COVID-19 Vaccine Effectiveness and the Evidence on Boosters: A Systematic Review (with Partial Evidence on the Omicron Variant)


Background. The need for COVID-19 vaccine booster shots is controversial. When boosters were under active review in the U.S. in 2021, Krause et al.[1] and others have argued that need for a COVID-19 booster for all adults has not been sufficiently established. In late 2021, U.S. regulators initially limited booster eligibility, waited months before allowing boosters for all adults, and even longer before recommending them, with public health officials sending mixed messages on booster value. We conduct a systematic review of COVID-19 vaccine effectiveness (VE) for primary and booster doses.

Methods. We conducted a systematic review of studies reporting COVID-19 vaccine efficacy or VE against four endpoints: any infection, symptomatic infection, hospitalization, and death for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S), waning VE, and booster VE, during the period of Delta-variant prevalence. We reviewed all studies appearing on PubMed over Jan. 1, 2021 through March 31, 2022, supplemented with our own knowledge of other sources. 63 studies met defined inclusion and exclusion criteria.

Findings. The mRNA vaccines (BNT162b2, mRNA1273) had very high initial VE but experienced significant VE waning after approximately six months, including against severe disease and mortality, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines outperformed the Ad26.CoV2.S and ChAdOx1-S viral vector vaccines. Booster doses reduced symptomatic infection, severe disease, and mortality. Initial evidence supports booster value against the Omicron variant.

Interpretation. Strong epidemiological evidence supports waning VE for primary COVID-19 vaccination and the value of a booster dose, roughly 6 months after initial vaccination. The emergence of the Omicron variant strengthens the value of booster doses to recipients. Boosters also provide spillover benefits to others, both vaccinated and unvaccinated, by reducing downstream infections; reducing shortage risk for scarce COVID treatments; and reducing hospital overload.