COVID-19-associated Guillain-Barre syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rinky Agnes Botleroo, M.B.B.S. Niloofarsadaat Eshaghhosseiny, MD[2]

Synonyms and keywords:

Overview

The coronavirus (COVID-19) pandemic originated in Wuhan (China) on December 2019.Although respiratory complications are more common, neurological manifestations are also increasingly reported. Guillain-Barre syndrome is preceded by upper respiratory infection or gastrointestinal illness.Few cases of COVID-19 associated Guillain-Barre syndrome have been reported.

Historical Perspective

• COVID-19 (SARS-CoV-2) outbreak initiated in December, 2019 in Wuhan, Hubei Province, China.

• In northern Italy five patients developed Guillain–Barré syndrome after the onset of coronavirus disease 2019 (Covid-19) from February 28 through March 21, 2020.
• In June 2020,the very first case of COVID-19 associated Guillain-barre syndrome in the United States was reported.

Classification

• There is no established system for the classification of COVID-19 associated Guillain-Barre Syndrome .
• Guillain-Barre Syndrome its self may be classified into various subtypes: demyelinating polyneuropathy (67.4%), acute axonal neuropathy (7.0%), Miller Fisher syndrome (7.0%), Bickerstaff brainstem encephalitis (7.0%), pharyngo-cervical-brachial variant (4.7%), and polyneuritis cranialis (4.7%).

• To view the classification of COVID-19, click here.

Pathophysiology

• Guillain–Barre syndrome causes immune-mediated damage to the peripheral nerves that usually follows gastrointestinal or respiratory illnesses. The polyneuropathy in Guillain–Barre syndrome is believed to be due to cross-immunity against epitopes of peripheral nerve components that it shares with the epitopes on the cell surface of bacteria that produces an antecedent infection . Most common antecedent infections are Campylobacter jejuni ,Zika virus and influenza virus.
  
• The mechanism of Guillain–Barre syndrome in patients infected with COVID-19 is not fully understood yet.
• COVID-19 stimulates inflammatory cells and produces various inflammatory cytokines and as a result, it initiates immune-mediated processes.'Molecular mimicry' as a mechanism of autoimmune disorder plays an important role in formation of Guillain–Barre syndrome. It is not yet clear whether COVID-19 induces the production of antibodies against specific gangliosides that usually appear with certain forms of Guillain–Barre syndrome.
  In the future further investigations should be conducted about the mechanism of GBS in patients with COVID-19 for better understanding.
  

Causes

• COVID-19 associated Guillain-Barre syndrome may be caused by SARS-CoV-2 virus.
  

Differentiating COVID-19-associated Guillain-Barre syndrome from other Diseases

• COVID-19 associated Guillain-Barre syndrome
  • It has been reported in Northern Italy,United States, Iran
  • Affects mostly elderly people
  • More males are affected than females
  • Presence of Fever, cough, dyspnea, ageusia, hyposmia before the onset of GBS
  • Takes 5-14 days to develop GBS
  • Facial Diplegia common
  • Dysautonomia less common
  • Outcome is poor, residual weakness, dysphagia, long ICU stay

• Differentiating from Typical Guillain-Barre syndrome:
  • Typical Guillain-Barre syndrome occurs worldwide
  • Affects all age groups,
  • Male 1.5 times more affected than females,
  • Presence of preceeding respiratory/gastrointestinal illness
  • Takes less than 6 weeks to develop GBS from initial illness
  • Facial Diplegia common
  • Dysautonomia common
  • Prognosis is good, persistent disability in 20%-30% cases

• Differentiating from Zika virus-related Guillain-Barre syndrome:
  • Zika virus-related Guillain-Barre syndrome was reported in Latin America, Europe, East Asia, North America
  • Affects Middle aged people to elderly people
  • Males are more affected than females
  • Presence of fever, headache, rash, arthralgia, diarrhea, conjunctivitis before the onset of Guillain-Barre syndrome
  • Takes 0–10 days to develop Guillain-Barre syndrome
  • Facial Diplegia common >50% cases
  • Dysautonomia common up to 30% cases
  • Outcome is good, half may require ICU care
• Here is table of Differential Diagnosis of Guillain-Barre syndrome below:

Diffrential Diagnosis Of Guillain-Barre syndrome

cereblarc	cerebellar	spinal	Neuromuscular junction	Peripheral nervous system	Muscle disease
Bilateral strokes	Posterior fossa structural lesion	Compressive myelopathy	Botulism	Acute onset chronic inflammatory demyelinating neuropathy (CIDP)	Acute inflammatory myopathies (eg, dermatomyositis, polymyositis)
Psychogenic symptoms		Neuromyelitis optica	Myasthenia gravis	Critical illness polyneuropathy	Acute viral myositis
Acute disseminated encephalomyelitis (ADEM)	Acute cerebellar ataxia syndrome	Anterior spinal artery syndrome	Neuromuscular blocking agents	Cytomegalovirus-related radiculitis	Acute rhabdomyolysis
		Poliomyelitis		Diphtheria	Critical illness myopathy
		Transverse myelitis		HIV-related radiculitis	Metabolic myopathies (eg, hypokalemic, hyperkalemic)
		Other infectious causes of acute myelitis (eg, West Nile virus, coxsackieviruses, echoviruses)		Leptomeningeal malignancy Lyme disease	Mitochondrial myopathies
				Metabolic and electrolyte disorders (eg, hypoglycemia, hypophosphatemia)	Periodic paralysis
				Porphyria
				Thiamine deficiency (beriberi)
				Toxic neuropathy
				Vasculitis

Epidemiology and Demographic

• • Five cases of Guillain-Barre syndrome (GBS) in patients with COVID-19 has been reported in three hospitals in Northern Italy from February 28 through March 21, 2020. Four of these patients had a positive nasopharyngeal swab for SARS-CoV-2 at the onset of the neurologic syndrome, and one had a negative nasopharyngeal swab and negative bronchoalveolar lavage but subsequently he developed a positive serologic test for the virus .
  • The first official case of Guillain-Barre syndrome (GBS) associated in patients with COVID-19 in the United States has been reported by neurologists from Allegheny General Hospital in Pittsburgh, Pennsylvania in June,2020.The patient was a 54-year-old man who was transferred to Allegheny General Hospital after developing ascending limb weakness and numbness that followed symptoms of a respiratory infection.The man reported that his wife was tested positive for COVID-19 infection and that his symptoms started soon after her illness. Later he also tested positive for COVID-19.
  • Another case of Guillain–Barre syndrome with COVID-19 has been reported in Iran.

Risk Factors

• There are no established risk factors for COVID-19 associated Guillain-Barre syndrome.

Screening

• There is insufficient evidence to recommend routine screening for COVID-19 associated Guillain-Barre Syndrome.
  

Diagnosis

History and Symptoms:

• The classic clinical manifestations of Guillain-Barre syndrome is
  • Progressive, ascending, symmetrical flaccid limbs paralysis
  • Areflexia or hyporeflexia and with or without cranial nerve involvement, which can progress over the course of days to several weeks
• In the Italian cases, Guillain-Barre syndrome symptoms began 5-10 days after the first COVID-19 symptoms. The first symptoms of GBS were lower limb weakness in four patients and facial diplegia with subsequent ataxia and paresthesia in one patient. Four patients had generalized flaccid tetraparesis or tetraplegia that developed over 3 to 4 days; No patient had dysautonomic features.

Patient no.	Onset of neurologic symptoms	Neurologic Signs & Symptoms
1	7 days after fever, cough, ageusia	Flaccid areflexic tetraplegia evolving to facial weakness, upper limb paresthesia(36 hr), and respiratory failure(day 6)
2	10 days after fever and pharyngitis	Facial diplegia and generalized areflexia evolving to lower limb paresthesia with ataxia (Day 2)
3	10 days after fever and cough	Flaccid tetraparesis and facial weakness evolving to areflexia (day 2) and respiratory failure( day 5)
4	5 days after cough and hyposmia	Flaccid areflexic tetraparesis and ataxia (day 4)
5	7 days after cough,ageusia and anosmia	facial weakness,flaccid areflexic paraplegia(day 2-3) and respiratory failure (day 4)

• In the US case, the deficits in the 54 year old man were characterized by quadriparesis and areflexia, burning dysesthesias, mild ophthalmoparesis, and dysautonomia. He did not have the loss of smell and taste documented in other COVID-19 patients.. The unique clinical features in the US case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia.

Laboratory Findings

• The findings of five Italian patients with Guillain- Barre syndrome after the onset of COVID-19 infection:

Patient no.	CSF findings	Antiganglioside Antibodies	MRI Findings
1	Day 2(first lumbar puncture): Protein level: Normal; No cells; Negative PCR assay for SARS-CoV-2 Day 10(second lumbar puncture): Protein level:101mg/dl; White cell count 4per mm3; Negative PCR assay for SARS-CoV-2	Negative	Head: Normal Spine:Caudal nerve roots enhanced
2	Day 3 Protein level :123mg/dl; No cells were found; PCR assay was negative for SARS-CoV-2	Not tested	Head: Bilateral enhancement of Facial nerve Spine: Normal
3	Day 3 Protein level :193mg/dl; No cells were found; PCR assay for SARS-CoV-2 negative	Negative	Head: Normal Spine: Caudal nerve roots enhanced
4	Day 5: Protein level: Normal; No cells; PCR assay for SARS-CoV-2 was negative	Not tested	Head: Normal Spine:Normal
5	Day 3 Protein level: 40mg/dl; WBC count 3 per mm3; PCR assay for SARS-CoV-2 was negative	Negative	Head: Not performed Spine:Normal

Electrocardiogram

• There are no ECG findings associated with COVID-19 associated Guillain-Barre Syndrome.

X-ray

• There are no x-ray findings associated with COVID-19 associated Guillain-Barre Syndrome.

Echocardiography or Ultrasound

• There are no echocardiography/ultrasound findings associated with COVID-19 associated Guillain-Barre Syndrome.

Treatment

Medical therapy

• All patients were treated with Intravenous Immune globulin
• Plasmapheresis can also be done

Surgery

Surgical intervention is not recommended for the management of COVID-19 associated Guillain-Barre Syndrome.

Primary Prevention

• The disease itself is associated with COVID-19 infection and it is believed that preventing the spread of the infection itself is the most promising primary prevention strategy at the moment.
• There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.
• According to the CDC, the measures to prevent the spread the COVID-19 infection include:
  • Frequent handwashing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% alcohol.
  • Staying at least 6 feet (about 2 arms’ length) from other people who do not live with you.
  • Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs.
  • Cleaning and disinfecting.

Secondary Prevention

• There are no established measures for the secondary prevention of COVID-19 associated Guillain-Barre Syndrome.

Prognosis

• Among the five Italian patients of Covid-19 associated GBS two patients had poor outcome including ICU admission due to respiratory failure,they remained in intensive care after 4 weeks of treatment ;two patients had mild improvement and receiving physical therapy, and one was discharged walking independently.
• The only US patient with COVID-19 associated GBS briefly required mechanical ventilation and was successfully weaned after receiving a course of Intravenous Immunoglobulin.

References

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