GP record data in OpenSAFELY is to monitor service use for CVD pathways, blood pressure tests taken, corresponding reading, and medical prescription across geographical deprivation and ethnic groups. These metrics will serve as potential indicators for access and outcomes (for people of different ethnicities/people living in areas with different levels of deprivation) in CVD related primary care activity. We will particularly be monitoring the variations in these indicators that occurred over the course of the COVID-19 pandemic and assessing the relative success or failure in recovering primary care services.

    Aims

    • To better understand and be able to interpret disparities in access and outcomes related to CVD to narrow health inequalities in this area.
    • To use CVD and this analysis as a test case in the processes necessary for developing primary care recovery of services indicators with OpenSAFELY

    • Organisation: NHS England and NHS Improvement
    Project #9
    • Type: Research (ongoing)

    This project will link ISARIC-4C and OpenSAFELY data in order to follow up hospitalised patients with COVID-19 following discharge. ISARIC-4C is a UK-wide consortium responsible for prospectively collecting data and biological samples from hospitalised patients with COVID-19.

    The aims of the project are to investigate children and young people under the age of 19 years with covid-19 to:

    • Assess the feasibility of combining a detailed clinical dataset of patients hospitalised with SARS-CoV-2 (ISARIC-4C dataset) with wide-ranging primary care data (OpenSAFELY dataset)
    • Investigate risk factors for hospital admission and disease severity
    • Investigate outcomes for children hospitalised with covid-19 stratified by severity, compared to those cared for in the community

    • Study leads: Olivia Swann
    • Organisation: ISARIC
    Project #8
    • Type: Research

    Recent research into coronavirus has shown that members of the public can play a crucial role in controlling infection outbreaks, by adopting simple behaviours to curb the spread of infection in the home such as handwashing, cleaning surfaces, wearing of face coverings and social distancing. Despite public health advice, evidence shows most people need to change their behaviour to help prevent infection.

    Germ Defence is an interactive website employing behaviour change techniques to supplement public health advice. Germ Defence was originally developed during the H1N1 swine flu pandemic using theory, evidence and extensive feedback from members of the public. It was then trialled in over 20,000 patients and shown to reduce the number and severity of infections of users and members of their household. Germ Defence has recently been updated for the COVID-19 pandemic. The website aims to help users with pre-planning about effective isolation of an infected household member; personalised goal setting for increasing a range of infection control behaviours; changing the home environment to support new habits and problem solving to overcome barriers.

    What is the aim of the project?

    This project aims to examine the effects of randomising dissemination of the Germ Defence website via GP practices on rates of respiratory infection, including COVID-19 and seasonal flu.

    What are we doing?

    We will contact every GP practice in England and ask them to share the link to Germ Defence with their patients. Half of the practices will be randomly chosen and asked to immediately send out the Germ Defence link to their patients in the Autumn of 2020. These practices will be known as the intervention arm or immediate implementation group. The other half of the practices will be contacted to send out Germ Defence in March 2021 and will be known as the usual care arm or delayed implementation group. We will assess usage of the Germ Defence link from anonymous data produced by the website. We will then use anonymised national data that is collected as part of routine care to compare whether infection rates are lower in practices that sent Germ Defence information to their patients immediately, compared to those that didn’t send the information until later.


    Project #7
    • Type: Service Evaluation (under review)

      Project #6
      • Type: Service Evaluation (under review)

        Project #5
        • Type: Service evaluation (ongoing)

        The aim of this work is to assess NHS England guidance issued at the peak of the COVID pandemic recommending FIT (stool) testing for all patients suspected of colo-rectal cancer which could be undertaken in primary or secondary care. The extent to which this advice has been implemented across the system, particularly in primary care, is unknown, since routine operational reporting from pathology systems is not a mandatory requirement.

        In addition FIT testing in patients aged <50 (who are at very low risk of colo-rectal cancer) may be adding to the demand for the cancer two week waits, Lower GI referrals and subsequent colonoscopy.

        Analysis of the data will allow us to determine if particular variables (e.g. age, gender, ethnicity, locality, FIT level, etc.) are related to an increased risk of colo-rectal cancer diagnosis, and importantly, if patients can be categorised into a very low risk of colo-rectal cancer. NHS England would then ensure that these outputs were included in further guidance to support more appropriate and targeted referral for colonoscopy when investigating suspected colo-rectal cancer.


        • Study leads: Nick Kennedy
        • Organisation: Royal Devon & Exeter NHS Foundation Trust and University of Exeter
        Project #4
        • Type: Research (ongoing)

        The effectiveness of COVID-19 vaccines against clinical outcomes: a test negative case control study using OpenSAFELY

        Background

        As soon as SARS-CoV2 was identified as the virus causing the ongoing COVID-19 pandemic, scientists and vaccine manufacturers worked rapidly to develop vaccines against it. Since late 2020, the UK has been rolling out a phased mass vaccination programme in the adult population, starting with people at greatest risk of severe infection. In clinical trials with volunteers, all three of the UK’s currently authorised vaccines were good at protecting recipients against infection but now that the vaccination programme is underway, it is important to look at how protective the vaccines are in the real world.

        Aims of the study

        • To determine the type-specific vaccine effectiveness of individual deployed COVID-19 vaccines in preventing laboratory-confirmed SARS-CoV2 infection in specified subgroups of the population.
        • To determine the type-specific vaccine effectiveness of individual COVID-19 vaccines used to vaccinate the UK population in preventing hospitalisation due to COVID-19 related disease in specified subgroups of the population.

        Methods

        In this study we will evaluate how good each vaccine is at protecting people against infection with SARS-CoV2, and also at preventing serious outcomes of COVID-19 such as hospitalisation. We will use a test-negative case control design study to compare COVID-19 vaccination status in people with symptoms of COVID19 who have a positive SARS-CoV2 test (cases) with people who also have symptoms but who have a negative test (controls). Using this study design, we will also look at the vaccines' effectiveness in particular subgroups, such as the elderly and people with poorly functioning immune systems, to see if the vaccines work less well in some groups.

        We will estimate the vaccines' effectiveness in preventing infection and serious outcomes at different time points after the first and second doses of the vaccine, and after a booster dose if this is recommended. Logistic regression will be used to determine adjusted type-specific vaccine effectiveness estimates and we will repeat analyses at intervals for up to 3 years after the start of the vaccine rollout to detect waning VE.

        We will use a secure analytic platform, OpenSAFELY, to run analysis codes against approximately 24 million routinely collected electronic health records (EHRs) for adult patients who are registered at GP practices. This study will complement other studies using different data sources or study design, and will add to the body of knowledge to inform the government’s expert independent advisory body, the JCVI, when it make recommendations on future vaccination policy.


        Project #3
        • Type: Research (ongoing)

        The aim of the study is to estimate the effectiveness of the vaccines for COVID-19 using the age thresholds in the JCVI COVID-19 vaccination first phase priority groups under a modelling approach known as a regression discontinuity design.


        • Study leads: Tom Palmer
        • Organisation: University of Bristol
        Project #2

        An online consultation enables a patient to contact their GP, other health professional or GP practice staff over the internet, typically by using a smartphone, tablet or computer. This is a fairly new technology in terms of adoption, though its use had been accelerated by the pandemic. NHSE/I, through its Digital First Primary Care (DFPC) programme, has been working on enabling and stimulating the use of online consultation systems as a means to improve access to primary care and make best use of clinicians' time.

        OpenSAFELY was identified as a way of providing intelligence on online consultations activity prior and alongside the pandemic, particularly in the way events are recorded or not in primary care records via dedicated codes. In this initial discovery piece, we looked at:

        • understanding how certain online consultation-relevant codes of were used in terms of adoption and volume
        • understanding broad demographics and past clinical history of those associated with online consultation-relevant codes

        These insights are being triangulated further with supplier data and qualitative findings as part of a wider research piece. Wider efforts on improving intelligence for operational, research and evaluation purposes are also underway.


        Project #1

        We attempted to calculate the counts of eligible patients for the Covid vaccine based on the priorities set out in the Green Book and GOV advice for clinically extremely vulnerable.

        The approach used primary care data mostly based on age and a list of high/moderate risk health conditions (without health care workers considered).

        This work was conducted between October 2020 and January 2021. In January 2021 this analysis was superseded by the “SARS-CoV2 (COVID-19) Vaccine Uptake Reporting Specification” — opensafely/primis-covid-vacc-uptake-spec.

        The work approved in this application is published here as a public record of analysis carried out on OpenSAFELY, but must not to be used for onward development, decision making or further analysis.

        A vaccine uptake report has since been pre-printed doi.org/10.1101/2021.01.25.21250356