COVID-19 is characterized by a wide range of symptoms where the genetic background plays a key role in SARS-CoV-2 infection. In this study, the relative expression ofIRF9, CCL5, IFI6, TGFB1, IL1B, OAS1, andTFRCgenes (related to immunity and antiviral activity) was analyzed in upper airway samples from 127 individuals (97 COVID-19 positive and 30 controls) by using a two-step RT-PCR. All genes exceptingIL1B(p=0.878) showed a significantly higher expression (p<0.005) in COVID-19 cases than in the samples from the control group suggesting that in asymptomatic-mild cases antiviral and immune system cells recruitment gene expression is being promoted. Moreover,IFI6(p=0.002) andOAS1(p=0.044) were upregulated in cases with high viral loads, which could be related to protection against severe forms of this viral infection. In addition, a higher frequency (68.7%) of individuals infected with the Omicron variant presented higher viral load values of infection when compared to individuals infected with other variants (p<0.001). Furthermore, an increased expression ofIRF9(p<0.001), IFI6(p<0.001),OAS1(p=0.011), CCL5, (p=0.003) andTGFB1(p<0.001) genes was observed in individuals infected with SARS-CoV-2 wildtype virus, which might be due to immune response evasion of the viral variants and/or vaccination. The obtained results indicate a protective role ofIFI6,OAS1andIRF9in asymptomatic -mild cases of SARS-CoV-2 infection while the role ofTGFB1andCCL5in the pathogenesis of the disease is still unclear. The importance of studying the dysregulation of immune genes in relation to the infective variant is stand out in this study.