Interplay of LncRNAs NEAT1 and TUG1 in Incidence of Cytokine Storm in Appraisal of COVID-19 Infection

Abstract

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.

Transcriptomic study reveals lncRNA-mediated downregulation of innate immune and inflammatory response in the SARS-CoV-2 vaccination breakthrough infections

“…Both MALAT1 and NEAT1 might be crucial for regulating the immune system and IL-6 mediated inflammation which is one of the key immune pathways that responds to the SARS-CoV-2 infection (64). Besides, NEAT1 also regulates the inflammation by modulating inflammasomes such as NLRP3, NLRC4, and AIM2, which may alter the immunological response to the COVID-19 infection (65).…”

COVID-19: Mechanisms, risk factors, genetics, non-coding RNAs and neurologic impairments

“…However, the strategy of using aptamer-miRNA-mediated HISLA knockdown, especially in associated macrophages, to treat COVID-19 needs further study. This chapter summarizes the involvement of lncRNAs in the regulation of COVID-19 ( Table 4 ) [ [141] , [142] , [143] , [144] , [145] , [146] , [147] ].…”

RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics

“…For example, lncRNA ROR1-AS1 and UGDH-AS1 have been reported to modulate immune response in the COVID-19 patients while NEAT1 , MALAT1 , and LINC00273 have been reported to modulate both immune and inflammatory response in severe COVID-19 patients. 31 , 32 , 33 , 34 Some of these lncRNAs, such as NEAT1 , MALAT1 , and UGDH-AS1 have been reported to regulate the pathophysiology and outcomes in other infectious diseases (such as influenza A virus, dengue virus, human immunodeficiency virus) as well. 35 , 36 , 37 Gaining insights into the host RNA editing would provide a clearer picture of the interplay between the host and the pathogen during an infection.…”