Introduction

On December 2019, the novel coronavirus (SARS-CoV-2) was detected in China and has spread worldwide causing a pandemic: the coronavirus disease-2019 (COVID-19).¹ After an incubation period of 5 days, the respiratory symptoms are the most frequent. Acute renal failure, gastrointestinal and cardiac damages have also been reported.² Several neurological symptoms have been related to the COVID-19: loss of taste and smell, headache, myalgia, dizziness and confusion.³ Neurological complication such as encephalitis and stoke have been occurred after COVID-19 infection.⁴

Guillain–Barré syndrome (GBS) is an acute, immune-mediated generalized polyradiculoneuropathy often preceded by several infections: mainly Campylobacter Jejuni, Epstein–Barr virus, Cytomegalovirus, Influenza, Zika, Human Herpes virus, less frequently H1N1, HIV and Hepatitis-E.⁵ Around 100 cases of a confirmed or a suspected GBS have been linked to SARS-CoV-2 worldwide.^6,7 Only few cases were reported in Tunisia.^8,9 We report on a case of a Tunisian GBS patient initially presenting without symptoms of COVID-19 in a regional hospital.

Case presentation

A 55-year-old man, retired teacher from ksar Hellal with no personal pathological history, family history of diabetes and high blood pressure, presented to the emergency department of Hadj Ali Soua regional hospital in Ksar Hellal, Monastir, Tunisia, complaining of acute lumbar pain, tingling and numbness in the right leg progressing within 1 day. He was treated for a lumbar discal hernia. After 2 days, he developed acute weakness in both legs and returned. He denied having respiratory or digestive symptoms. On examination, the patient was afebrile, vital parameters and lung auscultation were all normal. Neurological examination revealed a sensory-motor deficit in the distal lower extremities. As his wife was tested positive for SARS-CoV-2 five days previously, the patient was admitted to the COVID ward where he was treated symptomatically with paracetamols. He had a negative PCR for SARS-CoV-2. Laboratory testing revealed no significant abnormalities. Brain computed tomography revealed the presence of a hypodense area of the left centrum semiovale, which could be in line with a lacunar cerebral infarct.

The next day, a physical examination revealed that the lower extremities' deep tendon reflexes were absent, and their strength was significantly lower than that of the upper extremities. His symptoms progressed and he developed ascending flaccid symmetrical limb paralysis. On day 6 of admission, the patient manifested tetraplegia, peripheral facial paralysis, swallowing disorder, urinary incontinence and central respiratory depression with a respiratory rate of 35 cycles per minute and an oxygen saturation of 90 % under 15 L of oxygen. A clinical diagnosis of GBS was made. At biology control, there was an appearance of cytolisis, aspartate aminotransferase (ASAT) at 107 UI/L and alanine aminotransferase (ALAT) at 152 UI/L, at three times normal and biological inflammatory syndrome, CRP at 129 mg/L. The patient was immediately transferred to intensive care unit where he required invasive mechanical ventilation. Cerebrospinal fluid analysis revealed albuminocytologic dissociation: Glucose at 4.4 mmol/L, proteins at 1.21 g/L and chlorides at 123 mmol/L with normal levels of red and white cells at 2 elements /mm³ in the cytological formula. The diagnosis of GBS was confirmed. Serology test, in favor of a recent COVID-19 infection, explained the etiology of the GBS. The patient was treated with intravenous immunoglobulin (IV Ig) at 0.4 g/kg/day for 5 days.

His clinical condition improved gradually. On day 27, our patient was extubated and was transitioned out of the intensive care unit, after one month, with discharge to a rehabilitation facility as he was experiencing sequelae of trophic disorder in the right lower extremity and gait ataxia, after nine days.

Discussion 

We presented a case of GBS with a serology suggesting recent COVID-19 infection. GBS is a rare serious post-infectious immune-mediated disease of the peripheral nervous system. Previous studies have suggested that GBS was not associated with COVID-19.¹⁰ However, the incidence of GBS has significantly increased since the onset of the COVID-19 pandemic. Many reports have described the association between SARS-CoV-2 infection and GBS, which is supported by the chronology of the GBS cases following the same propagation pattern of COVID-19 worldwide.¹¹ Numerous hypotheses have been proposed to explain the pathogenesis of the association including essentially immune dysregulation and systemic inflammation.¹² Following infection, there is generation of antibodies against surface glycoproteins or epitopes (spike) of SARS-Cov-2. These antibodies bind the gangliosides present in peripheral neurons due to the structural resemblance of the SARS-Cov-2’s epitopes with gangliosides (molecular mimicry).¹³ The systematic inflammation theory is explained by the massive cytokine release in patients infected which may also contribute to the amplification of the dysimmune process underlying GBS.¹⁴ A mean age of 50 years and male predominance were noticed among patients with the association of both diseases.^7,11

Inconsistent with most literature data, which reported that respiratory symptoms typically precede the onset of neurologic symptoms,^6,7,11 our patient was asymptomatic but had evidence of a COVID-19 infection. The median latency duration between the COVID-19 infection and GBS was 14 days for most reported cases supporting the post infectious immunopathogenesis mechanism. This duration could be longer then reported, as COVID-19 can initially be asymptomatic.^6,7 Few GBS reported cases had a para-infectious profile^15–17 as reported with the Zika virus.¹⁸ Nevertheless, the chronology of GBS preceding COVID-19 symptoms, described with few cases, has not been previously reported with other viral agents.⁶ A systematic review of 73 GBS cases associated with COVID-19 published from January 2020 to July 2020 ¹¹ revealed that only two cases never developed COVID-19 respiratory or systemic symptoms but tested positive for SARS-CoV-2^19,20. Our findings were consistent with those of the literature in terms of common symptoms of GBS, their mean time to nadir, which was equal to 5 days (range, 1.5–10 days) according to JB. Caress et al. ⁷ and the results of cerebrospinal fluid analysis as albuminocytologic dissociation being the most frequent finding.^6,7,11 Similar to our patient, the majority of reported cases received intravenous immunoglobulin therapy.⁶ In terms of clinical outcomes, the admission to the intensive care unit and the requirement of mechanical ventilation were reported respectively in 40 and 33 of 109 cases, by M. Aladawi et al.⁶ JB. Caress et al., and have reported the response to therapy in 33 of 37 (89%) patients.⁷

Conclusion

Our case report raises several concerns about the few cases of GBS following an asymptomatic COVID 19 infection and brings more attention to the possible atypical association between them. However, the main clinical, radiological and CFS features of our case report are found to be similar to GBS cases associated with other infectious diseases. Therefore, during the pandemic, all patients with suspected GBS should have SARS-CoV-2 tests in order to allow eventual rapid isolation. We expect an increase in the rate of GBS without an obvious cause, as long as one can have GBS after an asymptomatic COVID infection. The doctor should be standing by to provide early adequate assistance if required to prevent worse outcomes. Further studies to explore the immunogenicity of COVID-19 in the development of GBS are necessary and should consider the variations between different populations.