Follow-up of a Cohort of Patients With Myasthenic Syndrome and COVID-19 Infection (CO-MY-COVID)

Follow-up of a Cohort of Patients With Myasthenic Syndrome and COVID-19 Infection: Consequences on the Severity of Myasthenic Syndrome and Reciprocal Impact of the Two Pathologies on Their Respective Treatments

Coronavirus disease 2019 (COVID-19), declared by the World Health Organization (WHO) as a "public health emergency of international concern" (January 31, 2020), has posed a significant threat to global health. This infectious disease, caused by the 'severe acute respiratory syndrome coronavirus-2'(SARS-CoV-2), was first reported in China at the end of 2019. As other coronaviruses, SARS-CoV-2 primarily targets the human respiratory system. The most common symptoms are fever, fatigue, and dry cough. During the second week of the disease, part of patients may progress to shortness of breath, then hypoxemia and severe pneumonia. Acute respiratory distress syndrome (ARDS), linked to some risk factors such as advanced age and underlying comorbidities (hypertension, diabetes, cardiovascular disease, and cerebrovascular disease), may be fatal and needs early supportive therapy and monitoring.

Some patients with COVID-19 experienced neurological complications including headache, dizziness, hypogeusia and/or anosmia, altered level of consciousness, strokes, seizures, and ataxia, less frequently neuromuscular disorders (NMD) such as acute inflammatory polyradiculoneuropathy. Among NMD, myasthenia gravis (MG) patients, particularly susceptible to infections causing crises, could be of special risk of COVID-19 ARDS. Some general recommendations were established for the management of NMD during the COVID-19 pandemic,with also specific recommendations for MG. However, only data on a small number of patients who were managed in hospital are currently available;in addition, only two cases of myasthenic crisis following COVID-19 were reported. For this reason, the French neuromuscular rare disease network (FILNEMUS: 'FILière NEuroMUSculaire') has created the 'CO-MY-COVID register' to describe the clinical course and prognosis of patients with COVID-19 and pre-existing myasthenic syndrome.

Study Overview

• Status: Completed
• Conditions: Myasthenia Gravis

Detailed Description

Coronavirus disease 2019 (COVID-19), declared by the World Health Organization (WHO) as a "public health emergency of international concern" (January 31, 2020), has posed a significant threat to global health. This infectious disease, caused by the 'severe acute respiratory syndrome coronavirus-2'(SARS-CoV-2), was first reported in China at the end of 2019. Nowadays, with the exception of Antarctica, COVID-19 is a worldwide pandemic that continues to spread around the world (8,065,966 known cases and 437,604 deaths in June 16, 2020; https://gisanddata.maps.arcgis.com/). As other coronaviruses, SARS-CoV-2 primarily targets the human respiratory system. Its most convincing mode of transmission is inhalation of infectious aerosols or direct contact of infected people's droplets. The most common symptoms are fever, fatigue, and dry cough. During the second week of the disease, part of patients may progress to shortness of breath, then hypoxemia and severe pneumonia. Acute respiratory distress syndrome (ARDS), linked to some risk factors such as advanced age and underlying comorbidities (hypertension, diabetes, cardiovascular disease, and cerebrovascular disease), may be fatal and needs early supportive therapy and monitoring.

Some patients with COVID-19 experienced neurological complications including headache, dizziness, hypogeusia and/or anosmia, altered level of consciousness, strokes, seizures, and ataxia, less frequently neuromuscular disorders (NMD) such as acute inflammatory polyradiculoneuropathy. Among NMD, myasthenia gravis (MG) patients, particularly susceptible to infections causing crises, could be of special risk of COVID-19 ARDS. Some general recommendations were established for the management of NMD during the COVID-19 pandemic,with also specific recommendations for MG. However, only data on a small number of patients who were managed in hospital are currently available;in addition, only two cases of myasthenic crisis following COVID-19 were reported. For this reason, the French neuromuscular rare disease network (FILNEMUS: 'FILière NEuroMUSculaire') has created the 'CO-MY-COVID register' to describe the clinical course and prognosis of patients with COVID-19 and pre-existing myasthenic syndrome.

• Study Type: Observational
• Enrollment (Actual): 34

Contacts and Locations

• Study Contact: Name: Guilhem SOLE, MD; Phone Number: 05-57-82-13-80; Email: guilhem.sole@chu-bordeaux.fr

Study Locations

• France
  • Angers, France, 49933
    • CHU d'Angers
  • Bordeaux, France, 33076
    • CHU de Bordeaux
  • Bron, France, 69677
    • Hospices Civils de Lyon
  • Garches, France, 92380
    • APHP - Hopital Raymond Poincarré
  • Lille, France, 59037
    • CHRU de Lille
  • Marseille, France, 13385
    • Assistance Publique Hopitaux de Marseille
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75013
    • APHP GH Pitié Salpétrière
  • Strasbourg, France, 67098
    • CHU de Strasbourg
  • Toulouse, France, 31059
    • CHU de Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Child or adult patients, living or deceased, presenting or having presented a myasthenic syndrome and a COVID-19 infection

Description

Inclusion Criteria:

• 1. Child or adult patients, living or deceased, presenting or having presented a myasthenic syndrome and a COVID-19 infection 2. Myasthenic syndrome is established by:

  • Either the presence of a specific antibody
  • Either the presence of specific electrophysiological abnormalities
  • Either an evocative symptomatology improved by a therapeutic test with an acetylcholinesterase inhibitor

  • Either one or two pathogenic mutation (s) in a gene involved in congenital myasthenic syndromes (dominant or recessive disease).

    3. COVID-19 infection is established by

  • Either a positive PCR test
  • Or a specific chest scanner
  • Either a positive serology
  • Either a clinical syndrome of COVID-19, validated by a committee of experts. 4. Patients affiliated or beneficiaries of a social security scheme 5. For living patients: patients who have been informed of the study and have not exercised their right of opposition or parents or holders of parental authority who have been informed of the study and have not exercised their right opposition.

For deceased patients: beneficiaries or parents / holders of parental authority having been informed of the study and not having exercised their right of objection.

Exclusion Criteria:

1. Persons placed under judicial protection

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Myasthenia Gravis evaluated by the Myasthenia Gravis of America (MGFA) score	The severity of MG is measured by using the MGFA (Myasthenia Gravis Foundation of America) classification, giving the status of 'MG-improvement' (when the scores decreased or remained stable) or 'MG-worsening' (when the scores increased) (Jaretzki A, 3rd, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 2000;55:16-23.)	1 month after the inclusion visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of Myasthenia Gravis evaluated by the Myasthenia Gravis of America (MGFA) score	The severity of MG is measured by using the MGFA (Myasthenia Gravis Foundation of America) classification, giving the status of 'MG-improvement' (when the scores decreased or remained stable) or 'MG-worsening' (when the scores increased) (Jaretzki A, 3rd, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 2000;55:16-23.)	at inclusion (at the time of the COVID-19 diagnosis)
Severity of Myasthenia Gravis evaluated by the variation of the Myasthenia Gravis of America (MGFA) score	The severity of MG is measured by using the MGFA (Myasthenia Gravis Foundation of America) classification, giving the status of 'MG-improvement' (when the scores decreased or remained stable) or 'MG-worsening' (when the scores increased) (Jaretzki A, 3rd, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 2000;55:16-23.)	3 months after the inclusion visit
Severity of Myasthenia Gravis evaluated by the variation of the Myasthenia Gravis of America (MGFA) score	The severity of MG is measured by using the MGFA (Myasthenia Gravis Foundation of America) classification, giving the status of 'MG-improvement' (when the scores decreased or remained stable) or 'MG-worsening' (when the scores increased) (Jaretzki A, 3rd, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 2000;55:16-23.)	6 months after the inclusion visit
The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale	The Myasthenia Gravis-specific Activities of Daily Living scale consists of the assessment of 8 parameters: speaking, chewing, swallowing, breathing, self-care activities (brushing the teeth or combing the hair), simple physical activities (getting up from a chair), double vision and eye lid dropping. Each parameter is subjected to assessment depending on the degree of symptoms intensification, awarding points from 0 to 3 points. The maximum number a patient may receive is 24 points. The higher the score of points, the bigger limitations of the patient in everyday life activities caused by intensification of myasthenia gravis (Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology 1999;52:1487-1489.)	at inclusion (at the time of the COVID-19 diagnosis)
The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale	The Myasthenia Gravis-specific Activities of Daily Living scale consists of the assessment of 8 parameters: speaking, chewing, swallowing, breathing, self-care activities (brushing the teeth or combing the hair), simple physical activities (getting up from a chair), double vision and eye lid dropping. Each parameter is subjected to assessment depending on the degree of symptoms intensification, awarding points from 0 to 3 points. The maximum number a patient may receive is 24 points. The higher the score of points, the bigger limitations of the patient in everyday life activities caused by intensification of myasthenia gravis (Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology 1999;52:1487-1489.)	1 month after the inclusion visit
The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale	The Myasthenia Gravis-specific Activities of Daily Living scale consists of the assessment of 8 parameters: speaking, chewing, swallowing, breathing, self-care activities (brushing the teeth or combing the hair), simple physical activities (getting up from a chair), double vision and eye lid dropping. Each parameter is subjected to assessment depending on the degree of symptoms intensification, awarding points from 0 to 3 points. The maximum number a patient may receive is 24 points. The higher the score of points, the bigger limitations of the patient in everyday life activities caused by intensification of myasthenia gravis (Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology 1999;52:1487-1489.)	3 months after the inclusion visit
The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale	The Myasthenia Gravis-specific Activities of Daily Living scale consists of the assessment of 8 parameters: speaking, chewing, swallowing, breathing, self-care activities (brushing the teeth or combing the hair), simple physical activities (getting up from a chair), double vision and eye lid dropping. Each parameter is subjected to assessment depending on the degree of symptoms intensification, awarding points from 0 to 3 points. The maximum number a patient may receive is 24 points. The higher the score of points, the bigger limitations of the patient in everyday life activities caused by intensification of myasthenia gravis (Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology 1999;52:1487-1489.)	6 months after the inclusion visit
Risk factors for severe forms of COVID-19	Risk factors for severe forms of COVID-19 are the following: age>65, 'obesity' (body mass index (, BMI), >30), 'chronic obstructive pulmonary disease' (COPD), 'obstructive sleep apnea syndrome' (OSAS), 'noninvasive ventilation' (NIV), 'arterial hypertension' , 'diabetes' and 'others'	at inclusion (at the time of the COVID-19 diagnosis)
Treatments for MG at the time of the diagnosis of COVID-19	Treatments for MG at the time of the diagnosis of COVID-19 are grouped into six categories: 'acetylcholinesterase inhibitors' (Ach-inh), 'corticosteroids', 'immunosuppressants', 'intravenous immunoglobulins' (IVIg) or 'subcutaneous immunoglobulins' (SCIg), 'plasmapheresis' (PLEX) and 'others	at inclusion (at the time of the COVID-19 diagnosis)
Diagnosis of COVID-19	The diagnosis of COVID-19 is considered as 'definite' if confirmed by a positive SARS-CoV-2 PCR (polymerase chain reaction) test and/or SARS-CoV-2 serology. The diagnosis of COVID-19 is considered 'probable' if: (i) the patient presented a viral syndrome and (ii) had contact with a confirmed patient considered to have a definite diagnosis of COVID-19 or had specific signs (anosmia, agueusia, skin signs) or had suggestive abnormalities on thoracic CT-scan.	at inclusion (at the time of the COVID-19 diagnosis)
Severity of COVID-19	The global severity of COVID-19 was based on the location of management of the patient during COIVD-19: 'home', 'medical unit' ('MU'), 'intensive care unit' ('ICU').	at inclusion (at the time of the COVID-19 diagnosis)
Treatments for MG during and after COVID-19	Treatments for MG at the time of the diagnosis of COVID-19 are grouped into six categories: 'acetylcholinesterase inhibitors' (Ach-inh), 'corticosteroids', 'immunosuppressants', 'intravenous immunoglobulins' (IVIg) or 'subcutaneous immunoglobulins' (SCIg), 'plasmapheresis' (PLEX) and 'others	1 month after the inclusion visit
Treatments for MG during and after COVID-19	Treatments for MG at the time of the diagnosis of COVID-19 are grouped into six categories: 'acetylcholinesterase inhibitors' (Ach-inh), 'corticosteroids', 'immunosuppressants', 'intravenous immunoglobulins' (IVIg) or 'subcutaneous immunoglobulins' (SCIg), 'plasmapheresis' (PLEX) and 'others	3 months after the inclusion visit
Treatments for MG during and after COVID-19	Treatments for MG at the time of the diagnosis of COVID-19 are grouped into six categories: 'acetylcholinesterase inhibitors' (Ach-inh), 'corticosteroids', 'immunosuppressants', 'intravenous immunoglobulins' (IVIg) or 'subcutaneous immunoglobulins' (SCIg), 'plasmapheresis' (PLEX) and 'others	6 months after the inclusion visit

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Guilhem SOLE, MD, Université Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Actual): June 18, 2020
• Study Completion (Actual): June 18, 2020

Study Registration Dates

• First Submitted: December 31, 2020
• First Submitted That Met QC Criteria: December 31, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Neuromuscular Diseases
• Additional Relevant MeSH Terms: Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neoplasms by Site; Neuromuscular Diseases; Neurodegenerative Diseases; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; COVID-19; Myasthenia Gravis; Lambert-Eaton Myasthenic Syndrome
• Other Study ID Numbers: CHUBX 2020/17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No