Discussion
Although the possibility of GBS associated with SARS-CoV-2 infection remains to be clarified, the number of GBS cases reported between March 2020 and April 2020 is greater than five times that reported in the last 3 years.17 Given that reports have begun to describe GBS and neurological complications following SARS-CoV-2 infection, the onset of GBS requires special attention.
Among the 37 patients described by Caress et al, 17 were tested for anti-ganglioside antibodies, 15 of whom were negative. In addition, two patients were positive for Miller-Fisher syndrome, and all were negative for GBS. However, specific description of types of the anti-ganglioside antibodies tested were not provided in many cases. Although some reports specifically described the types of antiganglioside antibodies tested, patients appear to have been tested only for anti-GM1, anti-GQ1b and anti-GD1b antibodies.9 10 14 Although we tested for various additional antiganglioside antibodies, all tests were negative in the present case as well. GBS was also reported in a case–control study of the 2016 Zika virus, where most patients were negative for antiganglioside antibodies, suggesting the existence of unknown antibodies.18 Therefore, it is important to test for as many kinds of antibodies as possible when suspecting GBS associated with SARS-CoV-2. However, some authors have reported nearly simultaneous development of neurological and respiratory symptoms in patients with COVID-19 and GBS.19 20 Thus, the cause of GBS may not be immune related in all cases. Previous research has suggested that SARS-CoV-2 damages the vascular endothelium.21 Therefore, axonopathy may have been caused by a microvascular disorder. In addition, McGonagle et al proposed that hyperinflammation following macrophage activation syndrome (ie, ‘cytokine storm’) may be a cause of GBS in patients with SARS-CoV-2 infection.22 Together, these findings suggest that, if neurological symptoms develop early following the appearance of respiratory symptoms in patients with COVID-19, both autoimmune and other factors should be considered in the diagnosis.
Whittaker et al noted that the GBS associated with SARS-CoV-2 infection manifests mainly as lower extremity weakness and paraesthesia.23 Similarly, neurological symptoms began in our patient’s lower limbs. Axonal disorders and lower extremity dominant symptoms may be similar in character to the length-dependent neuropathies observed in patients with microangiopathy. The present case satisfied the essential diagnostic criteria for GBS described by Asbury and Cornblath, and the patient’s clinical course supported the diagnosis of GBS. Nonetheless, the CSF test yielded atypical findings.
In conclusion, our report supports the notion that patients with GBS associated with SARS-CoV-2 infection tend to test negative for antiganglioside antibodies. In addition to careful diagnosis, further reports are required to elucidate the characteristics and the mechanisms underlying the onset of GBS due to SARS-CoV-2 infection.
Patient’s perspective
I was anxious when COVID-19 symptoms improved and neurological symptoms such as numbness and weakness developed. My symptoms gradually progressed and peaked in about 3–4 weeks. My doctor told me that I might have Guillain-Barré syndrome. I was told about gamma globulin treatment, but I declined that option due to the risk of side effects and the mild nature of my symptoms. After that, the symptoms gradually improved and the weakness disappeared, although the numbness remained. I was satisfied with the treatment protocol.
Learning points
Patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection may test negative for many known antiganglioside antibodies.
Careful diagnosis of GBS is required, because peripheral neuropathy in patients infected with SARS-CoV-2 may have causes other than autoimmune conditions.
Further studies and case reports are required to facilitate discussion of the mechanisms underlying GBS associated with SARS-CoV-2 infection.