Background: Safety and effectiveness of SARS-CoV-2 vaccines in inflammatory conditions is poorly understood.
Objectives: .Evaluate effectiveness of SARS-CoV-2 vaccines in inflammatory conditions treated with immune-suppressive medicines. .Compare clinical effectiveness of mRNA or vectored DNA vaccines in this population. .Examine association between SARS-CoV-2 vaccination and flare-up of inflammatory disease.
Methods: Data from Clinical Practice Research Datalink (CPRD) Aurum linked to Hospital Episode Statistics, COVID-19 Hospitalisation in England Surveillance System, Office of National Statistics, and Practice Level Index of Deprivation will be used. CPRD Aurum contains details of diagnoses, prescriptions, and immunisations including with the SARS-CoV-2 vaccines. Dates of vaccination and vaccine brand are recorded.
Study design: Cohort study (01/12/2020 to 31/05/2022)
Exposure: Age >18 years, diagnosed with inflammatory bowel, skin or rheumatic disease prescribed immune-suppressing medicine(s).
Unexposed: One age, sex, SARS-CoV-2 vaccine-type, vaccination date (+/-5 days), and time between first and second vaccine dose (+/-1 week) matched participant.
Outcomes: Primary: Hospitalisation with Covid-19. Secondary: Primary-care diagnosis of Covid-19, death due to Covid-19.
Follow-up: From 14 days after the first dose to earliest of date of outcome, death, last data collection, leaving GP-surgery or 31/05/2022.
Analysis: Cox regression will be used to calculate hazard ratios and 95% confidence intervals (CI), adjusted for covariates. Interaction terms will be fitted for prognostic factors and stratified analysis performed. Analyses will be restricted to 6, 9 and 12 months to examine the duration of protection.
Design: Self-controlled case series.
Population: Vaccinated and outcome of interest.
Exposed: Three-weeks following each of the SARS-CoV-2 vaccines.
Pre-exposure: 2-weeks before the vaccinations.
Unexposed: Remaining follow-up time.
Analysis: Poisson model will be used to calculate incidence rate ratios and 95% CI for the exposed period, including season as covariate.
Impact: The findings of this study have the potential to influence the timing of future booster vaccinations.
Clinical effectiveness study:
Primary: Hospitalisation with Covid-19 infection. Defined as present if there is an international classification of diseases (ICD)-10 code in either the inpatient HES or a positive record in Covid-19 Hospitalisation in England Surveillance System (CHESS) datasets.
a. Primary-care diagnosis of Covid-19. This will be defined as either a GP-consultation with valid Snomed code, or a positive PCR test result recorded in the CPRD. GP electronic health records get positive PCR results from NHS test and trace, and NHS digital.
b. Death due to Covid-19 infection defined using death certificate data available as ICD-10 codes in the ONS dataset.
c. Death within 28-days of a positive Covid-19 test.
The CPRD HES/ONS linked data are only available to November 2020 (Set 20). It is currently unclear when the next release of linked data will occur. Given the time sensitive nature of this study, we will first evaluate vaccine efficacy using primary-care diagnosis of Covid-19, and death within 28-days of a positive Covid-19 test. The latter outcome will be defined using death date and positive Covid-19 PCR test recorded in CPRD Aurum primary-care data. The results of these analyses will be published and disseminated to policy makers as soon as ready.
Once the HES and ONS linked data are available, we will examine the effectiveness of vaccines against Covid-19 on hospitalisation and re-examine the effectiveness of vaccines against Covid-19 on mortality using ONS data respectively.
Vaccine safety study:
 Primary care consultation for joint pain or autoimmune rheumatic disease with a new corticosteroid prescription within +/-1 day.
 Primary care consultation for diarrhoea, abdominal pain, rectal-bleeding with a new corticosteroid prescription within +/-1 day, or hospitalisation for inflammatory bowel disease.
 Primary care consultation for psoriasis, atopic dermatitis or eczema and prescription of a new topical treatment within +/-1 day.
Abhishek Abhishek - Chief Investigator - University of Nottingham
Abhishek Abhishek - Corresponding Applicant - University of Nottingham
Christian Mallen - Collaborator - Keele University
Georgina Nakafero - Collaborator - University of Nottingham
Hywel Williams - Collaborator - University of Nottingham
Matthew Grainge - Collaborator - University of Nottingham
Timothy Card - Collaborator - University of Nottingham