Table 1.
The host-encoded circulating miRNAs differentially expressed during SARS-CoV-2 infection
| Circulating miRNAs | Regulate direction | Viral/Human encoded | Type of fluid | Targets regulation | Biological effect | Reference |
|---|---|---|---|---|---|---|
| miR-423-5p | Up-regulation | Human | Plasma | - | Independently classified COVID-19 cases with an accuracy of 99.9% | 169 |
| miR-23a-3p | Down-regulation | Human | Plasma | - | Independently classified COVID-19 cases with an accuracy of 99.9% | 169 |
| miR-195-5p | Up-regulation | Human | Plasma | - | Independently classified COVID-19 cases with an accuracy of 99.9% | 169 |
| miR-776-3p | Down-regulation | Human | Plasma | Reduced the expression of IL-6 | Anti-inflammatory | 169 |
| miR-31-5p | Up-regulation | Human | Plasma | Transcription of miR-31-5p is induced by TNF-α and triggers a negative feedback loop involving E-selectin | Associated with inflammatory disorders | 169 |
| miR-192-5p | Down-regulation | Human | Plasma | Cytokine and chemokine synthesis | Relevant predictor of mortality during the ICU stay | 47 |
| miR-323a-3p | Down-regulation | Human | Plasma | Targeted the PB1 gene | Relevant predictor of mortality during the ICU stay | 47 |
| miR-148a-3p | Up-regulation | Human | Plasma | Targeted the ORF1a, E, S and M genes | Distinguish between ICU and ward patients; Regulation of virus infection | 47 |
| miR-451a | Down-regulation | Human | Plasma | Cytokine and chemokine synthesis | Distinguish between ICU and ward patients | 47 |
| miR-486-5p | Down-regulation | Human | Plasma | Targeted the gene OTUD7B | Distinguish between ICU and ward patients; Regulation of antiviral; Promoted acute lung injury | 47 |
| miR-155 | Up-regulation | Human | Serum | - | Discrimination between COVID‐19 and Influenza‐ARDS by these markers of myocardial damage; Predictor of chronic myocardial damage and inflammation | 46 |
| miR-208a | Up-regulation | Human | Serum | - | Discrimination between COVID‐19 and Influenza‐ARDS by these markers of myocardial damage; Predictor of chronic myocardial damage and inflammation | 46 |
| miR-499 | Up-regulation | Human | Serum | - | Discrimination between COVID‐19 and Influenza‐ARDS by these markers of myocardial damage; Predictor of chronic myocardial damage and inflammation | 46 |
| miR-21 | Up-regulation | Human | Serum | - | Predictor of chronic myocardial damage and inflammation | 46 |
| miR-126 | Down-regulation | Human | Serum | - | Protective from endothelial damage | 46 |
| miR-29a-3p | Down-regulation | Human | Serum | Regulation of COL5A3 expression | Regulated inflammatory response; Associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients | 170 |
| miR-31-3p | Down-regulation | Human | Serum | Regulation of ZMYM5 expression | Regulated inflammatory response | 170 |
| miR-126-3p | Down-regulation | Human | Serum | Regulation of CAMSAP1 expression | Regulated inflammatory response; Associated with ACE2 | 170 |
| miR-17-3p | Up-regulation | Human | Serum | Regulation of DICER1 expression | Regulated inflammatory response; Regulated the immune system | 170 |
| miR-146a-5p | Down-regulation | Human | Serum | Targeted TRAF6 and IRAK1; Associated with NF-κB and IL-6 | Provided clues about the molecular link between inflammaging and COVID-19 clinical course | 59 |
| miR-21-5p | Down-regulation | Human | Serum | Targeted molecules belonging to the nuclear factor κB (NF-κB) pathway | Inhibition of inflammation | 59 |
| miR-126-3p | Down-regulation | Human | Serum | Regulated the NF-κB inhibitor Iκ‐Bα and endothelial activation | Inhibition of inflammation; Regulator of endothelial inflammation and angiogenic processes | 59 |
| miR-21 | Down-regulation | Human | Serum | Regulation of IL-12p53 expression | Anti-neuroinflammatory activity | 171 |
| miR-124 | Down-regulation | Human | Serum | Regulation of Stat3 expression | Anti-neuroinflammatory activity | 171 |
| miR-146a | Down-regulation | Human | Serum | Regulation of TRAF6 expression | Anti-neuroinflammatory activity | 171 |
| miR-326 | Up-regulation | Human | Serum | Regulation of CEBPA expression | Pro-neuroinflammatory activity | 171 |
| miR-155 | Up-regulation | Human | Serum | Regulation of SOCS1 expression | Pro-neuroinflammatory activity | 171 |
| miR-27b | Up-regulation | Human | Serum | Regulation of PPARS expression | Pro-neuroinflammatory activity | 171 |
| hsa-miR-320a-3p | Up-regulation | Human | Plasma | Regulated immunity response | Distinguish mild from severe cases; Involved in the infection response, reflecting the molecular status of the lung tissue | 172 |
| hsa-miR-629-5p | Up-regulation | Human | Plasma | - | Distinguish mild from severe cases | 172 |
| hsa-miR-29a-3p | Down-regulation | Human | Plasma | - | Distinguish mild from severe cases | 172 |
| hsa-miR-342-3p | Down-regulation | Human | Plasma | - | Distinguish mild from severe cases | 172 |
| hsa-miR-185-5p | Up-regulation | Human | Plasma | - | Distinguish mild from severe cases | 172 |
| hsa-miR-4516 | Up-regulation | Human | Plasma | Regulated immunity response; Involved in STAT3 (MIM 102582) regulation | Associated with inflammation | 172 |
| miR-451a | Down-regulation | Human | Plasma | Promoted expression of IL-6R in COVID-19 patients at the protein level | Induced cytokine storm | 173 |
| miR-374a | Down-regulation | Human | Plasma | Targeted the CCL2 | Induced cytokine storm and ARDS | 173 |
| miR-155 | Down-regulation | Human | Serum | Targeted SHIP1 and SOCS | Antiviral response; Regulated inflammation; As a good predictor of COVID-19 mortality | 69 |
| miR-146b | Up-regulation | Human | Serum | Targeted IRAK1 and TRAF6, and the proinflammatory cytokines IL-6, and IL-8 | Regulated inflammatory response | 69 |
| miR-146a | Up-regulation | Human | Serum | Targeted IRAK1 and TRAF6, and the proinflammatory cytokines IL-6, and IL-8 | Regulated inflammatory response | 69 |
| miR-21 | Up-regulation | Human | Serum | Regulated the cytokine IL-12 | Regulated inflammatory response | 69 |
| miR-499 | Up-regulation | Human | Serum | Targeted SOX6 | Regulated inflammatory response | 69 |
| miR-2392 | Up-regulation | Human | Serum/Urine | Suppression of mitochondria activity while increasing inflammation, glycolysis, and hypoxia; Involved in immune and inflammatory pathways | As an effective biomarker of COVID-19; Regulated inflammation | 13 |
| miR-146a-5p | Down-regulation | Human | Blood | Targeted STAT1 | As biomarkers of severe COVID‐19 and as candidate therapeutic targets; As hub regulators of the host immune response | 62 |
| miR-21-5p | Down-regulation | Human | Blood | Targeted IRAK1 and CCL20 | As biomarkers of severe COVID‐19 and as candidate therapeutic targets; As hub regulators of the host immune response | 62 |
| miR-142-3p | Down-regulation | Human | Blood | Targeted IL6ST and induced gp130 production | As biomarkers of severe COVID‐19 and as candidate therapeutic targets; Promoted inflammatory processes | 62 |
| miR-15b-5p | Up-regulation | Human | Blood | Targeted the SARS-CoV-2 genome; Negatively correlated with IFNG and CD69 | As biomarkers of severe COVID‐19 and as candidate therapeutic targets; Promoted RNA virus replication and intensify the severity of COVID‐19; Induced T‐cell exhaustion | 62 |
| miR-486-3p | Up-regulation | Human | Blood | Targeted MAF | Induced dysregulation of immune response | 62 |
| miR-486-5p | Up-regulation | Human | Blood | Targeted NRP2 and inhibited OTUD7B | Regulated inflammatory response | 62 |
| miR-181a-2-3p | Down-regulation | Human | Blood | Associated with TLR4 and CXCL8 expression | Serum biomarker of chronic obstructive pulmonary disease; Regulated inflammatory response | 62 |
| miR-99a-5p | Down-regulation | Human | Blood | Targeted proinflammatory genes, IGF1R and MTMR3 | Induced weaker antiviral immunity | 62 |
| miR-106b-5p | Up-regulation | Human | Plasma | - | Distinguish between COVID-19 and CAP | 110 |
| miR-221-3p | Down-regulation | Human | Plasma | Targeted CXCL12 | Distinguish between COVID-19 and CAP | 110 |
| miR-25-3p | Up-regulation | Human | Plasma | - | Distinguish between COVID-19 and CAP | 110 |
| miR-30a-5p | Up-regulation | Human | Plasma | - | Distinguish between COVID-19 and CAP | 110 |
| miR-335-5p | Down-regulation | Human | Plasma | - | Inhibition of inflammatory processes | 110 |
| miR-146a-5p | Down-regulation | Human | Plasma | Targeted TRAF6 | Regulated inflammation; Associated with thrombosis | 110 |
| miR-16-2-3p | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-10399-3P | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-5695 | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| miR-6501-5p | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| miR-361-3P | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-4659a-3p | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-142-5p | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-4685-3p | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-30c-5p | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-454-5p | Up-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| miR-618 | Up-regulation | Human | Peripheral blood | - | Associated with immune dysfunction; Regulated the immune responses and viral replication during viral infection | 139 |
| miR-627-5p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| miR-183-5p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-941 | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-20a-5p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-21-5p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-340-5p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-17-5p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-18a-5p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| hsa-miR-454-3p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| miR-144-3p | Down-regulation | Human | Peripheral blood | - | Regulated the immune responses and viral replication during viral infection | 139 |
| miR-19a-3p | Up-regulation | Human | Plasma | Targeted the TGF-β signaling pathway | Immunosuppressive and anti-inflammatory effects; As potential diagnostic biomarkers for distinguishing SARS-CoV-2 infected patients from healthy individuals | 45 |
| miR-19b-3p | Up-regulation | Human | Plasma | Targeted the TGF-β signaling pathway | Immunosuppressive and anti-inflammatory effects; As potential diagnostic biomarkers for distinguishing SARS-CoV-2 infected patients from healthy individuals | 45 |
| miR -92a-3p | Up-regulation | Human | Plasma | - | As potential diagnostic biomarkers for distinguishing SARS-CoV-2 infected patients from healthy individuals | 45 |
| miR-133a | Up-regulation | Human | Plasma | Inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation | Related to 28-day mortality; Reflected inflammation-induced myocyte damage | 174 |
| miR-122 | Down-regulation | Human | Plasma | Correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association) | Related to 28-day mortality; Reflected the hepatic acute phase response | 174 |
| miR-200c-3p | Upregulated in patients with severe symptoms and ≥42 years old | Human | Saliva | - | Associated with deterioration of the clinical course of the disease the disease | 175 |
| miR-155 | Up-regulation | Human | Plasma | Regulated many target genes that encode for inflammatory-related proteins, immunomodulatory proteins and tumour-suppressor proteins | Plays a crucial role in pathogenesis and severity of COVID-19; Diagnostic clinical biomarker for the detection of COVID-19 disease and the severity of infection | 65 |
| miR-150-5p | Down-regulation | Human | Plasma | Regulation of nsp10 gene | Inhibited SARS-CoV-2 infection via directly interacting with MRE in the coding strand of nsp10; Signs of inflammation and an impaired immunity | 42 |
| miR-375 | Down-regulation | Human | Plasma | - | Signs of inflammation and an impaired immunity | 42 |
| miR-122-5p | Down-regulation | Human | Plasma | - | Signs of inflammation and an impaired immunity | 42 |
| miR-494-3p | Down-regulation | Human | Plasma | - | Signs of inflammation and an impaired immunity | 42 |
| miR-3197 | Up-regulation | Human | Plasma | - | Resulted in a significant decline of transcriptional activity, innate immunity, and antioxidant activity | 42 |
| miR-4690-5p | Up-regulation | Human | Plasma | - | Resulted in a significant decline of transcriptional activity, innate immunity, and antioxidant activity | 42 |
| miR-1915-3p | Up-regulation | Human | Plasma | - | Resulted in a significant decline of transcriptional activity, innate immunity, and antioxidant activity | 42 |
| miR-3652 | Up-regulation | Human | Plasma | - | Resulted in a significant decline of transcriptional activity, innate immunity, and antioxidant activity | 42 |
| miR-369-3p | Down-regulation | Human | Serum | Regulation of immune pathway | Regulated inflammatory response | 158 |
| miR-10b | Down-regulation | Human | Peripheral blood | Increased levels of IL-2 and IL-8 | Induced cytokine storm | 176 |
| hsa-miR-30a-3p | Down-regulation | Human | Blood | Negatively regulated BAFF by directly binding to the 3'UTR of the target gene | Protective effect against severe COVID-19; Related to immunity | 177 |
| hsa-miR-139-5p | Up-regulation | Human | Blood | - | As a risk factor for severe COVID-19 | 177 |
| miR-320b | Up-regulation | Human | Serum | Promoted glucose and lipid metabolism; Associated with eosinophils | Stratify older COVID-19 patients with an increased risk of in-hospital mortality | 178 |
| miR-483-5p | Up-regulation | Human | Serum | Targeted IGF1 | Stratify older COVID-19 patients with an increased risk of in-hospital mortality; As a relevant target in the prevention of cardiometabolic disease | 178 |