Re: “SARS-CoV-2 and Guillain-Barré Syndrome: Lessons from Viral Infections” by Meidaninikjeh et al

To the Editor,

With interest we read the review article by Maidaninikjhe et al (2022) about the immune-pathogenesis of Guillain–Barre syndrome (GBS) and its association with viral infections, the possible link of SARS-CoV-2 with GBS, and immunomodulatory therapeutic approaches. It was concluded that there is a possible relationship between SARS-CoV-2 and GBS and that intravenous immunoglobulins, plasma exchange, complement inhibitors, and corticosteroids could be useful therapeutic options (Meidaninikjeh et al, 2022). The study is promising but raises concerns that should be discussed.

We disagree with the statement that GBS causes chronic disorders, such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN) (Meidaninikjeh et al, 2022). The etiology of CIDP and MMN is largely unknown. A small subgroup of CIDP cases is due to antibodies against paranodal structures such as contactin-1, Caspr-1, or neurofascin-155 (paranodopathies) (Koike and Katsuno, 2020).

GBS may not only be related to infection with viruses such as SARS-CoV-2, cytomegaly, Ebstein–Barr, influenza, measles, enterovirus, herpes simplex, Zika, hepatitis E, HIV, H1N1, and bacteria, such as Haemophilus influenza, Mycoplasma pneumoniae, and Campylobacter jejunii, but also due to vaccinations against various agents such as influenza, polio, hepatitis A, hepatitis B, SARS-CoV-2, or rabies.

The spectrum of neurological disease caused by SARS-CoV-2 is much broader than just headache, seizures, encephalopathy, stroke, and neuropathy, as mentioned in the review (Meidaninikjeh et al, 2022). In addition, SARS-CoV-2 may cause intracerebral bleeding, subarachnoid bleeding, venous sinus thrombosis, immune encephalitis, acute disseminated encephalomyelitis, acute hemorrhagical leukoencephalitis, ventriculitis, hypophysitis, cerebellitis, cerebral vasculitis, myasthenia, myasthenic syndrome, myositis, Parsonage–Turner syndrome, or rhabdomyolysis. Knowing the broad spectrum of neurological complications of SARS-CoV-2 infections is crucial, as some of these conditions can be the initial manifestation of a SARS-CoV-2 infection (Finsterer et al, 2021).

Missing is a discussion about cytokines, chemokines, and glial factors in the cerebrospinal fluid (CSF) and their role in the pathogenesis of SARS-CoV-2–related GBS (Gigli et al, 2020). In a recent study, it has been shown that SARS-CoV-2–related GBS may develop even in patients with asymptomatic or only paucisymptomatic SARS-CoV-2 infection and that particularly interleukin (IL)-6, IL-8, and tumor necrosis factor alpha may be elevated in the CSF of patients with SARS-CoV-2–related GBS (Gigli et al, 2020).

There is no mention of autonomic manifestations that may accompany GBS. Involvement of the autonomic system may be responsible for manifestations such as pupillary dysfunction, dry eyes, sicca syndrome, orthostatic hypotension, arrhythmias, heart rate fluctuations, blood pressure instability, constipation, sexual dysfunction, urinary retention, and dry skin. GBS may manifest even as pure autonomic dysfunction (Biassoni et al, 2021).

We disagree with the statement that lopinavir, ritonavir, azithromycine, and hydroxychloroquine should be administered to patients with SARS-CoV-2–related GBS to improve dysphagia and muscle weakness, and to reduce length of hospitalization on the ICU (Meidaninikjeh et al, 2022). There is little evidence that any of these compounds is truly beneficial and there are indications that side effects outweigh the positive effects of these drugs.

Overall, the interesting study has several limitations that call the results and their interpretation into question. Clarifying these weaknesses would strengthen the conclusions and could enhance the study.

Ethics Approval

This study was in accordance with ethical guidelines. The study was approved by the institutional review board.

Consent to Participate

Consent was obtained from the patient.