Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

SARS-CoV-2 mRNA-vaccine and the heart
V. Zirkenbach1, R. Ignatz1, R. Oettl1, N. Frey1, M. R. Preusch1, Z. Kaya1
1Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie, Universitätsklinikum Heidelberg, Heidelberg;
Background

The novel coronavirus SARS-CoV-2 managed its way around the world. With several hundred million infected people worldwide, it has led to millions of deaths. To fight the virus, pharma industries developed different types of vaccines incl. mRNA-vaccines. As one of the side effects of BioNTech mRNA-vaccine the development of myocarditis particularly in young men after the 2nd immunization has been reported. But little data is available about safety and side effects in patients with autoimmune disease and in oncological patients treated with checkpoint inhibitors where myocarditis has also been reported as one of the treatment side effects. Therefore, we investigated the side effects esp. on myocardial damage in a susceptible mouse strain (A/J) for autoimmune diseases and in mice under immune checkpoint inhibition. 

Methods

To study the effect of age and gender we injected A/J mice at different ages (5-4/20weeks) and genders twice at a distance of three weeks with 0.2µg or 2.5µg BioNTech SARS-CoV-2 vaccine intramuscular to test the vaccine in a mouse strain susceptible for autoimmune myocarditis.
To investigate the effect of vaccination in novel immunotherapy (immune checkpoint inhibition) we applicated vaccine (2.5µg) to control mice (untreated BL6), BL6 PD-1 ko mice or BL6 PD-1 ko mice treated additionally with anti-CTLA-4 (200µg) every three days. 
To detect potential myocardial damage, we measured hsTnT levels [pg/ml] in mouse sera. Cardiac heart function was controlled by echocardiography and inflammation checked by histopathological staining of heart sections and other organs (lung, liver, kidney, intestine, pancreas, aorta, spleen, muscle).

Results

Histopathological staining in vaccination treated A/J mice did not show myocardial inflammation and analysis of echocardiography showed no sign for a deterioration of cardiac pump function, but we could observe a slight increase in hsTnT levels in some young mice at 0.2µg (♂=55±4,n=2/13, ♀=62±5.36, n=5/15) and in one out of 9 (1/9) old mice (60). 2.5µg led to a similar increase (♂=55±1.74, n=4/5, ♀=53.11±0.97, n=7/11).
 
In untreated C57BL/6 we did not find inflamed areas, nor could we observe changes in heart function. After vaccination only one out of six females had a minor increase in hsTnT levels (57.4). In C57BL/6 PD-1 ko mice higher hsTnT levels as in wild types were detected. In untreated PD-1 ko slightly elevated hsTnT amount (♂=55,7±2,173, n=3/5) and one high increase (♂=209, n=1/5) were measured. Vaccination led to an increase in 4/5 male (ø=64.13±6.612) and 2/7 female (ø=69.25±14.95). The combination of vaccine and anti-CTLA-4 treatment causes also a slight increase in hsTnT levels (♂=78±5, n=2/5). Here we could observe in one male a small area of infiltrating cells in heart tissue (Fig.1, 5%).
 

Fig.1: Inflamed area in C57BL/6 PD-1 ko after vaccination and anti-CTLA-4 treatment.

Conclusion

Even though, we do not see histopathological myocardial inflammation or echocardiographic deterioration of cardiac function neither in A/J nor in PD-1 ko and anti-CTLA-4 treated PD-1 ko mice after BioNTech vaccination, except in one C57BL/6 PD-1 ko mouse. There we found inflammation after vaccination and anti-CTLA-4 treatment. These data suggest that mRNA vaccines might not have a significant myocardial deterioration effect within an immune suppressive therapy. We do see in some a slight increase in cardiac specific troponin T levels. Still, patients should be tightly monitored.


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