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Feature Vaccine regulation

Covid-19 vaccines: In the rush for regulatory approval, do we need more data?

BMJ 2021; 373 doi: (Published 18 May 2021) Cite this as: BMJ 2021;373:n1244

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Myocarditis followed by CoViD-19 vaccines: A cause for concern or a reversible minor effect?

Dear Editor

European Medicines Agency recently started monitoring reports of myocarditis followed by CoViD-19 vaccines and requested marketing authorisation holders to provide detailed data including age and gender analysis for the agency’s review and consideration [1]. About a month ago, Israel reported several cases of myocarditis, many cases in young subjects (30 years or less) were, in particular, a concern and triggered further investigation [2,3]. Recently, similar cases were also reported in Connecticut in adolescents and young adults [4], and some US troops also developed myocarditis post-vaccination that triggered a Pentagon investigation [5].

An investigation report submitted to the Israeli Ministry of Health reported a myocarditis incidence rate between 1 in 3000 and 1 in 6000 among 16 to 24 years old post-CoViD vaccines but most cases were mild and resolved within a few weeks [6]. The Centers for Disease Control and Prevention (CDC) in the United States also investigated cases of myocarditis following mRNA vaccines from the Department of Defense (DoD), the Vaccine Adverse Event Reporting System (VAERS), and Vaccine Safety Datalink (VSD). CDC noted that cases were predominantly reported in adolescents and young adults, were more often in males than females, observed more often following the second dose than the first dose, and were typically observed within four days after vaccination. Although incidence rates in the United States were low, the CDC recommended that clinicians should be informed to help early recognition and prompt clinical management. They have also encouraged to form an interdisciplinary team comprising experts from infectious diseases, cardiology, and rheumatology to develop guidance on diagnosis, treatment, and management of post-vaccination myocarditis [7].

The myocarditis (inflammation of the heart muscle) has been reported so far with the mRNA CoViD vaccines (Pfizer and Moderna), however, the MHRA’s adverse event report lists many cases of myocarditis, suggesting a strong signal for both AstraZeneca (viral vector) and Prizer (mRNA) CoViD vaccines [8]. The MHRA adverse event report including data up until 2nd June 2021 listed 31 cases of myocarditis (1 fatal) with AstraZeneca and 34 cases with Pfizer. Moreover, there were 55 cases of pericarditis (inflammation of the membrane around the heart) with AstraZeneca and 26 cases (1 fatal) with Pfizer. In addition, there were 330 myocardial infarctions (55 fatal) with AstraZeneca and 123 with Pfizer (24 fatal) [8].

Myocarditis often manifests into rate and rhythm disorders, the report listed 2183 cases of cardiac rate and rhythm anomalies with AstraZeneca (36 deaths) and 966 cases with Pfizer (28 deaths). In total, there were 118 deaths recorded with AZ and 63 for Pfizer in the broader category of cardiovascular events [8]. The number of cardiac adverse events with Pfizer’s CoViD vaccine were about half the events from CoViD vaccine AstraZeneca, but it is likely to be associated with the number of subjects who received these vaccines. According to MHRA, there were about ~24.5 million peoples who received at least one dose of the AstraZeneca vaccine whereas 14.7 million peoples received the Pfizer as of 2nd June 2021 [8]. This suggests that the rate of cardiovascular events followed by the CoViD vaccine AstraZeneca and Pfizer was not too dissimilar in the United Kingdom.

The preliminary findings suggest that post-vaccination myocarditis may be explained by a direct spike mediated toxicity [9], either by post-immunisation circulatory spike proteins distribution into cardiac tissue or spike production by the vaccine transfected cardiac cells locally. The recently emerging evidence has shown preliminary reports of systemic circulation of spike proteins post-immunisation [10], and the presence of vaccine antigen (mRNA) in body fluids [11] in some vaccinated subjects. Notably, the CoViD vaccine distribution to the cardiac tissues was also evidenced during the pre-clinical evaluation of vaccines [12-13]. Cardiomegaly and myocarditis secondary to SARS-CoV-2 was also a common clinical finding in CoViD-19 patients and is a likely contributor to the increased mortality in severely ill CoViD patients.

The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK also investigated the cases of myocarditis and pericarditis following CoViD vaccines and concluded that the numbers were similar or even below expected population background rates [8]. MHRA is requested to further investigate these cases in association with cardiac rate and rhythm anomalies and publish age and gender analysis of cardiovascular events in their regular updates. CoViD mRNA vaccines have recently been considered for use in adolescents and young adults by various regulatory authorities, therefore, a comprehensive safety review is imperative to reassure that the risks associated with genetic vaccines in the young population do not outweigh the desired benefits.

Vaccines are one of the great discoveries in medicine that has improved life expectancy dramatically. Nevertheless, genetic vaccines are new, and their long-term safety evaluation is important in identifying the potentially contraindicated populations to ensure public safety.


Competing interests: No competing interests

14 June 2021
Hamid Merchant
Subject Leader in Pharmacy
University of Huddersfield
United Kingdom