COVID booster vaccination more effective relative to 2-dose series

By Dr. Sanchari Sinha Dutta, Ph.D.Mar 22 2022Reviewed by Benedette Cuffari, M.Sc.

In a recent study published on the medRxiv* preprint server, researchers have revealed that a booster dose of a messenger ribonucleic acid (mRNA)-based coronavirus disease 2019 (COVID-19) vaccine is more effective than the two-dose primary vaccination regimen in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. However, the effectiveness is higher against the Delta variant than the Omicron variant.

Study: Relative effectiveness of booster vs. 2-dose mRNA Covid-19 vaccination in the Veterans Health Administration: Self-controlled risk interval analysis. Image Credit: Exahardiwito / Shutterstock.com

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

Real-world studies investigating the effectiveness of COVID-19 vaccines have demonstrated satisfactory outcomes. However, due to the emergence of new SARS-CoV-2 variants with improved immune fitness, a sharp rise in vaccine breakthrough infections has been reported in many countries worldwide. This has prompted public health authorities to recommend booster vaccination against COVID-19 for the general population.

In September 2021, the United States began administering booster doses of mRNA COVID-19 vaccines. Preliminary findings of several observational studies have shown that the effectiveness of booster mRNA-based COVID-19 vaccine dose is lower against the SARS-CoV-2 Omicron variant as compared to that against the Delta variant. However, observational studies that compare vaccinated people with unvaccinated people to assess vaccine effectiveness may suffer from various confounding factors, including misclassification of vaccination status.

In the current study, the scientists have applied a self-controlled risk interval study design to reduce such confounding factors and assess the real-time effectiveness of COVID-19 booster vaccination against SARS-CoV-2 infection. The current study, which fully accounts for time-fixed confounding factors, relied on Veterans Health Administration data to collect vaccination details of U.S. veterans.

The primary benefit of the self-controlled risk interval study design is a complete adjustment for all time-fixed confounding factors. An additional advantage of this study design is that it is suitable for identifying an unbiased comparable study group of vaccinated as compared to unvaccinated, thus allowing the inclusion of only infection-positive cases and the identification of periods of exposure and non-exposure around the event of booster vaccination.  

Study design  

The study analysis included U.S. veterans who received the two-dose primary regimen of mRNA-based COVID-19 vaccines from either Pfizer or Moderna, followed by an mRNA booster vaccination of either of the primary vaccines.

Based on the self-controlled risk interval study design, the efficacy of booster vaccination over primary vaccination was analyzed at two fixed intervals referred to as control and booster exposure intervals during the Delta- and Omicron-dominated COVID-19 waves. The control interval was defined days four to six post-booster vaccination, which is before the vaccinated individual would gain booster immunity. The booster exposure interval is defined days 14 to 16 post-booster vaccination, which is after booster immunity should be acquired.

The scientists selected short intervals of exposure and non-exposure to reduce the impact of time-modified confounding factors. Moreover, since the control and risk intervals belonged to the same individual, a complete adjustment for all time-fixed confounding factors was possible in the study.

The vaccine efficacy at two study intervals was determined by estimating the incidence of SARS-CoV-2 infection in boosted veterans during the Delta- and Omicron-dominated waves.

Important observations

A total of 1,240,999 veterans were identified who had received the booster dose of mRNA-based COVID-19 vaccines between September 2021 and March 2022. The average interval between the second and third (booster) vaccine doses was eight months. Of boosted veterans, 301 tested positive for SARS-CoV-2 infection during the Delta wave and 7,621 tested positive during the Omicron wave.

Considering the study-defined intervals, a total of 42 and 14 cases were identified at the control and booster exposure intervals, respectively, during the Delta wave. During the Omicron wave, a total of 137 and 66 cases were identified at the control and booster exposure intervals, respectively.

The relative effectiveness, which is defined as the reduction in the risk of testing positive, of the booster vaccination over two-dose primary vaccination was calculated by analyzing the numbers of SARS-CoV-2-positive cases during the Delta and Omicron waves. The relative effectiveness of the booster vaccination was estimated to be 70% during the Delta wave and 56% during the Omicron wave. These estimates were similar for veterans aged below or above 65 years during the Omicron wave.

A separate set of analyses was conducted on boosted veterans who had a history of COVID-19. The findings revealed that the relative effectiveness of booster vaccination in this subset of the study participants over two-dose primary vaccination was 68% during the Delta wave and 56% during the Omicron wave. These estimates reveal that prior exposure to SARS-CoV-2 did not impact the efficacy of booster vaccination.

Study significance

The current study highlights the importance of booster COVID-19 vaccination in reducing the risk of SARS-CoV-2 infection. Based on the study findings, a booster dose of Pfizer- and Moderna-developed mRNA COVID-19 vaccines are more effective against Delta infections as compared to Omicron infections.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources