OP4-5 - Effect of COVID-19 vaccines on post-COVID cardiac and thromboembolic complications

Background

Previous research suggests that although some COVID-19 vaccines could increase rare thrombosis risk, SARS-CoV-2 infection leads to a much higher risk. The effects of vaccination on post-COVID thrombosis and cardiovascular risks remain unknown.

Objectives

We aimed to evaluate the effect of COVID-19 vaccines on the risk of cardiac and thromboembolic complications in up to 3 months after SARS-CoV-2 infection. 

Methods

We used UK primary care records from the Clinical Practice Research Datalink (CPRD) AURUM to conduct a staggered cohort study. All individuals aged >= 65 years or clinically extreme vulnerable were eligible. First cohort enrolled people aged >= 75 years (UK Government risk groups 2+3) between 4th January 2021 and 27th January 2021. People receiving first COVID-19 vaccine dose within the enrolment period constituted the vaccinated cohort. Second cohort enrollment went from 28th January 2021 to 28th February 2021. Eligible individuals were >= 65 years, adults clinically extreme vulnerable/at-risk patients (UK Government risk groups 4-6), and still unvaccinated persons from the first cohort.

At that time two vaccines were administrated in the UK, BNT162b2 and ChAdOx1. Therefore, vaccinated cohorts (VC) included any of these two vaccines.

First dose date was set as index for VC, while random dates within the enrolment periods were used for the unvaccinated cohort (UV). Individuals with a history of COVID-19, or vaccination against it before index were excluded.

Participants were followed up until the first occurrence of event of interest, death, end of follow-up/data availability, or change in exposure status (first vaccine dose for UV).

Outcomes of interest included venous thromboembolism (VTE), arterial thromboembolism (ATE), and heart failure (HF), ascertained in two-time windows separately: 0 to 30 days, and 31 to 90 days post-COVID.

Propensity Scores (PS) were used to minimise confounding. Variables in the PS included age, GP practice, region, prior observation years, number of previous visits, and number of previous PCR tests, in addition to variables predictive of vaccination based on lasso regression including all covariates with prevalence >0.5%. Unmeasured confounding was assessed using 43 Negative Control Outcomes (NCO). Fine-Gray models were used to estimate Subdistribution Hazard Ratios (sHR) for each outcome, and corrected using empirical calibration.

Results

A total of 555,868 (first cohort) + 1,647,664 (second) vaccinated people were compared to 349,699 + 2,157,496 unvaccinated. Vaccination was associated with lower risk of post-COVID VTE, with sHR 0.29 [0.12-0.69] and 0.20 [0.07-0.52] in days 0-30, and 0.37 [0.09-1.60] and 0.11 [0.01-0.90] in days 31-90 after COVID-19 diagnosis in cohorts 1 and 2, respectively. Post-COVID ATE risk was also lowered but only in 0-30 days in cohort 1 (sHR 0.30 [0.09-0.92]), with inconsistent effects in cohort 2 and days 31-90 of both cohorts. No consistent association was seen between vaccination and post-COVID HF.

Conclusions

COVID-19 vaccines were associated with a reduced risk of thromboembolic complications following SARS-CoV-2 infection. No similar effects were seen for arterial events or heart failure. More research is needed on the potential effect of COVID-19 vaccines to prevent long COVID and post-acute complications.