Effectiveness of Vaccination against SARS-CoV-2 Infection in the Pre-Delta Era: A Systematic Review and Meta-Analysis

Abstract

(1) Background: The objective of this study was to assess the effectiveness of SARS-CoV-2 vaccines in terms of prevention of disease and transmission in the pre-Delta era. The evaluation was narrowed to two mRNA vaccines and two modified adenovirus-vectored vaccines. (2) Methods: The overall risk of any SARS-CoV-2 infection confirmed by positive real-time Polymerase Chain Reaction (PCR) test was estimated in partially and fully vaccinated individuals. The evidence synthesis was pursued through a random-effects meta-analysis. The effect size was expressed as relative risk (RR) and RRR (RR reduction) of SARS-CoV-2 infection following vaccination. Heterogeneity was investigated through a between-study heterogeneity analysis and a subgroup meta-analysis. (3) Results: The systematic review identified 27 studies eligible for the quantitative synthesis. Partially vaccinated individuals presented a RRR = 73% (95%CI = 59-83%) for positive SARS-CoV-2 PCR (RR = 0.27) and a RRR=79% (95%CI = 30-93%) for symptomatic SARS-CoV-2 PCR (RR = 0.21). Fully vaccinated individuals showed a RRR = 94% (95%CI = 88-98%) for SARS-CoV-2 positive PCR (RR = 0.06) compared to unvaccinated individuals. The full BNT162b2 vaccination protocol achieved a RRR = 84-94% against any SARS-CoV-2-positive PCR and a RRR = 68-84% against symptomatic positive PCR. (4) Conclusions: The meta-analysis results suggest that full vaccination might block transmission. In particular, the risk of SARS-CoV-2 infection appeared higher for non-B.1.1.7 variants and individuals aged ≥69 years. Considering the high level of heterogeneity, these findings must be taken with caution. Further research on SARS-CoV-2 vaccine effectiveness against emerging SARS-CoV-2 variants is encouraged.

Keywords: SARS-CoV-2 infection; coronavirus disease 2019; vaccine effectiveness.

Figure 1

Experimental group follow-up: the dashed lines following the first and the second dose administration represent the induction time. The solid lines display the follow-up period considered in the analysis. Cases occurred within 14 days after the first dose uptake were not included. Cases occurred within one week from the second dose administration were attributed to the first dose effect. The length of the induction time for the Ad26.COV2.S vaccine was set at 14 days after the single dose administration (details in the text).

Figure 2

Forest plot, partially vaccinated. Any positive SARS-CoV-2 PCR RR (95%-CI) ≥ 14 days from first dose uptake (a). Forest plot, fully vaccinated. Any positive PCR RR (95%-CI) ≥ 7 days from full vaccination (b). Forest plot, any positive PCR RR (95%-CI), ≥14 days from vaccination with at least one dose. IV method (c).

Figure 2

Forest plot, partially vaccinated. Any positive SARS-CoV-2 PCR RR (95%-CI) ≥ 14 days from first dose uptake (a). Forest plot, fully vaccinated. Any positive PCR RR (95%-CI) ≥ 7 days from full vaccination (b). Forest plot, any positive PCR RR (95%-CI), ≥14 days from vaccination with at least one dose. IV method (c).

Figure 3

Forest plot, symptomatic positive SARS-CoV-2 PCR RR (95%-CI) ≥ 14 days from first dose uptake (a). Forest plot, fully vaccinated. Symptomatic positive PCR RR (95%-CI) ≥ 7 days from full vaccination (b). IV method.

Figure 4

L’Abbè plots. Partially vaccinated, any positive SARS-CoV-2 PCR RR ≥ 14 days from first SARS-CoV-2 dose administration (a). Fully vaccinated, any positive PCR RR, ≥7 days from full vaccination (b). At least one dose, any positive PCR RR ≥ 14 days from vaccination with first dose (c). Partially vaccinated, symptomatic positive PCR RR ≥ 14 days from first dose administration (d). Fully vaccinated, symptomatic positive SARS-CoV-2 PCR RR ≥ 7 days from full vaccination (e). The sizes of the plotted circles are proportional to the precision of the studies. The dashed lines mark the overall estimate of the log risk for RE (light) and FE (bold). The further the circle from the line of no effect, the greater the difference of event rates between intervention and control arms.