efficacy of vaccination against covid-19 in patients presenting a neuromuscular disease with severe amyotrophy

Conditions: Neuromuscular Diseases; COVID-19; Amyotrophy

Summary: des vaccins sont désormais disponibles en france, dont le vaccin moderna covid-19 qui est basé sur la technologie des arnm. la séquence génétique qu'il contient code pour la protéine spike (s) de l'enveloppe virale, protéine clé de la pénétration du virus dans les cellules qu'il infecte. le vaccin arnm est injecté par voie intramusculaire et pénètre dans les fibres musculaires, qui sont des cellules produisant des protéines en très grande quantité en continu, notamment pour la production de myofibrilles impliquées dans la contraction musculaire. une fois à l'intérieur de la fibre musculaire, l'arnm vaccinal est traduit par la machinerie de la fibre musculaire permettant une grande quantité de protéine spike (s) qui sera présentée au système immunitaire provoquant la réponse vaccinale et notamment les anticorps neutralisants anti-s (nab). ces nab anti-s agissent en perturbant l'interaction entre la protéine s du virus et le récepteur ace2 (angiotensin-converting enzyme 2), qui sert généralement de " passerelle " entre le virus et la cellule. une campagne de vaccination est actuellement en cours au mas-ydk avec le vaccin moderna. cette population est donc relativement homogène en termes d'amyotrophie, de non exposition au sars-cov-2 et de protocole vaccinal.

covid-19 is linked to sars-cov-2, a new coronavirus that can lead to death. some neuromuscular patientsare considered at risk for various reasons: cardiomyopathy or rhythm and/or conduction disorder, ventilator insufficiency, severe motor disability with the need for human support for daily activities. neuromuscular patients with severe amyotrophy are therefore at very high risk of severe forms of covid-19. a still unpublished study of the french neuromuscular network filnemus showed that in neuromuscular patients the risk of admission to icu was 21.2% and the lethality rate 9.1%, well above the values observed in the general population. the prevention of covid-19 is therefore key. until now, in the mas-ydk an extremely strict health protocol has been enacted to protect the residents: outings allowed only for medical appointments, 7-day quarantine for any resident returning from outside, routine systematic pcr of patients and caregivers, prohibition of visits by outsiders... this very stringent protocol has been very effective since no resident has presented any symptomatic covid-19 but this was achieved at the cost of social isolation. vaccination of both residents and staff is therefore the best avenue of hope for a return to a more normal life. will vaccines using the muscle cell machinery be effective in amyotrophic patients? vaccines are now available in france, including the moderna covid-19 vaccine which is based on mrna technology. the genetic sequence it contains encodes the spike protein (s) of the virus envelope, a protein which is key to the virus's penetration into the cells that it infects. the mrna vaccine is injected intramuscularly and penetrates muscle fibers, which are cells producing proteins in very large quantities continuously, especially for the production of myofibrils involved in muscle contraction. once inside the muscle fiber, the vaccine mnra is translated by the muscle fiber machinery allowing a large amount of spike protein (s) that will be presented to the immune system causing the vaccine response and in particular anti-s neutralizing antibodies (nab). these anti-s nabs work by disrupting the interaction between the virus's s protein and the ace2 receptor (angiotensin-converting enzyme 2), which usually serves as the "gateway" between the virus and the cell. a vaccination campaign is currently underway at the mas-ydk with the moderna vaccine. this population is therefore relatively homogeneous in terms of amyotrophy, lack of exposure to sars-cov-2 and vaccine protocol.

Eligibility criteria:
inclusion criteria - for patients with severe neuromuscular disease: 1. adult over 18 2. person with a defined severe neuromuscular pathology by a modified rankin score ≥ 4 3. person supported at the ydk pole 4. person who has received vaccination with the moderna vaccine, in the quadriceps or deltoid 5. non-objection of the patient and/or his legal representative to the participation in the study for patients in the negative control group : 1. non-objection of the patient to the storage and use in the framework of the cannemuss study of these blood samples from the routine care. 2. patient having had a blood sample taken as part of the treatment for virological analysis before anti-covid 19 vaccination. 3. patient matched in sex and age to a patient included in the study cannemuss. for patients in the positive control group : 1. non-objection of the patient to the storage and use in the framework of the cannemuss study of these blood samples from the routine care. 2. patient having had a blood sample taken as part of the treatment for virological analysis following infection with the omicron variant. exclusion criteria for patients with neuromuscular disease severe 1. person with symptomatic infection with sars-cov-2 proven by a positive pcr 2. person with amyotrophic lateral sclerosis

Keywords: neuromuscular amyotrophy mrna vaccines covid-19 protein neutralization s infection vaccine moderna