COVID-19-associated Guillain-Barre syndrome
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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.
- 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.
- 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.
- 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.
- 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.
- 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.
History and Symptoms:
- The most common symptoms of Guillain-Barre syndrome are
Less common symptoms
- Less common symptoms of Guillain Barre syndrome include:
- 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  |
||7 days after fever, cough, ageusia||Flaccid areflexic tetraplegia evolving to facial weakness, upper limb paresthesia(36 hr), and respiratory failure(day 6)|
||10 days after fever and pharyngitis||Facial diplegia and generalized areflexia evolving to lower limb paresthesia with ataxia (Day 2)|
||10 days after fever and cough||Flaccid tetraparesis and facial weakness evolving to areflexia (day 2) and respiratory failure( day 5)|
||5 days after cough and hyposmia||Flaccid areflexic tetraparesis and ataxia (day 4)|
||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.
- The findings of five Italian patients with Guillain- Barre syndrome after the onset of COVID-19 infection:
|Patient no.||CSF findings
Echocardiography or Ultrasound
- 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).
- 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.
- 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.
- There are no established measures for the secondary prevention of COVID-19 associated Guillain-Barre Syndrome.
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