Free spike proteins in the blood appear to play a role in myocarditis post-COVID mRNA vaccine

Following the large-scale rollout of the messenger ribonucleic acid (mRNA) vaccines developed to prevent infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptomatic coronavirus disease 2019 (COVID-19), some cases of myocarditis were reported, mostly among healthy young people.

A recent study published in the journal Circulation examines the immunological picture in this scenario, looking for clues to the etiology of this rare and potentially serious complication.

Study: Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis. Image Credit: Design_Cells / ShutterstockStudy: Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis. Image Credit: Design_Cells / Shutterstock


The development of myocarditis following mRNA vaccination is rare, occurring in <2 per 100,000 individuals. It remains an unpredictable mysterious occurrence. Some have suggested that it is linked to the overproduction of antibodies or abnormal immune responses.

Autoantibody production due to polyclonal B cell activation and proliferation has also been suggested, as has immune complex formation and inflammation. Finally, some think that cardiac antigens closely resembling the spike protein are targeted by autoantibodies formed as a result of molecular mimicry.

The immune response to these vaccines in these patients needs to be better understood in order to determine why and how it happens. It is imperative to study the role of male hormones since young male patients are most often affected.

The researchers in this study looked at blood samples from 16 myocarditis patients, confirmed to have high levels of serum cardiac troponin T. All developed myocarditis after receiving the COVID-19 vaccine, typically within a week of the second dose. However, a few became sick after the first dose or booster dose. Over 80% were male.

They were studied by antibody profiling, including antibodies to the virus, autoantibodies or antibodies to the virome, and the analysis of T cells specifically directed against the virus. In addition, cytokine and antigen profiles were determined. These measurements were compared with those of 45 vaccinated controls, who were of similar age and health.

What did the study show?

All subjects and controls showed a rise in anti-spike antibodies and antibodies to the receptor binding domain (RBD), of all immunoglobulin (Ig) subclasses, IgA, IgM, and IgG. Functional differences were not perceived either, with Fc effector functions being similar in both categories. In short, all vaccinated individuals showed evidence of a protective immune response against the virus.

We found no indication that a specific antibody response is associated with myocarditis.”

Additionally, these patients did not show evidence of increased autoantibody production or antibody production against other respiratory pathogens that differed in magnitude or range from the controls.

T cells of all relevant subtypes, including naïve, memory, and effector memory T cells, showed similar distributions in both groups. T cells also showed similar proportions of spike-specific memory CD4 T cells and activated CD4 and CD8 T cells. The only exceptions were the observation of small elevations in effector memory cells and PD-1-expressing bulk CD4 T cells in the myocarditis group.

The findings indicated that antibody and T-cell responses could not distinguish between post-vaccine myocarditis subjects and vaccinated controls. The only significant difference was a slight elevation in cytokine production in the former.

The exciting difference was the high level of circulating full-length spike protein in the plasma of myocarditis patients, at a mean of ~34 pg/mL. Furthermore, the protein was not bound to antibodies and remained detectable for up to three weeks from the vaccination date. In contrast, controls did not have free spike protein in their blood.

This difference could not be attributed to poor neutralizing capacity in the myocarditis group, which showed comparable neutralization relative to the control group.

Concordantly, myocarditis patients had cytokine release patterns resembling those found in multisystem inflammatory syndrome in children (MIS-C). This might indicate that the innate immune response was overactive, leading to elevations in interleukin (IL)-8, IL-10, IL-4, IL-6, tumor necrosis factor (TNF)-α, and interferon (INF)-γ relative to healthy controls. IL-8 was most closely associated with raised cardiac troponin T and antigen levels.

Alongside, leukocytes, especially neutrophils, were at higher mean levels in this group than controls, though still within normal range.

What are the implications?

The study shows that the immunological response elicited by the mRNA vaccine was very similar in those who developed post-vaccination myocarditis and others. In other words, myocarditis could not be associated with abnormal autoantibodies, viral infections other than SARS-CoV-2, or excessive production of antibodies elicited by the mRNA vaccine.

In vaccinated patients, infection with the virus was not likely to be a cause or contributing factor for myocarditis since anti-Nucleoprotein IgG was not found in these patients.

In contrast to controls, the finding of high levels of unbound full-length spike protein in myocarditis patients may point to the mechanism by which this condition arises. Similarly, MIS-C patients had circulating SARS-CoV-2 antigens.

The spike protein appears to evade immune antibodies found at normal levels in these patients, with adequate functional and neutralization capacity. The spike may damage the cardiac pericytes or endothelium, perhaps by reducing the expression of the angiotensin-converting enzyme 2 (ACE2), reducing nitric oxide production in the endothelium, or activating inflammation via integrins, causing the endothelium to become abnormally permeable.

Thus, the spike antigen itself, which evades antibody recognition rather than invoking immune hyperactivation, may contribute to myocarditis in these individuals.”

This finding does not amount to evidence against the benefit of vaccination with these vaccines, which effectively protect against severe COVID-19 outcomes. Therefore, current vaccine recommendations are unlikely to be altered due to these results.

Understanding the immunopathological mechanisms associated with postvaccine myocarditis will help improve safety and guide the development of future coronavirus disease 2019 (COVID-19) vaccines. These findings also suggest that administration of anti-spike antibodies, if spike antigenemia is detected, could potentially prevent or reverse postvaccine myocarditis.”

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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  1. Josh Josh United States says:

    And it doesn't even prevent you from getting the virus.  People still think it was worth it?

    • ?
      Justin Dougherty Justin Dougherty United States says:

      Isn't the spike part of the RNA the vax makes your cells produce..

    • Justin Dougherty Justin Dougherty United States says:

      It is... And mostly effects healthier people if it breaks off like what happens when the immune system attacks the thing your own body made from a non viral substance...

  2. Tony Cypriot Tony Cypriot Cyprus says:

    I thank you for the article in reflection to the previous medical article you posted. Another thing that ought to be considered for research is the mRNA vaccine given to those with existing high cholesterol (LDL - bad cholesterol) and whether there is a connection or possible higher percentage to lead to cardiac arrest.

    • Mark Gee Mark Gee United Kingdom says:

      Given that mRNA is an entirely new technology, and that the developing company Moderna never succeeded in bringing a product to market before 2020, is it not a good idea to now have a moratorium on this tech, whether for use with people who have high cholesterol or anyone else? Shouldn't we now pause and study risks/benefits properly?

    • Noemi Santana Noemi Santana United States says:

      Why isn’t anyone looking into the PEG factor? There are studies from Israel and a preponderance of anecdotal data from people allergic to PEG that go ignored in the US. There has to be a way to produce these and other vaccines as well as other meds without this preservative. The symptoms  described are the same for myocarditis as for the long-term allergic reaction.  [email protected]

  3. Dr. Mitch Holland - Vitality Health Group Inc. Dr. Mitch Holland - Vitality Health Group Inc. United States says:

    Both the spike protein and the lipid nanoparticle emulsion appear to he cardiotoxic. Even a small amount of heart damage can interfere with the electrical activity of the heart. It's tragic and irrational to give a potentially toxic medicine to healthy very low risk young adults.

  4. Simon Silvie Simon Silvie United Kingdom says:

    The 80% bias towards men, coupled with the inbound free spike proteins, could be linked to the higher development and vascularisation of the deltoids. In these cases a failure to aspriate when administering the vaccine could result in an unintended intravenous injection, instead of intramuscular.

  5. Glenna Moeller Glenna Moeller United States says:

    Could some of this be that the vaccine was injected in the blood stream instead of the muscle? It used to be standard proceedure to aspirate injections. We insisted our Novavax be done that way.

  6. Mark Gee Mark Gee United Kingdom says:

    At the end of this article we have 'This finding does not amount to evidence against the benefit of vaccination with these vaccines, which effectively protect against severe COVID-19 outcomes.' The key question is: are healthy young men ever likely to suffer such severe outcomes from a mild respiratory illness? i.e., at an individual level, is there a benefit to each of them from vaccination? I would suggest as follow-up reading, Seneff et al., 'Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs' in Food and Chemical Toxicology, June 2022.

  7. Stephanie Last Stephanie Last United States says:

    I thought Id read in another article that it was possible to discern between the spike protein from the viruses and the spike protein from the mRNA shot by staining it?  I still feel like the people performing the studies are biased and they don't bother with some of the tests they could be performing.  I've read studies that are also peer reviewed and published that contradict the studies published here.  That is why some of us remain sceptical towards the mRNA shots.  Because some studies that are published suggest otherwise and it's really deceiving to omit legitimate information because it goes against what some officials think or believe.  There were too many doctors and scientists discredited for providing factual information to trust any of these other ones.  I'm shocked that this is happening in medical and health areas and no one is allowed to say otherwise.

    • Dan Whipple Dan Whipple United States says:

      This is correct, but to the best of my knowledge the tissue samples required cannot be extracted from a living patient, requiring an autopsy. There may be exceptions based on risk to the patient for certain organs, but all the reports I've heard have been post mortem. To your point though, the autopsies to perform this type of test are not being conducted at the scale required to determine one way or the other as to what is causing the damage. This needs to change. There is obviously a clear signal surrounding the spike protein.

      The test is called immunohistochemical staining.

  8. Raj k Raj k India says:

    The title here appears to be bit contradicting the final assessment in the article

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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