Investigating the Association Between Low Levels of Type I Interferons (Type I Ifns) and the Severity of Covid-19 Infection in Hemodialysis Patients

Background: Hemodialysis patients are at increased risk for severe COVID-19 outcomes, yet the role of innate immune dysfunction, particularly type I interferon (IFN-I) deficiency, remains poorly characterized in this population. This study aimed to investigate the association between baseline type I interferon levels and COVID-19 severity in hemodialysis patients. Methods: This prospective cohort study enrolled 150 hemodialysis patients with RT-PCR-confirmed SARS-CoV-2 infection. Serum IFN-α and IFN-β levels were measured at baseline (within 48 hours of diagnosis), peak illness (day 7-10), and convalescence (day 28) using ELISA. Patients were classified according to WHO Clinical Progression Scale as non-severe (scores 1-5) or severe (scores 6-10). Multivariable logistic regression, ROC curve analysis, and Kaplan-Meier survival analysis were performed.Results: A total of 142 patients completed follow-up (78 non-severe, 64 severe). Patients with severe COVID-19 had significantly lower baseline IFN-α (3.1 vs. 8.4 pg/mL, p<0.001) and IFN-β (1.9 vs. 4.6 pg/mL, p<0.001) levels. Low IFN-I levels (below 25th percentile) were independently associated with severe disease (adjusted OR 4.82, 95% CI 2.34-9.91, p<0.001). ROC analysis identified IFN-α <4.2 pg/mL as optimal cut-off for predicting severity (AUC 0.84, sensitivity 76.6%, specificity 82.1%). Patients with low IFN-I had higher ICU admission (57.9% vs. 26.9%, p<0.001), prolonged hospitalization (18 vs. 10 days, p<0.001), and increased 28-day mortality (31.6% vs. 10.6%, p=0.002).Conclusion: Low baseline type I interferon levels are independently associated with severe COVID-19 and increased mortality in hemodialysis patients. Assessment of IFN-I levels may enable early risk stratification and guide personalized management in this vulnerable population.