Myasthenia Gravis and COVID-19 – A Clinical Checkmate

Abstract

Myasthenia gravis (MG) patients with coronavirus disease (COVID-19) pose a unique challenge for intensive care management. Higher risk of infection is observed in patients with MG due to the immunosuppressant medications they are prescribed. The underlying component of respiratory muscle weakness predisposes these patients to experience a more severe form of illness. In the case of diagnosis of COVID-19 in MG patients, judicious continuation of immunosuppressants, avoiding drugs that worsen MG along with the continuation of cholinesterase inhibitors is prudent. Early diagnosis in cases with high-index of suspicion, extra precautions, COVID-appropriate behavior, and early immunization is paramount for the health of MG patients during this pandemic.

INTRODUCTION

Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, causing fluctuating muscle weakness, respiratory insufficiency, and may lead to life-threatening symptoms. There is difficulty in determining as to which causes more respiratory weakness – COVID-19 or MG.[1] MG patients might have preexisting respiratory muscle weakness and hence vulnerable to develop a more severe form of disease.[2],[3] COVID-19 affecting people with MG is a unique challenge as most of these patients are on immunosuppressants.[4]

We report two cases of MG from our COVID-designated hospital in South India.

CASE REPORTS

Case one

A 67-years-old male patient had a history of breathlessness and myalgia. He was diagnosed COVID-19-positive by nasopharyngeal swab polymerase chain reaction (PCR) reverse transcription-PCR (RT PCR) test. His computed tomography (CT) thorax revealed features of mild COVID pneumonia apart from mild cardiomegaly and mediastinal adenopathy. He was a known case of systemic hypertension, coronary artery disease (CAD), MG for 15 years, postthymectomy and was on pyridostigmine 60 mg Q 8 h, antihypertensives, and oral anticoagulants. He was not vaccinated. He was prescribed azithromycin 500 mg once a day elsewhere, which he took for 3 days before admission. He initially maintained saturation of 96% with 8 L. min^{− 1} oxygen by face mask. We had started him on steroids, anticoagulants, and remdesivir, apart from continuing all his other medications. His echocardiogram done was unremarkable. Arterial blood gases showed Type-1 respiratory failure pattern. On the 3^rd day in the intensive care unit (ICU), he desaturated and was started on noninvasive ventilation (NIV). His D-dimer levels were elevated and was started on heparin infusion. His condition improved initially and he was maintaining on intermittent NIV and nonrebreathing mask. His progress over the next few days was very gradual, but by the end of the 2^nd week, he required continuous NIV. He developed dysphagia, and hence his medication was converted to equivalent parenteral dose intravenous neostigmine 0.5 mg Q 6 h was administered in place of pyridostigmine. The patient's attenders were not willing for invasive ventilation and the patient was continued on NIV, explaining the risks. On the 17^th day of admission, he sustained myocardial infarction (MI) and succumbed.

Case two

An 82-years-old male patient had a history of fever, cough, and breathlessness and was diagnosed to be COVID-19-positive by RT-PCR test. He was a known case of MG for 7 years, systemic hypertension, and CAD. He was on immunosuppressant azathioprine 50 mg Q 12 h, pyridostigmine 60 mg Q 6 h, antihypertensives, and oral anticoagulants. He had taken his 1^st dose of vaccine. His CT thorax revealed severe COVID pneumonia pattern. He was maintaining good oxygen saturation of 97% with 6 L. min^{− 1} oxygen by face mask. He received azithromycin 500 mg once a day for 5 days before admission. He was continued on all his medications, except azithromycin. His oxygen levels dropped on day 5 after admission and he was connected to NIV, on which he improved transiently but later succumbed to MI.

DISCUSSION

Viral infections trigger autoimmunity by increasing T-cell signaling, leading to a proinflammatory environment. COVID-19 and MG, both can cause cytokine dysregulation increasing proinflammatory cytokines affecting organ systems.[5]

Immunosuppressant use may lead to higher risk of acquiring more severe COVID-19, but there is also contrary evidence regarding their protective role in reducing immune response and preventing inflammatory cytokine storm.[6] Case two was continued on azathioprine, but still, his clinical course deteriorated. Hence, close monitoring of such patients is recommended during the COVID-19 pandemic and the use of corticosteroids and immunosuppressants should be decided based on their clinical status.[5] Corticosteroid dosage may be increased, as done with the infection steroid protocols. In severe infection with sepsis, it is recommended to pause immunosuppression temporarily. Cholinesterase inhibitors do not increase the risk of infection and should not be discontinued.[4] We had continued both patients on pyridostigmine. If dysphagia develops, the oral pyridostigmine dose should be converted to the equivalent parenteral dose of neostigmine, with close monitoring for adequacy of dosage based on symptoms.[7]

Drugs such as macrolides are known to potentially worsen MG. Azithromycin blocks neuromuscular transmission at the presynaptic level and is contraindicated in MG patients.[8] Both our patients received azithromycin before reaching our ICU, and probably would have been one of the causes of worsening of symptoms in them.

Intravenous immunoglobulin (IVIG) acts by blocking cytokine production. This causes a decrease in endogenous and exogenous immunoglobulin G which leads to reduced acetylcholine receptor antibodies, neutralization of autoantibodies by anti-idiotypic antibodies, and culminating in inhibition of complement activation. IVIG is recommended to be continued for those who are already on it, but starting IVIG should be reserved only for those with acute exacerbation of MG.[4] Thrombotic complications with IVIG may be high in critically ill COVID-19 patients.[9] We did not administer IVIG fearing its immunosuppressive and thromboembolic complications.

Therefore, all MG patients with new-onset neuromuscular weakness or with underlying known disorder should be evaluated for COVID-19 during the pandemic. Close monitoring of respiratory function indicating worsening of MG is recommended in all moderate-to-high-risk patients.[5] Prolonged COVID-19 disease duration in these patients is a possibility due to inappropriate immune response in patients with autoimmune diseases.[10] Comorbid conditions of MG patients play a crucial role on the outcome. Both patients had CAD and systemic hypertension, which could have contributed to their deterioration and negative outcome. When respiratory weakness is encountered, it may be difficult to determine whether COVID-19 or MG or some other cause contributed to it.

MG patients with COVID-19 have relatively poor outcomes than the general population with COVID-19. MG patients may have exacerbation of symptoms either due to infection “trigger” or due to drugs such as azithromycin “triggering” symptoms. It is a double-edged sword infection “triggering” MG crises and immunosuppressants leading to increased risk of infection. MG crisis secondary to COVID-19 vaccination has also been reported.[11] MG patients are recommended to get vaccinated at the earliest with adequate monitoring for symptoms exacerbation postvaccination while continuing the practice of COVID-appropriate behavior and masking with extra vigilant social distancing and avoiding public gatherings.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.