COVID-19-Associated Guillain-Barre Syndrome: Atypical Para-infectious Profile, Symptom Overlap, and Increased Risk of Severe Neurological Complications

Abstract

The concurrence of COVID-19 with Guillain-Barre syndrome (GBS) can increase the likelihood of neuromuscular respiratory failure, autonomic dysfunction, and other life-threatening symptoms. Currently, very little is known about the underlying mechanisms, clinical course, and prognostic implications of comorbid COVID-19 in patients with GBS. We reviewed COVID-19-associated GBS case reports published since the outbreak of the pandemic, with a database search up to August 2020, including a manual search of the reference lists for additional relevant cases. Fifty-one (51) case reports of COVID-19 patients (aged 23-84 years) diagnosed with GBS in 11 different countries were included in this review. The results revealed atypical manifestations of GBS, including para-infectious profiles and onset of GBS without antecedent COVID-19 symptoms. Although all tested patients had signs of neuroinflammation, none had SARS-CoV-2 in the cerebrospinal fluid (CSF), and only four (4) patients had antiganglioside antibodies. The majority had a 1- to 10-day time interval between the onset of COVID-19 and GBS symptoms, and many had a poor outcome, with 20 out of the 51 (39.2%) requiring mechanical ventilation, and two deaths within 12 to 24 h. The atypical manifestations of COVID-19-associated GBS, especially the para-infectious profile and short time interval between the onset of the COVID-19 and GBS symptoms, increase the likelihood of symptom overlap, which can complicate the treatment and result in worsened disease progression and/or higher mortality rates. Inclusion of a neurological assessment during diagnosis of COVID-19 might facilitate timely identification and effective management of the GBS symptoms and improve treatment outcome.

Keywords: Atypical; COVID-19; Guillain-Barre; Para-infectious; Prognosis; SARS-CoV-2.

Fig.1

A schematic representation of the likely pathophysiology of COVID-19-associated GBS. SARS-COV-2 has a high affinity for the angiotensin-converting enzyme 2 (ACE2) receptor [21], located on nasal and oral mucosa [22], neurons, glia cells, and blood vessels of the central nervous system [23, 24]. During an infection, SARS-COV-2 binds this receptor and is endocytosed. Due to similarity in the peptide sequences or epitopes of SARS-Cov-2 and gangliosides (molecular mimicry), the antibodies formed against the virus, through the T Cell-B cell interactions, may bind the gangliosides located on the peripheral neurons. This may result in an autoimmune response that destroys the myelin and/or axons. The demyelination or axonal damage disrupts neural transmission, which causes the GBS symptoms such as muscle weakness, paralysis, coordination problems, breathing difficulties, and autonomic dysfunction

Fig. 2

Number of COVID-19-associted GBS cases identified from each country. The number of COVID-19-associated GBS cases were highest in Italy, the USA, Spain, and Iran, which by August 2020 were among the countries hardest hit by the COVID-19 pandemic

Fig. 3

The atypical manifestation and prognosis of COVID-19-associated GBS. The results revealed that following SARS-CoV-2 infection, patients can experience GBS with or without developing COVID-19 symptoms. The GBS can manifest as a para-infectious profile, characterized by onset of symptoms during active SARS-CoV-2 infection and a COVID-19-GBS symptom overlap, while the post-infectious profile involves onset of GBS symptoms after recovering from the COVID-19. However, some of the post-infectious profile patients may still test positive for SARS-COV-2 at the onset of GBS symptoms. The outcome ranged from mild to severe GBS symptoms, requiring admission into intensive care units, mechanical ventilation, prolonged stay in hospital, or discharge with severe residual or permanent disability, with the para-infectious profile having a higher likelihood for poor functional outcomes, due to the COVID-19-GBS symptom overlap