Title: Impact of COVID-19 vaccination on preventing long COVID: a population-based cohort study using linked NHS data
Funder: Department of Health and Social Care

Abstract: Background: While many people fully recover after COVID-19, a substantial proportion continues to suffer from long-term complications. While vaccines have shown impressive efficacy to prevent severe COVID-19, their impact on long COVID is not investigated in ongoing trials. Objectives: 1) To test if the proposed observational analyses adequately account for confounding. 2) To evaluate the impact of covid vaccination on the prevention of long COVID. 3) To evaluate the comparative effectiveness of covid vaccines to prevent long COVID. Method: Data: NHS records from CPRD GOLD and AURUM Participants: All adults registered in CPRD GOLD/AURUM for >180 days WP1: a) To characterise long COVID in CPRD based on a positive test/clinical diagnosis with persistent symptoms for >28 days. Relevant symptoms will be defined based on a systematic literature review. b) To emulate the null effect of vaccines to prevent COVID-19 in the 10 days after first dose. To test this, 4 staggered cohort studies will be conducted, with eligibility criteria based on vaccination priority groups. Cohort-specific propensity scores (PS) will be estimated, and PS-weighted Poisson models fitted to calculate rate ratios (RR) for COVID-19 in the 10 days after first dose. Negative control outcomes will be used to calibrate for residual confounding. WP2: To estimate the effect of vaccines on the development of long COVID (as defined in WP1a) by comparing vaccinated vs. unvaccinated persons using the methods &ldquo;validated&rdquo; in WP1b. WP3: To study the comparative effectiveness of Oxford/AstraZeneca vs BioNTech/Pfizer vaccine to prevent long COVID using the methods in WP1b.

Lay abstract: Background: While many people fully recover after COVID-19, a substantial proportion continues to suffer from long-term complications such as persistent tiredness, chronic pain or breathing difficulties. Current vaccines prevent severe infections leading to hospitalisations or death, but we do not know yet if they also prevent long-term COVID complications. Aim: Our study will evaluate whether covid vaccination can prevent long COVID. We will first compare the risk for long COVID in adults who received their first dose of a covid vaccine vs. unvaccinated adults. Subsequently, we will compare different covid vaccines to determine whether they can prevent long COVID equally well. Method: We define &ldquo;long COVID&rdquo; as diagnosis or positive test for COVID-19, which is followed by persistent symptoms that last for >4 weeks. We will use de-identified primary care records to select adults eligible for covid vaccination between January and July 2021 based on UK Government vaccination priority groups. Part 1): For different stages of the vaccine roll-out, we select all adults who were vaccinated in that period. Subsequently, we will find people who were unvaccinated the same time. Since adults who have been vaccinated may have different characteristics and health conditions compared to unvaccinated adults, 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. We will again apply advanced statistical methods to balance differences in patient characteristics for the groups. PPI: A patient suffering from long COVID contributed to the development of the project plan and is a co-applicant for the project. Dissemination: We will share findings with scientists (conferences, manuscripts), NHS, the public and lay audiences.

Research activity codes: 3.4 VACCINES
Health categories: INFECTION