Overexpression of OAS Genes in Severe COVID-19: A Cross-Sectional Study of Hospitalized Patients Infected with Delta and Omicron Variants

Background/Objectives: COVID-19 is an infectious disease caused by SARS-CoV-2. The innate immune response constitutes the first line of antiviral defense. Notably, interferon-stimulated genes, such as those belonging to the oligoadenylate synthetase (OAS) family, have been implicated in host susceptibility and the response to SARS-CoV-2 infection. However, the extent to which OAS gene expression varies across SARS-CoV-2 variants remains insufficiently characterized. Its relationship with clinical outcomes in hospitalized patients is also unclear. This study aimed to evaluate OAS gene expression and its association with inflammatory markers and clinical outcomes in patients with severe COVID-19. Methods: An analytical cross-sectional study was conducted in patients hospitalized with severe COVID-19 between October 2021 and February 2022. SARS-CoV-2 infection and viral variants were prescreened at admission. Clinical parameters were recorded, including serum cytokine levels (IL-1β, IL-6, IL-8, MCP-1, IFN-α, IFN-β, IFN-γ, and TNF-α), and hematological indices (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio). The COVID-GRAM risk score, treatment, and hospitalization outcomes were recorded. Relative mRNA expression of OAS1, OAS2, OAS3, and OAS-L was quantified by quantitative PCR, using TaqMan probes. Results: A total of 76 hospitalized patients with severe COVID-19 were included. In-hospital mortality was 32.9%, with a predominance of male patients (60%). Nearly 50% of non-survivors were infected with the Omicron variant. OAS1, OAS2, and OAS3 were overexpressed in hospitalized patients with severe COVID-19 compared with healthy subjects (HS) (log2 fold change 95% CI: OAS2: 4.312 4.161–4.602, OAS3: 1.660 1.485–1.916; p = 0.0040 for both). Expression of OAS2 and OAS3 was significantly increased in survivors compared with HS (log2 fold change: 4.312 4.161–4.602 and 1.711 1.485–1.990, respectively; p = 0.0009 and p = 0.0025). Similar increases were observed in non-survivors (4.554 4.251–4.743 and 1.640 1.081–2.301, respectively; p = 0.0002 and p = 0.0061) compared with HS. Conclusions: OAS genes, particularly OAS2 and OAS3, are overexpressed in severe COVID-19. This upregulation was comparable between Delta and Omicron infections, suggesting that the activation of this antiviral pathway is driven more by disease severity than by the specific viral variant.