Background: In 2019, the coronavirus pandemic emerged, resulting in the highest mortality and morbidity rate globally. It has a prevailing transmission rate and continues to be a global burden. There is a paucity of data regarding the role of long non-coding RNAs (lncRNAs) in COVID-19. Therefore, the current study aimed to investigate lncRNAs, particularly NEAT1 and TUG1, and their association with IL-6, CCL2, and TNF-α in COVID-19 patients with moderate and severe disease.

Methods: The study was conducted on 80 COVID-19 patients (35 with severe and 45 with moderate infection) and 40 control subjects. Complete blood count (CBC), D-dimer assay, serum ferritin, and CRP were assayed. qRT-PCR was used to measure RNAs and lncRNAs.

Results: NEAT1 and TUG1 expression levels were higher in COVID-19 patients compared with controls (P< 0.001). Furthermore, CCL2, IL-6, and TNF-α expressions were higher in COVID-19 patients compared to controls (P< 0.001). CCL2 and IL-6 expression levels were significantly higher in patients with severe compared to those with moderate COVID-19 infection (P< 0.001). IL-6 had the highest accuracy in distinguishing COVID-19 patients (AUC= 1, P< 0.001 at a cutoff of 0.359), followed by TUG1 (AUC= 0.999, P< 0.001 at a cutoff of 2.28). NEAT1 and TUG1 had significant correlations with the measured cytokines, and based on the multivariate regression analysis, NEAT1 is the independent predictor for survival in COVID-19 patients (P= 0.02).

Conclusion: In COVID-19 patients, significant overexpression of NEAT1 and TUG1 was observed, consistent with cytokine storm. TUG1 could be an efficient diagnostic biomarker, whereas NEAT1 was an independent predictor for overall survival.