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Introduction
Myasthenia gravis (MG) is an autoimmune disease characterised by fluctuating muscle weakness with potentially life-threatening symptoms due to insufficiency of respiratory muscles. Treatment usually includes immunosuppressive drugs and cholinesterase inhibitors. COVID-19 is an infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), defined as a pandemic by the World Health Organisation (WHO).
Although guidelines for the management of patients with MG during the COVID-19 pandemic have been published,1 these recommendations are based on theoretical considerations only, as no clinical data are available.
We describe four patients with generalised MG affected by COVID-19 (around 10% of patients in our cohort). Clinical data are summarised in table 1.
Clinical data of four patients with generalised gravis and SARS-CoV-2
Case 1
A 36-year-old female patient, class IIa according to the Myasthenia Gravis Foundation of America (MGFA) score (166 cm, 67 kg), presented to Geneva University Hospital on 15 March 2020 with myalgia, coughing and fever >38°C on the same day. She was taking azathioprine (AZA) 50 mg, reintroduced at the end of January 2020, and pyridostigmine 60 mg five to six times per day. The last deterioration of MG had occurred in January 2020 requiring intravenous immunoglobulin (IVIG) treatment (Myasthenia Muscle Score 65/100). COVID-19 real-time PCR (RT-PCR) revealed a positive result. Chest X-ray showed no pulmonary infiltration and peak flow was at 400 mL (82%). The Myasthenia Muscle Score2 was at 71/100 (bulbar and trunk involvement, leg weakness). As the immunosuppressive therapy was supposedly not effective here (small dosage and short treatment period), it was interrupted to avoid aggravation of the viral infection. On 17 March, the patient developed acute hypophonia and her Myasthenia Muscle Score dropped to 58/100. Suspecting myasthenic deterioration with bulbar involvement, she was treated with IVIG over 5 days. Hypophonia resolved rapidly and her score increased to 79/100. She was discharged home on day 10 after onset. Four weeks after onset, the main complaints consisted of anosmia and ageusia, related to COVID-19.3 Her Myasthenia Muscle Score was at 90/100 and AZA was reinitiated.
Case 2
A 36-year-old female patient, MGFA class IIIb (100 kg, 165 cm), developed fever, headache, coughing and difficulty breathing on 16 March 2020. MG had been unstable prior, with deteriorations generally linked to worsening of her Behçet’s disease. The last deterioration had occurred in December 2019 (Myasthenia Muscle Score 65/100). She was taking pyridostigmine 60 mg four to five times per day, prednisone 25 mg/day and subcutaneous immunoglobulins 12 g every 4 days. She had also been under AZA 150 mg/day, but had stopped this medication by herself 2 weeks prior to admission. COVID-19 RT-PCR revealed a positive result on 17 March. She presented to the emergency room (ER) on 17, 20 and 27 March for follow-up. Chest X-ray did not show pulmonary infiltration and peak flow remained stable (250–300 mL/min). The Myasthenia Muscle Score (on 20 March) was at 68/100, without bulbar involvement. Serology testing (on 11 April) revealed positive SARS-CoV-2 antibody indices for IgA (7.8) and IgG (6.0). The patient suffered from fluctuating symptoms, namely breathing difficulty, headaches and chest pain until May 2020. A reinfection was excluded by two additional negative RT-PCR.
Case 3
A male patient, MGFA class IIa (55 years, 99 kg, 183 cm), presented with fever, coughing, shivering, odynophagia and fatigue since 12 March 2020, and was admitted on 19 March and tested positive for COVID-19. Chest X-ray showed no pulmonary infiltrate. He was taking pyridostigmine 3×30 mg/day and metoprolol succinate 25 mg/day (introduced by his general practitioner). Neurological examination revealed double vision and unilateral ptosis on Simpson test and no bulbar involvement (Myasthenia Muscle Score 90/100). His neurological status remained stable and he was discharged home without having received any MG-specific treatment on day 13 after onset. He fully recovered around 3 weeks after disease onset.
Case 4
A 25-year-old, obese, male patient (175 cm, 160 kg, body mass index >50) known for recidivating thymoma resected in 2017, entailing left phrenic nerve damage, was admitted to the ER on 6 April with shivering, headache, coughing and shortness of breath. He tested positive for SARS-CoV-2, but was dismissed without neurological evaluation, and returned on 9 April with fever (38.6°C), tachycardia and difficulty breathing necessitating intubation (MGFA class V). Chest X-ray showed bilateral pulmonary infiltrates, and antibiotic therapy was initiated (azithromycin, tazobactam/piperacilline). Pyridostigmine 60 mg three times a day was continued. The patient had been stable under rituximab 1 g two times per year (last dosage in December 2019; CD19 lymphocytes B count 0%, 4/µL absolute). Follow-up chest X-ray on 15 April showed clear regression of infiltrates. However, he presented a prolonged intubation period (>14 days) requiring high values of positive end-expiratory pressure, due to obesity4 and phrenic nerve damage. The patient developed weakness of pharyngeal muscles, and after increasing the dosage of pyridostigmine (360 mg/day) tracheostoma could be removed 9 weeks after intubation.
Discussion
Patients suffering from MG may be at high risk of developing severe symptoms when affected with COVID-19. Guidelines have been published without clinical data being available.
The evolution observed in these four patients was very variable and seemed to only partly depend on MG disease activity prior to infection, but also on other comorbidities, such as severe obesity or additional autoimmune diseases. One possible explanation for prolonged disease duration might be an inappropriate response of the immune system in patients suffering from several autoimmune diseases.
Decisions on management of patients with generalised MG with SARS-CoV-2 infection should be taken after careful consideration of patients’ individual medical history and under thorough neurological surveillance. IVIG (eg, 2 g/kg) treatment may be introduced in case of worsening of respiratory or neurological symptoms, taking also into account a potential benefit on the course of the SARS-CoV-2 infection itself.5
In our view, ongoing immunosuppressive therapy should not be stopped if it is considered to have a stabilising effect on the individual patient with MG. It may even be discussed that patients requiring immunosuppressive therapy show a prolonged but favourable outcome.
Our patients showed slight but no relevant worsening of MG symptoms during active infection, which may suggest that COVID-19 has poor impact on MG disease course. Further data would be necessary to substantiate this hypothesis.
Footnotes
Contributors AH and AML wrote the manuscript. AH and AML examined the patients and collected the clinical data. PHL reviewed the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication On hand.
Provenance and peer review Not commissioned; externally peer reviewed.