Effectiveness of COVID-19 vaccines on severe COVID-19 and post-acute cardiovascular events and diabetes following SARS-CoV-2 infection: A cohort study

Study type
Date of Approval
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Lay Summary

With high rates of COVID-19 in the community, many people receive additional COVID-19 vaccine “booster” doses. Some vaccines used for these additional doses have been adapted to particularly work well against new COVID-19 variants, such as omicron. However, we need to better understand how well additional vaccine doses prevent people from severe COVID-19 requiring hospitalisation or leading to death. Likewise, more data is needed on how long the protection against severe COVID-19 lasts.
In addition, long-term complications after COVID-19, including persisting symptoms, but also blood clots, heart problems or diabetes have been reported. Additional research is needed to better understand if and to what extend COVID-19 vaccines can reduce the risk for those complications after COVID-19.
We will use anonymous GP records from the NHS to select groups of people with one, two, three of four COVID-19 vaccine doses. We will then match people with e.g. 3 vaccine doses to people with 4 vaccine doses, and use advances statistical techniques to make sure people win both groups are similar in terms of their age, sex, previous covid-19 and other health conditions. We then compare how many of them had severe COVID-19 or new diabetes or problems of the heart or circulation after they had COVID-19.
This study will provide insight on the benefit of (additional) COVID-19 vaccine doses. Our findings will inform strategies for future vaccination program.

Technical Summary

The Vaccine Monitoring Platform jointly coordinated by European Medicines Agency (EMA) and the European Centre for Disease Prevention and Control includes the continuous assessment of COVID-19 vaccine effectiveness, as up-to-date real-world evidence is needed to guide regulatory and vaccination policies.

This study was requested to generate additional evidence on (1) the effectiveness of COVID-19 vaccine booster doses to prevent severe COVID-19, and (2) COVID-19 vaccine effectiveness to prevent post-acute outcomes of SARS-CoV-2 infection.

We will conduct population-level cohort studies including all people aged >=12 years, with at least 365 days of data availability before index date (ID) [ID = date of last vaccine dose] AND data availability from 12/2020 onwards (vaccination campaign start) in CPRD GOLD/AURUM with HES linkage.

WP1: Effectiveness of COVID-19 booster doses:
People with a 3rd-vaccine dose of Pfizer or Moderna vaccines will be included from the source population. Among those, sequential matching will be used to match people with/without a 4th vaccine dose using Propensity Scores. We will then estimate vaccine effectiveness (1- Hazard Ratio (HR)) to prevent severe COVID-19 using Cox proportions hazard models. Negative control outcomes will be used to measure potential residual confounding. HR will be calculated for subsequent time windows after index date to evaluate waning of vaccine effectiveness.

WP2: Post-acute COVID-19 complications:
Vaccine effectiveness to prevent (1) death in the 3/6 months after discharge from a COVID-19 hospitalisation, (2) new onset diabetes within 30-365days after SARS-CoV-2 infection and (3) new onset cardiovascular complications within 30-365days after SARS-CoV-2 infection. We will conduct the following comparisons using the same methodological approach as in WP1: 1st dose vs. 2nd dose vaccinated, 2nd vs. 3rd dose vaccinated, 3rd dose vs. 4th dose vaccinated.

Providing insight to the effectiveness of COVID-19 boosters, this study can support public health decisions for the vaccination campaign.

Health Outcomes to be Measured

Vaccine effectiveness to prevent (1) COVID-19 related hospitalisation; (2) COVID-19 related death; (3) all-cause mortality in the 3 months after discharge from a COVID-19 hospitalisation; (4) all-cause mortality in the 6 months after discharge from a COVID-19 hospitalisation; (5) new-onset type 1 Diabetes Mellitus after SARS-CoV-2 infection, (6) new-onset type 2 Diabetes Mellitus after SARS-CoV-2 infection; (7) cardiovascular events (cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease) after a SARS-CoV-2 infection


Martí Català Sabaté - 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
Edward Burn - Collaborator - University of Oxford
Hezekiah Omulo - Collaborator - University of Oxford
Wai Yi Man - Collaborator - University of Oxford
Xintong Li - Collaborator - University of Oxford


HES Accident and Emergency;HES Admitted Patient Care