Post-mRNA COVID-19 vaccines myocarditis: Not so rare in cardiology practice

Introduction In the context of large-scale anti-SARS-Cov-2 vaccination campaign by new mRNA vaccines, post-vaccination associated myocarditis (PVM) appeared as rare but potentially serious side effects. Few data are currently available on its prevalence in practice in intensive cardiac care unit (ICCU). Objective We carried out an exhaustive epidemiological multicentric collection of acute myocarditis managed in ICCU in Western Europe to describe PVM prevalence and acute prognosis. Method Patients managed for an acute myocarditis (AM) in 4 tertiary ICCU in France between May and September 2021 were included. Myocarditis was defined according to ESC guidelines and Lake Louise CMR criteria. PVM diagnosis was retained in case of compatible vaccination-myocarditis diagnosis delay (usually between 2 and 9 days) (5), with a negative etiologic assessment for other AM causes. Baselines characteristics and in-hospital complications were compared between PVM and others AM. Results Patients managed for an acute myocarditis (AM) in 4 tertiary ICCU in France between May and September 2021 were included. Myocarditis was defined according to ESC guidelines and Lake Louise CMR criteria. PVM diagnosis was retained in case of compatible vaccination-myocarditis diagnosis delay (usually between 2 and 9 days) (5), with a negative etiologic assessment for other AM causes. Baselines characteristics and in-hospital complications were compared between PVM and others AM. Conclusion Post-vaccination myocarditis is a rare, and most often benign, side effects of mRNA anti-COVID19 vaccine. However, healthcare professionals should be aware of it due to its higher prevalence in expert referrals centers especially in the context of mass vaccination campaign.

Myocarditis and pericarditis in adolescents after first and second doses of mRNA COVID-19 vaccines

Introduction: While some concerns about vaccination-related pericarditis and/or myocarditis have raised, no published data are available on pericarditis and/or myocarditis with mRNA COVID-19 vaccines in the age group of adolescents, particularly in 12-15 years. The objective of this study was to determine whether the risk of reporting pericarditis and/or myocarditis with mRNA COVID-19 vaccines varied according to dose-vaccination, age, sex and type of pericarditis and/or myocarditis in adolescents between 12-17 years. Material and methods: We performed an observational study reviewing all reports of adolescent vaccinated with mRNA COVID-19 vaccines and recorded in Vigibase®, the World Health Organization (WHO) Global Individual Case Safety Reports (ICSRs) database. We included all reports registered between January 1, 2021, and September 14, 2021. Reporting Odds Ratios (ROR) with their 95% confidence interval (CI) were calculated to estimate the risk of reporting pericarditis and/or myocarditis. Results: Among 4,942 reports with mRNA COVID-19 vaccines in adolescents, we identified 242 pericarditis and/or myocarditis. Compared with the first dose of mRNA COVID-19 vaccines, the second dose was associated with an increased risk of reporting pericarditis and/or myocarditis (ROR 4.95;95% CI 3.14, 7.89). The risk of reporting pericarditis and/or myocarditis was 10 times higher in boys than in girls and no difference between the two types of vaccines could be demonstrated. Discussion/Conclusion: This investigation including only adolescent data suggests for the first time that second dose of mRNA COVID-19 vaccines increase the risk of reporting myocarditis/pericarditis compared to the first dose particularly in boys without significant difference between Tozinameran and Elasomeran.

Ensuring quality control in a clinical trial during the COVID-19 pandemic: The experience of the Inserm C20-15 DisCoVeRy study in France

Introduction: Health measures taken during the pandemic, such as lockdowns, deeply modified the clinical research practices by restricting access to hospitals. Site personnel was also limited due to overload. At the same time, the demand for the results of the COVID-19 trials was urgent. Thus, the objective of this article is to share Inserm's experience in ensuring quality control in clinical trials in this challenging context. Material and methods: DisCoVeRy is a phase III adaptive, randomized study that aimed, in its first phase, at evaluating the safety and efficacy of four therapeutic strategies in hospitalized COVID-19 adult patients needing additional oxygen [1]. Between March 22, 2020, and January 20, 2021, 1,176 patients were included in France. In order to guarantee the best quality of data, the sponsor had to adapt to the current sanitary measures and to their impact on clinical research activity. There were notably adapted Monitoring Plan objectives (source data verification of 100% of critical data of all participants), involvement of the research departments (DRI) of the participating hospitals, a network of CRAs, and Inserm personnel. Results: Overall, 91 clinical research assistants (CRA) were involved in France and performed 834 monitoring visits from April 24, 2020, to October 15, 2021. The monitoring of 100% of critical data for all patients included in the analysis was achieved, and despite of the pandemic context, a conform consent was recovered for more than 99% of patients. Results of the study were published in May and September 2021 [2,3]. Discussion/Conclusion: Our main monitoring objective was met thanks to the mobilization of considerable personnel resources, within a very tight time frame and despite external hurdles. However, the implementation of such an organization emphasizes the importance of having easy indicators which can be accessed in due course to help steering the study and planning database usage and results publication.

Assurer le contrôle qualité d'un essai clinique pendant la pandémie de COVID-19 : l'expérience de l'étude Inserm C20-15 DisCoVeRy en France

Introduction Les mesures sanitaires mises en place pendant la pandémie, telles que la distanciation sociale et les confinements, ont profondément modifié les pratiques de recherche clinique en restreignant l'accès aux participants en raison des risques de contamination, et en limitant la disponibilité du personnel des sites en raison de la surcharge de travail. Dans le même temps, la demande de résultats issus des essais COVID-19 était urgente et soumise à la pression de la communauté scientifique, de la société civile et des médias. Ainsi, l'objectif de cette communication est de partager l'expérience de l'Inserm pour assurer le contrôle qualité d'un essai clinique dans ce contexte particulier. Methodes DisCoVeRy est une étude de phase III adaptative et randomisée qui visait, dans sa première phase, à évaluer la sécurité et l'efficacité de 4 stratégies thérapeutiques chez des patients adultes hospitalisés pour COVID-19 ayant un besoin de supplémentation en oxygène. Entre le 22 mars 2020 et le 20 janvier 2021, 1176 patients ont été inclus en France. Afin de garantir la qualité des données recueillies, le promoteur a dû s'adapter aux mesures sanitaires en vigueur et à leur impact sur l'activité de recherche clinique. Il s'agissait notamment : d'adapter les objectifs du Plan de Monitoring (vérification des données sources pour 100% des données critiques de tous les participants), d'impliquer les Direction de la Recherche et de l'Innovation (DRI) des hôpitaux participants, de solliciter un réseau d'assistants de recherche clinique (ARC) et des personnels Inserm. Resultats Au total, 91 ARCs ont été impliqués en France et ont effectué 834 visites de monitoring du 24 avril 2020 au 15 octobre 2021, donnant lieu à 539 rapports de monitoring. Parmi les 1176 patients inclus et randomisés, un consentement a été obtenu permettant l'analyse de toutes les données chez 1112 (94,6%), des données jusqu'à la levée de la sédation chez 23 (1,9%), des données jusqu'au retrait du consentement ou à la décision de l'investigateur principal chez 32 (2,7%). Neuf (0,8%) patients n'ont pu être analysés en l'absence de consentement conforme. Le contrôle de 100% des données critiques pour tous les patients inclus dans l'analyse a été réalisé, conformément au Plan de Monitoring. Les résultats de l'étude ont été publiés en mai et septembre 2021. Au regard de l'importance de rendre les résultats publics, ces premières publications ont été soumises sans que toutes les données critiques aient été contrôlées. Le monitoring du consentement, des critères de sélection et du critère d'évaluation principal avait été priorisé afin d'assurer la fiabilité des résultats sur ces éléments majeurs. Conclusion Malgré le démarrage contraint de l'étude avant la mise en place de l'équipe de monitoring, le rythme d'inclusion très élevé, et les contraintes majeures liées au contexte pandémique, l'ensemble des données critiques selon le Plan de Monitoring initial a été monitoré en seulement 18 mois. Ce résultat est notamment dû à la mobilisation de ressources en personnel considérables, dans un délai très court. Cependant, la mise en place d'une telle organisation souligne l'importance de disposer d'indicateurs faciles à consulter en temps réel pour aider au pilotage de l'étude et à la planification de l'utilisation de la base de données et de la publication des résultats. Mots clés contrôle qualité ;monitoring ;consentement ;promotion Déclaration de liens d'intérêts Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts

Acute coronary syndromes in the era of SARS-CoV-2 Infection: A registry of the French group of acute cardiac care

Background Cardiovascular complications are frequent in SARS-CoV-2 patients. The characteristics of acute coronary syndromes (ACS) in this population have not yet been reported. Purpose We aimed to report clinical characteristics and outcome of patients with and without SARS-CoV-2 infection referred for acute coronary syndrome (ACS) during the peak of the pandemic in France. Methods We included all consecutive patients referred for ST-elevation myocardial infarction (STEMI) or NSTEMI during the first 3 weeks of April 2020 in 5 university hospitals (Paris, south and north of France), all performing primary percutaneous coronary intervention (PCI). Results The study included 237 patients (67 ± 14, 69% of male), 111 (49%) with STEMI and 121 (51%) with NSTEMI. The prevalence of SARS-CoV-2 associated ACS was 11% (n = 26) and 11 patients had severe hypoxemia on presentation (mechanical ventilation or nasal oxygen >6L/min). Patients were comparable regarding medical history and risk factors, except higher prevalence of diabetes mellitus in SARS-CoV-2 patients (53.8% vs. 25.5%, P = 0.003). In SARS-CoV-2 patients, admission for cardiac arrest was more frequent (26.9% vs. 6.6%, P < 0.001), and significant coronary artery disease and culprit artery occlusion were reported in 76.5% and 92% of STEMI patients, and 88.9% and 50% of NSTEMI, respectively. PCI was performed in the same percentage of STEMI (82%) and NSTEMI (86%) cases, regardless of SARS-CoV-2 infection, but no-reflow after PCI (19.2% vs. 3.3%, P < 0.001) was greater in SARS-CoV-2 patients. In-hospital death occurred in 7 SARS-CoV-2 patients (5 from cardiac cause) and was higher compared to non-infected patients (26.9% vs. 6.2%, P < 0.001) Conclusion SARS-CoV-2 infection is frequent in ACS patients with higher incidence of coronary occlusion and no-reflow compared to non-SARS-CoV-2 ACS, which may explain the higher in-hospital mortality, despite a similar rate of PCI.