Cardiovascular RNA markers and artificial intelligence may improve COVID-19 outcome: a position paper from the EU-CardioRNA COST Action CA17129

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of February 8th, 2020 and causing more than 2.3 million deaths according the World Health Organization. Not only affecting the lungs and provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence a significant proportion of infected patients develop cardiac events such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts and the added value of artificial intelligence to achieve reliable advances.

The platelet paradox of injury versus protection in myocardial infarction—has it been overlooked?

“…This paper, however, overlooks one crucial aspect: the paradoxical role of platelets in the setting of MI. Activated platelets, beyond promoting arterial thrombus formation, may contribute to cardiac damage via different mechanisms, including the formation of coronary microvascular microthrombi, induction of platelet-leukocyte interactions, release of vasoconstrictor molecules (e.g., thromboxane A2), and (microRNA-containing) microvesicles [ 4 , 9 ]. However, increasing evidence supports the notion that platelets also carry and release multiple factors with the potential to reduce rather than promote IR injury (Fig.…”

(Epi)transcriptomics in cardiovascular and neurological complications of COVID-19

“…NcRNAs are transcribed by either RNA polymerase I, II or III, depending on the individual ncRNA [14] . According to their lengths, they can be divided into two main groups: (1) small or short ncRNAs including microRNAs (miRNAs), small interfering RNAs (siRNAs), PIWI-interacting RNA (piRNA) and small nucleolar RNAs (snoRNAs); and (2) long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) [15] . A rapidly growing number of studies has unravelled associations between aberrant ncRNA expression and human diseases.…”

“…A rapidly growing number of studies has unravelled associations between aberrant ncRNA expression and human diseases. NcRNAs have emerged as promising candidates for the treatment of a variety of diseases and play a potential significant role in host-virus interactions [15] . Dysregulated noncoding RNAs (ncRNAs) expression levels in lung tissue and liquid biopsies from COVID-19 patients indicate that ncRNAs may play an important role in the pathogenesis, and hence clinical outcomes of COVID-19.…”

Insights into Cardiovascular Defects and Cardiac Epigenome in the Context of COVID-19

“…Apart from histone modifications and DNA methylation, non-coding RNA (nc-RNA) is an important contributor of epigenetic changes. In COVID-19, several nc-RNA are upregulated or downregulated which render them as potential biomarkers of the disease [ 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Askari et al reported that several long nc-RNAs and micro RNAs (mi-RNAs) are differentially expressed in COVID-19, some with specific observations in female versus male patients [ 46 ].…”

“…Interestingly, nc-RNAs have significant roles in cardiac biology, including miR-29s and miR-30b reported in this study, which have anti-fibrotic roles in the heart and correlate with ischemic heart disease, respectively [ 46 ]. Badimon et al provides a comprehensive compilation of nc-RNAs, including miR-16-2-3p, lncRNA NEAT1 , which are upregulated in COVID-19 patients, and lncRNA DANCR , miR-183-5p, etc., which are downregulated [ 47 ]. Such differentially expressed nc-RNAa can serve as potential biomarkers of COVID-19.…”