COVID-19 infection in a patient with multiple sclerosis treated with fingolimod

Case presentation

A 42-year-old woman who was diagnosed with relapsing-remitting MS according to the McDonald criteria in 2001 and had been treated with methotrexate (2 years; discontinued because of elevated liver enzymes), interferon beta 1-a (13 years; discontinued because of disease activity), and recently on fingolimod (since 4 years ago) presented with muscle aches, gait difficulty, sensory disturbances, and weakness on the right side. Her other comorbidities included major depression disorder, hypothyroidism, recurrent urinary tract infection, and histories of pulmonary embolism on direct oral anticoagulation and myasthenia gravis (diagnosed 5 years before MS and status after thymectomy). At her most recent follow-up in September 2019, her expanded disability status scale (EDSS) score was 1.0 for a positive Babinski sign on the right side. MRI was notable for moderate disease burden in the brain and the presence of 2 right-sided cervical cord lesions. Her lymphocyte count at this visit was 842.4/μL.

On March 1, 2020, she started experiencing the symptoms that gradually worsened over the next few days. She sought medical attention on March 5 and was seen at the outpatient MS clinic. Neurologic examination revealed decreased sensation, reduced muscle strength (4/5), and brisk reflexes on the right and right positive Babinski sign (EDSS of 4). These findings were consistent with new relapse or recrudescence of old symptoms (pseudoexacerbation). She was then admitted for a relapse workup and treatment on the same day. On arrival, she was afebrile with vital signs within normal limits. Initial laboratory investigations were notable for C-reactive protein of 76 mg/L and erythrocyte sedimentation rate of 46 mm, raising suspicious for an underlying infectious etiology. There was also a decrease in absolute lymphocyte count (601.6/μL), which was attributed to fingolimod. Methylprednisolone IV 1,000 mg/d was initiated for 3 days for the treatment of a possible relapse. As part of the infectious workup, chest X-ray showed a ground glass opacity (figure, A), which raised a possibility of community-acquired pneumonia for which she was started on azithromycin 500 mg daily because she is allergic to fluoroquinolones. On March 7, she developed dry cough, dyspnea, and fever (38.7°C). She also had tachycardia (122), increased respiratory rate (30), and slight decrease in blood pressure (100/70 mm Hg) and in oxygen saturation (89%) with a decrease in lymphocyte counts to 440.8/μL. Fingolimod was stopped because of concern for sepsis. Ceftriaxone 1 g twice daily was added and started on oxygen via a nasal cannula. Chest CT was performed to rule out pulmonary embolism, given her history; however, it was indicative of ground glass opacities (figure, B).³ Given the clinical and imaging findings, COVID-19 was suspected, and a nasopharyngeal swab was obtained and sent to the Isfahan University of Medical Sciences reference laboratory for real-time PCR testing for COV. She was transferred to the special COVID ward and received a combination of hydroxychloroquine, oseltamivir (to cover for influenza), and piperacillin/tazobactam, whereas ceftriaxone and azithromycin were discontinued. Three days later (11th March), she felt well and vital signs were stabilized, and she became afebrile and the lymphocyte counts increased to 510.3/μL. On March 12, the COVID-19 test was reported positive, and all other medications except hydroxychloroquine were discontinued. The symptoms of cough and dyspnea together with neurologic symptoms gradually improved. She was discharged after a 13-day admission and started on glatiramer acetate to avoid potential MS rebound after the discontinuation of fingolimod (lymphocyte count: 1,000.5/ul). Until the last televisit (30 March), she has been self-quarantined at home with no respiratory or neurologic symptoms. Given that she did not get a new MRI during the admission because of hemodynamic instability and also testing positive for COVID, it remains unclear whether her neurologic symptoms were because of the new disease activity (relapse) or worsening of pre-existing symptoms (pseudorelapse).

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Figure Lung imaging findings suggestive of COVID-19

(A) Chest x-ray of the patient on the first day of hospitalization showing a ground glass opacity on the base of the right lung. (B) CT scan of the chest on the fourth day of hospitalization showing ground glass opacities/consolidation with crazy paving appearance highly suggestive for COVID-19.