SARS-CoV-2-associated organs failure and inflammation: a focus on the role of cellular and viral microRNAs

Abstract

SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.

Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A

“…This gene is particularly studied in cancer, where, depending on its type, MAPK9 may act as both a tumor suppressor and inducer [ 58 ]. Studies have also shown low levels of MAPK9 in COVID-19 patients [ 59 , 60 ], suggesting its role in the induction and development of the inflammatory process regardless of the type of disease. Our study revealed an increased level of miR-1275 in HaCaT culture after the addition of CsA compared to culture with LPS alone.…”

The biomarkers’ landscape of post-COVID-19 patients can suggest selective clinical interventions

“…Upon a viral infection, has-miR-146a is primarily produced to regulate the innate immune response and inflammation by negatively regulating the NF-κB pathway 60 , 61 . Therefore, its expression in COVID-19 decreases inflammatory disorders in target organs such as the lungs, heart, brain, skin, and underlying vascular disease 61 , 62 .…”

“…Upon a viral infection, has-miR-146a is primarily produced to regulate the innate immune response and inflammation by negatively regulating the NF-κB pathway 60 , 61 . Therefore, its expression in COVID-19 decreases inflammatory disorders in target organs such as the lungs, heart, brain, skin, and underlying vascular disease 61 , 62 . The hsa-miR-146a-5p increase we observed in post-COVID-19 patients is an indication of the path to recovery, as the levels of IL-1, IL-6 and TNF-α cytokines are inversely correlated to has-miR-146a production 63 , 64 .…”