Long non-coding RNAs ANRIL, THRIL, and NEAT1 as potential circulating biomarkers of SARS-CoV-2 infection and disease severity.

The current outbreak of coronavirus disease 2019 (COVID-19) is a global emergency, as its rapid spread and high mortality rate, which poses a significant threat to public health. Innate immunity plays a crucial role in the primary defense against infections, and recent studies have highlighted the pivotal regulatory function of long non-coding RNAs (lncRNAs) in innate immune responses. This study aims to assess the circulating levels of lncRNAs namely ANRIL, THRIL, NEAT1, and MALAT1 in the blood of moderate and severe SARS-CoV-2 infected patients, in comparison to healthy individuals. Additionally, it aims to explore the potential of these lncRNAs as biomarkers for determining the severity of the disease. The blood samples were collected from a total of 38 moderate and 25 severe COVID-19 patients, along with 30 healthy controls. The total RNA was extracted and qPCR was performed to evaluate the blood levels of the lncRNAs. The results indicate significantly higher expression levels of lncRNAs ANRIL and THRIL in severe patients when compared to moderate patients (P value= 0.0307, P value= 0.0059, respectively). Moreover, the expression levels of lncRNAs ANRIL and THRIL were significantly up-regulated in both moderate and severe patients in comparison to the control group (P value< 0.001, P value< 0.001, P value= 0.001, P value< 0.001, respectively). The expression levels of lncRNA NEAT1 were found to be significantly higher in both moderate and severe COVID-19 patients compared to the healthy group (P value< 0.001, P value< 0.001, respectively), and there was no significant difference in the expression levels of NEAT1 between moderate and severe patients (P value= 0.6979). The expression levels of MALAT1 in moderate and severe patients did not exhibit a significant difference compared to the control group (P value= 0.677, P value= 0.764, respectively). Furthermore, the discriminative power of ANRIL and THRIL was significantly higher in the severe patient group than the moderate group (Area under curve (AUC)= 0.6879; P-value= 0.0122, AUC= 0.6947; P-value= 0.0093, respectively). In conclusion, the expression levels of the lncRNAs ANRIL and THRIL are correlated with the severity of COVID-19 and can be regarded as circulating biomarkers for disease progression.