Case Investigated of Patient With Possible COVID-19–Induced Myasthenia Gravis

Wanting to learn more about the neurological manifestations of COVID-19 beyond the well-known respiratory complications, specifically among individuals who have myasthenia gravis (MG), investigators conducted a case study of a 46-year-old male patient who presented to the emergency department (ED) and received an ultimate diagnosis of COVID-19–induced seronegative MG.

They published their findings in Cureus.¹

“MG may be missed in patients after COVID-19 infections because of the comorbidities and anti-acetylcholine receptor [AChR] and anti–muscle-specific tyrosine kinase [MuSK] antibodies being negative,” the authors wrote. “Evidence from more studies will help analyze the pathological timeline of the disease process and the immunological characteristics of COVID-19–induced MG which can prove to have morbidity and mortality benefit in patients with COVID-19–induced MG.”

The patient’s medical history includes hypertension, hyperlipidemia, morbid obesity, obstructive sleep apnea, pes excavatum (sunken breastbone/funnel chest, and a condition that can worsen during a growth spurt²), interstitial lung disease, and hospitalization 5 months earlier due to acute hypoxic respiratory failure secondary to COVID-19 infection requiring mechanical ventilation. His symptoms upon presentation to the ED were shortness of breath and dry cough, with left-side opacities vs right seen on a chest x-ray. These were his vitals:

• Blood pressure: 128/82 mm Hg
• Heart rate: 93 bpm
• Temperature: 99.7°F
• Respiratory rate: 26 bpm
• Oxygen saturation: 91% on 3-L oxygen via a nasal cannula

Of the lab parameters analyzed, blood gas (pH), CO₂ partial pressure, arterial oxygen, and serum bicarbonate levels fell outside the accepted ranges.

Noninvasive ventilation did not lead to any improvement, with his blood gas dropping to 7.20 from 7.27 and CO₂ partial pressure increasing from 99 to 127 mm Hg; there was a also a decline in his mental status. A case of suspected pneumonia led to intubation after treatment with intravenous ceftriaxone and azithromycin.

When the patient could not be weaned off of mechanical ventilation, due to repeated failed spontaneous breathing trials, his care team found proximal muscle weakness and ptosis. The neurology team that was consulted found him negative for anti-AChR autoantibodies and anti–MuSK-MG, but also found him positive for antibodies against lipoprotein-related protein 4, “suggesting double-seronegative MG.”

Extubation followed successful treatment with thrice-daily 60-mg pyridostigmine, and a CT scan did not find a thymoma.

The case report authors noted that new-onset MG can be virus triggered and that previous research shows a connection between SARS-CoV-2 and autoimmune disease, including MG.³ Possible triggers of this reaction include increased release of type 1 interferon and other inflammatory cytokines 14, breakdown of self-tolerance mechanisms after infection, and activation of latent MG 1.

“There have been a few cases of MG after COVID19, but to our knowledge, seronegative MG post COVID-19 has not been described yet,” the authors highlighted. “It is important to recognize that seronegative MG can occur after COVID-19 as a delay in diagnosis can possibly worsen outcomes.”

Another important potential MG trigger was found: The patient received azithromycin for his suspected pneumonia, but evidence shows the drug is not recommended for use in individuals who have underlying MG, “as it can worsen their condition.”⁴

The authors underscore that while their findings may be of the first reported case of double-seronegative MG following COVID-19 infection, more investigation is needed on “the pathological timeline and the immunological characteristics of COVID-19–induced MG which can prove to have morbidity and mortality benefit in patients, especially with respiratory compromise,” they concluded.

References

1. Sadiq W, Waleed MS, Rizvi TA, Khan S, El Hage H. Myasthenia gravis associated with COVID-19 infection. Cureus. 2023;15(5):e39506. doi:10.7759/cureus.39506

2. Mayo Clinic staff. Pectus excavatum. Mayo Clinic. March 31, 2022. Accessed August 2, 2023. https://www.mayoclinic.org/diseases-conditions/pectus-excavatum/symptoms-causes/syc-20355483

3. Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19(9):767-83. doi:10.1016/S1474-4422(20)30221-0

4. Costamagna G, Abati E, Bresolin N, Comi GP, Corti S. Management of patients with neuromuscular disorders at the time of the SARS-CoV-2 pandemic. J Neurol. 2021;268(5):1580-1591. doi:10.1007/s00415-020-10149-2