Primary and Booster Vaccines Against SARS-CoV-2 Lose Effectiveness Quickly

Baseline vaccine effectiveness was significantly lower for the Omicron variant of SARS-CoV-2 than for other variants.

Primary series and booster vaccines against SARS-CoV-2 infections, hospitalizations, and mortality lose effectiveness in 3 to 8 months, according to meta-analysis findings published in The Lancet Respiratory Medicine.

Investigators in Canada sought to assess the change over time in primary series COVID-19 vaccine effectiveness against COVID-19 infections, hospitalizations, and mortality. Additionally, the researchers assessed the effectiveness of a primary series plus a single booster dose over a shorter time after the booster, and vaccine effectiveness against the Omicron variant for infections, hospitalizations, and mortality.

The investigators conducted a rapid living systematic evidence synthesis and meta-analysis, using data through November 2022 from EMBASE and the US National Institutes of Health’s iSearch COVID-19 Portfolio, supplemented by manual searches of COVID-19-specific sources, including the US Department of Veterans Affairs’ Evidence Synthesis Program. Investigators included studies in English or French that reported vaccine effectiveness immediately and at least 112 days following a primary vaccine series or at least 84 days following a booster dose.

Among all studies, 78% were published in peer-reviewed journals and 22% were preprints. Samples were from 23 countries, with 84% reporting primary series data and 25% reporting booster-dose data. The researchers noted overall risk of bias was serious for most studies (due to lack of adjustments for significant COVID-19 prognostic factors), with 19% of studies having moderate risk, 4% low risk, and 76% serious risk.

Reviewers included observational studies and controlled trials that reported vaccine effectiveness data that compared fully vaccinated participants with unvaccinated participants in adults or a predominantly adult general population. Fully vaccinated participants received 2 doses of BNT162b2, mRNA-1273, or ChAdOxAZD1222, or 1 dose of Ad26.COV2.S. Booster vaccine effectiveness participants received a full primary series and an additional dose of a Canadian-licensed COVID-19 vaccine.

From more than 16,000 screened records, investigators extracted data from 68 studies. They found vaccine effectiveness of the primary series for infections caused by any SARS-CoV-2 strain reduced from 83% (95% CI, 80-86) at baseline (14-42 days) to 62% (95% CI, 53-69) by 112 to 139 days.

For hospitalizations, vaccine effectiveness at baseline was 92% (95% CI, 88-94) and reduced to 79% (95% CI, 65-87) at 224 to 251 days. For mortality, vaccine effectiveness at baseline was 91% (95% CI, 85-95) and reduced to 86% (95% CI, 73-93) at 168 to 195 days.

Estimated vaccine effectiveness at baseline was lower for the Omicron variant vs other variants for infections, hospitalizations, and mortality. Subsequent reductions in vaccine effectiveness occurred at similar rates across variants.

Our analyses indicate that vaccine effectiveness reduces over time for both primary series and booster doses for preventing SARS-CoV-2 infections, hospitalizations, and mortality, a finding which is most pronounced for infections.

Investigators found pooled booster dose data covered mostly Omicron studies. Vaccine effectiveness at baseline was 70% against infections and 89% against hospitalizations. At 112 days or later, effectiveness reduced to 43% against infections and 71% against hospitalizations. There was insufficient data to report on booster effectiveness against mortality. Specifically for the Omicron variant, estimates of baseline vaccine effectiveness were not adequate for infections (61%) or hospitalizations (71%). Investigators found similar large reductions in vaccine effectiveness for infections and small reductions for hospitalizations against the Omicron variant vs the general data on any variant.

Among the vaccines included in the analysis, World Health Organization (WHO) criteria for vaccine effectiveness regarding adequate protection were met at baseline but not subsequently. Analysis of vaccine effectiveness for 7 discreet follow-up periods between 112 days to 307 days post vaccination revealed a statistical reduction in vaccine effectiveness for all follow-up periods, such that WHO criteria for adequate protection levels were not met after 112 days post vaccination.

Review and meta-analysis limitations include the design nature of the rapid review process; the inclusion of only the 4 COVID-19 vaccines licensed in Canada, limiting generalizability to populations vaccinated with inactivated virus vaccines; inclusion of symptomatic and asymptomatic data for which vaccine effectiveness may not be the same; and the lack of accounting for the effect of hybrid immunity. Additional limitations include the high risk of bias among included studies and significant heterogeneity, which made predicting vaccine effectiveness difficult.

“Our analyses indicate that vaccine effectiveness reduces over time for both primary series and booster doses for preventing SARS-CoV-2 infections, hospitalizations, and mortality, a finding which is most pronounced for infections,” investigators concluded. “We found similar reductions with the omicron variant, except that baseline levels of vaccine effectiveness were noticeably lower and did not meet the WHO criteria for an adequate vaccine response,” the investigators added.

Disclosure: 1 study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Wu N, Joyal-Desmarais K, Ribeiro PAB, et al. Long-term effectiveness of COVID-19 vaccines against infections, hospitalizations, and mortality in adults: Findings from a rapid living systematic evidence synthesis and meta-analysis up to December, 2022. Lancet Respir Med. Published online February 10, 2023. doi:10.1016/S2213-2600(23)00015-2