Thread by @vipintukur

#CDC has recently reported myocarditis & pericarditis cases following #mRNA #vaccination in adolescents & young adults in the US. Are these the first reported cases of cardiac involvement following mRNA vaccines? 1/
cdc.gov/coronavirus/20…

Fortunately, these incidents are extremely rare events. But, have the agencies overlooked earlier signals? Are these cases indeed related to mRNA vaccines? Are the vaccines responsible? If yes, what could be the probable mechanism? 2/

Few cases of post-vaccination myocarditis, heart failure & heart attacks have been reported in #Israel since December soon after the launch of #Pfizer mRNA vaccine. Health officials referred them as “A murky wave of heart attacks” 3/
israelnationalnews.com/News/News.aspx…

There were few other media reports claiming a higher incidence of certain cardiac ailments following mass vaccination drive with #BNT162b2 vaccine in Israel 4/
swprs.org/israel-why-is-…]

Israel initially refuted any association to #Pfizer Covid vaccines. But now they said, “it had found the small number of heart inflammation cases observed mainly in young men who received Pfizer’s vaccine were likely linked to their vaccination”. 5/
reuters.com/world/middle-e…

In Israel, 275 cases of myocarditis were reported between December 2020 and May 2021 among more than 5 million vaccinated people 6/

What could be the mechanism? Could it be due to #autoreactive antibodies responsible for #autoimmune myocarditis? Fortunately, majority of the cases are mild, self-limiting type. And above all, these events are extremely rare! 7/

A severe type might also be responsible for some of the post-mRNA vaccination sudden death reports which are being attributed to other adverse effects which are not directly related to #mRNA vaccine 8/

Several factors predispose the development of autoimmune myocarditis such as systemic/local primary autoimmunity, viral infection, HLA & gender bias, exposure of cryptic antigens, mimicry, & deficient thymic training/Treg induction pubmed.ncbi.nlm.nih.gov/28667560/ 9/

Once the anti-myocardium autoimmune process is triggered, several components of the immune response orchestrate a sustained attack toward myocardial tissues with particular timing and immunopathogenic features 10/

Covid19 itself can lead to fatal myocarditis. Proposed mechanisms include binding of Spike protein to ACE 2 which facilitates virus entry into the target cells, immune-related myocardial inflammation & direct injury caused by hypoxemia 11/ ebm.bmj.com/content/ebmed/…

There are some other possible mechanisms. It has been suggested that IL-6 plays an integral role in activation of helper T cells, which in turn release inflammatory cytokines ultimately resulting in myocardial inflammation and damage 12/

Another one...the SARS-CoV-2 spike protein disrupts the cooperative function of human cardiac pericytes - endothelial cells through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease 13/
biorxiv.org/content/10.110…

Different mechanisms may lead to #myocarditis. What needs to be done? Since the nucleic acid-based vaccines are the new entrants, every possible safety signal must be promptly evaluated. Transparency in risk-communication is essential & it further enhances vaccine confidence 14/

The supraphysiological expression levels of spike proteins in some individuals who receive nucleic acid based vaccines might share in development of autoimmune reactions. There is a need to optimize the dose of the nucleic acid based vaccines to the lowest possible dose 15/

There is a need to develop potential tools to prevent such reactions. Fortunately, the risk is still miniscule considering the huge number of vaccines delivered so far. Still, the benefits far outweigh the risks. #Moderna has already started working on this aspect 16/

Additionally, the techniques used in development of all types of #SARSCoV2 vaccines, especially the newly emergency approved ones, should focus on innovative methods to decrease their potential #autoimmunity 17/ authorea.com/doi/pdf/10.225…