BACKGROUND
With the surge of new COVID-19 variants and the waning of effectiveness against infection after the two-dose COVID-19 vaccination, many countries started booster immunization programs. While the effectiveness of booster dose has been reported previously, we yet do not know much about the risk-benefit of receiving two doses of the Oxford-Astra-Zeneca vaccine and one of Pfizer or Moderna compared to three doses of the same vaccine type (Pfizer or Moderna).
PURPOSE
In this study, we will investigate the comparative effects of different COVID-19 booster schedules in terms of COVID-19 prevention and complications and adverse reactions.
METHOD
We will use CPRD data to study adults who received at least 3 doses of COVID-19 vaccine/s. The effectiveness and risk of adverse events will be compared between different combinations of vaccines. We will then analyse the risks and benefits amongst subgroups including elderly frail patients and those with a complex medical history.
POTENTIAL IMPORTANCE
Our results will inform future vaccination and booster campaigns by providing key data on the risks and benefits of different vaccine combinations.
BACKGROUNDS:
While previous studies showed the real-world effectiveness of booster dose in preventing COVID-19 compared with only receiving the primary doses, the effectiveness and risk profile between heterologous versus homologous boosters remains unclear.
OBJECTIVES:
1). To estimate the comparative effectiveness in preventing COVID-19 infection between the heterologous(comparator) versus homologous (target) primary-boost COVID-19 vaccine regimens.
2). To compare the effectiveness in preventing long COVID-19, COVID-19 acute and post-acute complications.
3). To estimate the comparative risk of adverse events.
METHODS:
Data: NHS records from CPRD GOLD/Aurum, linked to HES inpatient data.
Participants: Adults received two doses of COVID-19 vaccine/s, and a booster (third) dose after 12 weeks or more.
Outcomes:
Obj1: COVID-19 infection based on positive PCR or lateral flow test/s, COVID-19 hospitalization, death with 28 days after COVID diseases.
Obj2: Acute (within 4 weeks) and ongoing symptomatic COVID-19 (from 4 weeks up to 12 weeks), long COVID-19.
Obj3: 15 pre-specified adverse events of special interest, and thrombosis-thrombocytopenia syndrome.
Statistical analysis:
Propensity score matching methods will be used to account for observed confounding, and negative control outcomes used to identify unobserved confounding.
Obj1&2: Hazard ratio estimated from Cox regression models among the matched cohorts. We will use Kaplan-Meier plots to visually inspect the difference between the two groups.
Obj3: Incidence rate ratio of each outcome with in the 28 days after booster dose estimated from Poisson models.
Sensitivity analysis include excluding patients who developed study outcomes within 14 days after vaccination (only for Obj1&2); restrict study period to Feb-2022; exclude patients with previous COVID-19 infections, and applying propensity score weighting.
All analysis will be conducted in subpopulations of people aged over 65 years with polypharmacy, and with frailty.
PUBLIC HEALTH BENEFIT: Understanding the comparative effectiveness and safety between different booster COVID-19 vaccines will inform future risk-benefit evaluation on national immunization program.
Objective 1: A first positive test/clinical diagnosis of COVID-19, COVID-19 hospitalization, death with 28 days after COVID diseases.
Objective 2: Acute and ongoing symptomatic COVID-19 complications, including cardiovascular events (stroke, myocardial infarction, arrhythmia), venous thromboembolism (deep vein thrombosis, pulmonary embolism), acute kidney injury, and acute respiratory distress syndrome (ARDS); Post-acute sequelae of SARS-CoV-2 infection (PASC), or “long COVID-19”.
Objective 3: Adverse events of special interests (AESI) for COVID-19 vaccines: Non-haemorrhagic and haemorrhagic stroke, acute myocardial infarction; deep vein thrombosis; pulmonary embolism; anaphylaxis; Bell’s palsy; myocarditis or pericarditis; narcolepsy; appendicitis; immune thrombocytopenia; disseminated intravascular coagulation; encephalomyelitis (including acute disseminated encephalomyelitis); Guillain-Barré syndrome; transverse myelitis; Thrombosis with thrombocytopenia syndrome/s and thromboembolic events.
Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Xintong Li - Corresponding Applicant - University of Oxford
Annika Jodicke - Collaborator - University of Oxford
Edward Burn - Collaborator - University of Oxford
Junqing Xie - Collaborator - University of Oxford
Leena Elhussein - Collaborator - Nuffield Dept of Orthopaedics
HES Admitted Patient Care