Duration of Effectiveness of Vaccines Against SARS-CoV-2 Infection and COVID-19 Disease: Results of a Systematic Review and Meta-Regression

Abstract

Background: Knowing whether and to what extent COVID-19 vaccine effectiveness wanes is critical to informing vaccine policy, such as the need for and timing of booster doses. Methods: We performed a systematic review from June 17 to October 27, 2021, using a structured search strategy of multiple databases. Studies with vaccine efficacy or effectiveness (VE) estimates for any WHO Emergency-Use-Listed COVID-19 vaccine at discrete time intervals after full vaccination and meeting pre-defined screening criteria underwent full-text review and risk of bias assessment. Random effects meta-regression was used to estimate the average change in VE from one to six months after full vaccination. Findings: Of 9,261 studies screened, 217 underwent full text review, and 14 were included in analyses. Vaccines evaluated were Pfizer/BioNTech-Comirnaty (n=11), Moderna-mRNA-1273 (n=8), Janssen-Ad26.COV2.S (n=3), and AstraZeneca-Vaxzevria (n=2). On average, VE against SARS-CoV-2 infection decreased between 1 and 6 months after full vaccination by 18·5 percentage points (95% CI 8·4-33·4, p=0·0006) among persons of all ages and 19·9 percentage points (95% CI 9·2-36·7, p=0·0007) among older persons; for symptomatic COVID-19 disease, VE decreased by 25·4 (95% CI 13·7-42·5) and 32·0 percentage points (95% CI 11·0-69·0), respectively; and for severe COVID-19 disease, VE decreased by 8·0 (95% CI 3·6-15·2) and 9·7 percentage points (95% CI 5·9-14·7), respectively. The majority of VE estimates against severe disease remained over 70% for all time points. Interpretation: COVID-19 vaccine efficacy or effectiveness against COVID-19 severe disease remained high (>70%) in most studies in the six months after full vaccination, although it did decrease some (on average, 8-10 percentage points) between one and six months after full vaccination. In contrast, VE against SARS-CoV-2 infection and symptomatic COVID-19 disease decreased approximately 20-30 percentage points during the six months after vaccination. The decrease in VE is likely due, at least in part, to waning immunity, although we cannot rule out the effect of bias. Continued follow-up of VE beyond six months is critical for updating COVID-19 vaccine policy. . Funding Information: Coalition for Epidemic Preparedness Innovations (CEPI)Declaration of Interests: MMH reports research grants from World Health Organization (WHO, Coalition for Epidemic Preparedness Innovations (CEPI), Asian Development Bank (ADB), Bill & Melinda Gates Foundation (BMGF), and Pfizer (all paid to the institution). RA reports a contract from the United States Centers for Disease Control and Prevention, a grant from the Chile Ministry of Science, and consulting fees from Mayo Clinic and Chile Ministry of Health. YG reports research grants from the United States-Israel Binational Science Foundation (BSF) and Israel Science Foundation. MJG reports research grants from South African Medical Research Council and BMGF (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 hospitalization and death. AH reports research grants from United States-Israel BSF. KLO serves as the Secretariat for the WHO Strategic Advisory Group of Experts on Immunization. MDK reports research grants from WHO, CEPI, ADB, and Pfizer (all paid to the institution) and consultancy fees from Merck. All other authors have nothing to declare.