Guillain-Barré syndrome after coronavirus disease 2019 vaccine: A temporal association.

Background: Guillain-Barré syndrome (GBS) is an acute monophasic immune-mediated polyradiculoneuropathy, preceded by gastrointestinal or respiratory infections in up to two-thirds of patients. On rare occasions, people develop GBS after vaccination, but no causal association has been proven. In the current coronavirus disease 2019 (COVID-19) pandemic, some cases have been reported associating COVID-19 vaccine with GBS. Case presentation: We report a case of a 62-year-old woman with GBS after the first dose of the Oxford/AstraZeneca vaccine against SARS-CoV-2. The symptoms started 3 weeks after the vaccine, and were characterized by ascending and progressive paresthesia in the upper and lower limbs, followed by loss of strength of the upper limbs and dysphagia for solids. The hypothesis of GBS was confirmed by clinical presentation compatible with albuminocytologic dissociation in cerebrospinal fluid and based on the Brighton criteria level 2. The treatment was a 5-day course of intravenous immunoglobulin with an improvement of symptoms. Conclusions: In the absence of other causes, the diagnosis of GBS was made, with evidence of a clear temporal association with COVID-19 vaccine. However, a cautious position is important when assigning a particular side-effect directly to a vaccine. It is important to emphasize that it is a temporal association only and the benefits of COVID-19 vaccination continue to outweigh the possible consequences.

INTRODUCTION

Guillain–Barré Syndrome (GBS) is an acute monophasic immune‐mediated polyradiculoneuropathy, preceded by gastrointestinal or respiratory infections in up to two‐thirds of cases. Among the most common causes are Campylobacter jejuni, cytomegalovirus, influenza, Mycoplasma pneumoniae, flaviviruses and alphaviruses. Clinically, GBS is a disorder that presents with symmetrical ascending flaccid acute paralysis of the limbs and areflexia, but has clinical variants. The recommendation is to use the Brighton criteria for defining GBS. These are based on clinical presentation, electrophysiological tests, cerebrospinal fluid (CSF) findings, and patients are classified as level 1 (high level of diagnostic certainty) to level 3 (lowest level of diagnostic certainty). In addition, treatment mainly consists of the use of intravenous immunoglobulin or plasma exchange, alongside supportive care.

Molecular mimicry and immune‐mediated phenomena are the most likely causes associated with the physiopathology of the disease. On rare occasions, GBS develops after vaccination, but no cause–effect relationship has been proven. In late 1976, the administration of outmoded anti‐rabies vaccines and the swine influenza vaccine campaign in the USA were associated with an increase in the number of GBS cases. In the SARS‐CoV‐2 pandemic, some cases have been reported with temporal association between coronavirus disease 2019 (COVID‐19) vaccine and development of GBS. Hence, the present study aimed to describe a case of GBS with temporal association with the first dose of the Oxford/AstraZeneca COVID‐19 vaccine.

CASE REPORT

A 62‐year‐old white Brazilian woman, with clinical history of high blood pressure and congestive heart failure, received a first dose of Oxford/AstraZeneca COVID‐19 vaccine. A total of 18 days later, the patient presented paresthesia of the distal extremities of the lower limbs with ascending progression. At her baseline, she was able to carry out her daily routine and walk without assistance, with a modified Rankin scale score of 1 and Hughes grade scale for assessing functional motor deficits score of 0, which is normal. Then, 2 weeks later, the patient noticed decreased strength of lower limbs with gait difficulties. The upper limbs were affected 7 days after, starting with weakness of the distal extremities. Two months after the onset of symptoms, the patient was referred to a neurological service located in Joinville, a city in southern Brazil, with tetraparesis, dysphagia, and urinary and fecal retention. The patient denied preceding respiratory or gastrointestinal symptoms.

The neurological examination findings showed facial diparesis, higher mental functions intact and normal eye movements. Reduced motor strength was observed in all four limbs (Medical Research Council scale 2/5 in lower limbs and 3/5 in upper limbs), affecting the proximal and distal muscles of the lower and upper limbs. At this point, the patient was confined to bed or a chair, with a Hughes functional grade scale score of 4. Arreflexia was present in the lower limbs, and the upper limbs reflexes were reduced, without ataxia or sensitive level. An important dysphagia was present, requiring a nasoenteral probe. Cardiorespiratory and abdominal examinations were normal. There was no fever or other signs of systemic infection.

Initial laboratory investigations showed a total white blood cell count of 12.8 × 10³/μL (reference range 4–10 × 10³/μL). Serology for HIV, syphilis, and hepatitis B and C was non‐reactive. Cranial computed tomography showed no abnormalities. CSF analysis showed protein levels of 110 mg/dL, an appropriate level of glucose (71 mg/dL) compared with concomitant serum glucose and the CSF white blood cell count was 1 cell/uL. No organisms were identified on Gram stain.

The clinical presentation and CSF analyses with albuminocytologic dissociation suggested GBS with Brighton criteria level 2. The diagnosis was made only with examinations available in the Brazilian public health system. A nerve conduction study is an examination not available in the hospital of the present patient. However, the diagnosis of GBS remains based on clinical characteristics and international criteria.

The patient was treated with a 5‐day course of intravenous immunoglobulin, with improvement of tetraparesis and dysphagia, being able to the remove nasogastric and vesical tubes. However, she persisted with gait difficulties, needing assistance, with moderately severe disability, modified Rankin scale 3 and Hughes functional grade 3, and able to walk with aid. She was discharged for rehabilitation and outpatient follow up.

DISCUSSION

GBS is the most frequently diagnosed cause of acute polyneuropathy, although its etiology is not completely defined. Vaccinations have been associated with GBS, mainly H1N1 immunization. However, the association between the influenza vaccine and GBS remains weak, and the presence of both is to be considered a rare event. An incidence rate of 1.6 cases of GBS per 1 000 000 was noted after the 2009 H1N1 influenza A vaccination. Regarding the COVID‐19 vaccine, we found reports of GBS variant after the Oxford/AstraZeneca vaccine and with the Pfizer vaccine (Table 1). , , ,

TABLE 1

Case reports with temporal association between Guillain–Barré syndrome and coronavirus disease 2019 vaccine

Authors (tear)	Vaccine	Age (sex)		No. days between vaccination and symptoms onset	Symptoms	Contents of treatment	Outcome
Hasan et al. 2	OAZ		62 years (Female)	11 days	Paresthesia and progressive weakness	IVIg	Clinical conditions worsen and mechanical ventilation was required
Allen et al. 7	OAZ		20, 54, 55 and 57 years (All male)	11–22 days	Profound bifacial weakness (facial diplegia)	IVIg, oral steroids or no treatment	No progression of neurological symptoms
Maramattom et al. 8	OAZ		43, 53, 67, 68, 69 and 69 years (Female) 70 years (Male)	10–14 days	Bilateral facial paresis, quadriplegia and required mechanical ventilatory support	IVIg, plasmapheresis	All patients progressed to areflexic quadriplegia and 6 of 7 cases required mechanical ventilation
Waheed et al. 9	Pfizer		82 years (Female)	14 days	Generalized body aches, paresthesia, and difficulty walking	IVIg	No complications were observed
Present case	OAZ		62 years (Female)	18 days	Ascending and progressive paresthesia, facial diparesis, loss of strength of upper limbs and dysphagia	IVIg	Persisted with gait difficulties

Abbreviations: IVIg, Intravenous immunoglobulin; OAZ, Oxford/AstraZeneca.

Furthermore, Maramattom et al. reported that the frequency of GBS was 1.4‐ to 10‐fold higher than expected in this period. They also concluded that increased frequency of bilateral facial weakness suggests a pattern associated with Oxford/AstraZeneca vaccine. Also noteworthy is the presence of quadriplegia, as in the present report, and the need for mechanical ventilatory support in six of the seven patients reported by them.

In the absence of other etiological causes, and despite limited diagnostic research resources, the clinical case presented here corroborates the diagnosis of GBS, with a temporal association with the Oxford/AstraZeneca COVID‐19 vaccine. Similar to the aforementioned case reports, a cause–effect relationship remains difficult to establish. Post‐vaccination neurological syndromes could be associated with host antibodies and a cross‐reaction with proteins in peripheral myelin. Possible origins for these antibodies could be a direct immune response to the SARS‐CoV‐2 spike protein; however, a specific response against the components of the adenovirus vector could also be plausible. The exact pathogenesis of GBS during COVID‐19 infection or immunization remains unknown. Perhaps the individual genetic characteristics, such as the human leukocyte antigen haplotype profile, could also play a role similar to other autoimmune neurological disorders.

Caution should be exercised when assigning any particular side‐effect directly to a vaccine. It is essential to highlight that the incidence of GBS associated with the Oxford/AstraZeneca COVID‐19 vaccine remains rare and the vaccination benefits continue to outweigh possible risks. Monitoring for vaccine side‐effects and carrying out broad‐spectrum observational studies are necessary to establish a better understanding between the vaccines and GBS.

DISCLOSURE OF ETHICAL STATEMENTS

Approval of the research protocol: N/A.

Informed consent: All informed consent was obtained from the participant.

Registry and the Registration No. of the study/trial: N/A.

Animal studies: N/A.

CONFLICT OF INTEREST

The authors declare no conflict of interest.