Inflammatory tropism in COVID-19: a comparative analysis of Delta and Omicron variants

The clinical presentation of COVID-19 varies significantly by viral variant; the Delta variant often causes severe lung inflammation, whereas Omicron tends to result in less severe respiratory disease but may more readily affect other organs. The autoimmune mechanisms behind these variant-specific complications, particularly the potential role of anti-neutrophil cytoplasmic (ANCA) antibodies, are still not well defined. This study investigated myeloperoxidase (MPO), proteinase 3 (PR3), and glomerular basement membrane (GBM) antibodies in patients infected with the Delta and Omicron SARS-CoV-2 variants to evaluate their associations with specific clinical complications, such as renal or respiratory involvement.

Samples were collected during Delta and Omicron outbreaks from hospitalized COVID-19 patients (40 Delta, 40 Omicron) and 40 healthy controls. Serum autoantibodies (MPO, PR3, GBM) were measured via ELISA, and laboratory/clinical data were collected.

All autoantibody levels remained within normal limits. Despite statistical significance (P < 0.05), effect sizes were small (η²=0.085-0.180). Anti-MPO was highest in the Delta group (1.08 U/mL) vs. Control (0.71 U/mL) and Omicron (0.77 U/mL). Anti-PR3 was lowest in the Delta group (0.83 U/mL) vs. Control (1.52 U/mL). Anti-GBM was lowest in the Omicron group (1.48 U/mL) vs. Control (3.48 U/mL) and Delta (3.10 U/mL). Clinically, the Delta group exhibited significantly lower oxygen saturation (92.28% ± 8.69) than the Omicron group (96.15% ± 2.77; P = 0.009). Markers of inflammation and tissue damage-including C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and coagulation parameters-were markedly elevated in the Delta group compared to the Omicron group (P < 0.001). Conversely, creatinine was significantly higher in the Omicron group (P < 0.001).

While autoantibody levels remained normal, clinical profiles diverged significantly between variants. The Delta variant was associated with heightened systemic inflammation, whereas Omicron was associated with greater organ involvement, suggesting the possibility of distinct pathogenic mechanisms.