Bivalent COVID-19 Booster Benefit Increases With Time Since Monovalent Vaccination

Receipt of a bivalent mRNA booster dose increased protection against COVID-19, and the benefit of the booster increased with time since receipt of monovalent vaccination.

A single dose of a bivalent mRNA COVID-19 vaccine booster provides significant additional protection against symptomatic COVID-19 infection in adults who have previously received monovalent vaccination. These study results were published in Morbidity and Mortality Weekly Report MMWR.

In this study, researchers evaluated 360,626 nucleic acid amplification test (NAAT) results performed among adult patients with symptoms suggestive of COVID-19 infection between September and November 2022 across 9995 pharmacies in areas of high social vulnerability. At this time, the Omicron variant (BA.4/BA.5 lineages) was the predominant SARS-CoV-2 strain.  Using multivariable logistic regression, NAAT results were assessed to determine the absolute and relative vaccine effectiveness (VE) of a single bivalent booster dose against COVID-19 infection by the number of monovalent vaccine doses previously received.

Results of NAAT were positive for COVID-19 infection in 121,687 patients (cases) and negative in 238,939. Among patients in the case and control groups, 56% and 63% were women, 50% and 46% were non-Hispanic White, 62% and 72% were aged 18 to 49 years, 25% and 18% were 50 to 64 years, and 14% were 65 and older, respectively.

Self-reports among patients who tested positive for infection indicated 28,874 (24%) were unvaccinated, 87,013 (72%) had received 2, 3, or 4 monovalent vaccine doses but no subsequent bivalent booster, and 5800 (5%) had received a bivalent booster dose. For patients in the control group, self-reports showed 72,010 (30%) were unvaccinated, 150,455 (63%) had received 2, 3, or 4 monovalent vaccine doses, and 16,474 (7%) had received a bivalent booster dose. The median time between bivalent booster dose administration and NAAT was 1 (range, 0-2) month.

Due to the waning immunity of monovalent doses, the benefit of a bivalent booster increased with time since the receipt of the most recent monovalent vaccine dose.

The researchers calculated the absolute VE of a single bivalent mRNA COVID-19 booster dose after patients were stratified by age and number of previous monovalent vaccine doses received. For patients aged between 18 and 49 years, the absolute VE of a bivalent booster dose was similar among those who previously received 2 (41%; 95% CI, 31-49), 3 (43%) or 2 or more (43%; 95% CI, 39-46) monovalent vaccine doses. For patients aged between 50 and 64 years and those aged 65 and older, absolute VE was highest among those who previously received 2 monovalent vaccine doses (50%; 95% CI, 35%-61% and 32%; 95% CI, 9%-49%, respectively) and lowest among those who previously received 3 monovalent doses (25%; 95% CI, 17%-33% and 19%; 95% CI, 8%-29%, respectively).

Irrespective of age and number of previously received monovalent vaccine doses, the relative VE of a single bivalent booster dose was found to increase with time since monovalent vaccination. The highest relative VE (range, 41%-56%) was observed among patients who received a bivalent booster dose at 8 months or more following receipt of at least 2 monovalent vaccine doses.        

Limitations of this study include the use of self-reported data, potential residual confounding due to the lack of data on COVID-19 exposure risk and mask use, and differences in testing behaviors between vaccinated and unvaccinated patients.

“Due to the waning immunity of monovalent doses, the benefit of a bivalent booster increased with time since the receipt of the most recent monovalent vaccine dose,” the researchers noted. “All persons should stay up to date with recommended COVID-19 vaccines, including bivalent booster doses, if it has been ≥2 months since their last monovalent vaccine dose,” they concluded.

References:

Link-Gelles R, Ciesla AA, Fleming-Dutra KE, et al. Effectiveness of bivalent mRNA vaccines in preventing symptomatic SARS-COV-2 infection — increasing community access to testing program, United States, September–November 2022. Morb Mortal Wkly Rep MMWR. 2022;71(48):1526-1530. doi:10.15585/mmwr.mm7148e1