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Al-Doboke, A. Guillain-Barré Syndrome in COVID-19 Pandemic. Encyclopedia. Available online: https://encyclopedia.pub/entry/18282 (accessed on 16 November 2024).
Al-Doboke A. Guillain-Barré Syndrome in COVID-19 Pandemic. Encyclopedia. Available at: https://encyclopedia.pub/entry/18282. Accessed November 16, 2024.
Al-Doboke, Amal. "Guillain-Barré Syndrome in COVID-19 Pandemic" Encyclopedia, https://encyclopedia.pub/entry/18282 (accessed November 16, 2024).
Al-Doboke, A. (2022, January 15). Guillain-Barré Syndrome in COVID-19 Pandemic. In Encyclopedia. https://encyclopedia.pub/entry/18282
Al-Doboke, Amal. "Guillain-Barré Syndrome in COVID-19 Pandemic." Encyclopedia. Web. 15 January, 2022.
Guillain-Barré Syndrome in COVID-19 Pandemic
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This entry is adapted from the peer-reviewed paper 10.3390/neurolint14010003

Guillain–Barré syndrome (GBS) is considered as one of the peripheral nervous system diseases usually present with lower motor neuron lesion signs: muscle atrophy, weakness, fasciculation, hypotonia, and hyporeflexia. COVID-19 is a systemic disorder that typically presents with fever and respiratory symptoms. Numerous case reports have indicated an association between the incidence of GBS and previous SARS-CoV-2 infection, which preceded GBS onset by up to four weeks. Therefore, a postinfectious dysregulation of the immune system, caused by SARS-CoV2, was found to be the most probable trigger.

Guillain–Barré syndrome GBS SARS-CoV-2 COVID-19 SARS

1. Introduction

Over the past two decades, coronaviruses have caused three pandemic infections, known as severe acute respiratory syndrome (SARS), the middle east respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). Each of these three infections is caused by coronaviruses belonging to the beta genus. Infections caused by these beta coronaviruses show various clinical symptoms, from asymptomatic to severe illness and mortality. The first pandemic was reported in 2002–2003 in Guangdong, China, due to severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), and middle east respiratory syndrome coronavirus (MERS-CoV) caused the second pandemic. It was first detected in the Kingdom of Saudi Arabia in 2012. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae subfamily and causes the COVID-19 pandemic [1].
The present-day pandemic resulted from a novel coronavirus named SARS-CoV-2 and was first identified in December 2019 in Wuhan in China. On 30 January 2020, the World Health Organization declared the SARS-CoV-2 an international public health emergency [2]. Up to now, millions of cases have been confirmed worldwide, and the USA has been one of the most affected countries [3].
SARS-CoV-2 is the most recent novel coronavirus to emerge and has spread globally in the last two years. At the beginning of the pandemic, it was thought that bats were the natural reservoir for SARS-CoV-2, but nowadays, it is suggested that individuals are infected via an intermediate host, such as a pangolin. The most common mode of transmission is thought to be from a droplet that is expelled during face-to-face exposure, either while talking, coughing, or sneezing. Another possible mode of transmission is through contact with surfaces. The viral load reaches the peak in the upper respiratory tract, usually when symptoms start to appear, but viral shedding begins about two to three days before symptoms become onset. According to this fact, the asymptomatic and presymptomatic carrier can transmit the virus to others at this phase. It is thought that the presymptomatic transmission of the virus is a significant cause of the spread of SARS-CoV-2, because asymptomatic or presymptomatic individuals do not yet know that they are carriers until the symptoms appear; by this time, they may infect other individuals. SARS-CoV-2, when it enters the individual’s body, targets certain cells, such as nasal, bronchial epithelium, and pneumocyte cells via the viral spike proteins, which bind to angiotensin-converting enzyme 2 (ACE2) receptors. In another site, the host cells have an enzyme called type 2 transmembrane serine protease (TMPRSS2), which enhances the viral uptake by the cleavage of ACE2 and activating the SARS-CoV-2 protein. SARS-CoV-2 is similar to any other respiratory viral disease, in that it can cause lymphopenia by infecting and killing the T-lymphocyte, and it impairs lymphopoiesis, inducing lymphocyte apoptosis. Besides cell-mediated immunity, it also disrupts humoral immunity. Furthermore, SARS-CoV-2 infects the pulmonary capillary endothelial cells, worsening the inflammatory response and increasing the infiltration of the monocytes and neutrophils. In the last stage of the infection, the epithelial endothelial barrier’s integrity will be compromised [4].
Recently, numerous case reports have indicated an association between the incidence of Guillain–Barré syndrome (GBS) and previous SARS-CoV-2 infection, which preceded GBS onset by up to four weeks. Therefore, a postinfectious dysregulation of the immune system, caused by SARS-CoV2, was found to be the most probable trigger [5].
COVID-19 is a systemic disorder that typically presents with fever and respiratory symptoms. Recently, the symptoms of COVID-19 were found to be dependent on age, the patient’s underlying medical conditions, and the condition of the immune system. There are increasing case reports of GBS in SARS-CoV-2 infection, which may suggest a possible association between GBS and COVID-19 [1][2][6].
SARS-CoV-2 infection may be associated with an increased incidence of neurological manifestations; studies from the current pandemic have reported COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia, and hyposmia. There were more severe symptoms involving GBS, myositis, cerebrovascular diseases, encephalitis, and encephalopathy. The clinical scale and consequences of neurologic manifestations related to SARS-CoV-2 infection were widely varied, indicating various underlying pathogenic processes [7][8].
One of the neurological complications of COVID-19 infection is GBS. GBS is an autoimmune neurological disorder that affects the peripheral nervous system. GBS manifests as progressive weakness of the limbs and loss or reduction in reflexes; the diagnosis of GBS depends on the results of clinical, electrophysiological, and cerebrospinal fluid (CSF) examinations [9][10]. In this disorder, protein concentrations in the CSF increase, while the white cell count is average. A viral or bacterial infection commonly triggers GBS. In response to the antigen, the immune system is stimulated, and the nerve roots and peripheral nerves are damaged due to the structural similarity of this antigen to axons and myelin. The symptoms peak within four weeks, and the patients should be observed because 20 to 30% of them will require mechanical ventilation [9].

2. Current Insights

GBS is considered as one of the peripheral nervous system diseases usually present with lower motor neuron lesion signs: muscle atrophy, weakness, fasciculation, hypotonia, and hyporeflexia [11]. GBS is triggered through an anomalous autoimmune response to a prior infection against ganglioside components of the peripheral nerves (molecular mimicry), affecting various antigens in the demyelinating and axonal subtypes of GBS. Earlier, they discovered that coronavirus-type viruses (SARS and MERS) and Zika virus have been associated with GBS as well. Evidence indicates an association between COVID-19 and immune-mediated neurological complications such as GBS, but this is still unclear [12].
Through the process of analyzing the symptoms of GBS in COVID-19, some patients developed hyperreflexia instead of hyporeflexia, especially with the AMAN subtype. Other studies also describe the association between different GBS subtypes and hyperreflexia. Therefore, the presence of hyperreflexia should not delay the diagnosis and treatment of GBS. GBS patients with hyperreflexia have favorable prognosis than patients with hyporeflexia. For that reason, hyperreflexia must be included in the future diagnostic criteria of GBS [11].
The presence of IgG antibodies against SARS-CoV-2 supports the diagnosis of post-COVID-19 GBS. Additionally, the clinical features of post-COVID-19 GBS did not vary from individuals of causes linked to other viruses, with the significant exception of a tremendous respiratory involvement [5].
Antibodies for various gangliosides, such as GM1, GD1a, GT1a, GM2, and GQ1b, have been found in a small percentage of GBS patients, and their disappearance after clinical improvement suggests a pathogenetic role in the neuropathy. Antibodies to these proteins have been linked to a variety of clinical and electrophysiological characteristics of GBS. Anti-GM1 and anti-GD1a antibodies have been linked to an antecedent Campylobacter jejuni (CJ) infection which results in widespread motor and axonal impairment and a poor prognosis. Anti-GM2 antibodies to an antecedent CMV infection result in severe sensory–motor impairment, frequent respiratory impairment, and demyelinating features [13].
Not all patients were tested for antiganglioside antibodies, but most of the tested patients did not have antigangliosides antibodies, except four patients. Kajumba et al. suggested that the presence of antibodies is consistent with the theory of immune-mediated mechanisms of GBS, and the improvement of patients after immunoglobulin therapy supports that [14]. However, the absence of antiganglioside antibodies suggests non-immunologic mechanisms such as direct infection of the nervous system [14].
CSF results can change throughout a patient’s illness [15]. It was previously reported that a positive CSF PCR is highest when CSF is obtained between 3 and 14 days after the onset of neurological symptoms [16].
The results show that only two patients had positive SARS-CoV-2 PCR in the CSF; possible explanations include the absence of disruption in the blood–brain barrier (BBB) that allows SARS-CoV-2 to cross the CSF space [17] and the low sensitivity of currently available rRT-PCR, at about 60% [18][19].
A cluster of eight Italian patients presented with GBS symptoms during the peak of SARS-CoV2 infection [20]. These cases prove the genetic factor’s role in the development of GBS in COVID-19 patients.
In almost all cases, intravenous immunoglobulins were used. IVIG and plasma exchange have the same efficacy [21]. Most patients had a favorable outcome.
GBS is usually a postinfectious syndrome, as demarcated by an onset that is later than the acute symptoms of infection and by a mechanism that is distinct from the infection [12]. The most identified precipitants are HIV, HSV, CMV, EPV, MP, Cj, Varicella-zoster virus (VZV), Influenza-A virus, and Haemophilus influenza [22].
Some cases and reports discussed the effect of SARS and MERS infection on the nervous system and GBS development and confirmed that patients might develop acute polyneuropathy. After the onset of SARS-CoV-2 by 21 days and according to one of the case reports, three patients showed neuropathy, myopathy, and peripheral nerve disorders. On the other hand, acute polyneuropathy is the common type of GBS in patients with MERS-CoV infection [9].
The association between COVID-19 and GBS has recently been described. It takes the form of a para-infectious profile as an alternative to the usual postinfectious profile. Para-infectious neuropathies could progress as an unusual hyperimmune response, and they could also represent a direct toxic or neuropathic effect. It has been described as a potential uncommon sequela of COVID-19 infection through the first reported case in Wuhan, which suggested a para infectious presentation. Evidence suggests multiple mechanisms behind it; the mechanism strongly associated with COVID-19 and immune-mediated neurological complication is molecular mimicry between SARS-CoV-2 and human autoantigens. It was found that there are two SARS-CoV-2 hexapeptides that mimic the human shock protein (HSP 90B, 90B2, and 60I). High levels of autoantibodies against different familial HSP were found in the CSF and serum of those patients [12].
Subtypes of GBS have different pathogenesis. In the AMAN subtype of GBS, the infecting organisms possibly share similar epitopes to a component of the peripheral nerves (molecular mimicry); therefore, the immune responses crossreact with the nerves, causing axonal degeneration. Patients with AMAN commonly have serum antibodies against GM1, GM1b, GD1a, and GalNAc-GD1a gangliosides. In the AIDP type, the immune system reacts against target epitopes in Schwann cells or myelin result in demyelination; however, the exact target molecules in the case of AIDP have not yet been identified. Patients with MFS commonly have antibodies against GD1b, GD3, GT1a, and GQ1b gangliosides, which are related to ataxia and ophthalmoplegia [4].
The scale of COVID-19 infection ranges from asymptomatic to serious infection, and varies from other viral pulmonary infections, which require particular care as they could be dominated by the severity of pulmonary and cardiac symptoms [23]. This implies that COVID-19 pneumonia may overlap with GBS-associated respiratory muscle weakness, increasing the number of cases requiring respiratory assistance [5]. The alarming respiratory markers indicate an overlap between SARS-CoV-2 pneumonia and a neuromuscular condition involving respiratory muscle such as GBS. Initially, the diagnosis of GBS needs to be assumed in patients with COVID-19 who develop symptoms of diaphragmatic weakness (basal atelectasis on chest x-ray, development of hypercapnia in arterial blood gas analysis). Next, in patients with supposed or diagnosed acute neuromuscular disease in the sequence of COVID-19 infection, the effective monitoring of the respiratory muscles is suggested additionally to a careful neurological assessment, and it is serious in determining the timing of intubation regardless of the degree of respiratory failure from SARS-CoV-2 infection. In intensive care unit (ICU) patients with COVID-19 infection, the development of diaphragmatic weakness is not rare; consequently, a delicate differential diagnosis between ICU-acquired weakness and GBS must be taken into consideration, as the two situations need different curative approaches [23].
Over time, variants of the SARS-CoV-2 virus were identified: Alpha, Beta, Gamma, and Delta. Variants produce the same symptoms of COVID-19 but spread faster than other variants of SARS-CoV-2, and their severity is different from each other’s. Beta and Gamma cannot cause severe illness or death. In contrast, Alpha and Delta may cause severe illness or death. All vaccines are considered effective against these variants. The effectiveness of vaccines may change against new variants that could arise in the future [24].

3. Conclusions

The association between COVID-19 and GBS is unclear, but there is one mechanism strongly associated with COVID-19 and immune-mediated neurological complications, which is the molecular mimicry between SARS-coV-2 and human autoantigens. The most common subtype is a classic sensorimotor, which accounted for 56.19% of all cases. It is crucial to assume GBS in COVID-19 patients who developed diaphragmatic weakness.

References

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Amal Al-doboke
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