Abstract
Myocarditis and pericarditis have been linked recently to COVID-19 vaccines without exploring the underlying mechanisms, or compared to cardiac adverse events post-non-COVID-19 vaccines. We introduce an informatics approach to study post-vaccine adverse events on the systems biology level to aid the prioritization of effective preventive measures and mechanism-based pharmacotherapy by integrating the analysis of adverse event reports from the Vaccine Adverse Event Reporting System (VAERS) with systems biology methods. Our results indicated that post-vaccine myocarditis and pericarditis were associated most frequently with mRNA COVID-19 vaccines followed by live or live-attenuated non-COVID-19 vaccines such as smallpox and anthrax vaccines. The frequencies of cardiac adverse events were affected by vaccine, vaccine type, vaccine dose, sex, and age of the vaccinated individuals. Systems biology results suggested a central role of interferon-gamma (INF-gamma) in the biological processes leading to cardiac adverse events, by impacting MAPK and JAK-STAT signaling pathways. We suggest that increasing the time interval between vaccine doses minimizes the risks of developing inflammatory adverse reactions. We also propose glucocorticoids as preferred treatments based on system biology evidence. Our informatics workflow provides an invaluable tool to study post-vaccine adverse events on the systems biology level to suggest effective mechanism-based pharmacotherapy and/or suitable preventive measures.
Highlights
Since the identification of SARS-CoV-2 virus in 2019 and the emergence of Coronavirus disease of 2019 (COVID-19) as a global pandemic, there has been an upsurge of vaccine research and development worldwide with several vaccines that completed the clinical evaluation phases and were authorized for COVID-19 [1,2]
ResOuultrssearch in Vaccine Adverse Event Reporting System (VAERS) databases indicated that myocarditis and pericarditis adverse events were not unique to COVID-19 vaccines; they were reported after receiving smalOlpuorxs,eaanrtchhrainx,VtAypEhRoSidd,ahteapbaastietsisinBd, iincafltueedntzhaa,tamndyooctahredritviascacnindeps etoricaasrmdiatilsleardevxetersnet. eHvoenwtesvwere,rme ynooctaurndiiqtius eantod pCeOriVcaIDrd-i1t9isveavcecnintsews;etrheemy owreerpereavlsaolernetpaofrtteerdreacfetievrinregcmeivRiNngA sCmOaVllpIDo-x1,9avnathccrainxe, stythpahnoiadn,yhoetphaetritvisacBc,iinnefl. uTehniszaco, aunlddboethpearrtvlyacdcuineetsotpooatesnmtiaalllleyrsemxtaelnletr
In an effort to understand post-vaccine myocarditis and pericarditis side effects that have been linked to mRNA vaccines lately, according to a statement from the Centers for Disease Control and Prevention (CDC) [13], we applied an informatics workflow to mine the VAERS database for post-vaccine myocarditis, followed by a systems biology analysis that relied on mining specialized chemogenomics databases for genes, proteins and chemicals that are linked to myocarditis
Summary
Since the identification of SARS-CoV-2 virus in 2019 and the emergence of Coronavirus disease of 2019 (COVID-19) as a global pandemic, there has been an upsurge of vaccine research and development worldwide with several vaccines that completed the clinical evaluation phases and were authorized for COVID-19 [1,2]. The theoretical and technological strategies used to develop the currently approved vaccines are diverse allowing for their preferential use in distinct groups of the human population [3]. Owing to COVID-19 vaccines’ rapid development and the innovation of the implemented technologies, it is reasonable to expect that some issues or problems, such as unexpected side effects, associated with the use of a new vaccine against a new disease may arise and would need to be addressed. Several worrisome reports have been released on the development of acute myocarditis after COVID-19 vaccination [4,5]
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