Case reports describe 'unusual' Guillain-Barre variants following COVID-19 vaccination
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Two studies published in Annals of Neurology reported small clusters “of an unusual variant of Guillain-Barre syndrome” following receipt of a COVID-19 vaccine, according to a press release from the American Neurological Association.
The 11 cases of Guillain-Barre syndrome occurred among individuals who received the vaccine 10 to 22 days prior to symptom onset, the press release noted. While the rate of Guillain-Barre syndrome in these clusters was approximately four to 10 times higher than the anticipated baseline frequency, the “unusually severe” bilateral facial weakness and timing in relation to receipt of the vaccine “made these occurrences stand out.”
In the first report, Christopher Martin Allen, of the department of neurology at Nottingham University Hospitals NHS Trust and the University of Nottingham School of Medicine, and colleagues reported four cases of a Guillain-Barre variant presenting as bifacial weakness with paresthesias. All cases occurred after the first dose of the AstraZeneca vaccine and developed within 10 days of each other, with symptom onset 11 to 22 days after the vaccine. The cases included a white man aged 54 years with no relevant medical history; a British-Iranian man aged 20 years with a medical history of ulcerative colitis; a white man aged 57 years with a medical history of asthma and osteoarthritis, as well as bilateral knee replacements and regular use of steroid and salbutamol inhalers, loratadine, omeprazole and tamsulosin; and a white man aged 55 years with a medical history of hypertension and regular use of amlodipine and lisinopril.
All patients presented with profound bifacial weakness and normal facial sensation. All patients also tested negative for COVID-19 infection. Patients received IV immunoglobulin, oral steroids or no treatment.
Allen and colleagues noted that, while the patients described in their case report experienced neurological symptoms “temporally” associated with receipt of the vaccine, “causality cannot be assumed.” The findings demonstrate the need for “robust post-vaccination surveillance,” according to the researchers. Allen and colleagues also noted that “SARS-CoV-2 vaccines are very safe.”
In the second report, Boby Varkey Maramattom, MD, DM, FRCP, of the department of neurology at Aster Medcity in India, and colleagues reviewed seven cases of severe Guillain-Barre syndrome that developed within 2 weeks of the first COVID-19 vaccine. Researchers identified these cases during a 4-week period between mid-March and mid-April of 2021, by which point approximately 1.5 million individuals in three regions of Kerala, India had been vaccinated against COVID-19. More than 80% of those individuals — or 1.2 million people — received the ChAdOx1-S/nCoV-19 vaccine, according to Maramattom and colleagues.
The rate of Guillain-Barre syndrome observed in this report “was 1.4- to 10-fold higher than that expected in this period for a population of this magnitude,” according to the researchers. Moreover, the rate at which bilateral facial weakness occurred, which generally develops in less than 20% of cases of Guillain-Barre syndrome, indicated “a pattern associated with the vaccination,” Maramattom and colleagues wrote.
More than half of the cases in India (n = 4) involved women aged between 40 and 70 years, most of whom (n = 3) required mechanical ventilation. All reported cases of Guillain-Barre syndrome in India involved bilateral facial paresis, according to Maramattom and colleagues, which generally develops in less than 20% of unselected cases. Other cranial neuropathies, including abducens palsy and trigeminal sensory nerve involvement, developed in four patients (57%), which are uncommon among reports of Guillain-Barre syndrome in India, as it occurs in less than 5% of cases, the researchers noted.
Maramattom and colleagues emphasized that a link between COVID-19 infection and Guillain-Barre syndrome has not been determined, making an increase in the rate of Guillain-Barre syndrome following COVID-19 vaccination “unlikely.” They also noted that the benefits of vaccination against COVID-19 “substantially outweigh the risk of this relatively rare outcome,” according to the case report. However, they stated that clinicians should be aware of this potential adverse event following COVID-19 vaccination, as most patients in their report required mechanical ventilatory support.
In a related editorial, the neuromuscular and statistical editors for Annals of Neurology detailed “an additional similar case” in a patient in the United States who received the Johnson & Johnson COVID-19 vaccine, according to the press release. The editors also examined cases of severe bilateral facial weakness with or without Guillain-Barre syndrome reported to the U.S.-based Vaccine Adverse Events Reporting System. More than half of the cases of Guillain-Barre syndrome with bilateral facial weakness in the United States (n = 5 of 8 cases) occurred in people who received the Johnson & Johnson vaccine, while only 3 such cases were observed in “the much larger number” of people who received the Pfizer and Moderna vaccines.
These findings indicated that, like the cases of thrombocytopenic thrombosis reported with adenovirus-based vaccines, Guillain-Barre syndrome with bilateral facial weakness represents “a rare, but specific complication,” according to the press release from the ANA. The release also noted that it is important for clinicians to be aware of this complication “so that they can identify it and promptly treat it with standard therapy,” such as IV Ig.
References:
Allen CM, et al. Ann Neurol. 2021;doi:10.1002/ana.26144.
American Neurological Association. Guillain-Barré Syndrome variant occurring after COVID-19 vaccines according to two new Annals of Neurology articles. Available at: https://myana.org/publications/news/guillain-barr%C3%A9-syndrome-variant-occurring-after-covid-19-vaccines-according-two. Accessed June 17, 2021.
Maramattom BV, et al. Ann Neurol. 2021;doi:10.1002/ana.26143.
Perspective
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Dhanashri P. Miskin, MD
Guillain-Barré syndrome is an acute polyneuropathy that is often preceded by infection or, occasionally, vaccination. These reports both highlight a cluster of cases of a serious Guillain-Barré syndrome variant occurring within 2 to 3 weeks of the first dose of the AstraZeneca COVID-19 vaccine. Guillain-Barré syndrome, and its variants, have been previously described in association with SARS-CoV-2 infection. However, an analysis of prior post-vaccination periods, such as the years after the swine flu and H1N1, have not revealed an increased incidence of post-vaccination Guillain-Barré syndrome. Therefore, although these clusters of patients developed Guillain-Barré syndrome temporally associated with vaccination, causality cannot be assumed. The benefits of vaccination substantially outweigh the risk for this relatively rare outcome and robust post-vaccination surveillance programs remain essential to definitively establish causality.
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