This article synthesises the latest findings and incorporates recent guidelines from regulatory bodies such as the CDC, FDA, and World Health Organization (WHO) to support clinicians in making informed decisions about RSV vaccination.

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The licensure of the first RSV vaccines—Pfizer’s Abrysvo and GSK’s Arexvy—signaled a major advancement in the fight against the respiratory syncytial virus (RSV), especially among older adults at high risk for hospitalisation and mortality. However, as with any newly introduced vaccines, safety monitoring remains critical. A potential link between these vaccines and Guillain-Barré Syndrome (GBS) has sparked debate and caution within the medical community.

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Understanding Guillain-Barré Syndrome (GBS)

GBS is a rare but severe autoimmune neuropathy that occurs when the immune system mistakenly attacks the peripheral nervous system. It typically follows bacterial & viral infections like Campylobacter jejuni, Zika virus, or influenza, and less commonly, dog bites and vaccinations.

Symptoms often begin with tingling and weakness in the legs, progressing to paralysis in severe cases. While most patients recover, the condition can lead to long-term disability or death. Incidence rates for GBS range between 1 and 2 cases per 100,000 persons annually, with a higher predisposition in individuals over 60.

Guillain-Barré Syndrome (GBS)  is a Demyelinating disease.

• Involves proximal predominant peripheral nerves and is symmetrical
• Polyradiculopathy
• Acute onset 4 weeks

Albuminocytological Dissociation:

Inflammation causing an increase in albumin to CSF

• 10 Classical
• <50: Acceptable
• >50 Evaluate for other conditions like HIV and Lyme disease

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Clinical Features

• Proximal symmetrical weakness
• Ascending paralysis (Descending paralysis (tetanus, Botulism and Diptheria)
• Cranial nerve symptoms: 15-65%
• Bifacial palsy 60% of GBS
• CIDP 5%
• Nerve involvement is more of upper nerves, out of which facial is more common in GBS
• Bulbar, ie, CN IX and x: more common for CIDPS*

Motor/Sensory

• Hyporeflexia, areflexia
• Proximal > Distal
• Ascending paralysis
• Cranial nerve involvement is present
• Autonomic involvement (65%)-Dreadful
• Most common due to cardiorespiratory arrest

During autonomical fluctuations: If the risk of death is high, shift the patient immediately to the ICU. Noradrenaline can be given

Triggers

1. 1-4 weeks before onset of disease, mostly Gl infection/ Respiratory tract infections.
2. m/c organism C. jejuni: Associated with 76% AMAN, mycoplasma, HIV, and CMV can also be present.
3. Vaccine-associated reactions can also be present.
4. Post-trauma -Damaged neurons release certain antigens from the nerve. The body produces autoimmunity against it.
5. Surgery.

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GBS Variants

1. AIDP: Acute inflammatory Demyelinating polyradiculopathy - No early wasting.
2. AMAN Acute motor axonal neuropathy. associated with GM1 ganglioside neuropathy, Zika virus and C. jejuni infections.
3. AMSAN: Acute motor sensory axonal neuropathy. Can progress < 7 days: Severe.
4. Miller Fischer syndrome: - Associated with GQIb antibodies.

• Ophthalmoplegia, Areflexia and Ataxia
• Weakness is not a classical feature
• (Corticospinal tract (sign + Loc+ weakness should be absent

Other Variants Include

• Bifacial facial diplegia + distal paresthesia
• Multiple cranial nerve variant
• Pharyngo-cervico-brachial variant. -GT la GD la
• Paraparietic variant
• Pañ dysautonomic variant
• Pure ataxic variant
• Pure small fibre variant

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Post-Marketing Surveillance: The Signal Emerges

While clinical trials of both Abrysvo and Arexvy reported isolated cases of GBS, large-scale post-marketing surveillance has provided further clarity:

FDA & Medicare Data:

1. A Medicare-based analysis observed:

• ~9 excess GBS cases per million with Abrysvo
• ~7 excess GBS cases per million with Arexvy

2. Most cases occurred within 21–42 days of vaccination.

3. The findings prompted updates to both vaccines’ labelling, warning of the "possible increased risk" of GBS.

CDC’s Vaccine Adverse Event Reporting System (VAERS):

1. Between May 2023 and April 2024, 28 GBS cases were reported after RSV vaccination in the U.S.

• Arexvy: ~1.5 cases per million doses
• Abrysvo: ~5 cases per million doses

2. Most patients developed neurological symptoms within three weeks post-vaccination.

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WHO and Global Positioning on RSV Vaccines

In its 2023 RSV Vaccine Landscape and Guidance Document, the World Health Organization (WHO) recognised both Abrysvo and Arexvy as essential tools to reduce RSV-associated morbidity, particularly among:

• Adults aged ≥60 years
• Immunocompromised individuals
• Patients with chronic lung, cardiac, or metabolic conditions

However, WHO recommended:

1. Continued pharmacovigilance in low- and middle-income countries (LMICs), where GBS may be underdiagnosed.
2. Use of active surveillance systems to track and investigate adverse events, including neurological syndromes.

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Clinical Considerations for Physicians

Given the rare but real association, clinicians should:

1. Conduct Thorough Risk-Benefit Analysis

Recommend RSV vaccination for:

• Adults ≥75 years
• Adults 60–74 with comorbidities (e.g., COPD, CHF, diabetes)

Exercise additional caution in individuals with:

• Prior history of GBS
• Recent neurological symptoms

Recent viral infections known to trigger autoimmune responses

2. Shared Decision-Making

Use a personalised approach for adults aged 60–74:

• Discuss individual risk factors for severe RSV
• Explain the very low but possible risk of GBS
• Provide literature or visual aids to help patients understand

3. Post-Vaccination Monitoring

Educate patients to monitor for:

• Numbness or tingling in extremities
• Muscle weakness, especially in the legs
• Difficulty walking or facial movements

Initiate early neurology referral if symptoms appear. Document and report adverse events promptly via VAERS or local equivalents.

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Differentiating GBS from Other Neurological Events

Not all neurological symptoms post-vaccination equate to GBS. Consider:

1. Bell’s Palsy: facial droop without limb involvement.
2. Transverse Myelitis: spinal cord inflammation, distinct from ascending GBS.
3. Peripheral neuropathy from diabetes, alcohol use, or chemotherapy.

Electromyography (EMG) and nerve conduction studies (NCS) remain the gold standards for diagnosing GBS.

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Looking Ahead: Future Research and Implications

Ongoing Surveillance Studies

1. Both GSK and Pfizer are conducting Phase IV long-term surveillance studies on vaccine safety.
2. Independent trials are also assessing the immunological mechanisms that may link RSV vaccination and GBS.

Improved Risk Stratification

Future vaccine recommendations may incorporate biomarkers to identify individuals at higher risk of autoimmune complications post-vaccination.

Alternative Preventive Strategies

1. Monoclonal antibodies like Nirsevimab (approved for infants) may eventually be repurposed or reformulated for adult use.
2. Non-vaccine strategies, such as air purification and infection control during RSV season, remain adjuncts.

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Conclusion

1. The emergence of Guillain-Barré Syndrome as a rare potential adverse event following RSV vaccination warrants careful consideration but not alarm. As with many vaccines, the absolute risk remains extremely low, especially when compared to the potentially severe impact of RSV in older adults.
2. Physicians are encouraged to stay current with evolving data, maintain open dialogue with patients, and participate in surveillance efforts to ensure both vaccine confidence and patient safety.

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Disclaimer: The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Khemeswar Agasti is an MD in General Medicine from Cuttack.