Effectiveness of bivalent boosters against severe omicron infection

Danyu Lin, Yangjianchen Xu, Yu Gu, Bradford Wheeler, Hayley Young, Shadia Khan Sunny, Zack Moore, Donglin Zeng

Abstract:

Since September 1, 2022, the Moderna and Pfizer-BioNTech bivalent Covid-19 vaccines have replaced their monovalent counterparts as booster doses for individuals 12 years of age and older in the U.S. Here, we present data on their effectiveness against severe infection with omicron BA.4/BA.5 strains from a large cohort study.

The data sources for this study have been described elsewhere. We focused on new data collected during two months of bivalent boosters, September 1 to November 3, 2022, and the preceding two months of monovalent boosters, July 1 to August 31, 2022. During the July 1–August 31 period, 162,280 of 6,407,930 eligible participants received monovalent boosters, and 127,047 cases of infection were reported, 1,114 and 469 of which were known to result in hospitalization and death, respectively. During the September 1–November 3 period, 804,474 of 6,432,553 eligible participants received bivalent boosters, and 53,883 cases of infection were reported, 638 and 335 of which were known to result in hospitalization and death, respectively.

We used the Cox proportional hazards model, stratified by vaccination status at the start of each study period and with the booster dose as a time-dependent exposure, to estimate the hazard ratio of severe infection (resulting in hospitalization or death) for a single booster dose (i.e., first booster versus primary vaccination, second booster versus first booster, or third booster versus second booster), while adjusting for baseline characteristics. We defined the relative vaccine effectiveness (rVE) as one minus the hazard ratio, multiplied by 100%.

For all participants 12 years of age and older, the rVE of one monovalent or bivalent booster dose against severe infection resulting in hospitalization was estimated at 45.7% (95% CI, –14.5 to 74.2) or 75.2% (95% CI, 43.8 to 89.0), respectively. Of note, the rVE pertains to the additional benefit of a single booster dose; the absolute vaccine effectiveness (compared with the unvaccinated) would be much higher. We obtained similar rVE values when restricting to participants aged ≥18 or ≥65 years or to mRNA primary vaccine recipients; rVE values were higher for Moderna than Pfizer-BioNTech boosters. The results for the composite endpoint of hospitalization and death were similar to those of hospitalization.

In conclusion, bivalent boosters provided substantial additional protection against severe omicron infection in persons who had previously been vaccinated or boosted. The estimated effectiveness of bivalent boosters was much higher than that of monovalent boosters, although the estimates had considerable uncertainties due to the small numbers of events.