Background: Knowing whether COVID-19 vaccine effectiveness wanes is crucial for informing vaccine policy, such as the need for and timing of booster doses. We aimed to systematically review the evidence for the duration of protection of COVID-19 vaccines against various clinical outcomes, and to assess changes in the rates of breakthrough infection caused by the delta variant with increasing time since vaccination. Methods: This study was designed as a systematic review and meta-regression. We did a systematic review of preprint and peer-reviewed published article databases from June 17, 2021, to Dec 2, 2021. Randomised controlled trials of COVID-19 vaccine efficacy and observational studies of COVID-19 vaccine effectiveness were eligible. Studies with vaccine efficacy or effectiveness estimates at discrete time intervals of people who had received full vaccination and that met predefined screening criteria underwent full-text review. We used random-effects meta-regression to estimate the average change in vaccine efficacy or effectiveness 1–6 months after full vaccination. Findings: Of 13 744 studies screened, 310 underwent full-text review, and 18 studies were included (all studies were carried out before the omicron variant began to circulate widely). Risk of bias, established using the risk of bias 2 tool for randomised controlled trials or the risk of bias in non-randomised studies of interventions tool was low for three studies, moderate for eight studies, and serious for seven studies. We included 78 vaccine-specific vaccine efficacy or effectiveness evaluations (Pfizer–BioNTech-Comirnaty, n=38; Moderna-mRNA-1273, n=23; Janssen-Ad26.COV2.S, n=9; and AstraZeneca-Vaxzevria, n=8). On average, vaccine efficacy or effectiveness against SARS-CoV-2 infection decreased from 1 month to 6 months after full vaccination by 21·0 percentage points (95% CI 13·9–29·8) among people of all ages and 20·7 percentage points (10·2–36·6) among older people (as defined by each study, who were at least 50 years old). For symptomatic COVID-19 disease, vaccine efficacy or effectiveness decreased by 24·9 percentage points (95% CI 13·4–41·6) in people of all ages and 32·0 percentage points (11·0–69·0) in older people. For severe COVID-19 disease, vaccine efficacy or effectiveness decreased by 10·0 percentage points (95% CI 6·1–15·4) in people of all ages and 9·5 percentage points (5·7–14·6) in older people. Most (81%) vaccine efficacy or effectiveness estimates against severe disease remained greater than 70% over time. Interpretation: COVID-19 vaccine efficacy or effectiveness against severe disease remained high, although it did decrease somewhat by 6 months after full vaccination. By contrast, vaccine efficacy or effectiveness against infection and symptomatic disease decreased approximately 20–30 percentage points by 6 months. The decrease in vaccine efficacy or effectiveness is likely caused by, at least in part, waning immunity, although an effect of bias cannot be ruled out. Evaluating vaccine efficacy or effectiveness beyond 6 months will be crucial for updating COVID-19 vaccine policy. Funding: Coalition for Epidemic Preparedness Innovations.
Bibliographical noteFunding Information:
MMH reports research grants from WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), the Asian Development Bank (ADB), the Bill & Melinda Gates Foundation, and Pfizer (all paid to the institution). RA reports a contract from the US Centers for Disease Control and Prevention, a grant from the Chile Ministry of Science, and consulting fees from the Mayo Clinic and Chile Ministry of Health. YG reports research grants from the United States-Israel Binational Science Foundation (BSF) and the Israel Science Foundation. MJG reports research grants from the South African Medical Research Council and the Gates Foundation (all paid to the institution) and participation on a data safety monitoring board for a study on the effectiveness of COVID-19 vaccination against SARS-CoV-2-associated hospitalisation and death. AH reports research grants from United States-Israel Binational Science Foundation. KLO'B serves as the Secretariat for the WHO Strategic Advisory Group of Experts on Immunisation. MDK reports research grants from WHO, CEPI, ADB, and Pfizer (all paid to the institution) and consultancy fees from Merck.
We want to acknowledge the important contribution of the following individuals in being able to undertake this analysis: Anurima Baidya, Karoline Walter, Siqi Li, Hanane Issa, Parisa ShamaeiZadeh, and Marely Jurgensmeyer. We thank Dan-Yu Lin from the University of North Carolina, Chapel Hill, NC, USA for providing exact vaccine effectiveness estimates and CIs for his study. We also thank Alison L Hill and Yu Bin Na for their technical assistance in producing the figures.
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
ASJC Scopus subject areas
- Medicine (all)