High coverage rates of vaccination against COVID-19 are envisaged to end the pandemic. However, waning of vaccine-induced protection is a growing concern that has been fostered by data on vaccine effectiveness against the currently circulating omicron SARS-CoV-2 variant of concern (VOC).
A systematic review and meta-regression by Daniel R Feikin and colleagues in The Lancet provides robust evidence of waning vaccine effectiveness over time. The authors identified 18 studies matching their inclusion criteria, of which three were randomised controlled trials (RCTs). Studies with participants of any age were included in the main analysis, with nine of 18 studies also including adolescents (aged ≥12 years). Information on sex or ethnicity distribution per study was not provided.
Evidence from the meta-regression suggested a decrease in protection against SARS-CoV-2 infection by 21·0% (95% CI 13·9–29·8; on the basis of evidence from six studies) over a 6-month period from full vaccination across all ages and for all investigated vaccine types (Pfizer–BioNTech Comirnaty, Moderna-mRNA-1273, Janssen-Ad26.COV2.S, and AstraZeneca-Vaxzevria).
Vaccine effectiveness against severe disease decreased by 10·0% (95% CI 6·1–15·4; on the basis of evidence from five studies); however, vaccine effectiveness against severe disease remained higher than 70% for 6 months. Subgroup analysis of studies with older adults (as defined per study, but with a minimum age of 50 years) showed no statistically significant difference when compared with analyses of all ages. Variant-specific time analysis supported that reduced vaccine effectiveness does not only relate to alternating effectiveness against specific variants, but that waning immunity is probable.
The authors raised concerns about the serious risk of bias caused by confounding of several non-RCTs that were included. Primary data were adjusted for incomplete and different sets of covariates across studies, and considerable heterogeneity was detected. The pooled analysis might therefore be considered controversial, and the magnitude of estimated effects should be interpreted with caution. Nevertheless, all but one of the identified studies (a phase 3 RCT on mRNA-1273 with completed follow-up of the masked phase, median 5·3 months, before the emergence of VOCs) reported waning vaccine effectiveness over time. Read more >>
Source: The Lancet