Circulating microRNAs as emerging regulators of COVID-19

Abstract

Coronavirus disease 2019 , 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-1β 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.

Differentially‐regulated miRNAs in COVID‐19: A systematic review

“…Interestingly, from this list miR‐15a‐5p and miR‐31‐5p appeared in two or more studies 56,57,73,78,82,84,86 and could potentially serve as biomarkers for disease severity. Table 3 summarises the targets and principle cellular pathways associated with miRNAs regulated during Inf vs C and S vs C stages and cited previously 46,56,73,88–120 . Most of the miRNAs were involved in targeting virus‐host interactions, viral replication, and host‐immune responses.…”

Intrinsic factors behind long‐COVID: II. SARS‐CoV‐2, extracellular vesicles, and neurological disorders

“…Furthermore, miR-181a-5p may control the release of pro-inflammatory cytokines and lower levels of IL-1, IL-6, and TNF-α. 122,123 These findings suggest that miRNA in exosomes may play a regulatory role in the immunopathogenesis of COVID-19.…”

“…These miRNAs reduced the pro‐inflammatory response that the virus caused in human cells and prevented the replication of SARS‐CoV‐2. Furthermore, miR‐181a‐5p may control the release of pro‐inflammatory cytokines and lower levels of IL‐1, IL‐6, and TNF‐α 122,123 . These findings suggest that miRNA in exosomes may play a regulatory role in the immunopathogenesis of COVID‐19.…”

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

“…These three cargoes have distinct metabolic dynamics [74] including a connection with the EV components' biogenesis machinery, a cellular homeostasis regulator with cytoplasmic DNA sensor activation, and parental cell function efficiency at different states [75]. The creation of biomarker vehicles [76] that employ the aforementioned pro-tumorigenic components and signalling pathways to circulate immune responses from OS cancer diseases remains a significant clinical trial challenge [77].…”