What is the incidence of Guillain-Barré syndrome (GBS) after COVID-19 vaccination versus COVID-19 infection?

Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination vs. COVID-19 Infection

COVID-19 infection carries approximately 3.35 times higher risk of developing Guillain-Barré syndrome compared to the background rate, while most COVID-19 vaccines (particularly mRNA vaccines) show no increased risk, with the exception of adenoviral vector vaccines which show a modest increased risk. 1

Comparative Risk Analysis

COVID-19 Infection

• SARS-CoV-2 infection significantly increases GBS risk with a relative incidence of 3.35 (95% CI: 1.83-6.11) 1
• This represents a substantially higher risk than most COVID-19 vaccines

COVID-19 Vaccines by Type

Adenoviral Vector Vaccines

• ChAdOx1-S/nCoV-19 (Vaxzevria/Covishield): Increased risk with relative incidence of 3.10 (95% CI: 1.12-8.62) 1
• Ad.26.COV2.S (Janssen): Elevated incidence rate of 32.4 per 100,000 person-years in the 1-21 days post-vaccination 2
  • Adjusted relative risk of 20.56 (95% CI: 6.94-64.66) when compared directly to mRNA vaccines 2

mRNA Vaccines

• BNT162b2 (Pfizer-BioNTech): Decreased risk with relative incidence of 0.48 (95% CI: 0.27-0.85) 1
• Overall mRNA vaccines: Unadjusted incidence rate of only 1.3 per 100,000 person-years in the 1-21 days post-vaccination 2
• No significant increased risk compared to background rates 2, 1

Inactivated Vaccines

• CoronaVac/Sinovac: Significantly decreased risk with relative incidence of 0.04 (95% CI: 0.00-0.61) 1

Clinical Characteristics of Vaccine-Associated GBS

• Mean age: 54-58 years 3, 4
• Gender distribution: 56% male 3
• Onset timing:
  • Average of 7-14.4 days after vaccination 3, 4
  • Range: 3-30 days post-vaccination 5
• Most cases occur after first dose 3
• Typical presentation: Symmetric weakness and paresthesia 5
• CSF findings: Albuminocytological dissociation 3, 5
• Electromyography: Predominantly demyelinating pattern 3

Historical Context

For perspective, the risk of GBS following influenza vaccination is estimated at approximately 1 additional case per 1,000 persons vaccinated 6. This is substantially lower than the risk of GBS following actual influenza infection, for which there is substantial evidence of association 6.

Clinical Implications

1. The risk of GBS from COVID-19 infection exceeds the risk from most COVID-19 vaccines, particularly mRNA vaccines
2. Adenoviral vector vaccines carry a modestly increased risk of GBS compared to background rates
3. mRNA vaccines show no increased risk and may even have a protective effect against GBS
4. Healthcare providers should be vigilant for GBS symptoms 5-30 days after vaccination, particularly:
   • New severe headaches
   • Unexplained pinprick bruising or bleeding
   • Shortness of breath, leg swelling
   • Persistent abdominal pain 6

Conclusion

When considering the risk-benefit profile, the risk of developing GBS from COVID-19 infection (3.35 times higher than background) substantially outweighs the risk from mRNA COVID-19 vaccines (which show no increased risk). Even for adenoviral vector vaccines, which do show some increased risk, the absolute risk remains very low compared to the protection offered against severe COVID-19 disease and its complications.