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

• ClinicalTrials.gov Identifier: NCT04695379
• Recruitment Status: Unknown
• First Posted: January 5, 2021
• Last Update Posted: January 5, 2021
• Sponsor: University Hospital, Bordeaux
• Information provided by (Responsible Party): University Hospital, Bordeaux

Study Description

Brief Summary:

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.

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 150 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: 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
• Actual Study Start Date: May 26, 2020
• Estimated Primary Completion Date: November 26, 2022
• Estimated Study Completion Date: November 26, 2022

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Severity of Myasthenia Gravis evaluated by the Myasthenia Gravis of America (MGFA) score [ Time Frame: 1 month after the inclusion visit ]
   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.)

Secondary Outcome Measures :

1. Severity of Myasthenia Gravis evaluated by the Myasthenia Gravis of America (MGFA) score [ Time Frame: at inclusion (at the time of the COVID-19 diagnosis) ]
   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.)
2. Severity of Myasthenia Gravis evaluated by the variation of the Myasthenia Gravis of America (MGFA) score [ Time Frame: 3 months after the inclusion visit ]
   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. Severity of Myasthenia Gravis evaluated by the variation of the Myasthenia Gravis of America (MGFA) score [ Time Frame: 6 months after the inclusion visit ]
   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.)
4. The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale [ Time Frame: at inclusion (at the time of the COVID-19 diagnosis) ]
   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.)
5. The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale [ Time Frame: 1 month after the inclusion visit ]
   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. The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale [ Time Frame: 3 months after the inclusion visit ]
   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.)
7. The autonomy of the patients evaluated with the MG-ADL (Myasthenia Gravis-Activities of Daily Living) scale [ Time Frame: 6 months after the inclusion visit ]
   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.)
8. Risk factors for severe forms of COVID-19 [ Time Frame: at inclusion (at the time of the COVID-19 diagnosis) ]
   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'
9. Treatments for MG at the time of the diagnosis of COVID-19 [ Time Frame: at inclusion (at the time of the COVID-19 diagnosis) ]
   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
10. Diagnosis of COVID-19 [ Time Frame: at inclusion (at the time of the COVID-19 diagnosis) ]
    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.
11. Severity of COVID-19 [ Time Frame: at inclusion (at the time of the COVID-19 diagnosis) ]
    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').
12. Treatments for MG during and after COVID-19 [ Time Frame: 1 month after the inclusion visit ]
    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
13. Treatments for MG during and after COVID-19 [ Time Frame: 3 months after the inclusion visit ]
    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
14. Treatments for MG during and after COVID-19 [ Time Frame: 6 months after the inclusion visit ]
    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

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Criteria

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

Contacts and Locations

Contacts

Contact: Guilhem SOLE, MD; 05-57-82-13-80; guilhem.sole@chu-bordeaux.fr

Contact: Aurore CAPELLI, PhD; 0557820877; aurore.capelli@chu-bordeaux.fr

Locations

France

CHU d'Angers; Recruiting

Angers, France, 49933

Principal Investigator: Marco SPINAZZI, MD

CHU de Bordeaux; Recruiting

Bordeaux, France, 33076

Principal Investigator: Guilhem Solé, MD

Hospices Civils de Lyon; Recruiting

Bron, France, 69677

Principal Investigator: Françoise BOUHOUR, MD

APHP - Hopital Raymond Poincarré; Recruiting

Garches, France, 92380

Principal Investigator: Pascal Laforet, MD PHD

CHRU de Lille; Recruiting

Lille, France, 59037

Principal Investigator: Céline Tard, MD

Assistance Publique Hôpitaux de Marseille; Recruiting

Marseille, France, 13385

Principal Investigator: Emmanuelle CAMPANA-SALORT, MD

CHU de Nantes; Recruiting

Nantes, France, 44093

Principal Investigator: Armelle Magot, MD

APHP GH Pitié Salpétrière; Recruiting

Paris, France, 75013

Principal Investigator: Tanya STOJKOVIC, MD

CHU de Strasbourg; Recruiting

Strasbourg, France, 67098

Principal Investigator: Jean-baptiste CHANSON, MD

CHU de Toulouse; Recruiting

Toulouse, France, 31059

Principal Investigator: Pascal CINTAS, MD

Sponsors and Collaborators

University Hospital, Bordeaux

More Information

• Responsible Party: University Hospital, Bordeaux
• ClinicalTrials.gov Identifier: NCT04695379
• Other Study ID Numbers: CHUBX 2020/17
• First Posted: January 5, 2021
• Last Update Posted: January 5, 2021
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Bordeaux:

COVID-19; Neuromuscular Diseases

Additional relevant MeSH terms:

COVID-19; Myasthenia Gravis; Lambert-Eaton Myasthenic Syndrome; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases