Functional Relationship of Interferon Regulator Factor-5, Interferon-γ, and Hypoxia-Induced Factor-1α with COVID-19 During Pregnancy Outcomes

Abstract Objective: Interferon-gamma (IFN-γ), interferon regulator factor-5 (IRF5), and hypoxia-induced factor-1 Alpha (HIF-1α) are amongst the key immune molecules that function in Coronavirus Disease 2019 (COVID-19). Herein, we aimed to investigate the levels of IFN-γ, IRF5, and HIF-1α in cases who had COVID-19 during their pregnancy.Methods: Thirty-three unvaccinated pregnant women with COVID-19, and 129 unvaccinated healthy pregnant women (control) were included in the study. IRF5, IFN-γ, and HIF-1α levels were investigated in blood samples taken from pregnants and newborns, and in tissue samples of placenta.Results: Mean IRF5 and IFN-γ levels in pregnant women with COVID-19 were significantly lower, whereas mean HIF-1α levels were significantly higher than the controls (p<0.001, for each). In the receiver operating characteristic (ROC) analyses of maternal samples for determination of post-COVID-19 infection; the cutoff value of 2.015 ng/mg protein for IRF5 level had a sensitivity of 81.8% and a specificity of 82.5% [area under the ROC curve (AUC): 0.161; p<0.001; lower bound (LB): 0.08; upper bound (UB): 0.241; confidence interval (CI) 95%)], and the cutoff value of 225.63 pg/mg protein for IFN-γ level had a sensitivity of 81.8% and a specificity of 85.7% (AUC: 0.147; p<0.001; LB:0.08; UB: 0.241; CI 95%).Conclusion: Our findings show that COVID-19 has a significant effect on IRF5, IFN-γ and HIF-1α levels in pregnant women, and thus these levels can be used as a reliable biomarker for the diagnosis of COVID-19 in pregnant women. To the best of our knowledge, the present study is first attempt to evaluate the funational implications of these immunoregulatory biomarkers in pregnant women with COVID-19.