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.