Relative effectiveness of booster vs. 2-dose mRNA Covid-19 vaccination in the Veterans Health Administration: Self-controlled risk interval analysis

Objective: To estimate relative effectiveness of the booster mRNA Covid-19 vaccination versus the 2-dose primary series for both Delta and Omicron variants with self-controlled study design. Methods: We used the Veterans Health Administration (VHA) Corporate Data Warehouse to identify U.S. Veterans who received the 2-dose primary mRNA Covid-19 vaccine series and a mRNA Covid-19 booster, and who had a positive SARS-CoV-2 test during the Delta (9/23/2021-11/30/2021) or Omicron (1/1/223/19/22) predominant period. Among them, we conducted a self-controlled risk interval (SCRI) analysis to compare odds of SARS-CoV-2 infection during a booster exposure interval versus a control interval. Exposures were a control interval (days 4-6 post-booster vaccination, presumably prior to gain of booster immunity), and booster exposure interval (days 14-16 post-booster vaccination, presumably following gain of booster immunity). Cases had a positive PCR or antigen SARS-CoV-2 test. Separately for Delta and Omicron periods, we used conditional logistic regression to calculate odds ratios (OR) of a positive test for the booster versus control interval and calculated relative effectiveness of booster versus 2dose primary series as (1-OR)*100. The SCRI approach implicitly controlled for time-fixed confounders. Results: We found 42 individuals with a positive SARS-CoV-2 test in the control interval and 14 in the booster exposure interval during the Delta period, and 141 and 70, respectively, in the Omicron period. For the booster versus 2-dose primary series, the odds of infection were 70% (95 %CI: 42%, 84%) lower during the Delta period and 54% (95 %CI: 38%, 66%) lower during Omicron. In sensitivity analyses among those with prior Covid-19 history, and age stratification, ORs were similar to the main analysis. Conclusions: Booster vaccination was more effective relative to a 2-dose primary series during the Delta and Omicron predominant periods, and the relative effectiveness was consistent across age groups. (c) 2022 Published by Elsevier Ltd.

Automated summary

This study aimed to compare the relative effectiveness of booster mRNA Covid-19 vaccination versus the 2-dose primary series for both Delta and Omicron variants. The results showed that booster vaccination was more effective during the Delta and Omicron predominant periods compared to the 2-dose primary series.