COVID-19-associated Guillain-Barre syndrome

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.

• COVID-19 (SARS-CoV-2) outbreak initiated in December, 2019 in Wuhan, Hubei Province, China.^[1]

• 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.^[2]
• In June 2020,the very first case of COVID-19 associated Guillain-barre syndrome in the United States was reported.^[3]

• 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%).^[4]

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

• 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 ^[5].
• 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.^[6][7]
• 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^[7].
• In the future further investigations should be conducted about the mechanism of GBS in patients with COVID-19 for better understanding.

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

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

• 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 ^[2].
• 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.^[8]
• Another case of Guillain–Barre syndrome with COVID-19 has been reported in Iran^[9].
• 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.^[10]
• 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.^[11]
• 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.^[12]

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

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

• 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.^[13][2]
• The only US patient with COVID-19 associated GBS briefly required mechanical ventilation and was successfully weaned after receiving a course of Intravenous Immunoglobulin.^[3]

• 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 of Guillain Barre syndrome include:
  • Dysautonomic features
  • Symptoms of papilledema such as
  • Headache
  • Visual disturbance^[14]
  • Involuntary facial movement ^[15]
  • Hearing loss^[16]
  • 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.^[2]

• 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.^[3].
• The unique clinical features in the US case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia.^[3]

• The findings of five Italian patients with Guillain- Barre syndrome after the onset of COVID-19 infection:^[2]

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

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

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

• All patients with COVID-19 associated Guillain-Barre syndrome were treated with intravenous immune globulin (0.4 g/kg/day).^[18]
• Plasmapheresis can also be done in patients with COVID-19 associated Guillain-Barre Syndrome.

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

• 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.^[19]
• According to the CDC, the measures to prevent the spread the COVID-19 infection include:^[20]
  • 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.

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

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