Impact of pre-Omicron COVID-19 vaccine boosters on the risk of Omicron variant infections: A systematic review and meta-regression.

BACKGROUND

An argument against COVID-19 vaccine boosters is that immune imprinting may impair immune responses to new SARS-CoV-2 variants, as some epidemiological studies found a paradoxical increase in Omicron variant infections correlated with the number of prior pre-Omicron vaccine doses. However, substantial variability between studies has left the true impact of boosters uncertain, warranting further investigation.

METHODS

We systematically reviewed available data and applied meta-regression to identify sources of heterogeneity among studies that examined the impact of pre-Omicron COVID-19 vaccine boosters-compared with primary vaccination series without boosters-on the risk of Omicron variant infections and severe diseases.

RESULTS

We screened 1703 articles and included 35 eligible studies. Heterogeneities in the impact of pre-Omicron boosters on the risk of Omicron infections and severe diseases are attributable to differences in time after boosters, age, and vaccine products (meta-regression R2: 70.4 % and 67.7 %, respectively). During the first month post-vaccination, pre-Omicron mRNA boosters decrease-rather than increase-the risk of Omicron infections and severe diseases by 58 % (95 % CI: 54 %-62 %) and 80 % (95 % CI: 68 %-87 %). This effectiveness declines to 9 % (95 % CI: 7 %-23 %) and 55 % (95 % CI: 49 %-60 %) by the sixth and fifth month, respectively. The certainty for evidence is moderate for protection against infections and high for protection against severe diseases.

CONCLUSION

Our findings refute the immune imprinting hypothesis that COVID-19 boosters impair immunity against new SARS-CoV-2 variants and support current recommendations to stay protected through updated booster vaccination once or twice a year.