Follow-up of a Cohort of Patients With Myasthenic Syndrome and COVID-19 Infection

Myasthenia Gravis Clinical Trial

— CO-MY-COVID  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04695379
• Other study ID #: CHUBX 2020/17
• Status: Completed
• Start date: April 27, 2020
• Est. completion date: June 18, 2020

Study information

• Verified date: October 2023
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: June 18, 2020
• Est. primary completion date: June 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Lambert-Eaton Myasthenic Syndrome
• Myasthenia Gravis

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU de Bordeaux	Bordeaux
France	Hospices Civils de Lyon	Bron
France	APHP - Hopital Raymond Poincarré	Garches
France	CHRU de Lille	Lille
France	Assistance Publique Hôpitaux de Marseille	Marseille
France	CHU de Nantes	Nantes
France	APHP GH Pitié Salpétrière	Paris
France	CHU de Strasbourg	Strasbourg
France	CHU de Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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