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In 2022, use of bivalent COVID-19 vaccine (i.e., ancestral strain with an Omicron subvariant BA.4-5 or BA.1) was authorized in Nordic countries. To determine the relative effectiveness of vaccine containing BA.4-5 versus BA.1, investigators analyzed data from nationwide cohorts in four Nordic countries. Primary outcomes were hospitalization and death due to COVID-19 in persons who received a fourth dose of bivalent vaccine compared with three doses, and in those who received BA.4-5 versus BA.1-based bivalent vaccines as their fourth dose.
Among 2.7 million adults (mean age, 72) who received a fourth dose, 61% were in the BA.4-5 group and 39% in the BA.1 group. Compared with three doses, a fourth dose of BA.4-5 was associated with a relative vaccine effectiveness (VE) of 67.8% against hospitalization and 69.8% against death. For BA.1, relative VEs were 65.8% (hospitalization) and 70.0% (death). The risk differences for BA.4-5 versus BA.1 against COVID-19 hospitalization and death were −14.9% and −40.7%, respectively. In an additional analysis, no differences in severe outcomes were seen between those who received a monovalent vaccine as a fourth dose versus those who received any of the bivalent vaccines as a fourth dose.
Andersson NW et al. Comparative effectiveness of bivalent BA.4-5 and BA.1 mRNA booster vaccines among adults aged ≥50 years in Nordic countries: Nationwide cohort study. BMJ 2023 Jul 25; 382:e075286. (https://doi.org/10.1136/bmj-2022-075286)
Comment
In this population-based study, a fourth COVID-19 vaccine dose yielded relative reductions in COVID-19 hospitalization and death compared with three doses, and no differences were observed among the particular vaccines administered for the fourth dose. Study limitations include potential residual confounding, healthy user bias, and differential health-seeking behavior; however, these differences probably affected whether the additional dose was received, but not necessarily the specific vaccine. The standard procedure of updating the vaccine strain to more closely match the circulating strain may be advantageous regarding immune responses — and it stands to reason that the new boosters expected to be rolled out this fall will give results similar to these studies — but estimates of the added clinical benefit remain to be determined in future studies.