Post SARS-CoV-2 Guillain-Barré syndrome.

On March 26, 2020, a 64-year-old man presented himself to the Emergency department of Avicenne University Hospital with a 7-day history of cough, dyspnea, diarrhea and fever. He had not recently traveled. His body temperature was 38.5 °C, his respiratory rate was 30 breaths/min and the oxygen saturation was 93% on ambient air. Lung auscultation revealed diffuse crackles. A chest computed tomography (CT) showed bilateral, diffuse and subpleural ground-glass opacities with a crazy-paving appearance, and a band of air space consolidation. The real-time polymerase-chain-reaction assay (RT-PCR) of nasal swab returned positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Regarding the severity of the initial picture, he received a treatment by Cefotaxime, Azithromycin and Hydroxychloroquine. The patient progressively recovered without intensive care and left the hospital on April 8.

On April 15, 2020, the patient was again hospitalized, this time because of a 4-day history of fast progressive lower-limb weakness. He was apyretic and displayed no respiratory symptoms. The neurological examination showed generalized areflexia, severe flaccid paraparesis, mainly affecting proximal muscles, and a decreased proprioceptive length-dependent sensitivity involving the four limbs. We also found hypoesthesia to light touch and pinprick in lower extremities rather related to his medical history of diabetes mellitus type 2. The cerebral CT was normal. Serological tests for Campylobacter jejuni, HIV, syphilis, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were negative. Serum antiganglioside and anti-neuronal antibodies were absent. Cerebrospinal fluid (CSF) analyses (day 6) revealed an increased protein level at 1.65 g/L, no pleocytosis and no intrathecal synthesis of immunoglobulins. PCR assays of the CSF were negative for SARS-CoV-2, CMV and EBV. Electrodiagnostic testing performed five days after the onset of neurological symptoms mainly showed delayed motor distal latencies in the upper limbs, absence of F-waves in the 4 limbs, conduction blocks in peroneal and tibial nerves bilaterally, very low motor conduction velocities, and absent sensory nerve action potentials except for radial nerves and median nerves at the palm (Table 1 ). These electrophysiological results were compatible with a demyelinating neuropathy.

Table 1

Peripheral nerve conduction studies.

	Distal latency (ms)	Amplitude	Conduction velocity (m.s-1)	Amplitude ratio (%)	Area ratio (%)
Motor nerve conduction
Right median nerve
Wrist- abductor pollicis brevis	5.29 (n < 3.5)	10.3 mV (n > 5)
Antecubital fossa-wrist	11.4	9.2 mV	49.1 (n > 50)	−10.7	−14.1
Axillary-Antecubital fossa	14.4	9.7 mV	53.3	5.4	4.4
Erb-Axillary	19.3	7.3 mV	53.1	−24.7	−21.8
Left median nerve
Wrist- abductor pollicis brevis	5.13 (n < 3.5)	7.9 mV (n > 5)
Antecubital fossa-wrist	11.3	8.0 mV	47.0 (n > 50)	1.27	20.5
Axillary-Antecubital fossa	14.0	8.5 mV	55.6	6.3	3.9
Erb-Axillary	18.5	5.8 mV	53.3	−31.8	−19.0
Right ulnar nerve
Wrist-abductor digiti minimi	3.49 (n < 3)	7.3 mV (n > 6)
Below-elbow wrist	9.06	6.9 mV	47.6 (n > 50)	−5.5	−9.0
Above elbow-below elbow	12.0	6.9 mV	37.4	0	−2.1
Axillary-Above elbow	13.8	6.0 mV	44.4	−13.0	−5.1
Erb-Axillary	20.0	4.1 mV	41.9	−31.7	−34.4
Left ulnar nerve
Wrist-abductor digiti minimi	3.50 (n < 3)	7.4 mV (n > 6)
Below-elbow wrist	8.75	5.5 mV	50.5 (n > 50)	−25.7	−25.0
Above elbow-below elbow	11.5	4.9 mV	40.0	−10.9	1.11
Axillary-Above elbow	14.2	5.0 mV	51.9	2.0	−2.4
Right peroneal nerve
Ankle-extensor digitorum brevis	4.88 (n < 5)	3.8 mV (n > 3)
Below fibula–ankle	16.5	1.60 mV	29.7 (n > 40)	−57.9	−51.0
Above fibula– below fibula	18.7	1.56 mV	38.6	−2.5	−3.1
Left peroneal nerve
Ankle-extensor digitorum brevis	5.19 (n < 5)	4.3 mV (n < 3)
Below fibula–ankle	16.9	1.65 mV	30.7 (n > 40)	−61.6	−57.5
Above fibula– below fibula	19.5	1.62 mV	30.8	−1.82	6.7
Right tibial nerve
Ankle-abductor hallucis brevis	5.07 (n < 5.5)	2.1 mV (n > 6)
Popliteal fossa–ankle	25.2	0.41 mV	20.9 (n > 40)	−80.5	−83.1
Left tibial nerve
Ankle-abductor hallucis brevis	4.71 (n < 5.5)	2.9 mV (n > 6)
Popliteal fossa–ankle	18.3	0.74 mV	28.0 (n > 40)	−74.5	−66.7
Sensory nerve conduction
Right median nerve
Digit 1 – wrist		0
Digit 2 – wrist		0
Digit 3 – wrist		0
Palm – wrist		6.7 μV (n > 15)	23.0 (n > 45)
Left median nerve
Digit 1 – wrist		0
Digit 2 – wrist		0
Digit 3 – wrist		0
Palm – wrist		4.0 μV (n > 15)	27.8 (n > 45)
Right ulnar nerve
Digit 5 – wrist		0
Left ulnar nerve
Digit 5 – wrist		0
Right radial nerve
Lateral forearm – wrist		23.7 μV (n > 15)	44.1 (n > 45)
Left radial nerve
Lateral forearm – wrist		18.6 µV (n > 15)	40.0 (n > 45)
Right superficial fibular nerve
Lateral calf – lateral ankle		0
Left superficial fibular nerve
Lateral calf – lateral ankle		0
Right sural nerve
Calf – posterior ankle		0
Left sural nerve
Calf – posterior ankle		0

Subacute peripheral neurological disorder, albuminocytological dissociation in the CSF and demyelinating abnormalities with conduction blocks on electrodiagnostic testing were strongly suggestive of Guillain-Barré syndrome. The patient was successfully treated with intravenous immunoglobulin for five days.

To the best of our knowledge, six cases of Guillain-Barré syndrome associated with SARS-CoV-2 have been described so far. One in Jingzhou, China with a parainfectious profile (H. Zhao et al., 2020), and five in northern Italy with a 5 to 10-days interval between the onset of the infection and the neurological symptoms (Toscano et al., 2020). In our case report, this interval was longer, as the Guillain-Barré syndrome started three weeks after the beginning and 7 days after the recovery from the SARS-CoV-2 infection, without documentation of any other infection during that period. Therefore, our case responds to the classic post-infectious pattern, as is seen in Guillain-Barré syndrome associated with Zika virus infections (Barbi et al., 2018, Cao-Lormeau et al., 2016). In addition, a critically illness neuropathy and/or myopathy secondary to intensive care is unlikely since our patient was not transferred to such a unit, alongside a relatively mild course of the disease. We suspect that the underlying mechanism is autoimmune cross-reactivity responsible for the subacute polyradiculoneuritis. It has been demonstrated that the seroconversion seems in place around 15 days after the onset of the disease, which is compatible with an autoimmune response in our patient (J. Zhao et al., 2020). However, since serological tests for antibodies to SARS-CoV-2 are not currently available, this hypothesis cannot yet be fully proven.

Overall, this new case reinforces the idea of a possible association between SARS-CoV-2 infection and Guillain-Barré syndrome through an autoimmune cross-reactivity mechanism, but further data and analyses will be necessary to precisely determine the prevalence of Guillain-Barré syndrome and its causal link with SARS-CoV-2.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.