We eagerly read the article by Chavez et al. about an 82 year old male who was diagnosed with late-onset myasthenia gravis being attributed to a SARS-CoV-2 vaccination with the BNT162b2 vaccine [1]. The patient profited initially from pyridostigmine, but experienced a relapse within two weeks after initiation of the treatment [1]. Not before re-starting pyridostigmine and adding steroids and intravenous immunoglobulins, the patient slowly recovered [1]. The study is appealing but raises concerns, which require discussion. 

We do not agree with the notion that the SARS-CoV-2 vaccination triggered newly onset myasthenia [1]. Bulbar symptoms had been present “for a few weeks” but the first jab of the vaccine was given only four weeks prior to symptom onset [1]. If symptoms of myasthenia had begun already prior to the vaccination, a causal relation between the vaccination and myasthenia is unlikely. Thus, we should be informed about the exact onset date of myasthenic symptoms, particularly what “for a few weeks” means. A further argument against a causal relation between vaccination and myasthenia is that, according to our knowledge, no case has been reported in which a SARS-CoV-2 vaccination triggered a myasthenic crisis. 

Arguments in favour of a causal link between vaccination and new onset myasthenia in the index patient, however, are, that previous cases with vaccination induced myasthenia had been reported, that it is well known that SARS-CoV-2 vaccinations may trigger new or flares of immunological disease [2], and that no other plausible trigger of myasthenia had been found in the index patient. In a previous report about the side effects among 232603 vaccinees from Germany, one of these patients developed new onset myasthenia [3]. In a study of 27 patients with SARS-CoV-2 vaccination associated immune-mediated disease, two had developed newly onset myasthenia [2].

It is not comprehensible why the patient did not receive immune-modulating or immune-suppressive treatment, with steroids, immunoglobulins, azathioprine, mycophenolate, rituximab, or bortezomib immediately after establishing the diagnosis. He had high acetyl-choline receptor antibodies, a decremental response on low-frequency repetitive nerve stimulation, was old, and had no thymoma. More than two months were letting past before steroids and immunoglobulins had been started. Within this period, the patient developed generalised manifestations of myasthenia. 

Missing in the case report is the exclusion of myasthenic syndrome by high-frequency repetitive nerve stimulation and determination of antibodies against the voltage gated calcium channels as the patient had a history of laryngeal carcinoma and as laryngeal carcinoma can trigger myasthenic syndrome [4]. Missing is the exclusion of a SARS-CoV-2 infection, considering that SARS-CoV-2 infections can trigger myasthenia [5]. Missing is the determination of acetyl-choline receptor antibodies after treatment. We should be told if immune-modulating treatment was also effective with regard to the antibody titres. 

Overall, the interesting study has some limitations which    challenge    the results  and their interpretation. A causal link between vaccination and development of myasthenia remains unproven. Myasthenic syndrome needs to be excluded. Immuno-suppression should start early in myasthenia patients with high antibody titres, even if generalisation of myasthenic symptoms is not present yet.   

Declarations

The authors declare no conflicts of interest. No funding was received

Author Contribution

• JF: design, literature search, discussion, first draft, critical comments

• RG: literature search, discussion, critical comments, final approval

Informed Consent

Was obtained. The study was approved by the institutional review board. The study complies with the declaration of Helsinki