The following is a summary of “Annual variant-targeted vaccination to prevent severe COVID-19 disease in cohorts with vaccine-derived and hybrid immunity,” published in the March 2025 issue of Clinical Infectious Diseases by Kelly et al. 

Researchers conducted a retrospective study to estimate the strength and durability of protection from annual variant-targeted vaccination against individuals with severe COVID-19 illness and with vaccine-derived and hybrid immunity.  

They emulated a target trial using an electronic health record-based, propensity-score matched (1:1) cohort of U.S. adults. Booster-vaccinated individuals became eligible for a variant-targeted mRNA booster starting September 1, 2022. Weekly, matched sets of those who received and did not receive the booster were identified, and follow-up continued until August 31, 2023. Outcomes included hospitalization due to COVID-19 pneumonia and in-hospital6 severe illness. Cox models were used to estimate relative vaccine effectiveness (VE), both overall and stratified by last documented SARS-CoV-2 infection (pre-Omicron, Omicron).  

The results showed that the propensity-score matched included 15,766,26 COVID-19 booster-vaccinated adults. The relative vaccine effectiveness (rVE) of the variant-targeted mRNA booster against hospitalization due to COVID-19 pneumonia was 29% (95%CI: 25%, 34%) in those with vaccine-derived immunity and 38% (95%CI: 27%, 47%) in those with hybrid immunity. Significant protection was observed from 0-6 months post-vaccination but not from 6-12 months, and protection remained consistent during both pre-XBB and XBB variant periods. Similar findings were noted for in-hospital severe illness.  

Investigators concluded that variant-targeted booster doses provided short-term, modest protection against severe COVID-19 in individuals with vaccine-derived or hybrid immunity, but this protection did not persist beyond 6 months. 

Source: academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf124/8078340