Case Reports

Myasthenic Crisis After Recurrent COVID-19 Infection

A patient with myasthenia gravis who survived 2 COVID-19 infections required plasmapheresis to recover from an acute crisis.

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COVID-19 is still in the early stages of understanding, although it is known to be complicated by individual patient comorbidities. The management and treatment of COVID-19 continues to quickly evolve as more is discovered regarding the virus. Multiple treatments have been preliminarily tested and used under a Food and Drug Administration emergency use authorization (EUA) determination. The long-term success of these therapies, however, is yet to be determined. Additionally, if a patient has a second clinical presentation for COVID-19, it is not known whether this represents latency with subsequent reactivation from the previous infection or a second de novo infection. The uncertainty calls into question the duration of immunity, if any, following a primary infection.

COVID-19 management becomes more complicated when patients have complex medical conditions, such as myasthenia gravis (MG). This autoimmune neuromuscular disorder can present with varying weakness, and many patients are on immunomodulator medications. The weakness can worsen into a myasthenic crisis (MC), resulting in profound weakness of the respiratory muscles. Therefore, patients with MG are at increased risk for COVID-19 and may have a more complicated course when infected.

Our patient with MG presented for severe COVID-19 symptoms twice and later developed MC. He received 2 treatment modalities available under an EUA (remdesivir and convalescent plasma) for COVID-19, resulting in symptom resolution and a negative polymerize chain reaction (PCR) test result for the virus. However, after receiving his typical maintenance therapy of IV immunoglobulin (IVIG) for his MG, he again developed symptoms consistent with COVID-19 and tested positive. After recovering from the second episode of COVID-19, the patient went into MC requiring plasmapheresis.

Case Presentation

A 56-year-old male, US Army veteran presented to Carl R. Darnall Army Medical Center emergency department (ED) 6 days after testing positive for COVID-19, with worsening sputum, cough, congestion, dyspnea, and fever. Due to his MG, the patient had a home oxygen monitor and reported that his oxygenation saturation dropped below 90% with minimal exertion. His medical history was significant for MG, status postthymectomy and radiation treatment, left hemidiaphragm paralysis secondary to phrenic nerve injury, and corticosteroid-induced insulin-dependent diabetes mellitus. His current home medications included pyridostigmine 60 mg 3 times a day, mycophenolate (MMF) 1500 mg twice daily, IV immunoglobulin (IVIG) every 3 weeks, insulin aspart up to 16 U per meal, insulin glargine 30 U twice a day, dulaglutide 0.75 mg every week, and metformin 1000 mg twice daily.

On initial examination, the patient’s heart rate (HR) was 111 beats/min, respiratory rate (RR), 22 breaths/min, blood pressure (BP), 138/88 mm Hg, temperature, 100.9 oF, and his initial pulse oximetry, 91% on room air. On physical examination, the patient was tachypneic, though without other signs of respiratory distress. Lung auscultation revealed no adventitial lung sounds. His cardiac examination was notable only for tachycardia. His neurologic examination demonstrated intact cranial nerves, with 5 out of 5 (scale 1 to 5) strength throughout the upper and lower extremities, sensation was intact to light touch, and he had normal cerebellar function. The rest of the examination was normal.

Initial laboratory investigation was notable for a white blood cell count of 14.15x103 cells/mcL with 84% neutrophils, and 6% lymphocytes. Additional tests revealed a C-reactive protein (CRP) level, 17.97 mg/dL (reference range, 0-0.5 mg/dL), ferritin level, 647 ng/mL (reference range, 22-274 ng/mL), d-dimer, 0.64 mcg/mL (reference range, 0-0.47mcg/mL), and a repeated positive COVID-19 PCR test. A portable chest X-ray showed bibasilar opacities (Figure 1).

Chest X-ray First Presentation to Emergency Department and Chest X-ray First Hospital Discharge figures

The patient was diagnosed with COVID-19 and admitted to the intensive care unit (ICU). In the ICU, the patient received 1 U of convalescent plasma (CP) and started on a course of IV remdesivir 100 mg/d consistent with the EUA. He also received a 5-day course of ceftriaxone and azithromycin for possible community acquired pneumonia (CAP). As part of the patient’s MG maintenance medications, he received IVIG 4 g while in the ICU. Throughout his ICU stay, he required supplemental nasal cannula oxygenation to maintain his oxygen saturation > 93%. After 8 days in the ICU, his oxygen requirements decreased, and the patient was transferred out of the ICU and remdesivir was discontinued. On hospital day 10, a repeat COVID-19 PCR test was negative, inflammatory markers returned to within normal limits, and a repeat chest X-ray showed improvement from admission (Figure 2). Having recovered significantly, he was discharged home.

Three weeks later, the patient again presented to the MTF with 3 days of dyspnea, cough, fever, nausea, and vomiting. One day before symptom onset, he had received his maintenance IVIG infusion. The patient reported that his home oxygen saturation was 82% with minimal exertion. On ED presentation his HR was 107 beats/min, RR, 28 breaths/min, temperature, 98.1 oF, BP 118/71 mm Hg, and oxygen saturation, 92% on 2L nasal cannula. His examination was most notable for tachypnea with accessory muscle use. At this time, his neurologic examination was unchanged from prior admission with grossly intact cranial nerves and symmetric 5 of 5 motor strength in all extremities.

At this second ED visit, laboratory results demonstrated a CRP of 3.44 mg/dL, ferritin 2019 ng/mL, d-dimer, 3.39 mcg/mL, and a positive COVID-19 PCR result. His chest X-ray demonstrated new peripheral opacities compared with the X-ray at discharge (Figure 3). He required ICU admission again for his COVID-19 symptoms.

Chest X-ray Emergency Department Second Presentation figure

During his ICU course he continued to require supplemental oxygen by nasal cannula, though never required intubation. This second admission, he was again treated empirically for CAP with levofloxacin 750 mg daily for 5 days. He was discharged after 14 days with symptom resolution and down trending of inflammatory markers, though he was not retested for COVID-19.

Four days after his second discharge, he presented to the ED for a third time with diffuse weakness, dysphagia, and dysarthria of 1 day. His HR was 87/beats/min; RR, 17 breaths/min; temperature, 98.7 oF; BP, 144/81 mm Hg; and oxygen saturation, 98% on room air. His examination was significant for slurred speech, bilateral ptosis, 3 of 5 strength in bilateral finger flexion/abduction, wrist extension, knee and ankle flexion/extension; 4 of 5 strength in bilateral proximal muscle testing of deltoid, and hip; normal sensation, cerebellar function and reflexes. His negative inspiratory force (NIF) maximal effort was −30 cmH2O. He was determined to be in MC without evidence of COIVD-19 symptoms, and laboratory results were within normal limits, including a negative COVID-19 PCR. As he received IVIG as maintenance therapy, plasmapheresis was recommended to treat his MC, which required transfer to an outside civilian facility.

At the outside hospital, the patient underwent 5 rounds of plasmapheresis over 10 days. By the third treatment his strength had returned with resolution of the bulbar symptoms and no supplemental oxygen requirements. The patient was discharged and continued his original dosages of MMF and pyridostigmine. At 3 months, he remained asymptomatic from a COVID-19 standpoint and stable from a MG standpoint.


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