Vaccination against COVID‐19 does not lead to exacerbation in patients with myasthenia gravis

Short abstract

See article on pages 558‐561 in volume 66, Issue 5, November issue.

Abbreviations

GBS

guillain‐Barre syndrome

MG

myasthenia gravis

PASS

patient acceptable symptom state

SSQ

single simple question

vMGII

virtual myasthenia gravis impairment index

Myasthenia gravis (MG) is an autoimmune neuromuscular condition resulting in fatigable muscle weakness affecting ocular, bulbar, limb, or respiratory muscles. Disease exacerbations have been linked to a variety of infections ¹ ; or use of specific medications, including neuromuscular junction blockers, antibiotics, and others. ² However, the relationship between vaccination and myasthenia gravis is less certain. In other immune‐mediated neuromuscular diseases, particularly Guillain‐Barré syndrome (GBS), some association has been noted. A 2015 meta‐analysis showed a slight but statistically significant increase in risk (relative risk 1.41, 95% confidence limit 1.20–1.66) for GBS following influenza vaccination. ³ In myasthenia gravis, historically, there was not felt to be a link between influenza vaccination and disease exacerbation. This is based on retrospective, population‐based data (in 3667 MG patients) showing that the frequency of serious MG exacerbations during the first 6 wk after influenza vaccination was not different from the frequency of serious exacerbations at other time points. ⁴

Since the onset of the coronavirus disease 2019 (COVID‐19) pandemic and the subsequent availability of vaccines, several reports concerning the link between vaccination and myasthenic exacerbations have emerged. Most of these have been case reports or small case series in MG patients who have received mRNA vaccinations ⁵ , ⁶ , ⁷ , ⁸ , ⁹ ; and from these reports, only a few isolated cases of significant MG exacerbations occurred. More substantial population‐based data (reflecting 32 million patients captured by the National Immunization Management System database in England) did report a slightly higher risk of hospitalization or death from myasthenic disorders 15–21 days after the first dose of adenoviral COVID‐19 vaccine, although heightened risks with mRNA vaccines were not reported. ¹⁰

In a previous issue of the Journal, Urra Pincheira et al. ¹¹ have attempted to provide more detailed information regarding the safety of COVID‐19 vaccination in a larger cohort of patients with myasthenia gravis. The study design allowed the authors to provide information not only regarding severe exacerbations, but also mild ones that did not result in hospitalization or death, but were still relevant to the patients. The study was a retrospective case series, examining detailed medical records for 200 MG patients who: (1) received two doses of any available COVID‐19 vaccine, and (2) underwent regular telephone assessments between February and August 2021 (overlapping with the administration of vaccines in Canada). These virtual assessments were performed prior to vaccination, then roughly 2 wk after each dose. The primary outcome measures used for the assessment of disease severity were the virtual Myasthenia Gravis Impairment Index (vMGII), single simple question (SSQ), and Patient Acceptable Symptom State (PASS). In particular, the MGII is a well‐validated scale for the assessment of MG severity and comprises 22 patient‐reported items, as well as 6 physical examination items (which are deferred if performed virtually). Other information gleaned from the chart review included demographic information, baseline disease severity, medication use, and thymectomy status.

Several findings emerged from the study. The cohort was comprised of 200 MG patients, of whom 36 had purely ocular MG and 107 were confirmed to be antibody positive. The relevant outcome measures were essentially unchanged after both vaccine doses and did not differ significantly from baseline levels. At the last follow‐up visit, almost 90% of patients found their current disease state acceptable (PASS ‘yes’); and the mean values for the SSQ and vMGII scores were 90% and 7.05; implying that overall disease was well‐controlled. There were no patients who required emergency room visits or hospitalizations owing to vaccine‐associated exacerbations. Of note, the cohort also included one pregnant MG patient who received vaccinations at 13 and 22 wk of pregnancy and did not experience any worsening of disease. Finally, the authors noted adverse event rates of 56%–60% with COVID‐19 vaccination, mainly comprising local reactions and fatigue. These rates were similar to what has been reported in the non‐myasthenic population. ¹²

The study does have several limitations, some of which were acknowledged by the authors. The study reflects the experience at a single center, and the patient population was mainly composed of stable/well‐controlled, chronic MG patients. This may limit the generalizability of the study, and it would be difficult for the authors to extrapolate their results to unstable or newly diagnosed MG patients. In addition, as the study was performed retrospectively, it may be susceptible to information bias or selection bias. These sources of error may have been lessened through the prospective enrollment of MG patients into a cohort. Finally, the authors do not provide information on their MG patients who did not receive any vaccination. Therefore, comparison of disease severity scores could not be made between vaccinated and unvaccinated groups.

Based on the results of this study, it would be fair to state that COVID‐19 vaccination did not result in disease exacerbation, or even worsening of stable MG, in a group of 200 MG patients exposed to either mRNA or adenoviral vaccines. Therefore, patients who undergo COVID‐19 vaccination likely do not require more frequent or more intensive monitoring than other MG patients. In addition, this study can aid clinicians in counseling MG patients that COVID‐19 vaccination is safe and does not confer an added risk of disease exacerbation. Although not specifically examined in this study, bivalent booster doses against COVID‐19 omicron variants are likely also safe for MG patients, as the mechanism of action is unchanged from the original mRNA vaccines. Finally, although this study focused principally on patients with chronic stable MG, we believe that vaccines are still indicated in patients with newly‐diagnosed or less stable MG, based on the principle that viral infection likely poses higher risk than vaccination.

ETHICS STATEMENT

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

AUTHOR CONTRIBUTIONS

Ari Breiner: Writing – original draft; writing – review and editing. Pierre R. Bourque: Writing – original draft; writing – review and editing.

CONFLICT OF INTEREST

AB reports grant funding from Muscular Dystrophy Canada. PB reports no relevant conflicts of interest.

DATA AVAILABILITY STATEMENT

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.