Real-world data about the side effects of SARS-CoV-2 vaccinations can be obtained only from representative samples undergoing comprehensive investigations.

Letter to the Editor

We read with interest the article by Lotan et al. about a study of the side effects to SARS-CoV-2 vaccinations in 438 patients with rare neuro-immunological disorders, such as neuromyelitis optica (NMO), myelin oligodendrocyte glycoprotein (MOG) antibody disease, transverse myelitis, optic neuritis, or acute, disseminated encephalomyelitis (ADEM) (Lotan et al., 2021). It was concluded that the safety profile of COVID-19 vaccines in patients with rare neuro-immunological diseases seems favourable and that the rate of adverse events may be lower in patients receiving immunotherapies, particularly B-cell depletion therapies (Lotan et al., 2021). The study is appealing but raises concerns that need to be discussed.

We do not agree that the survey represents real-world data for the following reasons: 1. to answer the questionnaire it is necessary that a particular patient is in a mentally stable condition, alert, and able to respond to each of the questions. We should be told how many of those receiving the questionnaire responded but were mentally handicapped when answering the questions. 2. it was not mentioned if only the patient himself was allowed to answer the questionnaire or also his relatives or caregivers. It is important to know who responded as patients aware of their deficits may give different answers than their supervisors. 3. patients hospitalised for side effects of the vaccination may have not received the questionnaire and may have not been able to respond. We should be told how many of those who did not respond were hospitalised for side effects of the vaccination at the time of the survey. 4. the diagnosis of the included patients remained unconfirmed as data were collected in an anonymous way without confirmation of the results that led to the diagnosis. 5. not all patients of the facebook platform “The NMO clinic” might have had access to social media at the time of the survey and therefore the possibility to receive the questionnaire. Furthermore, the sample size might have been too small to detect patients with severe side effects or those who experience long-term deterioration of their underlying neuro-immunologic disease.

A further limitation of the study is that the patients neither underwent clinical investigations nor instrumental investigations to substantiate their complaints, to assess if there was a dynamic change regarding symptoms, signs, and results of instrumental investigations. It would have been interesting to know how many of the patients presented with signs they might not have recognised by themselves and in how many of the patients previous MRI abnormalities deteriorated due to the vaccination.

Only marginally discussed was the issue that SARS-CoV-2 vaccinations can trigger neuro-immunological disease, such as multiple sclerosis, or can induce flares of known neuro-immunological disorders such as multiple sclerosis or NMO (Khayat-Khoei et al., 2021 Sep 4). An example of such an adverse reaction is the case of a 32 years-old male with an uneventful previous history who presented with a confusional state, dizziness, headache, and imbalance starting one week after the second dose of the Sputnik-V vaccine (Badrawi et al., 2021). Since cerebral MRI showed typical morphology of NMO and aquaporin-4 IgG were positive, the patient was diagnosed with NMO (Badrawi et al., 2021). Repeated plasmaphereses was beneficial (Badrawi et al., 2021).

The spectrum of neuro-immunologic disease triggered by SARS-CoV-2 vaccinations is broader than anticipated. Not only the central nervous system (CNS) but also the peripheral nervous system (PNS) may be affected. Regarding the CNS, cases with immune encephalitis, limbic encephalitis, hypophysitis, cerebellitis, cerebral vasculitis, or venous sinus thrombosis due to immune thrombocytopenia have been reported in addition to those included in the survey. Regarding the PNS, Guillain-Barre syndrome, Parsonage Turner syndrome, myasthenia, myasthenic syndrome, or immune myositis have been published as side effects of SARS-CoV-2 vaccinations (Finsterer, 2022).

Overall, the interesting study has limitations that call into question the results and their interpretation. Data from questionnaires may only tell half of the truth as its questions may be answered by subjects other than the patient, by handicapped patients, or may not even reach the patient. SARS-CoV-2 vaccinations may not only evoke mild or moderate side effects but also severe or even fatal adverse reactions.

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

Declaration of Competing Interest

The authors declare no conflicts of interest