Abstract
A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-β were screened in COVID-19 patients’ serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-β/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-β/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.
Keywords: COVID-19; ISG; Interferon; autoantibodies, SARS-CoV-2; binding antibodies; neutralizing antibodies.
【저자키워드】 COVID-19, Neutralizing antibodies, interferon, binding antibodies, ISG, autoantibodies, SARS-CoV-2, 【초록키워드】 neutralizing antibody, Gene Expression, severe COVID-19, Antiviral, Neutralizing antibodies, disease severity, interferon, LDH, CRP, D-dimer, outcome, ICU, cross-reactivity, serum, specificity, autoantibodies, sera, male, Patient, IFN, laboratory biomarkers, respiratory, binding antibodies, hematological parameters, Respiratory samples, patients, ISGs, binding, association, IFN response, COVID-19 patient, binding antibody, IFN-α, biochemical, IFN-stimulated genes, dimer, positive, transcript levels, fluctuation, shown, tested, proportion, reduced, screened, characterized, subset, positive patient, IFN-stimulated gene, quantified, laboratory biomarker, 【제목키워드】 neutralizing antibody, IFN response, COVID-19 patient, downregulation, laboratory biomarker,