Non-Coding RNAs in COVID-19: Emerging Insights and Current Questions

Abstract

The highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, igniting an unprecedented pandemic. A mechanistic picture characterising the acute immunopathological disease in severe COVID-19 is developing. Non-coding RNAs (ncRNAs) constitute the transcribed but un-translated portion of the genome and, until recent decades, have been undiscovered or overlooked. A growing body of research continues to demonstrate their interconnected involvement in the immune response to SARS-CoV-2 and COVID-19 development by regulating several of its pathological hallmarks: cytokine storm syndrome, haemostatic alterations, immune cell recruitment, and vascular dysregulation. There is also keen interest in exploring the possibility of host–virus RNA–RNA and RNA–RBP interactions. Here, we discuss and evaluate evidence demonstrating the involvement of short and long ncRNAs in COVID-19 and use this information to propose hypotheses for future mechanistic and clinical studies.

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

“…Despite their proven value as mechanism-based clinical stratification indicators, miRNAs have only started being explored in the context of COVID-19. It has been proposed that miRNAs might be involved in controlling inflammation during COVID-19 (Aslani et al, 2021;Gasparello et al, 2021;Houshmandfar et al, 2021;Matarese et al, 2020;Plowman and Lagos, 2021). Theoretical CC/miRNA regulatory networks have been proposed but not validated (Khokhar et al, 2022), whereas the potential of miRNA-like therapeutics has also been suggested (Ahn et al, 2021;Dash et al, 2021;Hum et al, 2021;Park et al, 2021).…”

Non-coding RNAs and their bioengineering applications for neurological diseases

“…Currently, approximately 10 RNA-based therapeutics are approved by the FDA and multiple small RNA therapeutic approaches are in stages of clinical investigation for complex CNS and rare genetic disorders [ 17 , 225 ]. Importantly, we and others have discussed on the scope of ncRNA-based therapeutic applications in diseases such as COVID-19-induced neurological disorders, systemic inflammation and cardiovascular diseases [ 6 , 230 , 236–240 ]. As an example, in 2018, the FDA approved ‘Patisiran’- the first therapy based on administration of RNAi (siRNA-based) for the treatment of rare progressive polyneuropathy caused by hereditary transthyretin-mediated amyloidosis.…”

Integrated miRNA/Cytokine/Chemokine Profiling Reveals Severity-Associated Step Changes and Principal Correlates of Fatality in COVID-19

“…Despite their proven value as mechanism-based clinical stratification indicators, miRNAs have only started being explored in the context of COVID-19. It has been proposed that miRNAs might be involved in controlling inflammation during COVID-19 (Aslani et al, 2021;Gasparello et al, 2021;Houshmandfar et al, 2021;Matarese et al, 2020;Plowman and Lagos, 2021). Theoretical CC/miRNA regulatory networks have been proposed but not validated (Khokhar et al, 2022), whereas the potential of miRNA-like therapeutics has also been suggested (Ahn et al, 2021;Dash et al, 2021;Hum et al, 2021;Park et al, 2021).…”