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Peer reviewedOpen accessCOVID-19SARS

Implications for future pandemics from a living systematic review and critical evaluation of observational studies of the effectiveness of COVID-19 vaccination against the Omicron variant

Vaccine·

Fatema Kazi, Chin Yang Shapland, Francesca Spiga, Gemma Villanueva, Rosie P. Cornish, Nicholas Henschke, Elise Cogo, Meghan Sebastianski, Mohsen Aarabi, Hanna Bergman, Brian Buckley, Gemma L. Clayton, Clare E. French, James Liu, Paul Madley-Dowd, Ferruccio Pelone, Jennifer Petkovic, Katrin Probyn, Rosella Saulle, Jelena Savović, Rebecca Wilson, Charles R. Beck, Julian P.T. Higgins

DOI
10.1016/j.vaccine.2026.128993
PMID
42594644
PMCID
OpenAlex
W7202331386
Study type
Systematic review
Publisher
Elsevier BV
Article type
journal-article
Integrity
current

Why this research matters now

These aggregated results guide international immunization planning and highlight structural improvements needed for future outbreak responses, such as unified research methodologies and integrated health databases.

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Structured evidence summary

Research question

How effective are approved immunizations against the Omicron lineage across different dosing regimens and demographic cohorts?

Study design

A continuously updated systematic review that critically appraises comparative observational research utilizing the ROBINS-I framework to assess analytical validity.

Population and setting

The synthesis aggregates data from seventy-nine observational investigations encompassing more than fifty-three million participants.

Main findings

Immunization demonstrated substantial defense against severe or critical illness, with messenger RNA formulations showing the highest efficacy. Pooled estimates indicated varying protection levels across infection severity categories, while most included analyses carried moderate to serious bias risks primarily driven by confounding factors.

Public-health relevance

These aggregated results guide international immunization planning and highlight structural improvements needed for future outbreak responses, such as unified research methodologies and integrated health databases.

Important limitations

Most synthesized estimates exhibited moderate or serious methodological weaknesses, with residual confounding identified as the primary threat to validity.

GIDS interpretation

This publication establishes a documented reference point for historical vaccine performance during the Omicron circulation period, offering methodological benchmarks for evaluating observational research quality during emerging respiratory threats.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 8 auditable classifier relationships to diseases, places, topics, and study design.

about diseaseabout diseaseaddresses topicaddresses topicevaluates interventionstudied population settingstudies pathogenuses study design