Background
Some small studies have shown an association with certain skin conditions (bullous pemphigoid: a rare blistering disease; shingles: a painful and often disabling condition, and urticaria sometimes known as ‘hives’; a painful swelling condition) and the COVID-19 vaccine. All three conditions can lead to serious complications and affect quality of life if not recognised early on.
It is important for GPs and other healthcare professionals like nurses and pharmacists to be aware of post-vaccination skin conditions so that patients receive appropriate treatment and do not get worse. It is also important for patients to make informed decisions with their doctors about risks when they consent to vaccination. To purpose of this study is to determine if there is an association between the COVID-19 vaccine and bullous pemphigoid, shingles and urticaria.
Methods
We will use routinely collected patient data from over 1700 GP surgeries across the UK to calculate the risk of developing bullous pemphigoid, shingles or urticaria following administration of the COVID-19 vaccine. This is an efficient way to undertake research on uncommon conditions and it will reveal what happens in healthcare settings across the whole country. We will consider different vaccine types and find out if these skin conditions have increased in the UK since the mass vaccination programme started.
Anticipated impact
A greater awareness of the potential side-effects of the COVID-19 vaccines and which vaccine type may have higher risk. Alternatively, patients may be reassured that bullous pemphigoid, urticaria and shingles are not associated with the vaccines.
Aim
The aim of this project is to determine if there is any association with COVID-19 vaccines and skin conditions. The objectives are to determine:
1. the prevalence of bullous pemphigoid (BP), herpes zoster (HZ) and/or urticaria following the COVID-19 vaccine programme
2. relative risk of BP, HZ and/or urticaria following COVID-19 vaccination
3. if relative risk is influenced by type of vaccine and COVID-19 infection.
Methods
Data sources: GOLD, AURUM and HES to obtain hospitalisations.
Study 1: The effect of the COVID-19 vaccine on the occurrence of BP, HZ and Urticaria.
Study design: cohort study, 2019-2023.
Outcome: BP, HZ and urticaria (≥18 years)
Negative controls: cases of venous leg ulcers (≥18 years)
Exposure: calendar period
Analysis: interrupted time series to determine if prevalent rates of BP, HZ and urticaria changed after the COVID-19 vaccine programme.
Study 2: COVID-19 vaccine and BP
Study design: nested case-control 2021-2023; this is an appropriate design as BP is uncommon.
Outcome: incident cases of BP (≥18years).
Controls: up to 4 controls per BP case matched by age, sex and GP practice.
Exposure: COVID-19 vaccination
Analysis: conditional logistic regression to calculate unadjusted/adjusted odds ratios for exposure to the COVID-19 vaccine, overall and by vaccine type and number of doses.
Study 3: COVID-19 vaccine and HZ and Urticaria
Study design: self-controlled case series, 2021-2023, to account for within-person confounding.
Outcome: HZ or urticaria (≥18 years).
Negative control: cases of venous leg ulcer (>18 years)
Exposure: COVID-19 vaccination. The study period will be divided into 0-21 vaccine-exposed, 14-days pre-vaccination, and the remaining vaccine-unexposed periods.
Analysis: conditional Poisson regression adjusted for season; stratified by vaccine dose and by type, and restriction by COVID-19 infection.
Patient benefit: knowledge on potential Covid-19 vaccine side-effects so patients can make informed decisions with regards Covid-19 vaccination.
Study 1: Prevalent cases of bullous pemphigoid (≥18 years) in primary or secondary care; prevalent cases of herpes zoster (≥18 years) in primary or secondary care; prevalent cases of urticaria (≥18 years) in primary care or secondary care.
Study 2: incident cases of bullous pemphigoid (≥18 years) in primary or secondary care.
Study 3: incident cases of herpes zoster (≥18 years) in primary or secondary care; incident cases of urticaria (≥18 years) in primary or secondary care.
Sonia Gran - Chief Investigator - University of Nottingham
Sonia Gran - Corresponding Applicant - University of Nottingham
Antonia Lloyd-Lavery - Collaborator - Oxford University Hospitals NHS Foundation Trust
Matthew Ridd - Collaborator - University of Bristol
Mikolaj Swiderski - Collaborator - University of Nottingham
Yana Vinogradova - Collaborator - University of Nottingham
Zenas Yiu - Collaborator - University of Manchester
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation