Heterologous booster schedules are associated with increased protection against severe, omicron related COVID-19 outcomes

By Dr. Sanchari Sinha Dutta, Ph.D.Reviewed by Lily Ramsey, LLMJul 26 2023

A recent study published in the British Medical Journal compared different coronavirus disease 2019 (COVID-19) vaccination regimens. The study reveals that heterologous booster vaccination provides more protection against severe COVID-19 than homologous booster and primary vaccination.

Study: Comparative effectiveness of heterologous third dose vaccine schedules against severe covid-19 during omicron predominance in Nordic countries: population based cohort analyses. Image Credit: ViacheslavLopatin/Shutterstock.com

Background

With the waiving of non-pharmacological control measures, COVID-19 vaccination has become the most valuable strategy to control the pandemic worldwide. The primary vaccination regimen comprising two doses of vaccines has initially shown promising outcomes in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and severe COVID-19.

A drop in vaccine efficacy was observed later with the emergence of novel viral variants with improved immune fitness. To preserve vaccine efficacy, a third booster dose of COVID-19 vaccines has been introduced globally. Real-world evidence indicates that COVID-19 booster vaccination is more effective than primary vaccination in controlling the pandemic.

In this population-based cohort study, scientists have compared the effectiveness of different heterologous booster vaccination regimens in four Nordic countries (Denmark, Finland, Norway, and Sweden. Moreover, they have compared the effectiveness of heterologous vaccination with primary and homologous vaccination.

Heterologous booster vaccination refers to administering a booster dose different from that used for primary vaccination. Homologous booster vaccination refers to administering the same vaccine dose as previously administered.

Study design

The study population included all adults aged 18 years or older residing in Nordic countries who had received at least a primary vaccination regimen with adenovirus vector-based Oxford/AstraZeneca vaccine, Pfizer mRNA vaccine, Moderna mRNA vaccine, or mixed vaccine.

Two types of heterologous booster vaccination regimens were considered in the study. One regimen included the AstraZeneca vaccine followed by Pfizer or Moderna vaccine. The other regimen included a combination of Pfizer and Moderna vaccines.

The homologous booster vaccination regimen tested in the study involved three doses of the Pfizer or Moderna vaccine.

Country-combined risks of COVID-19-related hospitalization and mortality, as well as admission to intensive care unit (ICU) and SARS-CoV-2 infection rate during the omicron-dominated wave, were analyzed as measures of vaccine efficacy.

Important observations

In the four Nordic countries, about 1,086,418 individuals had received AstraZeneca – Pfizer/Moderna heterologous booster vaccination, and 2,505,093 individuals had received Pfizer – Moderna heterologous booster vaccination.

Comparison between booster and primary vaccination regimens

Compared to primary vaccination, the AstraZeneca – Pfizer/Moderna heterologous booster vaccination showed vaccine effectiveness of 83% against COVID-19 hospitalization and 96% against disease-related mortality. Similarly, the Pfizer – Moderna heterologous booster vaccination showed vaccine effectiveness of 81% against COVID-19 hospitalization and 87% against mortality.

For both heterologous vaccination regimens, significantly higher vaccine efficacy against COVID-19-related ICU admission was observed than the primary vaccination regimen. However, compared to the protection against severe COVID-19 outcomes, both heterologous booster vaccination regimens showed the lowest efficacy against SARS-CoV-2 infection.     

Alike heterologous booster vaccination, homologous booster vaccination showed higher protective efficacy than primary vaccination against COVID-19-related hospitalization and mortality.

Comparison between heterologous and homologous vaccination regimens

The AstraZeneca – Pfizer/Moderna heterologous booster vaccination showed vaccine effectiveness of 27% against COVID-19 hospitalization and 22% against disease-related mortality compared to homologous booster vaccination.

Similarly, the Pfizer – Moderna heterologous booster vaccination showed vaccine effectiveness of 23% against COVID-19 hospitalization and 18% against disease-related mortality.

Compared to homologous booster vaccination, the AstraZeneca – Pfizer/Moderna heterologous booster vaccination and the Pfizer – Moderna heterologous booster vaccination showed vaccine efficacies of 58% and 4% against ICU admission, respectively.    

Compared to homologous Pfizer booster vaccination, homologous Moderna booster vaccination showed protective efficacies of 32%, 30%, 37%, and 10% against COVID-19-related hospitalization, mortality, ICU admission, and SARS-CoV-2 infection, respectively.

Study significance

The study finds that heterologous and homologous booster vaccination regimens provide higher protection against severe COVID-19 outcomes than primary vaccination regimens.

Considering different booster vaccination regimens, the study finds that heterologous booster vaccination is associated with higher protective efficacy against COVID-19-related hospitalization than homologous mRNA booster vaccination.

These observations are made during the omicron wave in the Nordic countries for a follow-up period of 75 days from day 14 post-booster vaccination. However, a decline in vaccine efficacy has been observed upon extension of the follow-up period to 365 days.