Prescrire International - Free Special Edition - 2022

ADVERSE EFFECTS

Update onmyocarditis linked to the covid-19messenger RNAvaccines tozinameran ( comirnaty °) and elasomeran ( spikevax °)

● As of autumn 2021, a number of peer-reviewed articles and drug regulatory agency reports have been published around the world about cases of myocarditis attributed to the covid-19 messen ger RNAvaccines tozinameran (Comirnaty°) and elasomeran (Spikevax°). What is currently known about the incidence, severity and risk factors for this adverse effect? I nmid-2021, after analysing reports in Europe and elsewhere, the European Pharmacovigilance Risk Assessment Com mittee (PRAC) concluded that the covid-19 messenger RNA vaccines tozinameran (Comirnaty°) and elasomeran (Spikevax°) provoke very rare cases of myocarditis (1). These generally occurred within 14 days of the second injection in adolescents or men under the age of 30 years, and regressed within a few days. Similar data were obtained in the United States. A few months on, what more is known about this adverse effect, in particular its incidence, severity and risk factors? Do both vaccines carry the same risk? This article summarises a few key findings from Prescrire’s literature search. Increased incidence of myocarditis detected at the population level in studies involving several million individuals. A study analysing data from 40 hos pitals belonging to a private healthcare network in the United States showed that the mean monthly incidence of myocarditis in these hospitals was about 60% higher after the start of the covid-19 vaccination campaign using tozinameran or elaso meran than during the previous 24 months (p<0.001) (2). An analysis of the medical records of about 2 million (mostly adult) patients in this network who had received at least one dose of either of these vaccines identified about 10 cases ofmyocarditis for every million doses of vaccine administered. The risk of myocarditis appeared more marked in men, in younger vac cinees, after the second dose, and with elasomeran . Similar results were obtained in a study in Israel, based on a national healthcare database that included about 5 million tozinameran recipients (3). The incidence of myocarditis was clearly (and statistically significantly) higher after the vaccin ation campaign than during the previous 3 years, especially after the second dose, when it was about five times higher. The risk of myocarditis was more marked in men, after the second dose, and in younger vaccinees (aged 16 to 24 years). A few dozen reports of myocarditis per million doses of messenger RNA vaccine. On 30 September 2021, the French Health Products Agency (ANSM) had received

377 reports of myocarditis attributed to tozinameran , corres ponding to a total incidence of about 5 cases per million doses. The incidencewasmoremarked inmen than inwomen, after the second dose than after the first dose, and in young vaccinees than in older vaccinees. For example, about 40 cases were re ported per million second doses in men aged 18 to 24 years, versus about 2 cases per million first doses in women aged 30 years or older (4). With elasomeran , about 11 cases of myocarditis were report ed per million doses, with similar variations between subgroups, ranging from about 140 reported cases per million second doses of elasomeran in men aged 18 to 24 years, down to only about 1 reported case per million first doses of elasomeran in women aged 30 years or older (4). On 20 October 2021, the British Medicines and Healthcare Products Regulatory Agency (MHRA) had received about 8 re ports ofmyocarditis permillion doses of tozinameran and about 31 permillion doses of elasomeran. By way of comparison, there were about 3 reports of myocarditis per million doses of the viral vector vaccine covid-19 vaccine ChAdOx1-S (Vaxzevria°) (5). On 24 October 2021, the Australian Therapeutic Goods Ad ministration (TGA) had received about 17 reports ofmyocarditis per million doses of tozinameran in men and 7 per million doses in women. Only 500 000 doses of elasomeran had been administered (6). Especially in young men after the second dose. The US Centers for Disease Control and Prevention (CDC) pub lished the data available as of 6 October 2021, based on about 2500 reports, focusing on reports ofmyocarditis that occurred within a week of vaccination (7). The highest incidence seenwith tozinameran was about 69 re ports of myocarditis per million second doses in boys aged 16 or 17 years (and about 37 formen aged 18 to 24 years), versus fewer than 1 permillion first doses inwomen, even youngwomen (7). With elasomeran , which was only authorised for use from the age of 18 years in the United States, the CDC received about 38 reports per million second doses given to men aged 18 to 24 years, versus fewer than 1 per million first doses for women, even young women (7). Mainly within days of vaccination. In the study based on the medical records of about 2 million patients seen in a private US healthcare network, half of the cases of myocarditis occurred within 3.5 days following vaccination (2).

Full review(2 pages) available to subscribers at english.prescrire.org

▶ Translated from “Dans l’actualité”, 5 November 2021 - www.prescrire.org

Prescrire Int • February 2022

Prescrire International Special Edition 2022 • Page 11 private US healthcare network, half of the cases of myocarditis occurred within 3.5 days follow ing vaccination (2). In the Israeli study in about 5 million tozinameran recipients, P ri n