Statement on Vaccine Safety Covid subcommittee on reports of Guillain-Barré Syndrome following adenovirus vector Covid vaccines

On 13 and 20 July 2021, the COVID-19 subcommittee of the WHO Global Advisory Committee on Vaccine Safety (GACVS) met virtually to discuss rare reports of Guillain-Barré Syndrome (GBS) following vaccination with the Janssen and AstraZeneca COVID-19 vaccines. Both vaccines use an adenovirus platform as their backbone.

GBS is a rare immune system disorder that results in muscle weakness, pain or numbness, and, in more severe cases, paralysis. GBS could result from different causes, including infections, and occurs more frequently in males and persons over 50 years old. Cases may occur coincidentally following vaccination. For example, rare cases of GBS have been observed following seasonal influenza vaccines and vaccines to protect against shingles, but it is not known if the vaccines cause GBS (1, 2). A systematic review and meta-analysis in 2011 estimated the background incidence for GBS as 0.8-1.9/100 000 in Europe and Northern America (3)

For Vaxzevria (the AstraZeneca COVID-19 vaccine manufactured in Europe), the European Medicines Agency (EMA)’s Pharmacovigilance Risk Assessment Committee (PRAC) issued a statement on 9 July recommending the addition of a warning to raise awareness of GBS following vaccination, although they could not confirm nor rule out an association with the vaccine (4). A total of 227 cases of GBS had been reported from the EU/EEA to EMA with Vaxzevria by 27 June 2021, while around 51.4 million doses of Vaxzevria had been given to people in the EU/EEA by 20 June 2021(5).

For Johnson & Johnson (Janssen) COVID-19 vaccine, the US FDA announced on 13 July a revision to the vaccine recipient and vaccination provider fact sheets to include information pertaining to an observed increased risk of GBS following vaccination (6). The US Advisory Committee on Immunization Practices (ACIP) reviewed the information at its meeting on 22 July and noted that as of 30 June, 100 cases of GBS had been reported in the Vaccine Adverse Events Reporting System, the US nationwide passive surveillance system, with approximately 12.2 million of doses of the Janssen vaccine.

Similarly, on 22 July the EMA issued a statement that GBS will be listed as a very rare side effect of COVID-19 Vaccine Janssen and that a warning will be included in the product information to raise awareness among healthcare professionals and people taking the vaccine (7).

The GACVS sub-committee has reviewed the statements and measures put in place by the US FDA and the EMA. The sub-committee also reviewed preliminary data from Vigibase, the WHO global database of Individual Case Safety Reports (ICSR), which indicated 164 unconfirmed cases of GBS in countries outside the EEA and US for Astrazeneca (Vaxzevria and Covishield) vaccines, of which 14 unconfirmed GBS cases were reported (within 14 days) following 19.5 million doses of (different brands of) the Astrazeneca vaccines from Central and South American countries.

Based on a careful scientific review of the available information, the GACVS subcommittee came to the following conclusions and recommendations:

  • Rare cases of GBS have been reported following vaccinations with adenovirus vector COVID-19 vaccines.
  • Increased reports of GBS have not been observed following mRNA COVID-19 vaccines.
  • More rigorous studies using alternative data sources and robust study designs, and comparison of vaccinated and unvaccinated populations would be needed, to fully assess the significance of these events. The GACVS subcommittee will continue to monitor GBS and any other safety concerns and review further as more data become available.
  • Healthcare professionals should monitor for and report all adverse events including GBS. Countries should continue to collate detailed data on cases. Ideally, data should be gathered through active surveillance within hospitals to provide a more thorough understanding of this safety issue. The WHO COVID-19 vaccine safety surveillance manual provides guidance to countries on the safety monitoring and adverse events data sharing for COVID-19 vaccines(8).
  • Individuals receiving Janssen or AstraZeneca COVID-19 vaccines should be alert to signs and symptoms of GBS and should seek immediate medical attention if they develop weakness/tingling and paralysis in the extremities that may progress to other parts of the body including the chest and face. Symptoms may include difficulty in walking; difficulty with facial movements; double vision or inability to move eyes; or difficulty controlling bladder or bowel functions. Healthcare professionals should be aware of these signs and symptoms to allow for early diagnosis and treatment. Most people fully recover from GBS.
  • Though countries should always consider their individual pandemic circumstances and benefit-risk profiles, overall the subcommittee concludes that the potential benefits of both the Janssen and AstraZeneca COVID-19 vaccines continue to outweigh any potential risk of GBS, particularly given the increase in the more transmissible Delta (B.1.617.2) variant.

The GACVS COVID-19 subcommittee will continue to review the safety data from all COVID-19 vaccines and will update any advice as necessary. Open, transparent, and evidence-based communication about the potential benefits and risks to recipients and the community is essential to maintain trust. WHO is carefully monitoring the rollout of all COVID-19 vaccines and will continue to work closely with countries to manage potential risks, and to use science and data to drive response and recommendations.

References:

(1) Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009; 32(4): 309-23. doi: 10.2165/00002018-200932040-00005. PMID: 19388722.

(2) Miller ER, McNeil MM, Moro PL, Duffy J, Su JR. The reporting sensitivity of the Vaccine Adverse Event Reporting System (VAERS) for anaphylaxis and for Guillain-Barré syndrome. Vaccine. 2020; 38(47):7458-7463. doi: 10.1016/j.vaccine.2020.09.072. Epub 2020 Oct 7. PMID: 33039207.

(3) Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population incidence of Guillain – Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology, 2011; 36: 123 – 33. doi:10.1159/000324710. PMID: 21422765.

(4) Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 5-8 July 2021.European Medicines Agency (EMA); 9 July 2021 (https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-5-8-july-2021)

(5) COVID-19 vaccine safety update VAXZEVRIA AstraZeneca AB Public Statemen. European Medicines Agency (EMA); 14 July 2021 (https://www.ema.europa.eu/en/documents/covid-19-vaccine-safety-update/covid-19-vaccine-safety-update-vaxzevria-previously-covid-19-vaccine-astrazeneca-14-july-2021_en.pdf)

(6) Coronavirus (COVID-19) update. Food and Drug Administration (FDA); July 13 2021 (https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-july-13-2021)

(7) COVID-19 Vaccine Janssen: Guillain-Barré syndrome listed as a very rare side effect. European Medicines Agency (EMA); 22 July 2021 (https://www.ema.europa.eu/en/news/covid-19-vaccine-janssen-guillain-barre-syndrome-listed-very-rare-side-effect)

(8) Covid-19 vaccines: safety surveillance manual. Geneva: World Health Organization (WHO); 22 December 2020 ( https://www.who.int/publications/i/item/10665338400 )

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