BACKGROUND
While many people fully recover after COVID-19, a substantial proportion continue to suffer from long-term complications such as persistent tiredness, chronic pain or breathing difficulties. The combination of these is also called “long COVID”. Current vaccines prevent severe infections leading to hospitalisations or death, but we do not know yet if they also prevent long COVID.
PURPOSE
We will evaluate whether covid vaccines can prevent long COVID. We will first compare the risk for long COVID in vaccinated vs. unvaccinated adults. Subsequently, we will compare different vaccines to determine whether they can prevent long COVID equally well.
METHOD
We define “long COVID” as diagnosis/positive test for COVID-19 followed by persistent symptoms lasting for >4 weeks. We will use de-identified primary care records to select adults eligible for covid vaccination based on UK Government vaccination priority groups.
Part 1): For different stages of the vaccine roll-out, we will select all adults vaccinated in that period.
Subsequently, we will find people who were unvaccinated in the same dates. Since adults who have been
vaccinated may be different compared to unvaccinated ones, we will use advanced statistical methods to balance
these differences. We will then compare risk for long COVID between vaccinated and unvaccinated adults.
Part 2): We will compare risk for long COVID between adults from similar priority groups for covid vaccination,
who received different covid vaccines.
POTENTIAL IMPORTANCE
Our results will inform patients and clinicians to weight risks/benefits of covid vaccines and will inform the development of future prevention programs.
BACKGROUND
While many people fully recover after COVID-19, a substantial proportion continues to suffer from long-term complications. The impact of vaccination on long COVID prevention remains unclear.
OBJECTIVES
1a) To characterise long COVID and calculate its incidence.
1b) To test if the proposed observational analyses adequately account for confounding.
2) To evaluate the effectiveness of covid vaccination to prevent long COVID.
3) To evaluate the comparative effectiveness of covid vaccines to prevent long COVID.
METHODS
Data: NHS records from CPRD GOLD/AURUM, linked to publicly available infection/vaccination rates.
Participants: All adults registered in CPRD GOLD/AURUM for >180 days
WP1:
a) To characterise long COVID based on a positive test/clinical diagnosis with persistent symptoms for >28 days. Relevant symptoms will be identified from WHO definition and systematic literature review. We will calculate incidence rates for long COVID, and compare summary characteristics of people with long COVID, COVID-19 infection and a COVID-19 negative cohort.
b) To emulate the null effect of vaccines to prevent COVID-19 in the 10 days after first dose and calculate vaccine effectiveness (first dose). 4 staggered cohort studies will be conducted, with eligibility criteria based on vaccination priority groups. Cohort-specific propensity score (PS) will be estimated, PS matching or weighting applied respectively, and cox models fitted to calculate hazard ratios for COVID-19. Negative control outcomes will be used to calibrate for residual confounding.
WP2:
To estimate the effect of vaccines on the development of long COVID by comparing vaccinated vs. unvaccinated persons using the study design “validated” in WP1b and fine-gray regression.
WP3:
To study the comparative effectiveness of Oxford/AstraZeneca vs BioNTech/Pfizer vaccine to prevent long COVID using the methods in WP1b/WP2.
PUBLIC HEALTH BENEFIT:
Understanding the impact vaccination has on preventing long COVID will inform future risk-benefit evaluations for COVID vaccines.
WP1A: Diagnoses/symptoms characterising long COVID, which were recorded >28days after a positive test/clinical diagnosis of COVID-19 in CPRD; Baseline characteristics of patients with long COVID, COVID-19 and a test-negative comparison cohort, stratified by first infection/subsequent re-infections; Incidence rates for long COVID stratified by age, sex, time period and first infection/subsequent re-infections and vaccination status;
WP1B: A first positive test/clinical diagnosis of COVID-19 recorded (in the first 10 days; anytime) after the first dose of a covid vaccine;
WP2 and WP3: Long COVID; post-acute COVID-19 sequalae (e.g. thromboembolic events, severe complications).
Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Annika Jodicke - Corresponding Applicant - University of Oxford
Albert Prats Uribe - Collaborator - University of Oxford
Antonella Delmestri - Collaborator - University of Oxford
Daniel Dedman - Collaborator - CPRD
Edward Burn - Collaborator - University of Oxford
Elena Roel - Collaborator - Nuffield Dept of Orthopaedics
Junqing Xie - Collaborator - University of Oxford
Kim López-Güell - Collaborator - University of Oxford
Kristin Kostka - Collaborator - University of Oxford
Martí Català Sabaté - Collaborator - University of Oxford
Nuria Mercade Besora - Collaborator - University of Oxford
Trishna Rathod-Mistry - Collaborator - University of Oxford
Victoria Y Strauss - Collaborator - University of Oxford
Xintong Li - Collaborator - University of Oxford
Zara Cuccu - Collaborator - CPRD
Núria Mercadé Besora - Collaborator - Polytechnic University of Catalonia
Nuria Mercade Besora - Collaborator - University of Oxford
Patient Level Index of Multiple Deprivation