SARS-CoV-2 vaccine effectiveness against infection, symptomatic and severe COVID-19: a systematic review and meta-analysis

Abstract

Background: The temporal evolution of SARS-CoV-2 vaccine efficacy and effectiveness (VE) against infection, symptomatic, and severe COVID-19 is incompletely defined. The temporal evolution of VE could be dependent on age, vaccine types, variants of the virus, and geographic region. We aimed to conduct a systematic review and meta-analysis of the duration of VE against SARS-CoV-2 infection, symptomatic COVID-19 and severe COVID-19.

Methods: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched and studies were selected. Independent reviewers selected randomized controlled trials and cohort studies with the outcome of interest. Independent reviewers extracted data, and assessed the risk of bias. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. Primary outcomes included VE as a function of time against SARS-CoV-2 infection, symptomatic and severe COVID-19.

Results: Eighteen studies were included representing nearly 7 million individuals. VE against all SARS-CoV-2 infections declined from 83% in the first month after completion of the original vaccination series to 22% at 5 months or longer. Similarly, VE against symptomatic COVID-19 declined from 94% in the first month after vaccination to 64% by the fourth month. VE against severe COVID-19 for all ages was high overall, with the level being 90% (95% CI, 87-92%) at five months or longer after being fully vaccinated. VE against severe COVID-19 was lower in individuals ≥ 65 years and those who received Ad26.COV2.S.

Conclusions: VE against SARS-CoV-2 infection and symptomatic COVID-19 waned over time but protection remained high against severe COVID-19. These data can be used to inform public health decisions around the need for booster vaccination.

Keywords: COVID-19; Vaccine effectiveness; Waning immunity.

Fig. 1

PRISMA 2020 flow diagram for systematic reviews and meta-analysis of vaccine efficacy/effectiveness (VE) against SARS-CoV-2 infection, symptomatic and severe COVID-19

Fig. 2

Scatterplot of Vaccine efficacy/effectiveness (VE) % against SARS-CoV-2 infection (A), symptomatic COVID-19 (B) and severe COVID-19 (C) plotted according to time from the second dose for mRNA vaccines and one dose of adenovirus vector-based vaccine. Each circle represents a study, and its size is proportional to the study’s sample size and annotated according to vaccine type. Effectiveness estimates include studies that estimated efficacy. The red line represents the fitted mean VE using the natural cubic spline model. The horizontal blue line represents the 50% protection level stipulated by the WHO [7]

Fig. 3

Forest plot of vaccine efficacy/effectiveness (VE) against SARS-CoV-2 infection stratified by months since full vaccination. Mean VE values represent the mean vaccine protection expressed as percentage. Blue squares and their corresponding lines are the point estimates and 95% confidence intervals (95% CI). Maroon diamonds represent the pooled VE estimates for each month (width denotes 95% CI). Effectiveness estimates include studies that estimated efficacy

Fig. 4

Scatterplot of Vaccine efficacy/effectiveness (VE) against infection and severe disease stratified by age. VE against infection in subjects < 65 years (A) ≥ 65 years (B), against severe COVID-19 disease in those < 65 years (C) and ≥ 65 years (D) plotted according to time since full vaccination (14 days after second dose for mRNA vaccines and after one dose of adenovirus vector-based vaccine). Each circle represents a study, and its size is proportional to the study’s sample size and annotated according to vaccine type. The red line represents the fitted mean VE using the natural cubic spline model. The horizontal blue line represents the 50% protection level stipulated by the WHO [7]

Fig. 5

Forest plot of vaccine efficacy/effectiveness (VE) against symptomatic COVID-19 stratified by months since full vaccination. Mean VE values represent the mean vaccine protection expressed as a percentage. Blue squares and their corresponding lines are the point estimates and 95% confidence intervals (95% CI). Maroon diamonds represent the pooled VE estimates for each month (width denotes 95% CI)

Fig. 6

Forest plot of vaccine efficacy/effectiveness against severe COVID-19 stratified by months since full vaccination. Mean VE values represent the mean expressed as a percentage. Blue squares and their corresponding lines are the point estimates and 95% confidence intervals (95% CI). Maroon diamonds represent the pooled VE estimates for each month (width denotes 95% CI)