COVID-19 May Accelerate Onset of Myasthenia Gravis, Case Study Suggests

Findings from a new case study, coupled with learnings from previously documented cases, are suggesting that COVID-19 infection can accelerate the onset of myasthenia gravis (MG).

The group, publishing their findings in Journal of Neurology, hypothesizes that SARS-CoV-2 infection may have triggered thymic inflammation, spearheading initial expression of muscle-like epitopes and T-cell dysregulation. With just over a dozen of these case studies documented to date, the researchers highlighted the importance of more case series that analyze the pathological timeline and immunological characteristics of MG induced by COVID-19.

“In the literature, the debut of MG in connection with a specific infection has been reported in several case series. Some of the patients reported having thymoma as a cofactor and others were familiar with autoimmune diseases,” wrote the researchers. “In general, microbes are thought to precipitate an unwanted immunological response against self-antigens. Molecular mimicry, epitope diffusion, and polyclonal activation have all been suggested as responsible for the induction of MG by viral agents, but the exact mechanisms have not been proven. Moreover, no correlation between a specific preceding infection and MG has been documented.”

In the current case study, a 19-year-old female patient developed MG nearly 2 weeks after having COVID-19, presenting to the clinic with fluctuating double vision, moderately slurred speech, some difficulty swallowing solids, drooping of the right upper eyelid, and generalized weakness.

Based on examination, MG was expected. Her Myasthenia Gravis Composite score was 26/50. Facial and ulnar repetitive nerve stimulation was performed, showing a 60% and 37% decrement, respectively. Consistent with MG, the patient showed a significantly prolonged jitter on single-fiber electromyography on the frontalis muscle. The patient’s condition was complicated by a myasthenic crisis with respiratory failure 2 days after being hospitalized to receive intravenous immunoglobulin. Circulating anti-acetylcholine (AChR) antibodies were above 5 mMol/L.

After receiving treatment and being discharged, the patient was readmitted to the unit twice with worsening symptoms, leading to the removal of her thymus gland, a biopsy of which showed diffuse lympho-follicular hyperplasia. Notably, this is the first documented case of new-onset MG associated with thymic hyperplasia.

“There is evidence that the thymus is involved in the pathogenesis of MG in the subset of patients with anti-AChR antibodies and viral infections could trigger the onset of MG; thymic epithelial cells can express cross-reactive epitopes with skeletal muscle proteins, and these are presented to T lymphocytes; in a second step, thymic cells activate antigen presenting cells and diversify the antibody response,” explained the group. “Viral infection could affect the initial expression of muscle-like epitopes within the thymus, as well as T lymphocytes’ regulation and thus initiate the immunization process. Similarly, in our patient, SARS-CoV-2 infection could have triggered thymic inflammation, influencing the initial expression of muscle-like epitopes, as well as T-cell dysregulation.”

Eleven reports have detailed the cases of 15 patients with new-onset MG potentially brought on by COVID-19, with mild symptoms in 10 patients and severe symptoms in 2. Just 2 patients had evidence of thymoma, although the outcome of 1 patient is unknown, and 13 patients were positive for anti-AChR antibodies.

In these reported cases, as well as the case documented in the recent report, patients received a thymus CT rather than an MRI to determine thymic pathology, resulting in an inability to exclude thymus involvement based on imaging alone.

Manifestation of MG in these patients tended to come as generalized muscle weakness. Five patients received at least 1 course of intravenous immunoglobulin, 2 underwent plasmapheresis, and 12 were treated with pyridostigmine and/or prednisone before or after receiving intravenous immunoglobulin or plasmapheresis. There were 3 patients who also required azathioprine.

Reference

Tereshko Y, Gigli G, Pez S, De Pellegrin A, Valente M. New‐onset myasthenia gravis after SARS‐CoV‐2 infection: case report and literature review. J Neurol. Published online November 9, 2022. doi:10.1007/s00415-022-11472-6