Circulating miRNAs as biomarkers for SARS-CoV-2 and long COVID: Mechanisms and prognostic potential

Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that modulate versatile epigenetics of crucial host and viral factors. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manipulates the miRNA crosstalk between the host and virus to impair host immunity and amplify its virulence. Despite significant efforts to develop miRNA-based therapeutics for the constantly evolving SARS-CoV-2, there has been limited research that focused on the application of miRNAs as biomarkers specifically for SARS-CoV-2 infections. Circulating exosome-associated miRNAs, such as miRNA-21, have shown to have atypical miRNA profiles for both short-term SARS-CoV-2, and long-term cognitive dysfunction of Long COVID. This article will aim to elucidate the link between miRNAs and biomarkers by first 1) exploring the potential mechanisms of action of circulating miRNAs on the host factors during COVID infection, with a focus on miRNA-21, and 2) looking at the prognostic potential of miRNAs for acute SARS-CoV-2 and Long COVID. Through mechanistic understanding of the shifts in miRNAs profile from baseline levels, there is possibility for the development of a clinical prognosis method. This new molecular diagnostic could predict the severity of acute SARS-CoV-2 infection to distinguish critical patients from the overall infected population and provide further insights towards the cognitive dysfunction of Long COVID. This applicability could be extended towards other viral infections that cause dysregulation of circulating miRNAs levels. This article will also consider the implications of developing this prognosis method by emphasizing the practicality and current limitations of miRNAs as biomarkers. The progression from fundamental understanding of miRNA to potential applications could result in a significant impact on clinical diagnostics for SARS-CoV-2 and other viral pathogens.