Myocarditis post-COVID-19 mRNA Vaccination: Time Matters
JAMA recently published a study on the long-term prognosis of myocarditis after COVID-19 RNA vaccination in comparison to myocarditis due to COVID-19 or of other origins.
In their primary analysis, the authors defined postvaccine myocarditis as those leading to hospital admission for myocarditis within 7 days after receipt of any dose of a COVID-19 mRNA vaccine. Using such definition, they show that, in comparison to conventional myocarditis, postvaccine myocarditis had a lower incidence of rehospitalization for myopericarditis, other cardiovascular events, or all-cause death, while no differences were observed with post–COVID-19 myocarditis.
Remarkably, when in the sensitivity analysis they extend the definition of postvaccine myocarditis to include hospital admissions occurring within 30 days (rather than 7) after receipt of the COVID-19 mRNA vaccine, the difference between postvaccine myocarditis and conventional myocarditis disappeared.
In our opinion, this finding is consistent with the notion that postvaccine myocarditis may occur several weeks or even months after vaccination, and that the Spike protein may represent a causal factor. We therefore sent a letter to the journal to suggest that avoiding the exclusion of COVID-19 vaccines as possible causal agent of myocarditis that occur even more than one week after the vaccination can help to better define the risk-benefit ratio of these vaccines.
Unfortunately the letter was rejected with this reason:
Unfortunately, because of the many submissions we receive and our space limitations in the Letters section, we are unable to publish your letter in JAMA.
After considering the opinions of our editorial staff, we determined your letter did not receive a high enough priority rating for publication in JAMA. We are able to publish only a small fraction of the letters submitted to us each year, which means that published letters must have an extremely high rating.
Interestingly enough, the reason is very similar to the one given on previous occasions. It is therefore possible that the Internet is “too small a space for us, too tiny”. We are therefore publishing the text of our letter below, which we will also send to the authors of the study should they wish to reply with their own comment.
To the Editor
Semenzato and coworkers used the French National Health Data System to identify all individuals aged 12 to 49 years who were hospitalized for myocarditis in France between December 27, 2020, and June 30, 2022, and studied the cardiovascular complications of post–COVID-19 mRNA vaccination myocarditis in comparison to post–COVID-19 myocarditis, or conventional myocarditis.1 Using a composite outcome, they show that, in comparison to conventional myocarditis, postvaccine myocarditis had a lower incidence of rehospitalization for myopericarditis, other cardiovascular events, or all-cause death (weighted hazard ratio [wHR], 0.55 [95% CI, 0.36-0.86]), while no differences were observed with post–COVID-19 myocarditis (wHR, 1.04 [95% CI, 0.70-1.52]).1
In the primary analysis however postvaccine myocarditis were defined as those leading to hospital admission for myocarditis within only 7 days after receipt of any dose of a COVID-19 mRNA vaccine. Remarkably, when in the sensitivity analysis the definition of postvaccine myocarditis was extended to include hospital admissions occurring within 30 days (rather than 7) after receipt of the COVID-19 mRNA vaccine, the difference between postvaccine myocarditis and conventional myocarditis disappeared (wHR, 0.84 [95% CI, 0.64-1.09] for the composite clinical outcome in the postvaccine myocarditis group).1
This finding is consistent with the notion that elevated plasma levels of COVID-19 mRNA vaccine-induced free Spike protein occur in people with postvaccine myocarditis, but not in asymptomatic people, up to more than 3 weeks after COVID-19 vaccination.2 We and others have extensively discussed the role of COVID-19 vaccine-induced Spike protein in the adverse effects of COVID-19 mRNA vaccines.3,4 Indeed, both vaccine mRNA and vaccine-induced Spike protein can be detected in axillary lymph nodes up to 60 days after vaccination, and the Spike protein has been identified in endomyocardial biopsies of patients with myocarditis up to nearly two months following vaccination [reviewed in 3]. Available evidence thus supports the possibility that postvaccine myocarditis may occur several weeks or even months after vaccination, and that the Spike protein may represent a causal factor.
Avoiding the exclusion of COVID-19 vaccines as possible causal agent of myocarditis that occur even more than one week after the vaccination can help to better define the risk-benefit ratio of these vaccines. Moreover, understanding the role of the Spike protein in myocarditis may lead to a more accurate diagnosis as well as eventually to the development of targeted drug therapies for postvaccine and possibly also post–COVID-19 myocarditis.5
Marco Cosentino, MD, PhD; Franca Marino, BSc, PhD
Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy
Author Contributions: all the authors contributed equally and have read and agreed to the published version of the manuscript.
Conflict of Interest Disclosures: none.
Funding/Support: none.
References
1. Semenzato L, Le Vu S, Botton J, Bertrand M, Jabagi MJ, Drouin J, Cuenot F, Zores F, Dray-Spira R, Weill A, Zureik M. Long-Term Prognosis of Patients With Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2 Infection, or Conventional Etiologies. JAMA. 2024; Aug 26:e2416380. doi: 10.1001/jama.2024.16380.
2. Yonker, LM, Swank, Z, Bartsch, YC, Burns, MD, Kane, A, Boribong, BP, Davis, JP, Loiselle, M, Novak, T, Senussi, Y, et al. Circulating spike protein detected in post–COVID-19 mRNA vaccine myocarditis. Circulation. 2023;147:867–876. doi: 10.1161/CIRCULATIONAHA.122.061025
3. Cosentino M, Marino F. Understanding the Pharmacology of COVID-19 mRNA Vaccines: Playing Dice with the Spike? Int J Mol Sci. 2022;23:10881. doi: 10.3390/ijms231810881.
4. Trougakos IP, Terpos E, Alexopoulos H, Politou M, Paraskevis D, Scorilas A, Kastritis E, Andreakos E, Dimopoulos MA. Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis. Trends Mol Med. 2022;28(7):542-554. doi: 10.1016/j.molmed.2022.04.007
5. Cosentino M, Marino F. Letter by Cosentino and Marino Regarding Article, "Circulating Spike Protein Detected in Post-COVID-19 mRNA Vaccine Myocarditis". Circulation. 2023;148(11):906-907. doi: 10.1161/CIRCULATIONAHA.123.064000.
Why would they use a cutoff of 7 days to detect vaccine-associated myocarditis hospitalization? Most of the official statistics for "vaccinated" status say it starts 14 days after the dose. For example Health Canada defines "Primary series completed" Covid cases as "Cases whose episode date was 14 days or more after receipt of a second dose in two-dose series, 14 days or more after receipt of one dose of a one-dose vaccine, or 0 to <14 days after receipt of a first additional dose (e.g., third or booster) of a Health Canada authorized COVID-19 vaccine."
Seems like a cherry-picked cutoff to make the jab look safer.
What does your method show about 14 day cutoff? How did you pick 30?
Egregio Professore,
grazie per il suo punto di vista, ma (chiedo) perché non è invece lecito pensare che dopo tot giorni la proteina spike, venendo eliminata dall’organismo, non possa più contribuire all’insorgenza di miocardite e che quindi l’incidenza sia comparabile a quella “convenzionale”
Grazie in anticipo