4.DISCUSSION
This study reviewed the safety studies of COVID-19 vaccination in
patients with autoimmune neurological conditions and conducted a
systematic review and meta-analysis. The results of the study showed
that the general adverse event pooled incidence rate of ANC patients
post-vaccination with COVID-19 was similar to the healthy
people(35%:25%-38%), vaccination had little effect on the original
neurological autoimmune disease, the disease exacerbation rate caused by
the vaccine was very low(5%), and COVID-19 vaccination was generally
safe for ANC patients.
Infection is a clear predisposing or aggravating factor for some
autoimmune diseases, and it has been documented that COVID-19 infection
induces neuroimmune diseases or leads to the aggravation of pre-existing
diseases[41]. Patients with ANC are at increased
risk of acute respiratory distress syndrome and multiple organ failure
after infection with the SARS-CoV-2 virus because of their
immunosuppressed status[42], therefore, the
protection of this group of patients is a priority, and some
international consensus also recommends that people with neuroimmune
diseases be vaccinated against SARS-CoV-2 as soon as
possible[43].However, it is troubling that
vaccination activates autoimmune responses, and theoretically, the
vaccine may also induce ANC or lead to deterioration or recurrence of
the disease in ANC patients. Although more than 5 billion people have
been vaccinated worldwide(https://covid19.who.int.),results from some
investigative studies demonstrate that there are still 10%-20% of
patients with neuroimmune diseases are hesitant to
vaccinate[44], and there are many reasons for
hesitation, but the most common reasons were concerns about vaccine
safety[45].A better clarification of the safety of
COVID-19 vaccination in ANC patients is therefore crucial to help reduce
their vaccine hesitancy and bring the COVID-19 pandemic under control.
After vaccination, we found a pooled incidence rate of general adverse
events to be approximately 35%. Most of the symptoms were characterized
by transient post-vaccination adverse reactions, such as pain, swelling,
redness, fever, chills, fatigue, headache, myalgia and weakness at the
injection site, and the incidence of these common adverse reactions was
similar to that in healthy people[4]. Subgroup
analysis of disease category showed that patients with multiple
sclerosis had a slightly higher general adverse event rate (43%) than
those with neuromyelitis optica and myasthenia gravis, but less than
half overall. Due to ethnic and geographical differences in the
prevalence of different diseases, and large heterogeneity between
studies, the incidence of adverse events in the three common neuroimmune
diseases cannot be directly compared. In general ,a similar incidence of
general adverse events in all three diseases to that observed with
healthy people, with no significant difference. Subgroup analysis of
different vaccinations showed that the incidence of general adverse
reactions caused by different doses was essentially the same for
patients with neuroimmune diseases. Because the virus mutates
continuously during transmission, breakthrough infections occur at a
high incidence in patients receiving routine doses of the vaccine, and
many studies have shown that universal booster vaccination could be a
current strategy to prevent breakthrough infections from
COVID‐19[46]. From the pooled analysis, there was
no increase in the incidence of general adverse reactions in patients
with ANC who received three vaccinations, this finding could be
considered that providing booster needles to further enhance the
protective effect of ANC patients. Currently, the most widely used
vaccine types worldwide are mRNA vaccines and inactivated vaccines, and
subgroup analysis results show that there is little overall difference
in the incidence of general adverse events between these two vaccines,
so it is reasonable to recommend these two types of vaccines to patients
with neuroimmune diseases from a safety point of view.
Whether COVID‐19 vaccination leads to the exacerbation of underlying
neuroimmune diseases has been a controversial topic and a significant
cause of vaccine hesitation in patients with neuroimmune diseases. A
questionnaire survey on vaccination willingness conducted on South
Korean people with myasthenia gravis by researchers KIM et al reported
that patients who had experienced myasthenic crises were more resistant
to vaccination in 160 questionnaire results, which may be related to
their greater concern about the exacerbation of underlying
diseases[47].Yap, S. M. et al. surveyed COVID-19
vaccination willingness among people with multiple sclerosis in Northern
Ireland, and the results showed that about 20% of MS patients are
antipathy to vaccines[48].Most of this antipathy
stems from concerns that vaccination may trigger or aggravate the
disease[49]. The association of vaccination with
disease recurrence has been reported previously in several studies,A
review incorporated 10 observational articles with a total of 1299
myasthenia gravis patients revealed that only 60 (4.26%) patients
developed an acute exacerbation of MG after
vaccination[9];In a study conducted in Kuwait, the
probability of disease worsening and recurrence was carried out a 5.5%
and 1.8% following Vaccination in MS patients,
respectively[2]. Giannoccaroet al. reported no
difference in the recurrence rate of NMOSD before and after
vaccination[29].In a multicenter prospective
clinical study conducted by Ad´aja E. Baars et al, 1152 patients with
neurological autoimmune diseases including GBS, CIDP, or
multifocal motor neuropathy (MMN)
were enrolled. The results showed that the exacerbation rates of these
three underlying diseases after vaccination were 0%, 3%, and 4%,
respectively. Those studies suggest that vaccination does not increase
the risk of disease exacerbation and provides evidence of the safety of
vaccination in patients with ANC[50]. Despite the
majority of research indicating no significant exacerbation of
pre-existing neurological and immunological conditions following
vaccination, divergent outcomes exist due to variations in the disease
under study, population inclusion criteria, sample size, geographic
location, and vaccine type employed. Our meta-analysis demonstrate that
the rate of recurrence or exacerbation of underlying diseases after
SARS-CoV-2 vaccination is low, at approximately 7%. Due to the lack of
control groups in most vaccine studies and the proportion may be even
lower given that mass vaccination of the population may coincide with
natural deterioration or relapse of the disease. Furthermore, for
patients with exacerbations of pre-existing conditions, most have a good
prognosis, and there are almost no reports of severe deterioration
(requiring adjustment of current treatment plans) reported, and this
exacerbation is mostly transient, after the steroid of treatment,
patients can partially or completely return to baseline
values[16, 32], Exacerbating symptoms have also
been reported to be self-limiting in some patients and recover without
the need for any medical treatment[29]. In
addition, we also found that the proportion of neurological adverse
reactions caused by vaccination is relatively low(around 11%), which
further confirmed that vaccination had a minor impact on the course of
ANC and that COVID-19 vaccination was safe for patients with
neurological autoimmune diseases. Due to significant heterogeneity
between studies, we conducted categorical subgroup analysis based on
vaccination dose, vaccine type, and different ANC types. However, the
heterogeneity did not significantly decrease, suggesting that it may be
due to factors such as age, gender, ethnicity, and different study
countries, which could introduce systematic errors and result in high
heterogeneity. This is consistent with our research conclusion, which
demonstrates that SARS-CoV-2 vaccines are safe in patients with
neuroimmune disorders.