Is an Increased Risk of Developing Guillain-Barré Syndrome Associated with Seasonal Influenza Vaccination? A Systematic Review and Meta-Analysis

Abstract

While the weight of epidemiological evidence does not support a causal link with influenza vaccination evaluated over the last 30 years, Guillain-Barré syndrome (GBS) has been considered a vaccine-associated adverse event of interest since 1976. To investigate the existence of GBS risk after vaccination against seasonal influenza, a systematic review and meta-analysis have been conducted based on 22 eligible epidemiological studies from 1981 to 2019 reporting 26 effect sizes (ESs) in different influenza seasons. The primary result of our meta-analysis pointed to no risk of vaccine-associated GBS, as documented by a pooled ES of 1.15 (95% CI: 0.97-1.35). Conversely, an obvious high risk of GBS was observed in patients with previous influenza-like illness (ILI), as demonstrated by a pooled ES of 9.6 (95% CI: 4.0-23.0) resulting from a supplementary analysis. While the meta-analysis did not confirm the putative risk of vaccine-associated GBS suggested by many epidemiological studies, vaccination against seasonal influenza reduced the risk of developing ILI-associated GBS by about 88%. However, to obtain strong evidence, more epidemiological studies are warranted to establish a possible coincidence between vaccination and ILI prior to GBS onset.

Keywords: Guillain–Barré syndrome; influenza-like illness; vaccine against seasonal influenza; vaccine-associated autoimmune disease.

Figure 1

Flowchart.

Figure 2

Forest plot of effect sizes of Guillain–Barré syndrome after seasonal influenza vaccination; weights from random effects analysis (dashed line in point of pooled ES).

Figure 3

Forest plot of effect sizes of Guillain–Barré syndrome after influenza-like illness; weights from random effects analysis.