Coronaviruses are not primarily neurotropic viruses and their primary targets are respiratory and cardiovascular systems. The virus is attached to host cells through the Angiotensin-converting enzyme 2 (ACE-2) receptors leading to internalization and subsequent viral replication. This receptor is also found in glial cells in the Central Nervous System (CNS) and spinal neurons. The virus can invade peripheral nerves and lead to retrograde transfer via synapse mediated route to CNS [5, 6].
Also, the cytokine release syndrome (CRS), caused by an exacerbated recruitment and activation of macrophages, neutrophils, and natural killer cells (NK) in response to SARS-CoV-2 infection result in releasing many activated leukocytes during the inflammatory phase can lead to extensive tissue damage, including the peripheral nervous system, and appears to correlate with COVID-19 severity [7, 8].
COVID-19 may not directly invade nerves, its roots or the anterior horn cells as seen in polio virus or West Nile virus leading to their damage. Even the cerebrospinal fluid (CSF) and the polymerase chain reaction (PCR) for coronavirus in multiple reported cases of COVID-19 related GBS has been negative [9]. It is likely to be a post infectious or a para-infectious complication resulting from an aberrant immune response which can be considered a second mechanism explaining GBS in COVID-19 by production of antibodies against ganglioside components of the peripheral nerves, owing to molecular mimicry with surface antigens of the infectious pathogen [10].
Our study was conducted on 42 patients, included the first and second waves of the pandemic, through the period from March 2020 till the end of February 2021. We found that COVID and post COVID polyneuropathies with its different types and forms are of the common neurological complications of COVID virus infection that may affect and threaten the health if not taken in consideration.
In our study we reported that more than half of our patients (59.9%) presented with typical pattern of AIDP which was against Yaranagula and Koduri who reported that more than half of the patients in the their cohort had paraparesis [11]. The paraparetic variant is an uncommon form of GBS and constitutes about 5–10% of all GBS cases [12].
In the current study, most of our patients presented with demyelinating neuropathy rather than the axonopathy which was in accordance with Yaranagula and Koduri who found that the proportion of patients with demyelinating neuropathy was higher than previously reported COVID-19-associated neuropathies (84.62%) [11].
In a study done by Zhao and colleagues described two patients did not experience preceding fever, respiratory, or GI symptoms and GBS was the initial presentation [3], also Yaranagula and Koduri reported that three patients presented with acute neuropathy in the first week of their covid 19 infection suggesting a para-infectious process [11], as has been reported with Zika virus [13] and that agreed with our study.
In 2020, Virani and colleagues reported a 54-year-old male with confirmed COVID-19 and a history of fever, cough and Clostridium difficile colitis of recent onset developed difficulty breathing and weakness and diminished reflexes of arms and legs eventually diagnosed as GBS [10]. A 65 years old male was reported by Sedaghat and colleagues, with ascending quadrparesis, areflexia and bifacial palsy, after positive nasal swab and normal CSF, when EMG and nerve conductions were done on day 9 of weakness that revealed GBS variant-AMSAN [14].
El-Otmani and colleagues reported 70 years old female with quadriplegia, hypotonia and areflexia, that her MRI was normal but EMG and nerve conductions revealed axonal pattern of atypical GBS and diagnosed as ASAN, that it’s CSF protein was 100 mg/dL and normal WBCs [15] which agreed with our study.
Camdessanchi and colleagues reported a 64 years old male with flaccid paralysis and parasthesia. On day 5 EMG and NCV were done that revealed polyneuropathy of mixed demyelinating pattern, the CSF protein was 54 mg/dL [16].
In 2020, two other studies done by Scheidl and colleagues and Padroni and colleagues reported two patients with paraparesis and areflexia, EMG/NCS revealed demyelinating pattern and diagnosed as GBS and CSF proteins are elevated [17, 18].
Ottaviani and colleagues reported 66 years old Female with difficulty in walking, paraparesis and arefexia then progressed to quadriparesis with facial weakness. On day 10 EMG/NCS revealed mixed axonal and demyelinating patterns and diagnosed as GBS. The CSF protein was 108 mg/dL, normal WBCs and serum antiglycolipid antibodies were absent [19], which agreed with our study.
Abdelnour and colleagues reported 69 years old male presented with bilateral lower limb weakness and areflexia, brain and spine MRIs were normal, EMG/NCS were not performed however he was diagnosed as GBS, inspite that the CSF was not performed [20].
Caamaño DS and colleagues reported a 61 years old male with bilateral facial weakness, unresponsive blink reflex on both eyes. Brain MRI was normal. EMG/NCS were not performed. Diagnosed as atypical GBS variant with facial diplegia. The CSF protein was 44 mg/dL [21].
Toscano and colleagues reported 5 patients with GBS from three hospitals in northern Italy during the COVID-19 outbreak. In sum, GBS occurred 5 to 10 days after onset of COVID-19 symptoms, a typical interval. Clinical neurophysiology was consistent with axonal-type GBS in 3 cases and demyelinating-type in 2 patients. Post-Gadolinium MRI showed enhancement of caudal nerve roots in 2 patients and the facial nerve in one. All patients were treated with IVIG and Patients 1 and 3 received two cycles. A similar treatment was used in GBS patients during the MERS outbreak [22].
With the emergence of more cases of polyneuropathies temporally linked to SARS-CoV-2 infection, we can understand the improvement of such patients on steroids, plasma exchange and IVIG. We should gain a better understanding of the underlying pathophysiology and potential therapeutic options of GBS related to COVID-19.
Several therapeutic options are still under study, with the intent to stabilize the immune system in COVID-19 and either prevent or minimize the consequences of this storm, as reviewed by Diamanti and colleagues [23].
Since these neuropathies are treatable and they pose increased morbidity and mortality, physicians working with COVID-19 patients must be aware of this association.
In our study, we noticed different types of polyneuropathy which vary according to age groups and also it may be the initial COVID symptoms between Group A and Group B, this could be due to the genetic change in the corona virus phenotype or change in the autoimmune response of the body to the virus in the second wave.
The presentation of the neurological complications attacked the younger age in the second wave may be due to the eased of the global restrictions of closure, opening of the schools and nurseries, making the children in this age group more vulnerable for infection, or may the adults gained immunity from previous exposure to the first coronavirus season as they were more exposed for infection for the sake of keeping their works and the individual financial income.
