Is Guillain Barre syndrome truly caused by SARS-CoV-2?

Letter to the Editor

With interest we read the article by Nanda et al. about 4 patients with Guillain Barre syndrome (GBS) suspected to have been caused by an infection with SARS-CoV-2 [1]. It was concluded that these were the first cases with SARS-CoV-2 associated GBS from India and that the frequency of neuro-COVID may have been underestimated so far [1]. We have the following comments and concerns.

The main shortcoming of the study is the diagnosis GBS. Patient-1 had diabetes, and patient-3 had diabetes plus renal insufficiency requiring chronic hemodialysis [1]. How did the authors exclude that quadruparesis in these two patients was due to diabetic respectively uremic polyneuropathy? The HbA1c value in patient-1 was 9.4% and in patient-3 8.4%. Cerebrospinal fluid (CSF) glucose was markedly elevated in patient-1, patient-2, and patient-3. Was the HbA1c value also elevated in patient-2? The creatinine value in patient-3 was 4.74 mg/dl. How did the authors exclude diabetic plexopathy? We should know the results of proximal nerve conduction studies (NCSs) by means of proximal stimulation or F-wave responses. Arguments against the diagnosis GBS are that in none of the four patients did the spinal MRI show enhancement of the nerve roots, and that elevated CSF protein is frequent in diabetes [2] and may pretend “dissociation” (pseudo-dissociation). An argument against GBS in patient-2 is that immunoglobulins were ineffective. It should be discussed if treatment of hyperglycemia in patient-1 and patient-3 was responsible for the recovery of neuromuscular manifestations in these patients.

A further shortcoming of the study is that antibodies against C. jejuni, GM1, and GT1a, frequently elevated in GBS, were not determined. Even in the absence of gastrointestinal manifestations C. jejuni may trigger GBS [3]. In a recent prospective study of 50 GBS patients, 30% had serological evidence of a C. jejuni infection but only 8% of these patients reported symptoms [3].

Missing is also the exclusion of various other infectious or non-infections triggers of GBS. These include mycoplasma pneumoniae, Ebstein-Barr virus, cytomegaly virus, influenza-A virus, or hepatitis-E virus [4] and more rarely scrub typhus (Tsutsugamishi fever), Chikungunya, rubella virus, varicella-zoster virus, Toscana virus, hepatitis-C virus, hepatitis-A virus, hepatitis-B virus, West Nile virus, Zika, hyponatriemia, or bariatric surgery [5].

A further shortcoming is that the CSF was not investigated for virus-RNA. Among COVID-19 patients with GBS so far reported, SARS-CoV-2 could not be found in the CSF in any of 62 GBS patients with COVID-19 [6].

Concerning patient-4 we should know if also diplegia recovered under immunoglobulins. It would be interesting to know if GQ1b antibodies were elevated in patient-4, since they are elevated inn 100% of the patients with Miller-Fisher syndrome.

Overall, this interesting case study has shortcomings regarding the diagnosis GBS and regarding identification of triggering factors of GBS. As long as GBS in patients infected with SARS-CoV-2 is automatically attributed to COVID-19 and no other differential causes are excluded or considered, the pathophysiology of SARS-CoV-2 associated GBS will not be elucidated.

The authors declare no conflicts of interest.

No funding was received.

Author contribution: JF: design, literature search, discussion, first draft, critical comments.

Informed consent: was obtained.

The study was approved by the institutional review board.