A recent study posted to the medRxiv* preprint server evaluated the waning efficacy of the coronavirus disease 2019 (COVID-19) ChAdOx1 and BNT162b2 vaccines over six months following the second dose. The study was based on linked electronic health records (EHR).

Study: Waning effectiveness of BNT162b2 and ChAdOx1 COVID-19 vaccines over six months since second dose: a cohort study using linked electronic health records. Image Credit: Telnov Oleksii/Shutterstock
Study: Waning effectiveness of BNT162b2 and ChAdOx1 COVID-19 vaccines over six months since second dose: a cohort study using linked electronic health records. Image Credit: Telnov Oleksii/Shutterstock


The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations, which was initially proven in randomized trials, has been verified in previous observational studies with extended follow-up. Yet, as time passes following vaccination, neutralizing antibody titers diminish, and vaccine efficacy against SARS-CoV-2 infection decreases. 

The degree of declining vaccination efficacy against severe SARS-CoV-2 infection is unclear. Prior studies have shown no indication of waning, either substantial or modest. The pace at which the SARS-CoV-2 vaccine’s efficacy deteriorates over time is critical for devising booster immunization policies. However, it remains unclear due to inconsistent findings from existing investigations.

About the study

In the current cohort study authorized by the National Health Service (NHS) of the United Kingdom (UK), the researchers assigned individuals without COVID-19 history to vaccination priority groups 2-12 employing the OpenSAFELY-The Phoenix Partnership (TPP) database.

OpenSAFELY-TPP comprises pseudonymized primary care data connected through NHS numbers to emergency and accident visits, inpatient hospital stay records, national COVID-19 testing records, and national mortality registry records. Primary care record provides details about vaccination status through the National Immunization Management System (NIMS). NHS Digital’s SARS-CoV-2 data repository provided the healthcare worker status. Further, the vaccine groups 2-12 were set by the Joint Committee on Vaccination and Immunization (JCVI) of the UK.

The researchers compared the SARS-CoV-2 vaccine efficacy among people who had received two ChAdOx1 or BNT162b2 vaccine doses with unvaccinated subjects during the six four-week comparison periods. These comparisons were performed separately for the people in subgroups 1) clinically suspectable and over 65 years (JCVI groups 2-5); 2) clinically vulnerable and between 16 to 64 years (JCVI groups 4 or 6); 3) 18 to 39 years (JCVI groups 11-12) and 4) 40 to 64 years (JCVI groups 7-10). The unvaccinated, ChAdOx1, and BNT162b2 vaccine groups included 2,433,988; 2,961,011; and 1,773,970 subjects, respectively. 

The team assessed adjusted hazard ratios (aHRs) comparing unvaccinated and vaccinated individuals using Cox regression, filtered by geographical location, the first dose eligibility, and adjusted for calendar time. Thereby, they estimated the declining vaccine efficacy as ratios of aHRs every four weeks. The outcomes of the study were SARS-CoV-2-related hospitalization and death, COVID-19-positive test, and non-SARS-CoV-2 mortality.

Results and discussions

The results demonstrated that the deterioration of COVID-19 vaccine efficacy was comparable between the outcomes and the BNT162b2 and ChAdOx1 vaccines. The aHRs for SARS-CoV-2-linked hospitalization, COVID-19 mortality, and SARS-CoV-2-positive test between the 65 years and above subgroup and the unvaccinated varied between 1.16 and 1.20 for ChAdOx1 vaccine and between 1.23 and 1.27 for the BNT162b2 group. 

Besides waning, the SARS-CoV-2-linked hospitalization and mortality rates were dramatically lower among the vaccinated participants relative to the unvaccinated cohorts nearly 26 weeks following COVID-19 vaccination with the second dose. The approximated aHRs for COVID-19-related death and hospitalization in the BNT162b2 vaccine cohort was less than 0.20, i.e., more than 80% vaccine effectiveness.

The aHRs for SARS-CoV-2-associated death and hospitalization in the ChAdOx1 vaccinated individuals was less than 0.26, i.e., more than 74% vaccine efficacy. These data indicated that the SARS-CoV-2-linked hospital admission and mortality were lower in the two-dose BNT162b2 vaccinated group than the two-dose ChAdOx1 vaccinees.

Around weeks 23 to 26, the SARS-CoV-2 infection rates among the two-dose COVID-19 vaccinated people were comparable or greater than the unvaccinated subjects. At this point, the aHRs for COVID -19 across vaccinated and unvaccinated subjects varied between 1.21 and 1.99 for the ChAdOx1 vaccine. Further, the aHRs varied between 0.85 and 1.53 for the BNT162b2 vaccine and unvaccinated cohorts. Additionally, non-COVID-19 mortality rates were markedly lower among the two-dose vaccinated people than the unvaccinated people.


The study findings depicted that for SARS-CoV-2 hospitalization, COVID-19 mortality, and a SARS-CoV-2-positive test, the pace at which predicted vaccination efficacy dropped was remarkably constant for both ChAdOx1 and BNT162b2 COVID-19 vaccines. It was also equivalent over subgroups characterized by clinical susceptibility and age. If these findings were applied to the SARS-CoV-2 Omicron infection outcomes and booster vaccinations, it would probably aid in determining the COVID-19 booster immunization doses in the current scenario.

By 26 weeks following the second SARS-CoV-2 vaccine shot, the rates of COVID-19 cases were comparable to or greater in the two-dose vaccinated people than in the uninfected people, showing that vaccination had only a temporary effect on SARS-CoV-2 transmissibility. This might be because of the benefits of immunization that it enables more social mixing due to the lower chance of severe SARS-CoV-2 infection.

Even in the elderly and clinically susceptible people, protection against SARS-CoV-2-related hospitalization and mortality was significant up to 26 weeks following the second vaccine dose.

Lastly, the discontinuation of publicly available population-based testing methods probably limits the use of the test-negative case-control (TNCC) methodology, which has so far produced quick estimates of vaccination efficacy. However, for severe SARS-CoV-2 outcomes, cohort techniques based on comprehensive linked EHR data, such as those utilized in this study, should remain plausible.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.


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