Different Expression of Nuclear Respiratory Factor 1 (NRF-1) Gene in COVID-19: An Insight into Disease Severity

Mitochondrial quality control is carried out through mechanisms such as mitochondrial biogenesis, dynamics, and mitophagy. Recent studies have shown that SARS-CoV-2 can directly modulate mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is an important mediator of genes involved in mitochondrial biogenesis. A key role of NRF-1 in innate antiviral immunity and a link between innate immunity and mitochondrial quality control has been suggested. This study aims to investigate the NRF-1 levels in COVID-19 patients and compare between asymptomatic and symptomatic cases. Also, the diagnostic values ​​of NRF-1 in SARS-CoV-2 infection have been evaluated based on disease severity subgroups. Buffy coat samples were collected from 37 COVID-19 patients and 33 healthy individuals. The patient group was divided into the following subgroups: asymptomatic (n = 17), mild/moderate (n = 12), and severe (n = 8) based on clinical and laboratory parameters. After RNA extraction and cDNA synthesis, real-time PCR was used to determine relative expression levels of NRF-1. Our results showed that the NRF-1 levels were significantly higher in COVID-19 patients than in healthy individuals. Also, NRF-1 levels were increased in symptomatic, mild/moderate, and severe cases compared to asymptomatic COVID-19 patients. In addition, the results of ROC curve analysis showed that the level of NRF-1 has high discriminative power to differentiate between COVID-19 severity subgroups. NRF-1 mRNA levels are a promising biomarker for the COVID-19 severity. Further understanding of the role of NRF-1 and mitochondrial quality control in disease severity, and outcome of SARS-CoV-2 infection may help in COVID-19 managements.