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Guillain-Barré syndrome, a rare peripheral nerve disorder that can occur after certain types of viral and bacterial infections, has not to date been definitively linked to infection by SARS-CoV-2 or with vaccination against the virus, despite surveillance searching for such associations.

Spikes in Guillain-Barré syndrome incidence have previously, but rarely, high igf 1 levels low testosterone been associated with outbreaks of other viral diseases, including Zika, but not with vaccination, except for a 1976-1977 swine influenza vaccine campaign in the United States that was seen associated with a slight elevation in risk, and was halted when that risk became known. Since then, all sorts of vaccines in the European Union and United States have come with warnings about Guillain-Barré syndrome in their package inserts — a fact that some Guillain-Barré syndrome experts lament as perpetuating the notion that vaccines cause Guillain-Barré syndrome.

Epidemiologic studies in the United Kingdom and Singapore did not detect increases in Guillain-Barré syndrome incidence during the COVID-19 pandemic. And as mass vaccination against COVID-19 got underway early this year, experts cautioned against the temptation to attribute incident Guillain-Barré syndrome cases following vaccination to SARS-CoV-2 without careful statistical and epidemiological analysis.

Until now reports of Guillain-Barré syndrome have been scant: clinical trials of a viral vector vaccine developed by Johnson & Johnson saw one in the placebo arm and another in the intervention arm, while another case was reported following administration of a Pfizer mRNA SARS-Cov-2 vaccine.

Recent Case Reports

Two reports published this month in the Annals of Neurology — one from India and one from the United Kingdom — describe multiple cases of Guillain-Barré syndrome following a first dose of the ChAdOx1-S/nCoV-19, (Covishield, AstraZeneca) vector vaccine. None of the patients had evidence of current SARS-CoV-2 infection.

From India, Boby V. Maramattom, MD, of Aster Medcity in Kochi, India, and colleagues reported on seven severe cases of Guillain-Barré syndrome occurring between 10 and 14 days after a first dose of the AstraZeneca vaccine. All but one of the patients were women, all had bilateral facial paresis, all progressed to areflexic quadriplegia, and six required respiratory support. Patients’ ages ranged from 43 to 70. Four developed other cranial neuropathies, including abducens palsy and trigeminal sensory nerve involvement, which are rare in reports of Guillain-Barré syndrome from India, Maramattom and colleagues noted.

The authors argued that their findings “should prompt all physicians to be vigilant in recognizing Guillain-Barré syndrome in patients who have received the AstraZeneca vaccine. While the risk per patient (5.8 per million) may be relatively low, our observations suggest that this clinically distinct [Guillain-Barré syndrome] variant is more severe than usual and may require mechanical ventilation.”

The U.K. cases, reported by Christopher Martin Allen, MD, and colleagues at Nottingham (England) University Hospitals NHS Trust, describe bifacial weakness and normal facial sensation in four men between 11 and 22 days after their first doses of the Astra-Zeneca vaccine. This type of facial palsy, the authors wrote, was unusual Guillain-Barré syndrome variant that one rapid review found in 3 of 42 European patients diagnosed with Guillain-Barré syndrome following SARS-CoV-2 infection.

Allen and colleagues acknowledged that causality could not be assumed from the temporal relationship of immunization to onset of bifacial weakness in their report, but argued that their findings argued for “robust postvaccination surveillance” and that “the report of a similar syndrome in the setting of SARS-CoV-2 infection suggests an immunologic response to the spike protein.” If the link is casual, they wrote, “it could be due to a cross-reactive immune response to the SARS-CoV-2 spike protein and components of the peripheral immune system.”

“The Jury Is Still Out”

Asked for comment, neurologist Anthony Amato, MD, of Brigham and Women’s Hospital, Boston, said that he did not see what the two new studies add to what is already known. “Guillain-Barré syndrome has already been reported temporally following COVID-19 along with accompanying editorials that such temporal occurrences do not imply causation and there is a need for surveillance and epidemiological studies.”

Robert Lisak, MD, of Wayne State University, Detroit, and a longtime adviser to the GBS-CIDP Foundation International, commented that “the relationship between vaccines and association with Guillain-Barré syndrome continues to be controversial in part because Guillain-Barré syndrome, a rare disorder, has many reported associated illnesses including infections. Many vaccines have been implicated but with the probable exception of the ‘swine flu’ vaccine in the 1970s, most have not stood up to scrutiny.”

With SARS-Cov-2 infection and vaccines, “the jury is still out,” Lisak said. “The report from the U.K. is intriguing since they report several cases of an uncommon variant, but the cases from India seem to be more of the usual forms of Guillain-Barré syndrome.”

Lisak noted that, even if an association turns out to be valid, “we are talking about a very low incidence of Guillain-Barré syndrome associated with COVID-19 vaccines,” one that would not justify avoiding them because of a possible association with Guillain-Barré syndrome.

The GBS-CIDP Foundation, which supports research into Guillain-Barré syndrome and related diseases, has likewise stressed the low risk presented by SARS-CoV-2 vaccines, noting on its website that “the risk of death or long-term complications from COVID in adults still far exceeds the risk of any possible risk of Guillain-Barré syndrome by several orders of magnitude.”

None of the study authors reported financial conflicts of interest related to their research. Amato is an adviser to the pharmaceutical firms Alexion and Argenx, while Lisak has received research support or honoraria from Alexion, Novartis, Hoffmann-La Roche, and others.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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