Alterations in Circulating miRNA Levels after Infection with SARS-CoV-2 Could Contribute to the Development of Cardiovascular Diseases: What We Know So Far.

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses significant complications for cardiovascular disease (CVD) patients. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and influence several physiological and pathological processes, including CVD. This critical review aims to expand upon the current literature concerning miRNA deregulation during the SARS-CoV-2 infection, focusing on cardio-specific miRNAs and their association with various CVDs, including cardiac remodeling, arrhythmias, and atherosclerosis after SARS-CoV-2 infection. Despite the scarcity of research in this area, our findings suggest that changes in the expression levels of particular COVID-19-related miRNAs, including miR-146a, miR-27/miR-27a-5p, miR-451, miR-486-5p, miR-21, miR-155, and miR-133a, may be linked to CVDs. While our analysis did not conclusively determine the impact of SARS-CoV-2 infection on the profile and/or expression levels of cardiac-specific miRNAs, we proposed a potential mechanism by which the miRNAs mentioned above may contribute to the development of these two pathologies. Further research on the relationship between SARS-CoV-2, CVDs, and microRNAs will significantly enhance our understanding of this connection and may lead to the use of these miRNAs as biomarkers or therapeutic targets for both pathologies.

Circulating microRNAs as emerging regulators of COVID-19.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has high incidence rates, spreads rapidly, and has caused more than 6.5 million deaths globally to date. Currently, several drugs have been used in the clinical treatment of COVID-19, including antivirals (e.g., molnupiravir, baricitinib, and remdesivir), monoclonal antibodies (e.g., etesevimab and tocilizumab), protease inhibitors (e.g., paxlovid), and glucocorticoids (e.g., dexamethasone). Increasing evidence suggests that circulating microRNAs (miRNAs) are important regulators of viral infection and antiviral immune responses, including the biological processes involved in regulating COVID-19 infection and subsequent complications. During viral infection, both viral genes and host cytokines regulate transcriptional and posttranscriptional steps affecting viral replication. Virus-encoded miRNAs are a component of the immune evasion repertoire and function by directly targeting immune functions. Moreover, several host circulating miRNAs can contribute to viral immune escape and play an antiviral role by not only promoting nonstructural protein (nsp) 10 expression in SARS coronavirus, but among others inhibiting NOD-like receptor pyrin domain-containing (NLRP) 3 and IL-1ß transcription. Consequently, understanding the expression and mechanism of action of circulating miRNAs during SARS-CoV-2 infection will provide unexpected insights into circulating miRNA-based studies. In this review, we examined the recent progress of circulating miRNAs in the regulation of severe inflammatory response, immune dysfunction, and thrombosis caused by SARS-CoV-2 infection, discussed the mechanisms of action, and highlighted the therapeutic challenges involving miRNA and future research directions in the treatment of COVID-19.