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], Fahimeh Shojaei, M.D.

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. In June 2020,the very first case of COVID-19 associated Guillain-barre syndrome in the United States was reported. 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. If left untreated, COVID-19 associated GBS may cause respiratory failure. The classic clinical manifestations of Guillain-Barre syndrome is progressive, ascending, symmetrical flaccid limbs paralysis.

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

• For further information about the differential diagnosis, click here.
• To view the differential diagnosis of COVID-19, click here.

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.
• One case of Guillain–Barre syndrome with COVID-19 was reported in the UK.The patient was a 49-year-old man of South Asian descent with no medical history and reported a 3-week history of shortness of breath, headache and cough.He came to emergency department with worsening cough and distal lower limb paraesthesia during the previous week, resulting in difficulty mobilising.
• There was also one case of SARS-CoV-2 infection associated Guillain-Barre syndrome in a child.The patient was an eleven year old boy who presented with typical features of GBS.The diagnosis of the SARS-CoV-2 infection was confirmed by oropharyngeal swab on reverse transcription polymerase chain reaction assay.
• Familial occurrence of Guillain-Barré syndrome after COVID-19 infection has also been reported.2 members of a family affected by COVID-19 presented with ascending paresthesia with the final diagnosis of Guillain-Barre syndrome.The patient was a 38-year-old man who presented with a history of ascending paresthesia and bilateral facial droop for 5 days before admission and was treated with a diagnosis of Guillain-Barre syndrome, his 14-year-old daughter also presented with a history of progressive paresthesia and weakness. Similar to her father, the paraclinical evaluations were consistent with Guillain-Barre syndrome.

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.

Natural History, Complications, and Prognosis

• If left untreated, COVID-19 associated GBS may cause respiratory failure.
• 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.

Diagnosis

History and Symptoms:

Common symptoms

• The most common symptoms of Guillain-Barre syndrome are
  • 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

Less common symptoms

• Less common symptoms of Guillain Barre syndrome include:
  • Dysautonomic features
  • Symptoms of papilledema such as
  • Headache
  • Visual disturbance
  • Involuntary facial movement
  • Hearing loss
  • Difficulty speaking (vocal cord paralysis)
  • Mental status changes

• 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 with COVID-19 associated Guillain-Barre syndrome were treated with intravenous immune globulin (0.4 g/kg/day).
• Plasmapheresis can also be done in patients with COVID-19 associated Guillain-Barre Syndrome.

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.

References

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