Publication date: Jul 09, 2025
Background/Objectives: Neutralizing autoantibodies against type I interferons, particularly interferon-alpha (IFN-α), have been implicated in severe COVID-19 outcomes. This study investigated the prevalence and functional significance of anti-IFN-α autoantibodies (AAbs) in hospitalized unvaccinated COVID-19 patients and their association with COVID-19 disease severity. Methods: We retrospectively analyzed serum samples from 122 hospitalized COVID-19 patients (asymptomatic/mild: n = 69, moderate: n = 35, severe/critical: n = 18) and 32 healthy uninfected controls. Anti-IFN-α AAbs were quantified using a commercial enzyme-linked immunosorbent assay (ELISA) kit, with functional neutralization assessed via competitive ELISA and STAT1 phosphorylation inhibition. Statistical comparisons were performed using one-way ANOVA for parametric data and the Kruskal-Wallis test for non-parametric variables. Results: Anti-IFN-α AAbs were detected in 24. 6% of COVID-19 patients, with all clinical subgroups showing significantly higher titers compared to healthy controls (p < 0. 05). Although no significant differences in anti-IFN-α AAb levels were found between mild, moderate, and severe cases, patients with severe or critical COVID-19 had markedly higher mean titers (10,511. 3 ng/mL) compared to non-severe (mild + moderate) cases (375. 2 ng/mL, p < 0. 001). Strongly neutralizing anti-IFN-α AAbs, with high titers (>20,000 ng/mL) and the ability to inhibit STAT1 phosphorylation, were identified in three severe COVID-19 cases. Anti-IFN-α AAb levels correlated positively with CRP (r = 0. 80, p < 0. 0001), LDH (r = 0. 80, p = 0. 001), and neutrophil count (r = 0. 52, p = 0. 003), and negatively with lymphocyte count (r = -0. 59, p = 0. 0006). Conclusions: Elevated and functionally neutralizing anti-IFN-α AAbs were associated with severe COVID-19. These findings support their role as a risk factor for poor outcomes and emphasize the importance of early COVID-19 vaccination. Screening may help identify high-risk individuals, particularly those unvaccinated or with immune vulnerabilities.
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| Concepts | Keywords |
|---|---|
| Elisa | autoantibody |
| Lymphocyte | COVID-19 vaccination |
| Severe | IFN-α |
| Vaccination | SARS-CoV-2 |
| type I interferon |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | role |
| disease | MESH | COVID-19 |
| disease | IDO | assay |
| disease | MESH | Allergy |
| disease | MESH | Infectious Disease |
| pathway | REACTOME | Infectious disease |
| drug | DRUGBANK | Coenzyme M |
| drug | DRUGBANK | Natural alpha interferon |
| drug | DRUGBANK | Indoleacetic acid |
| drug | DRUGBANK | Tretamine |
| disease | MESH | viral infections |
| disease | IDO | host |
| disease | IDO | production |
| pathway | KEGG | Viral replication |
| disease | MESH | pneumonia |
| disease | IDO | history |
| disease | MESH | infections |
| drug | DRUGBANK | Omega-3 fatty acids |
| disease | IDO | blood |
| disease | MESH | Comorbidity |
| disease | MESH | sore throat |
| drug | DRUGBANK | Medical air |
| disease | MESH | respiratory failure |
| disease | MESH | septic shock |
| disease | IDO | symptom |
| drug | DRUGBANK | Sodium lauryl sulfate |
| disease | MESH | inflammation |