In a recent study published in the JAMA Network Open, researchers performed a systematic review and meta-analysis using secondary data from 40 published studies reporting time-varying, population-level coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) estimates against laboratory-confirmed infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, Omicron or Delta, and symptomatic disease.

The primary outcome for this secondary data analysis was to project VE variations since receipt of the last vaccine dose to improve comparability across all examined studies considering two SARS-CoV-2 variants, i.e., Omicron and Delta. Additionally, the researchers evaluated the VE half-life and waning rate of vaccine-induced immune protection.

Evaluation of Waning of SARS-CoV-2 Vaccine–Induced Immunity - A Systematic Review and Meta-analysis. Image Credit: SergeiShimanovich / ShutterstockEvaluation of Waning of SARS-CoV-2 Vaccine–Induced Immunity - A Systematic Review and Meta-analysis. Image Credit: SergeiShimanovich / Shutterstock


The threat of the resurgence of the COVID-19 pandemic raises the need to assess vaccine effectiveness (VE) waning rates at population levels against new, more lethal SARS-CoV-2 variants which have either emerged, e.g., Omicron or are yet-to-emerge.

About the study

In the present study, researchers extensively searched Web of Science and PubMed databases from their inception to October 19, 2022, to curate articles (including preprints) quantifying the waning of VE against infections by the Delta and Omicron variants stratified by the number of vaccine doses and time of their receipt regardless of the type of COVID-19 vaccine used.

The researchers used the Newcastle-Ottawa quality assessment scale to classify all included studies based on their risk of bias, with ≤3, 4-6, and ≥7 points indicating high, moderate, and low risk of bias, respectively. Further, two authors independently evaluated the methodologic quality of included studies to assign quality points.

They modeled VE as an exponential decay function of time to estimate the vaccine-induced protection. Then, they pooled modeled VE estimates using the inverse variance method at one, three, six, and nine months since the last vaccine dose administration. It helped the researchers compare the estimated protection conferred by different vaccine products against SARS-CoV-2 Delta and Omicron variants at four-time points stratified by vaccine timing and project VE beyond the final observation in the original studies.

Apart from two sensitivity analyses to explore potential biases in the analyzed data points, the team also conducted an additional analysis to investigate possible variations in VE between children/younger adults aged zero to 25 years and older adults aged ≥60 years.


The researchers identified 799 original articles and 149 reviews based on this review's eligibility criteria; however, the final dataset comprised only 40 studies. It amounted to 115 VE time series encompassing 454 time-varying data points for COVID-19 vaccines against Delta/Omicron. The VE of the primary vaccination series against symptomatic disease and laboratory-confirmed Omicron infection waned more rapidly than against the SARS-CoV-2 Delta variant.

The booster dose increased VE against Omicron by 125% initially, but it declined to below 30% within nine months. The projections also estimated that the mean VE against symptomatic disease fell below 20% within nine months. Against Omicron infections, estimated VEs did not vary between younger and older age groups. However, VE estimates were lower in both age groups against Omicron compared to Delta.

The VE half-life for symptomatic infection by Omicron vs. Delta was 87 and 316 days (95% CI), respectively. Nevertheless, again, VE rates waned at similar rates across all examined age groups.


The study showed that COVID-19 booster shots restored immune protection against symptomatic disease to levels comparable to the primary COVID-19 vaccination series. However, it also waned as rapidly against Omicron infection and symptomatic disease. These estimates could help evaluate the susceptibility of people based on their age, vaccination levels, and vaccine type to design more targeted vaccination programs in the future.

Journal reference:

  • Evaluation of Waning of SARS-CoV-2 Vaccine–Induced Immunity: A Systematic Review and Meta-analysis, Francesco Menegale, Mattia Manica, Agnese Zardini, Giorgio Guzzetta, Valentina Marziano, Valeria d'Andrea, Filippo Trentini, Marco Ajelli, Piero Poletti, Stefano Merler, JAMA Netw Open. 2023;6(5):e2310650. DOI: 10.1001/jamanetworkopen.2023.10650,

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