ABSTRACT
Introduction: À ce jour, près de 2 milliards de doses vaccinales anti-COVID-19 ont été administrées. Divers effets indésirables dermatologiques ont été décrits (réactions locales au point d'injection, urticaire, éruptions morbilliformes, etc.). Douze cas de nécrolyse épidermique (NE, incluant les syndromes de Stevens–Johnson et de Lyell) ont été publiés. Notre objectif était d'analyser les cas de NE post-vaccin anti-COVID-19 notifiés en pharmacovigilance (PV) et de faire une revue de la littérature. Matériel et méthodes: Nous avons extrait de la base de données mondiale de PV (VigiBase), en requêtant avec le « Prefered terms » NE et les vaccins anti-COVID-19 comme médicaments « suspect », les cas de NE déclarés jusqu'au 03/03/2022. Nous avons analysé les caractéristiques de la NE, le déclarant, le délai d'apparition des symptômes, le type de vaccin et la dose (1re : D1, ou 2e : D2), la présence éventuelle d'un autre médicament suspect. Nous avons décrit plus précisément les cas rapportés dans la base de données de PV française et calculé le score ALDEN pour chaque molécule suspectée. Enfin, nous avons analysé les cas de la littérature en revoyant les photos et les données cliniques publiées. Résultats: Nous avons identifié dans VigiBase 240 cas de NE pour lesquels les vaccins anti-COVID-19 étaient considérés comme « suspects », dans 64 % des cas en provenance des États-Unis, et pour 60,5 % survenus chez des femmes, majoritairement entre 45–64 ans. Il s'agissait de syndrome de Stevens–Johnson (décollement < 10 %) dans 80 % des cas, 7 % sont décédés. Le vaccin le plus souvent suspect était à ARNm (82 %). Ces cas étaient difficiles à interpréter en raison d'un manque de données (biopsies, symptomatologie, nature du déclarant).La base française de PV comporte 8 cas de NE. Un cas survenu chez une patiente asiatique avec HLA favorisant était plutôt lié à la lamotrigine d'après le calcul du score ALDEN (6 pour lamotrigine et 2 pour le vaccin), 4 cas étaient probablement des erreurs diagnostiques ou non médicamenteux (1 érythème polymorphe, 1 NE post-mycoplasme, 1 éruption morbiliforme et 1 surdosage en méthotrexate) et pour 1 cas, les données descriptives étaient manquantes. Nous avons donc retenu 2 cas de NE potentiellement en lien avec le vaccin : un homme de 40 ans dont la NE a débuté dans les 24 heures suivant la D1 du vaccin Pfizer®, et un homme de 81 ans ayant débuté 3 jours après la D2 du vaccin Pfizer® une NE d'issue fatale.Après analyse critique des 12 cas de la littérature, nous n'en avons retenu que 3 correspondant sémiologiquement à une NE possiblement en lien avec le vaccin. Discussion: Notre étude de PV, conjuguée à l'analyse critique de la littérature, ne retient au total que 5 cas de NE possiblement induite par le vaccin anti-COVID-19, sans toutefois pouvoir affirmer le lien de causalité. La majorité des autres cas ne sont pas des NE ou ont d'autres médicaments suspects. Comme avec les autres vaccins, l'éventualité d'une NE post-vaccinale anti-COVID-19 semble donc exceptionnelle et ne remet pas en question le bénéfice attendu de cette vaccination au regard de la morbi-mortalité du SARS-CoV-2.
ABSTRACT
Introduction: Several case reports and pharmacoepidemiological studies suggested a potential association between the mRNA) COVID-19 vaccine, tozinameran (Comirnaty) and elasomeran (Spikevax) and SSNHL. However, data remain controversed because of scarcity of this adverse effect (1,2). Objective(s): To assess an descriptive analysis of all spontaneous reporting of mRNA COVID-19 vaccines induced-Sudden Sensorineural Hearing Loss (SSNHL) to the French Pharmacovigilance system and to estimate the incidence of SSNHL reported cases. Method(s): All cases of mRNA COVID-19 vaccines induced-SSNHL recorded in the FPDB from the beginning of the campaign of COVID- 19 vaccination in France until 2 February 2022 were included. Following data were collected: demographic data (age, gender), risk factors, history of immunologic disease, other factors leading to SSNHL (trauma, infections,), the range and the month of vaccination, the delay of onset of SSNHL, associated symptoms (dizziness and tinnitus), the degree of hearing loss and the outcome. Audiogramm and/or medical reports were requested in order to guarantee a better informativeness of data. All cases were reviewed by a staff including two pharmacologists and two otorhinolaryngologists. All cases with a delay onset>30 days were excluded. Cases were split in ''well completed'' and (non completed) based on the availability of audiogram and medical reports. Result(s): A total of 250 cases were recorded during this period for the 2 vaccines (60 Spikevax/190) (23 cases excluded because of other reasons or missed data). 226 cases were analyzed and will described according to over mentioned criteria, corresponding to 151 cases classed as ''well completed'' (31 Spikevax/120 Comirnaty). The estimated incidence of SSNHL was estimated as 0.18/100000 for serious cases for Comirnaty and 0.27/100000 for both serious and non serious cases for Spikevax. For Spikevax, the median age was 50 years with a sex ratio of 0.9, the half of cases occurred after D1, 5 cases of positive rechallenge and hearing loss was associated with tinnitus in 50% and dizziness in 21.6%. For Comirnaty, the median age was 56 years with a sex ratio of 0.8, 76% of cases occurred after D1, 1 case of positive rechallenge, associated with tinnitus in 84% and dizziness in 39% of cases. Conclusion(s): In our knowledge, it is the first study analysing all cases of mRNA vaccines-induced SSNHL supporting by audiogram analysis. This adverse effect remains rare but should be considered in patients with audio-vestibular risk factors. Other studies would be necessary in order to understand the mechanism which remains unclear.
ABSTRACT
Introduction: Several case reports and pharmacoepidemiological studies suggested a potential association between the mRNA) COVID-19 vaccine, tozinameran (Comirnaty) and elasomeran (Spikevax) and SSNHL. However, data remain controversed because of scarcity of this adverse effect (1,2). Objective: To assess an descriptive analysis of all spontaneous reporting of mRNA COVID-19 vaccines induced-Sudden Sensorineural Hearing Loss (SSNHL) to the French Pharmacovigilance system and to estimate the incidence of SSNHL reported cases. Methods: All cases of mRNA COVID-19 vaccines induced-SSNHL recorded in the FPDB from the beginning of the campaign of COVID19 vaccination in France until 2 February 2022 were included. Following data were collected: demographic data (age, gender), risk factors, history of immunologic disease, other factors leading to SSNHL (trauma, infections,...), the range and the month of vaccination, the delay of onset of SSNHL, associated symptoms (dizziness and tinnitus), the degree of hearing loss and the outcome. Audiogramm and/or medical reports were requested in order to guarantee a better informativeness of data. All cases were reviewed by a staffincluding two pharmacologists and two otorhinolaryngologists. All cases with a delay onset[30 days were excluded. Cases were split in "well completed" and (non completed) based on the availability of audiogram and medical reports. Results: A total of 250 cases were recorded during this period for the 2 vaccines (60 Spikevax/190) (23 cases excluded because of other reasons or missed data). 226 cases were analyzed and will described according to over mentioned criteria, corresponding to 151 cases classed as "well completed" (31 Spikevax/120 Comirnaty). The estimated incidence of SSNHL was estimated as 0.18/100000 for serious cases for Comirnaty and 0.27/100000 for both serious and non serious cases for Spikevax. For Spikevax, the median age was 50 years with a sex ratio of 0.9, the half of cases occurred after D1, 5 cases of positive rechallenge and hearing loss was associated with tinnitus in 50% and dizziness in 21.6%. For Comirnaty, the median age was 56 years with a sex ratio of 0.8, 76% of cases occurred after D1, 1 case of positive rechallenge, associated with tinnitus in 84% and dizziness in 39% of cases. Conclusion: In our knowledge, it is the first study analysing all cases of mRNA vaccines-induced SSNHL supporting by audiogram analysis. This adverse effect remains rare but should be considered in patients with audio-vestibular risk factors. Other studies would be necessary in order to understand the mechanism which remains unclear.
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Introduction: Post-mRNA vaccine myocarditis emerged as a rare adverse effect quickly after adolescents and young adult populations started to be vaccinated, and it was labelled as such for both vaccines. This work aimed to study the Reporting rates (Rr) of myocarditis after mRNA-1273 and BNT162b2 injections. Material and methods: mRNA vaccine exposures were retrieved from the French SI-VAC database, while cases of myocarditis were retrieved from the French spontaneous reporting database (Base Nationale de Pharmacovigilance, BNPV) up to 30 September 2021. All cases were routinely evaluated by drug safety medical professionals and repeated at national level in the context of an intensive pharmacovigilance monitoring. Reporting rates (Rr) per 100.000 injections were calculated according to age, gender and injection rank;Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI). Results: Over the study period, almost 73 million BNT162b2 and 10 million mRNA-1273 doses were injected, and 376 and 106 confirmed cases of myocarditis were reported, respectively. These occurred in the week following the injection for 76.4% of cases reported after mRNA-1273 (n = 81) vs. 58.4% after BNT162b2 (n = 219). Rr per 100.000 injections was 1.1 (95% CI 0.9 to 1.3) for mRNA-1273 and 0.5 (0.5 to 0.6) for BNT162b2. After the second injection, the difference among vaccines was more pronounced in men aged 18-24 years (13.9 [9.2 to 20.1] for mRNA-1273 vs. 4.3 [3.4 to 5.5] for BNT162b2) and aged 25-29 years (7.0 [3.4 to 12.9] vs. 1.9 [1.2 to 2.9]);in younger people, the low number of cases did not allow any meaningful conclusion. In women, Rrs were globally lower, but differences between vaccines were close to those found for men. Discussion/Conclusion: The present study suggests that mRNA-1273 is related with a higher risk of myocarditis than BNT162b2 in people aged under 30, especially after the second injection.