BREAKING! Chinese Scientists Discover That SARS-CoV-2 Causes Dysregulation Of Host miRNAs And Also Produces Novel miRNAs, Resulting In Varying Clinical Manifestations!
New concerning findings have been discovered from a new study conducted by Chinese researchers from the First Affiliated Hospital of Xi’an Jiaotong University, along with experts from Wuhan University, in which it was found that SARS-CoV-2 causes dysregulation of host miRNAs and also produces novel miRNAs, resulting in varying clinical manifestations! The study findings also have numerous new implications for the various symptoms and conditions seen in Long COVID.
MicroRNAs (miRNAs) are a recently discovered class of ∼18–24 nucleotide RNA molecules that negatively regulate target mRNAs. All studied multicellular eukaryotes utilize miRNAs to regulate basic cellular functions like cell metabolism, cell proliferation, cell differentiation, apoptosis, developmental timing and even cell fate. They play a critical role in various human diseases.
MicroRNAs have also been shown to play important roles in viral infections, but their associations with SARS-CoV-2 infection remain poorly understood.
The study team detected 85 differentially expressed miRNAs (DE-miRNAs) from 2,336 known and 361 novel miRNAs that were identified in 233 plasma samples from 61 healthy controls and 116 COVID-19 patients using the high throughput sequencing and computational analysis.
Interestingly, these DE-miRNAs were associated with SASR-CoV-2 infection, disease severity, and viral persistence in the COVID-19 patients, respectively.
Detailed gene ontology and KEGG pathway analyses of the DE-miRNAs revealed their connections to viral infections, immune responses, and lung diseases.
The study team also established a machine learning model using the DE-miRNAs between various groups for classification of COVID-19 cases with different clinical presentations.
The study findings may help understand the contribution of miRNAs to the pathogenesis of COVID-19 and identify potential biomarkers and molecular targets for diagnosis and treatment of SARS-CoV-2 infection and also Long COVID.
The study findings were published in the peer reviewed journal: l iSCIENCE (science Direct by Elsevier). https://www.sciencedirect.com/science/article/pii/S2589004222005806
Significantly, the study findings demonstrated different micro ribonucleic acids (miRNAs) linked with various presentations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.
The COVID-19) pandemic, caused by SARS-CoV-2, has presented unprecedented problems globally.
So far, the SARS-CoV-2 pandemic has caused over 516 million cases and almost 6.25 million deaths worldwide. https://coronavirus.jhu.edu/map.html
However, the actual number of infections globally is now though to be close to 3 billion.
In term of COVID-19 deaths, the WHO now has revealed that about 13.3 to 16.6 million people have died from COVID-19 in just the period 2020 to 2021. https://www.france2
The COVID-19 disease has a wide range of clinical manifestations and illness courses, ranging from asymptomatic (AS) SARS-CoV-2 infection to a critical or severe condition. Notably, the underpinnings for short-term nucleic acid test positive (STNP) and long-term nucleic acid test positive (LTNP) in SARS-CoV-2 infection are not known.
MicroRNAs which are short single-stranded RNA compounds harboring a genome of 18 to 28 nucleotides, have been linked to several pathological and physiological mechanisms in animals and humans, like immunological responses, development, apoptosis, and inflammation. Interestingly, although miRNAs have been demonstrated to play significant roles in viral infections, their relationships with COVID-19 are unknown.
The study team investigated the possible roles of miRNAs in the pathogenesis of SARS-CoV-2 infection by performing a high throughput analysis of the plasma miRNA library.
The research team developed and evaluated a machine learning model based on differentially expressed miRNAs (DE-miRNAs) between several compared cohorts to categorize COVID-19 patients with distinct clinical manifestations.
The study findings presented the heatmap of 85 DE-miRNAs derived by comparing 11 groups, including SARS-CoV-2-infected, healthy controls, AS, severe disease (SD), and moderate disease (MD) COVID-19.
Further, DE-miRNAs associated with various severity of COVID-19 and SARS-CoV-2 persistence were determined.
The study team also discovered miRNAs addressing cellular genes linked with the SARS-CoV-2 lifecycle and viral genome.
The study team elucidated the possible functions of the representative DE-miRNAs in COVID-19 pathogenesis.
The study findings revealed 361 new and 2,336 established miRNAs in 233 plasma samples from 116 SARS-CoV-2 patients and 61 healthy controls employing high throughput sequencing test.
The study team found 85 DE-miRNAs among the currently identified miRNAs.
Interestingly, in the COVID-19 patients, these DE-miRNAs like homo sapiens (hsa)-main immunogenic region (miR)-370-3p, hsa-miR-885-5, hsa-miR-146a-3p, hsa-miR-10b-5p, and hsa-miR-214-3p were linked to SARS-CoV-2 infection, viral persistence, and illness severity.
Importantly, a panel of miRNAs was identified that could directly attack SARS-CoV-2 viral genes.
The study team also discovered several miRNAs that could address the cellular genes implicated in the life cycle of SARS-CoV-2, such as angiotensin-converting enzyme 2 (ACE2), translocase of outer mitochondrial membrane 70 (TOMM70), AXL, and transmembrane protein 106B (TMEM106B). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology analysis demonstrated that DE-miRNAs were correlated with viral infections, lung diseases, and immunological responses.
The study team tested their machine learning technique for the categorization of COVID-19 patients with diverse clinical presentations based on DE-miRNAs among different groups.
The findings depicted six DE-miRNAs, including hsa-miR-302a-3p and hsa-miR-302b-3p_R-2, that might be utilized as biomarkers to differentiate the COVID-19 patients from the healthy controls.
It should be noted that previous studies have correlated four out of the six biomarkers with inflammation, virus infection, lung disease, and immune response.
The study findings also showed that miR-302 might protect COVID-19 patients by addressing the C-X-C motif chemokine ligand 8 (CXCL8)-linked pathways. In addition, the hsa-miR-146a-3p might have a protective function in AS COVID-19 patients and could be a biological marker for therapeutic and diagnostic approaches aiming at this category.
The study findings also revealed numerous De-miRNAs, such as hsa-miR-122-5p and hsa-miR-1246, that could distinguish AS and symptomatic (SM) SARS-CoV-2 patients.
In the LTNP versus STNP groups, the study team found 20 DE-miRNAs, nine of which, including hsa-miR-429 and hsa-miR-483-5p, were substantially linked with the length of viral persistence in SARS-CoV-2 patients. This could have important implications for long COVID manifestations.
Corresponding author, Professor Dr Cheng Sheng Zhang from the Precision Medicine center at the First Affiliated Hospital of Xi’an Jiaotong University told Thailand Medical News
, “This was the initial large-scale analysis of miRNA characteristics using high throughput investigation on the plasma samples procured from SARS-CoV-2 AS volunteers in tandem with the SM patients harboring different clinical presentations and the healthy control subjects.
In conclusion, the study findings discovered a multitude of DE-miRNAs linked to SARS-CoV-2 infection, disease severity, viral persistence, and clinical symptoms in COVID-19 patients. It also recognized a screen of miRNAs possibly addressing the viral genomic regions or host genes implicated in a range of pathways of SARS-CoV-2.”
The study team said that the current findings should help researchers better understand how miRNAs play a role in the pathophysiology of SARS-CoV-2 infection and uncover possible molecular targets and biomarkers for COVID-19 therapy and diagnostics, and also for long COVID treatments.
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