https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779784

COVID-19 vaccination in patients with multiple sclerosis: Safety and humoral efficacy of the third booster dose

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder which is characterized by presence of antibodies against acetylcholine receptors (AChRs) or other proteins of the postsynaptic membrane resulting in damage to postsynaptic membrane, decreased number of AChRs or blocking of the receptors by autoantibodies. A number of drugs such as immune checkpoint inhibitors, penicillamine, tyrosine kinase inhibitors and interferons may induce de novo MG by altering the immune homeostasis mechanisms which prevent emergence of autoimmune diseases such as MG. Other drugs, especially certain antibiotics, antiarrhythmics, anesthetics and neuromuscular blockers, have deleterious effects on neuromuscular transmission, resulting in increased weakness in MG or MG-like symptoms in patients who do not have MG, with the latter usually being under medical circumstances such as kidney failure. This review summarizes the drugs which can cause de novo MG, MG exacerbation or MG-like symptoms in nonmyasthenic patients.

Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update.

Abstract Background Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. Methods We searched PubMed and EMBASE covering the period between January 1 st 2020 and August 6 th , 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. “traditional” vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. Results Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18–27%) of subjects after the first dose of vaccine and in 29% (95% CI 23–35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10–12% of cases. No differences were detected across different vaccines or by mRNA-based vs. “traditional” ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. Conclusions Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40–60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid. 

/pdf/headache-onset-after-vaccination-against-sars-cov-2-a-3bg9plp0.pdf

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis

Current knowledge on Multiple Sclerosis (MS) etiopathogenesis encompasses complex interactions between the host's genetic background and several environmental factors that result in dysimmunity against the central nervous system. An old-aged association exists between MS and viral infections, capable of triggering and sustaining neuroinflammation through direct and indirect mechanisms. The novel Coronavirus, SARS-CoV-2, has a remarkable, and still not fully understood, impact on the immune system: the occurrence and severity of both acute COVID-19 and post-infectious chronic illness (long COVID-19) largely depends on the host's response to the infection, that echoes several aspects of MS pathobiology. Furthermore, other MS-associated viruses, such as the Epstein-Barr Virus (EBV) and Human Endogenous Retroviruses (HERVs), may enhance a mechanistic interplay with the novel Coronavirus, with the potential to interfere in MS natural history. Studies on COVID-19 in people with MS have helped clinicians in adjusting therapeutic strategies during the pandemic; similar efforts are being made for SARS-CoV-2 vaccination campaigns. In this Review, we look over 18 months of SARS-CoV-2 pandemic from the perspective of MS: we dissect neuroinflammatory and demyelinating mechanisms associated with COVID-19, summarize pathophysiological crossroads between MS and SARS-CoV-2 infection, and discuss present evidence on COVID-19 and its vaccination in people with MS.

/pdf/multiple-sclerosis-and-sars-cov-2-has-the-interplay-started-4oea1kotkq.pdf

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

https://link.springer.com/content/pdf/10.1007/s13311-021-01165-9.pdf

Immunogenicity and safety of mRNA COVID-19 vaccines in people with multiple sclerosis treated with different disease-modifying therapies.

Background and purpose Although the COVID-19 vaccines are currently recommended for people with multiple sclerosis (MS), the fact that they were not specifically tested in people with MS raises uncertainty regarding their safety in this population. The purpose of this study was to report real-life safety data of the BNT162b2 COVID-19 vaccine in a cohort of MS patients. Methods An anonymous survey was distributed to 425 MS patients. Participants were asked general demographic and disease-related questions and specific questions regarding the safety profile of the COVID-19 vaccine. Results Of the 425 MS patients, 262 completed the questionnaire. The median (range) participant age was 42 (22-79) years, 199 participants were women (75.9%), and 66 participants (25.2%) had associated comorbidities. A total of 198 participants (75.6%) were treated with disease-modifying therapies. In all, 239 participants (91.2% of the responders) had received the BNT162b2 COVID-19 vaccine. Of these, 182 (76.1%) were aged 55 years. Adverse events were reported by 136 participants (56.9%; 52.5% of those aged 55 years; p = 0.1517) and 36 participants (15.1%) reported new or worsening neurological symptoms following the vaccination, the most frequent being sensory disturbances (21 participants, 58.3%). Most symptoms occurred within the first 24 h after vaccination and resolved within 3 days. A total of 28 participants (77.8%) did not require any medication to treat their symptoms. Conclusions This survey indicates an overall favorable safety profile of the BNT162b2 vaccine in people with MS. These data should be confirmed in further prospective, large-scale studies.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ene.15028

Safety of the BNT162b2 COVID-19 vaccine in multiple sclerosis (MS): Early experience from a tertiary MS center in Israel.

Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness in MG is documented and supported in the clinical practice over several decades, one of the main drawbacks of treatment results from the notion that MG patients may experience symptom worsening following CS treatment initiation. This may lead to the administration of lower than necessary doses of CS for the disorder, or even avoiding them altogether. As a consequence, some patients may not receive the optimal treatment to control their disease. In the present review, we analyzed 27 relevant publications and determined the prevalence of clinical exacerbation following CS treatment, its' severity and relation to the type and dose of CS. The rate of MG exacerbation is highest with the administration of cortisone, intermediate with prednisone, and lowest with methylprednisolone. High dose daily or alternate-day prednisone is associated with exacerbation more frequently than low-dose treatment, but most exacerbations are of mild to moderate severity. Other factors related to increased risk of an initial exacerbation include older age, generalized MG, bulbar symptoms, disease severity, presence of thymoma, and thymectomy. However, the current information is based mostly on heterogeneous studies of low quality, and prospective clinical trials designed to compare between the various agents and doses and assess the rate and severity of the exacerbation by a unified scale are warranted.

Adi Wilf-Yarkoni

Papers

Safety of the BNT162b2 COVID-19 vaccine in multiple sclerosis (MS): Early experience from a tertiary MS center in Israel.

Exacerbation of myasthenia gravis following corticosteroid treatment: what is the evidence? A systematic review